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Uric acid tied to pediatric diabetic kidney disease
ORLANDO – , according to a 7-year investigation of 539 children.
Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).
The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.
Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.
The 539 children, all part of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial, were assessed annually over a mean of 5.7 years. At baseline, they were 13.9 years old and had T2DM for 7.9 months, on average. The mean body mass index was 34.6 kg/m2, mean hemoglobin A1c was 6%.
Almost 20% of the children were hypertensive at baseline (130/80 mm Hg or higher); 26% were hyperuricemic (6.8 mg/dL or higher); and 6.1% had elevated urine albumin excretion (urine albumin creatinine ratio of at least 30 mg/g), a marker of renal pathology. At the end of follow-up, 18% had elevated albumin excretion and 37.4% were hypertensive.
“Hyperuricemia was common in youth with type 2 diabetes,” just as it’s been shown in adults with the disease. “Higher baseline SUA independently increase[s] risk for onset of hypertension and elevated urine albumin excretion,” Dr. Bjornstad said.
However, the association between SUA and elevated albumin excretion was statistically significant only in boys – 36% of the study population – and non-Hispanic whites, 20% of the subjects, after adjustment for BMI, hemoglobin A1c, estimated glomerular filtration rate, and use of ACE inhibitors and angiotensin II receptor blockers.
The National Institutes of Health funded the work. Dr. Bjornstad is a consultant for Boehringer Ingelheim.
SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.
ORLANDO – , according to a 7-year investigation of 539 children.
Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).
The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.
Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.
The 539 children, all part of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial, were assessed annually over a mean of 5.7 years. At baseline, they were 13.9 years old and had T2DM for 7.9 months, on average. The mean body mass index was 34.6 kg/m2, mean hemoglobin A1c was 6%.
Almost 20% of the children were hypertensive at baseline (130/80 mm Hg or higher); 26% were hyperuricemic (6.8 mg/dL or higher); and 6.1% had elevated urine albumin excretion (urine albumin creatinine ratio of at least 30 mg/g), a marker of renal pathology. At the end of follow-up, 18% had elevated albumin excretion and 37.4% were hypertensive.
“Hyperuricemia was common in youth with type 2 diabetes,” just as it’s been shown in adults with the disease. “Higher baseline SUA independently increase[s] risk for onset of hypertension and elevated urine albumin excretion,” Dr. Bjornstad said.
However, the association between SUA and elevated albumin excretion was statistically significant only in boys – 36% of the study population – and non-Hispanic whites, 20% of the subjects, after adjustment for BMI, hemoglobin A1c, estimated glomerular filtration rate, and use of ACE inhibitors and angiotensin II receptor blockers.
The National Institutes of Health funded the work. Dr. Bjornstad is a consultant for Boehringer Ingelheim.
SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.
ORLANDO – , according to a 7-year investigation of 539 children.
Every 1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02).
The finding adds to growing evidence that serum uric acid (SUA) isn’t just a marker of diabetic kidney disease, but a contributor to it. “There is definitely” cross-talk between gout and diabetes, said lead investigator Petter Bjornstad, MD, assistant professor of pediatric endocrinology at the University of Colorado, Aurora.
Elevated SUA is common in both conditions and a risk factor for kidney disease. Newer studies have linked higher levels to nephron number decline and other pathologies, perhaps through renal inflammation. Allopurinol, the traditional uric acid lowering agent in gout, is already under investigation to prevent kidney decline in adults with type 1 diabetes mellitus. There’s also evidence that the potent uric acid lowering agent, febuxostat (Uloric), attenuates hypofiltration in early diabetic kidney disease.
The 539 children, all part of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial, were assessed annually over a mean of 5.7 years. At baseline, they were 13.9 years old and had T2DM for 7.9 months, on average. The mean body mass index was 34.6 kg/m2, mean hemoglobin A1c was 6%.
Almost 20% of the children were hypertensive at baseline (130/80 mm Hg or higher); 26% were hyperuricemic (6.8 mg/dL or higher); and 6.1% had elevated urine albumin excretion (urine albumin creatinine ratio of at least 30 mg/g), a marker of renal pathology. At the end of follow-up, 18% had elevated albumin excretion and 37.4% were hypertensive.
“Hyperuricemia was common in youth with type 2 diabetes,” just as it’s been shown in adults with the disease. “Higher baseline SUA independently increase[s] risk for onset of hypertension and elevated urine albumin excretion,” Dr. Bjornstad said.
However, the association between SUA and elevated albumin excretion was statistically significant only in boys – 36% of the study population – and non-Hispanic whites, 20% of the subjects, after adjustment for BMI, hemoglobin A1c, estimated glomerular filtration rate, and use of ACE inhibitors and angiotensin II receptor blockers.
The National Institutes of Health funded the work. Dr. Bjornstad is a consultant for Boehringer Ingelheim.
SOURCE: Bjornstad P et al. ADA 2018, abstract 339-OR.
REPORTING FROM ADA 2018
Key clinical point: Serum uric acid lowering might help prevent kidney disease in children with T2DM.
Major finding: Every1-mg/dL climb in baseline serum uric acid increased the risk of subsequent elevated urine albumin excretion 1.23 fold, after adjustment for potential confounders (P = .02)
Study details: Seven-year investigation of 539 children with new-onset T2DM.
Disclosures: The National Institutes of Health funded the work. The study lead is a consultant for Boehringer Ingelheim.
Source: Bjornstad P et al. ADA 2018 Abstract 339-OR.
Chronic kidney disease is 40% more common in T2DM than T1DM
ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.
“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”
According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m2 or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.
Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.
The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.
Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).
These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.
Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.
“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.
“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”
No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.
SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.
“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”
According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m2 or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.
Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.
The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.
Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).
These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.
Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.
“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.
“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”
No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.
SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.
“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”
According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m2 or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.
Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.
The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.
Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).
These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.
Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.
“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.
“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”
No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.
SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
REPORTING FROM ADA 2018
Key clinical point: CKD is significantly more common in patients with T2DM than those with T1DM, and albumin testing provides crucial warning signs.
Major finding: Of subjects with T2DM, 44% had signs of CKD, compared with 32% of those with T1DM.
Study details: Analysis of LabCorp blood testing of more than 1.5 million U.S. adults with diabetes from 2014-2017.
Disclosures: No study funding was reported. Authors reported various disclosures, mostly employment for Covance or its parent company, LabCorp.
Source: Cressman M et al. ADA 2018, Abstract 544-P.
CANVAS program analysis: Canagliflozin benefits patients with T2DM and poor kidney function
ORLANDO – according to an analysis of data from the CANVAS program.
The findings suggest that it may be time to reconsider limitations on usage of the sodium-glucose transporter 2 inhibitor in patients with poor kidney function, Dick de Zeeuw, MD, PhD, said at the annual scientific sessions of the American Diabetes Association.
Despite the smaller glycemic effects in patients with reduced estimated glomerular filtration rate (eGFR) seen in CANVAS (CANagliflozin cardioVascular Assessment Study), the relative effects on the primary – and most other – cardiovascular outcomes in CANVAS were similar in patients with low (less than 60 mL/min per 1.72 m2 [2,029 patients]) versus high (greater than 60 mL/min per 1.72 m2 [8,101 patients]) eGFR, and across four eGFR subgroups (less than 45 mL/min per 1.72 m2 [554 patients], 45-60 mL/min per 1.72 m2 [1,485 patients], 60-90 mL/min per1.72 m2 [5,625 patients], and 90 or greater mL/min per 1.72 m2 [2,684 patients]), reported Dr. de Zeeuw of the University Medical Center Groningen, the Netherlands.
An exception was a possible finding of heterogeneity of treatment effect for the exploratory outcome of stroke, he noted.
As expected, the effects of canagliflozin versus placebo on the surrogate marker of HbA1c was significantly smaller with lower renal function, with reductions of 0.35%, 0.45%, 0.57%, and 0.76% across the four eGFR subgroups, respectively.
“But most interestingly, the three other cardiovascular risk markers show no difference in the effect of canagliflozin when we compare them for the four different eGFR groups,” he said, explaining that reductions in systolic blood pressure, body weight, and albuminuria were “very consistent” across the groups.
For the CANVAS 3-point major cardiac adverse event primary endpoint, which included a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (and which was reduced by 14% [hazard ratio, 0.86] with canagliflozin treatment in the primary CANVAS analysis), no significant heterogeneity for treatment effect was noted between the high versus low eGFR groups or the four eGFR groups (P = .08 and .33, respectively), Dr. de Zeeuw said.
“If anything, there was more effect in the low eGFR group than in the high eGFR group [HRs, 0.92 and 0.70, respectively; 0.65, 0.71, 0.95, and 0.84 for the four eGFR groups, respectively]”, he added, noting that the same was true for the cardiovascular death and MI components of the primary endpoint.
For stroke, however, possible heterogeneity by baseline kidney function was noted. In the primary CANVAS analysis, canagliflozin was associated with a nonsignificant 13% reduction in stroke risk (HR, 0.87), and the hazard ratios for low versus high eGFR in the current analysis were 0.50 and 1.01, respectively, and in the four eGFR groups they were 0.32, 0.56, 0.89, and 1.42 , respectively (P = .01 for both comparisons).
For the secondary endpoints of hospitalizations for heart failure and renal function (a composite of eGFR, end-stage kidney disease, or renal death), which both were important outcomes in the CANVAS program with each showing highly significant reductions with canagliflozin treatment versus placebo in the primary analysis (HRs, 0.67 and 0.60), no heterogeneity by eGFR was seen in the current analysis.
As for safety outcomes, which included serious adverse events, adverse events leading to treatment discontinuation, amputation, fractures, and renal safety (serious renal-related adverse events, serious acute kidney injury, and serious hyperkalemia), no heterogeneity was seen in the outcomes across eGFR groups, he said.
“The CANVAS program ... is a composite of two cardiovascular safety trials that have been conducted over the past [8+] years,” Dr. de Zeeuw said, noting that participants included patients with type 2 diabetes mellitus and cardiovascular disease or high cardiovascular risk who were treated with either 300 mg or 100 mg of canagliflozin or with placebo after a 2-week placebo run-in.
The outcomes favored canagliflozin across all endpoints, and particularly for the secondary endpoints of hospitalization for heart failure and the composite of renal outcomes.
“The interest [in terms of the current analysis] is that this drug supposedly works better in those that have a functioning kidney and a filtering kidney, where the tubule is actually the target of this drug. It was anticipated that there would be less effect of this drug on low renal functions,” he said, adding that although the effect on HbA1c is progressively attenuated with declining renal function, as expected, the effects on other cardiovascular risk markers were, surprisingly, very comparable across the eGFR subgroups.
“And with that, more importantly, the effect on the hard outcomes – like the primary outcomes, most of the CV outcomes [maybe except stroke], the renal and safety outcomes – are very consistent across the different kidney function levels,” he said, adding that these beneficial findings in patients with 30-45 eGFR who are at high cardiovascular and renal risk suggest that reconsideration of the current limitation on the use of canagliflozin inhibitors to patients with eGFR above 45 is warranted.
The CANVAS program was sponsored by Janssen Research & Development. Dr. de Zeeuw is a consultant and/or speaker for AbbVie, Astellas, Bayer, Boehringer Ingelheim, Fresenius, Janssen, and Mitsubishi Tanabe.
SOURCE: de Zeeuw D et al. ADA 2018, Abstract 258-OR.
ORLANDO – according to an analysis of data from the CANVAS program.
The findings suggest that it may be time to reconsider limitations on usage of the sodium-glucose transporter 2 inhibitor in patients with poor kidney function, Dick de Zeeuw, MD, PhD, said at the annual scientific sessions of the American Diabetes Association.
Despite the smaller glycemic effects in patients with reduced estimated glomerular filtration rate (eGFR) seen in CANVAS (CANagliflozin cardioVascular Assessment Study), the relative effects on the primary – and most other – cardiovascular outcomes in CANVAS were similar in patients with low (less than 60 mL/min per 1.72 m2 [2,029 patients]) versus high (greater than 60 mL/min per 1.72 m2 [8,101 patients]) eGFR, and across four eGFR subgroups (less than 45 mL/min per 1.72 m2 [554 patients], 45-60 mL/min per 1.72 m2 [1,485 patients], 60-90 mL/min per1.72 m2 [5,625 patients], and 90 or greater mL/min per 1.72 m2 [2,684 patients]), reported Dr. de Zeeuw of the University Medical Center Groningen, the Netherlands.
An exception was a possible finding of heterogeneity of treatment effect for the exploratory outcome of stroke, he noted.
As expected, the effects of canagliflozin versus placebo on the surrogate marker of HbA1c was significantly smaller with lower renal function, with reductions of 0.35%, 0.45%, 0.57%, and 0.76% across the four eGFR subgroups, respectively.
“But most interestingly, the three other cardiovascular risk markers show no difference in the effect of canagliflozin when we compare them for the four different eGFR groups,” he said, explaining that reductions in systolic blood pressure, body weight, and albuminuria were “very consistent” across the groups.
For the CANVAS 3-point major cardiac adverse event primary endpoint, which included a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (and which was reduced by 14% [hazard ratio, 0.86] with canagliflozin treatment in the primary CANVAS analysis), no significant heterogeneity for treatment effect was noted between the high versus low eGFR groups or the four eGFR groups (P = .08 and .33, respectively), Dr. de Zeeuw said.
“If anything, there was more effect in the low eGFR group than in the high eGFR group [HRs, 0.92 and 0.70, respectively; 0.65, 0.71, 0.95, and 0.84 for the four eGFR groups, respectively]”, he added, noting that the same was true for the cardiovascular death and MI components of the primary endpoint.
For stroke, however, possible heterogeneity by baseline kidney function was noted. In the primary CANVAS analysis, canagliflozin was associated with a nonsignificant 13% reduction in stroke risk (HR, 0.87), and the hazard ratios for low versus high eGFR in the current analysis were 0.50 and 1.01, respectively, and in the four eGFR groups they were 0.32, 0.56, 0.89, and 1.42 , respectively (P = .01 for both comparisons).
For the secondary endpoints of hospitalizations for heart failure and renal function (a composite of eGFR, end-stage kidney disease, or renal death), which both were important outcomes in the CANVAS program with each showing highly significant reductions with canagliflozin treatment versus placebo in the primary analysis (HRs, 0.67 and 0.60), no heterogeneity by eGFR was seen in the current analysis.
As for safety outcomes, which included serious adverse events, adverse events leading to treatment discontinuation, amputation, fractures, and renal safety (serious renal-related adverse events, serious acute kidney injury, and serious hyperkalemia), no heterogeneity was seen in the outcomes across eGFR groups, he said.
“The CANVAS program ... is a composite of two cardiovascular safety trials that have been conducted over the past [8+] years,” Dr. de Zeeuw said, noting that participants included patients with type 2 diabetes mellitus and cardiovascular disease or high cardiovascular risk who were treated with either 300 mg or 100 mg of canagliflozin or with placebo after a 2-week placebo run-in.
The outcomes favored canagliflozin across all endpoints, and particularly for the secondary endpoints of hospitalization for heart failure and the composite of renal outcomes.
“The interest [in terms of the current analysis] is that this drug supposedly works better in those that have a functioning kidney and a filtering kidney, where the tubule is actually the target of this drug. It was anticipated that there would be less effect of this drug on low renal functions,” he said, adding that although the effect on HbA1c is progressively attenuated with declining renal function, as expected, the effects on other cardiovascular risk markers were, surprisingly, very comparable across the eGFR subgroups.
“And with that, more importantly, the effect on the hard outcomes – like the primary outcomes, most of the CV outcomes [maybe except stroke], the renal and safety outcomes – are very consistent across the different kidney function levels,” he said, adding that these beneficial findings in patients with 30-45 eGFR who are at high cardiovascular and renal risk suggest that reconsideration of the current limitation on the use of canagliflozin inhibitors to patients with eGFR above 45 is warranted.
The CANVAS program was sponsored by Janssen Research & Development. Dr. de Zeeuw is a consultant and/or speaker for AbbVie, Astellas, Bayer, Boehringer Ingelheim, Fresenius, Janssen, and Mitsubishi Tanabe.
SOURCE: de Zeeuw D et al. ADA 2018, Abstract 258-OR.
ORLANDO – according to an analysis of data from the CANVAS program.
The findings suggest that it may be time to reconsider limitations on usage of the sodium-glucose transporter 2 inhibitor in patients with poor kidney function, Dick de Zeeuw, MD, PhD, said at the annual scientific sessions of the American Diabetes Association.
Despite the smaller glycemic effects in patients with reduced estimated glomerular filtration rate (eGFR) seen in CANVAS (CANagliflozin cardioVascular Assessment Study), the relative effects on the primary – and most other – cardiovascular outcomes in CANVAS were similar in patients with low (less than 60 mL/min per 1.72 m2 [2,029 patients]) versus high (greater than 60 mL/min per 1.72 m2 [8,101 patients]) eGFR, and across four eGFR subgroups (less than 45 mL/min per 1.72 m2 [554 patients], 45-60 mL/min per 1.72 m2 [1,485 patients], 60-90 mL/min per1.72 m2 [5,625 patients], and 90 or greater mL/min per 1.72 m2 [2,684 patients]), reported Dr. de Zeeuw of the University Medical Center Groningen, the Netherlands.
An exception was a possible finding of heterogeneity of treatment effect for the exploratory outcome of stroke, he noted.
As expected, the effects of canagliflozin versus placebo on the surrogate marker of HbA1c was significantly smaller with lower renal function, with reductions of 0.35%, 0.45%, 0.57%, and 0.76% across the four eGFR subgroups, respectively.
“But most interestingly, the three other cardiovascular risk markers show no difference in the effect of canagliflozin when we compare them for the four different eGFR groups,” he said, explaining that reductions in systolic blood pressure, body weight, and albuminuria were “very consistent” across the groups.
For the CANVAS 3-point major cardiac adverse event primary endpoint, which included a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (and which was reduced by 14% [hazard ratio, 0.86] with canagliflozin treatment in the primary CANVAS analysis), no significant heterogeneity for treatment effect was noted between the high versus low eGFR groups or the four eGFR groups (P = .08 and .33, respectively), Dr. de Zeeuw said.
“If anything, there was more effect in the low eGFR group than in the high eGFR group [HRs, 0.92 and 0.70, respectively; 0.65, 0.71, 0.95, and 0.84 for the four eGFR groups, respectively]”, he added, noting that the same was true for the cardiovascular death and MI components of the primary endpoint.
For stroke, however, possible heterogeneity by baseline kidney function was noted. In the primary CANVAS analysis, canagliflozin was associated with a nonsignificant 13% reduction in stroke risk (HR, 0.87), and the hazard ratios for low versus high eGFR in the current analysis were 0.50 and 1.01, respectively, and in the four eGFR groups they were 0.32, 0.56, 0.89, and 1.42 , respectively (P = .01 for both comparisons).
For the secondary endpoints of hospitalizations for heart failure and renal function (a composite of eGFR, end-stage kidney disease, or renal death), which both were important outcomes in the CANVAS program with each showing highly significant reductions with canagliflozin treatment versus placebo in the primary analysis (HRs, 0.67 and 0.60), no heterogeneity by eGFR was seen in the current analysis.
As for safety outcomes, which included serious adverse events, adverse events leading to treatment discontinuation, amputation, fractures, and renal safety (serious renal-related adverse events, serious acute kidney injury, and serious hyperkalemia), no heterogeneity was seen in the outcomes across eGFR groups, he said.
“The CANVAS program ... is a composite of two cardiovascular safety trials that have been conducted over the past [8+] years,” Dr. de Zeeuw said, noting that participants included patients with type 2 diabetes mellitus and cardiovascular disease or high cardiovascular risk who were treated with either 300 mg or 100 mg of canagliflozin or with placebo after a 2-week placebo run-in.
The outcomes favored canagliflozin across all endpoints, and particularly for the secondary endpoints of hospitalization for heart failure and the composite of renal outcomes.
“The interest [in terms of the current analysis] is that this drug supposedly works better in those that have a functioning kidney and a filtering kidney, where the tubule is actually the target of this drug. It was anticipated that there would be less effect of this drug on low renal functions,” he said, adding that although the effect on HbA1c is progressively attenuated with declining renal function, as expected, the effects on other cardiovascular risk markers were, surprisingly, very comparable across the eGFR subgroups.
“And with that, more importantly, the effect on the hard outcomes – like the primary outcomes, most of the CV outcomes [maybe except stroke], the renal and safety outcomes – are very consistent across the different kidney function levels,” he said, adding that these beneficial findings in patients with 30-45 eGFR who are at high cardiovascular and renal risk suggest that reconsideration of the current limitation on the use of canagliflozin inhibitors to patients with eGFR above 45 is warranted.
The CANVAS program was sponsored by Janssen Research & Development. Dr. de Zeeuw is a consultant and/or speaker for AbbVie, Astellas, Bayer, Boehringer Ingelheim, Fresenius, Janssen, and Mitsubishi Tanabe.
SOURCE: de Zeeuw D et al. ADA 2018, Abstract 258-OR.
REPORTING FROM ADA 2018
Key clinical point: Cardioprotective benefits of canagliflozin in patients with type 2 diabetes mellitus were apparent across varying levels of kidney function.
Major finding: No heterogeneity for treatment effect for the primary major cardiac adverse event endpoint was noted between the high versus low estimated glomerular filtration rate groups (P = .08).
Study details: An analysis of data from the CANVAS program studies involving 10,142 patients.
Disclosures: The CANVAS program was sponsored by Janssen Research & Development. Dr. de Zeeuw is a consultant and/or speaker for AbbVie, Astellas, Bayer, Boehringer Ingelheim, Fresenius, Janssen, and Mitsubishi Tanabe Pharma.
Source: de Zeeuw D et al. ADA 2018, Abstract 258-OR.
High risk of low glucose? Hospital alerts promise a crucial heads-up
ORLANDO – Researchers have been able to sustain a dramatic reduction in hypoglycemia incidents at nine St. Louis–area hospitals, thanks to a computer algorithm that warns medical staff when patients appear to be on the road to dangerously low blood sugar levels.
The 6-year retrospective system-wide study, which was released at the annual scientific sessions of the American Diabetes Association, found that the use of the alert system lowered the annual occurrence of severe hypoglycemia events by 41% at the hospitals.
In at-risk patients – those with blood glucose levels under 90 mg/dL – the system considers several variables, such as their weight, creatinine clearance, insulin therapy, and basal insulin doses. If the algorithm considers that a patient is at high risk of a sub–40-mg/dL glucose level – dangerously low – it sends a single alert to medical staff during the patient’s stay.
The idea is that the real-time alerts will go to nurses or pharmacists who will review patient charts and then contact physicians. The doctors are expected to “make clinically appropriate changes,” Dr. Tobin said.
Earlier, Dr. Tobin and colleagues prospectively analyzed the alert system’s effectiveness at a single hospital for 5 months. The trial, a cohort intervention study, tracked 655 patients with a blood glucose level under 90 mg/dL.
In 2014, the researchers reported the results of that trial: The alert identified 390 of the patients as being at high risk for severe hypoglycemia (blood glucose under 40 mg/dL). The frequency of severe hypoglycemia events was just 3.1% in this population vs. 9.7% in unalerted patients who were also deemed to be at high risk (J Hosp Med. 2014[9]: 621-6).
For the new study, researchers extended the alert system to nine hospitals and tracked its use from 2011 to 2017.
During all visits, the number of severe hypoglycemic events fell from 2.9 to 1.7 per 1,000 at-risk patient days. (P less than .001)
At one hospital, Dr. Tobin said, the average monthly number of severe hypoglycemia incidents fell from 40 to 12.
Researchers found that the average blood glucose level post alert was 93 mg/dL vs. 74 mg/dL before alert. They also reported that the system-wide total of alerts per year ranged from 4,142 to 5,649.
“The current data reflected in our poster show that the alert process is sustainable over a wide range of clinical settings, including community hospitals of various size and complexity, as well as academic medical centers,” Dr. Tobin said.
The alert system had no effect on hyperglycemia, Dr. Tobin said.
In regard to expense, Dr. Tobin said it’s small because the alert system uses existing current staff and computer systems. Setup costs, he said, included programming, creating the alert infrastructure, and staff training
No study funding is reported. Dr. Tobin reports relationships with Novo Nordisk (advisory board, speaker’s bureau) and MannKind (speaker’s bureau). The other authors report no relevant disclosures.
SOURCE: Tobin G et al. ADA 2018. Abstract 397-P.
ORLANDO – Researchers have been able to sustain a dramatic reduction in hypoglycemia incidents at nine St. Louis–area hospitals, thanks to a computer algorithm that warns medical staff when patients appear to be on the road to dangerously low blood sugar levels.
The 6-year retrospective system-wide study, which was released at the annual scientific sessions of the American Diabetes Association, found that the use of the alert system lowered the annual occurrence of severe hypoglycemia events by 41% at the hospitals.
In at-risk patients – those with blood glucose levels under 90 mg/dL – the system considers several variables, such as their weight, creatinine clearance, insulin therapy, and basal insulin doses. If the algorithm considers that a patient is at high risk of a sub–40-mg/dL glucose level – dangerously low – it sends a single alert to medical staff during the patient’s stay.
The idea is that the real-time alerts will go to nurses or pharmacists who will review patient charts and then contact physicians. The doctors are expected to “make clinically appropriate changes,” Dr. Tobin said.
Earlier, Dr. Tobin and colleagues prospectively analyzed the alert system’s effectiveness at a single hospital for 5 months. The trial, a cohort intervention study, tracked 655 patients with a blood glucose level under 90 mg/dL.
In 2014, the researchers reported the results of that trial: The alert identified 390 of the patients as being at high risk for severe hypoglycemia (blood glucose under 40 mg/dL). The frequency of severe hypoglycemia events was just 3.1% in this population vs. 9.7% in unalerted patients who were also deemed to be at high risk (J Hosp Med. 2014[9]: 621-6).
For the new study, researchers extended the alert system to nine hospitals and tracked its use from 2011 to 2017.
During all visits, the number of severe hypoglycemic events fell from 2.9 to 1.7 per 1,000 at-risk patient days. (P less than .001)
At one hospital, Dr. Tobin said, the average monthly number of severe hypoglycemia incidents fell from 40 to 12.
Researchers found that the average blood glucose level post alert was 93 mg/dL vs. 74 mg/dL before alert. They also reported that the system-wide total of alerts per year ranged from 4,142 to 5,649.
“The current data reflected in our poster show that the alert process is sustainable over a wide range of clinical settings, including community hospitals of various size and complexity, as well as academic medical centers,” Dr. Tobin said.
The alert system had no effect on hyperglycemia, Dr. Tobin said.
In regard to expense, Dr. Tobin said it’s small because the alert system uses existing current staff and computer systems. Setup costs, he said, included programming, creating the alert infrastructure, and staff training
No study funding is reported. Dr. Tobin reports relationships with Novo Nordisk (advisory board, speaker’s bureau) and MannKind (speaker’s bureau). The other authors report no relevant disclosures.
SOURCE: Tobin G et al. ADA 2018. Abstract 397-P.
ORLANDO – Researchers have been able to sustain a dramatic reduction in hypoglycemia incidents at nine St. Louis–area hospitals, thanks to a computer algorithm that warns medical staff when patients appear to be on the road to dangerously low blood sugar levels.
The 6-year retrospective system-wide study, which was released at the annual scientific sessions of the American Diabetes Association, found that the use of the alert system lowered the annual occurrence of severe hypoglycemia events by 41% at the hospitals.
In at-risk patients – those with blood glucose levels under 90 mg/dL – the system considers several variables, such as their weight, creatinine clearance, insulin therapy, and basal insulin doses. If the algorithm considers that a patient is at high risk of a sub–40-mg/dL glucose level – dangerously low – it sends a single alert to medical staff during the patient’s stay.
The idea is that the real-time alerts will go to nurses or pharmacists who will review patient charts and then contact physicians. The doctors are expected to “make clinically appropriate changes,” Dr. Tobin said.
Earlier, Dr. Tobin and colleagues prospectively analyzed the alert system’s effectiveness at a single hospital for 5 months. The trial, a cohort intervention study, tracked 655 patients with a blood glucose level under 90 mg/dL.
In 2014, the researchers reported the results of that trial: The alert identified 390 of the patients as being at high risk for severe hypoglycemia (blood glucose under 40 mg/dL). The frequency of severe hypoglycemia events was just 3.1% in this population vs. 9.7% in unalerted patients who were also deemed to be at high risk (J Hosp Med. 2014[9]: 621-6).
For the new study, researchers extended the alert system to nine hospitals and tracked its use from 2011 to 2017.
During all visits, the number of severe hypoglycemic events fell from 2.9 to 1.7 per 1,000 at-risk patient days. (P less than .001)
At one hospital, Dr. Tobin said, the average monthly number of severe hypoglycemia incidents fell from 40 to 12.
Researchers found that the average blood glucose level post alert was 93 mg/dL vs. 74 mg/dL before alert. They also reported that the system-wide total of alerts per year ranged from 4,142 to 5,649.
“The current data reflected in our poster show that the alert process is sustainable over a wide range of clinical settings, including community hospitals of various size and complexity, as well as academic medical centers,” Dr. Tobin said.
The alert system had no effect on hyperglycemia, Dr. Tobin said.
In regard to expense, Dr. Tobin said it’s small because the alert system uses existing current staff and computer systems. Setup costs, he said, included programming, creating the alert infrastructure, and staff training
No study funding is reported. Dr. Tobin reports relationships with Novo Nordisk (advisory board, speaker’s bureau) and MannKind (speaker’s bureau). The other authors report no relevant disclosures.
SOURCE: Tobin G et al. ADA 2018. Abstract 397-P.
REPORTING FROM ADA 2018
Key clinical point: Hospitals were able to sustain lower numbers of severe hypoglycemia events over 6 years by using a prewarning alert system.
Major finding: The number of severe hypoglycemic events (below 40 mg/dL) fell from 2.9 per 1,000 at-risk patient-days to 1.7 per 1,000 at-risk patient-days.
Study details: Retrospective, system-wide study of nine hospitals with alert system in place from 2011 to 2017.
Disclosures: No funding is reported. One author reports relationships with Novo Nordisk and MannKind. The other authors report no relevant disclosures.
Source: Tobin G et al. ADA 2018. Abstract 397-P.
Study questions canagliflozin amputation risk, but concerns remain
ORLANDO – but clinicians should still favor other options in patients at risk for amputations, according to investigator John Buse, MD, PhD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill.
Canagliflozin is the only sodium-glucose transporter 2 (SGLT2) inhibitor that carries a black box warning of “lower limb amputations, most frequently of the toe and midfoot” but also the leg. The drug doubled the risk versus placebo in its approval trials, particularly in patients with baseline histories of prior amputations, peripheral vascular disease, neuropathy, or diabetic foot ulcers.
One trial, for instance, reported 7.5 amputations per 1,000 patient years versus 4.2 with placebo, according to labeling.
The new, observational study, which was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of Dr. Buse, conducted by its employees, found no such connection. Investigators reviewed claims data from 142,800 new users of canagliflozin, 110,897 new users of the competing SGLT2 inhibitors empagliflozin (Jardiance) and dapagliflozin (Farxiga), and 460,885 new users of other diabetes drugs except for metformin, Dr. Buse said when he presented the results at the annual scientific sessions of the American Diabetes Association.
The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30). The ratio versus other SGLT2 inhibitors was 1.14 (95% CI, 0.67-1.93; P = 0.53). Overall, there were 1-5 amputations per 1,000 patient years with the drug.
However, the median follow-up was a few months, far shorter than the median follow-up of over 2 years in the randomized trials. “Therefore, the current study had limited statistical power to detect differences in the 6-12 month time period, the time at which amputation risk began to emerge” in the trials, the study report noted. Also, the investigators didn’t parse out results according to baseline amputation risk. Overall, “none of the analyses were sufficiently powered to rule out the possibility of a modest effect” on amputation rates (Diabetes Obes Metab. 2018 Jun 25. doi: 10.1111/dom.13424).
When moderator Robert H. Eckel, MD, a professor in the division of endocrinology, metabolism, and diabetes at the University of Colorado at Denver, Aurora, asked the 150 or so people who heard the presentation if they use SGLT2 inhibitors in their practices, only a small number raised their hands. Few, if any, raised their hands when he asked if the new results would make them more comfortable prescribing canagliflozin.
“I find [the study] somewhat informative,” Dr. Eckel said in an interview afterwards, “but I think the issue is that the prescribing label still demands that patients be informed of the black box warning. I think we are going to have to wait for the longer term outcomes to determine if [amputation] is a molecule effect or a class effect.”
Dr. Buse later said that “I think for the general population of patients with diabetes, they are at low risk for an amputation,” but “if you are at high risk for having an amputation, we really have to take this risk very seriously. [Canagliflozin] may increase your risk for amputation.
“If I have a patient who has had an amputation and I want to use an SGLT2 inhibitor, I wouldn’t use canagliflozin because of the label. I would use empagliflozin because [amputation] is not in the label, and there was no evidence” of it in trials, he added.
The new study, meanwhile, confirmed the cardiac benefits of SGLT2 inhibitors in type 2 patients. Canagliflozin, for instance, reduced the risk of hospitalization for heart failure by about 60%, compared with non-SGLT2 inhibitors in patients with cardiovascular disease, but it offered no statistically significant heart benefit over other members of its class.
Dr. Buse is an investigator for Johnson and Johnson.
ORLANDO – but clinicians should still favor other options in patients at risk for amputations, according to investigator John Buse, MD, PhD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill.
Canagliflozin is the only sodium-glucose transporter 2 (SGLT2) inhibitor that carries a black box warning of “lower limb amputations, most frequently of the toe and midfoot” but also the leg. The drug doubled the risk versus placebo in its approval trials, particularly in patients with baseline histories of prior amputations, peripheral vascular disease, neuropathy, or diabetic foot ulcers.
One trial, for instance, reported 7.5 amputations per 1,000 patient years versus 4.2 with placebo, according to labeling.
The new, observational study, which was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of Dr. Buse, conducted by its employees, found no such connection. Investigators reviewed claims data from 142,800 new users of canagliflozin, 110,897 new users of the competing SGLT2 inhibitors empagliflozin (Jardiance) and dapagliflozin (Farxiga), and 460,885 new users of other diabetes drugs except for metformin, Dr. Buse said when he presented the results at the annual scientific sessions of the American Diabetes Association.
The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30). The ratio versus other SGLT2 inhibitors was 1.14 (95% CI, 0.67-1.93; P = 0.53). Overall, there were 1-5 amputations per 1,000 patient years with the drug.
However, the median follow-up was a few months, far shorter than the median follow-up of over 2 years in the randomized trials. “Therefore, the current study had limited statistical power to detect differences in the 6-12 month time period, the time at which amputation risk began to emerge” in the trials, the study report noted. Also, the investigators didn’t parse out results according to baseline amputation risk. Overall, “none of the analyses were sufficiently powered to rule out the possibility of a modest effect” on amputation rates (Diabetes Obes Metab. 2018 Jun 25. doi: 10.1111/dom.13424).
When moderator Robert H. Eckel, MD, a professor in the division of endocrinology, metabolism, and diabetes at the University of Colorado at Denver, Aurora, asked the 150 or so people who heard the presentation if they use SGLT2 inhibitors in their practices, only a small number raised their hands. Few, if any, raised their hands when he asked if the new results would make them more comfortable prescribing canagliflozin.
“I find [the study] somewhat informative,” Dr. Eckel said in an interview afterwards, “but I think the issue is that the prescribing label still demands that patients be informed of the black box warning. I think we are going to have to wait for the longer term outcomes to determine if [amputation] is a molecule effect or a class effect.”
Dr. Buse later said that “I think for the general population of patients with diabetes, they are at low risk for an amputation,” but “if you are at high risk for having an amputation, we really have to take this risk very seriously. [Canagliflozin] may increase your risk for amputation.
“If I have a patient who has had an amputation and I want to use an SGLT2 inhibitor, I wouldn’t use canagliflozin because of the label. I would use empagliflozin because [amputation] is not in the label, and there was no evidence” of it in trials, he added.
The new study, meanwhile, confirmed the cardiac benefits of SGLT2 inhibitors in type 2 patients. Canagliflozin, for instance, reduced the risk of hospitalization for heart failure by about 60%, compared with non-SGLT2 inhibitors in patients with cardiovascular disease, but it offered no statistically significant heart benefit over other members of its class.
Dr. Buse is an investigator for Johnson and Johnson.
ORLANDO – but clinicians should still favor other options in patients at risk for amputations, according to investigator John Buse, MD, PhD, chief of the division of endocrinology at the University of North Carolina at Chapel Hill.
Canagliflozin is the only sodium-glucose transporter 2 (SGLT2) inhibitor that carries a black box warning of “lower limb amputations, most frequently of the toe and midfoot” but also the leg. The drug doubled the risk versus placebo in its approval trials, particularly in patients with baseline histories of prior amputations, peripheral vascular disease, neuropathy, or diabetic foot ulcers.
One trial, for instance, reported 7.5 amputations per 1,000 patient years versus 4.2 with placebo, according to labeling.
The new, observational study, which was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of Dr. Buse, conducted by its employees, found no such connection. Investigators reviewed claims data from 142,800 new users of canagliflozin, 110,897 new users of the competing SGLT2 inhibitors empagliflozin (Jardiance) and dapagliflozin (Farxiga), and 460,885 new users of other diabetes drugs except for metformin, Dr. Buse said when he presented the results at the annual scientific sessions of the American Diabetes Association.
The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30). The ratio versus other SGLT2 inhibitors was 1.14 (95% CI, 0.67-1.93; P = 0.53). Overall, there were 1-5 amputations per 1,000 patient years with the drug.
However, the median follow-up was a few months, far shorter than the median follow-up of over 2 years in the randomized trials. “Therefore, the current study had limited statistical power to detect differences in the 6-12 month time period, the time at which amputation risk began to emerge” in the trials, the study report noted. Also, the investigators didn’t parse out results according to baseline amputation risk. Overall, “none of the analyses were sufficiently powered to rule out the possibility of a modest effect” on amputation rates (Diabetes Obes Metab. 2018 Jun 25. doi: 10.1111/dom.13424).
When moderator Robert H. Eckel, MD, a professor in the division of endocrinology, metabolism, and diabetes at the University of Colorado at Denver, Aurora, asked the 150 or so people who heard the presentation if they use SGLT2 inhibitors in their practices, only a small number raised their hands. Few, if any, raised their hands when he asked if the new results would make them more comfortable prescribing canagliflozin.
“I find [the study] somewhat informative,” Dr. Eckel said in an interview afterwards, “but I think the issue is that the prescribing label still demands that patients be informed of the black box warning. I think we are going to have to wait for the longer term outcomes to determine if [amputation] is a molecule effect or a class effect.”
Dr. Buse later said that “I think for the general population of patients with diabetes, they are at low risk for an amputation,” but “if you are at high risk for having an amputation, we really have to take this risk very seriously. [Canagliflozin] may increase your risk for amputation.
“If I have a patient who has had an amputation and I want to use an SGLT2 inhibitor, I wouldn’t use canagliflozin because of the label. I would use empagliflozin because [amputation] is not in the label, and there was no evidence” of it in trials, he added.
The new study, meanwhile, confirmed the cardiac benefits of SGLT2 inhibitors in type 2 patients. Canagliflozin, for instance, reduced the risk of hospitalization for heart failure by about 60%, compared with non-SGLT2 inhibitors in patients with cardiovascular disease, but it offered no statistically significant heart benefit over other members of its class.
Dr. Buse is an investigator for Johnson and Johnson.
REPORTING FROM ADA 2018
Key clinical point: A large, observational study found no increased risk of below-the-knee amputations with canagliflozin for type 2 diabetes, but clinicians should still favor other options in patients at risk for amputations.
Major finding: The hazard ratio for below-knee amputations with canagliflozin versus non-SGLT2 inhibitors was 0.75 (95% confidence interval, 0.40-1.41; P = 0.30).
Study details: An observational study of over 700,000 patients with type 2 diabetes.
Disclosures: The work was funded by canagliflozin’s maker Johnson & Johnson and, with the exception of the presenter, conducted by its employees.
Pancreas volume studies may offer insight into T1DM
ORLANDO – The pancreas is drawing wider interest among scientists: In one study, researchers report that already-shrunken organs keep atrophying in young people with recently diagnosed type 1 diabetes mellitus (T1DM) even as they go through adolescent growth. And another study finds that the pancreas is smaller in first-degree relatives of people with T1DM, especially relatives with pre-T1DM.
“Pancreas volume is a really exciting area of research because it may tell us something about diabetes that we just didn’t understand before,” said pediatric endocrinologist Michael J. Haller, MD, of the University of Florida, Gainesville, in an interview. Dr. Haller is coauthor of the study into pancreas volume in first-degree relatives. That study’s findings, along with the results of a Vanderbilt University/University of Texas study into pancreas volume in early T1DM, were presented at the annual meeting of the American Diabetes Association.
Scientists already know that the pancreas is 40% smaller in people who have lived with T1DM, Dr. Haller said, and “we now know that occurs long before the clinical diagnosis has been made.”
The pancreas volume mystery, he said, revolves around the fact that only 2%-3% of the organ is made up of beta cells, which make insulin. So why is there a 40% reduction in the pancreas overall? “It tells you the other parts of the pancreas are experiencing considerable damage because of the process,” he said.
In the Vanderbilt/UT study, led by Jack Virostko, PhD, at Vanderbilt University, Nashville, Tenn., researchers examined pancreas volume via MRI in patients with recent-onset T1DM (n = 51; mean age = 14 years, range 8-24 years).
The patients had a smaller median pancreas volume (29.6 mL) than similarly aged controls (49.6 mL; n = 51; P less than .001), and the gap held up after adjustment for factors like age, weight, and body mass index.
Pancreas volumes increased in controls over time as the subjects grew, but shrank even more in those with T1DM over the next year (P less than .001).
“Their research suggests there is a bit of ongoing reduction in volume,” Dr. Haller said. “That’s an area of debate in the literature, and additional larger datasets are being collected to prove or disprove that.”
For his study, Dr. Haller and University of Florida colleagues examined pancreas volume in 223 subjects (average age = 20 years; 45% males).
They found that relative pancreas volume was significantly lower vs. age-matched controls in subjects with recent-onset T1DM and in their first-degree relatives, regardless of their T1DM-related autoantibody status. First-degree relatives whose T1DM-related autoantibody status was positive – a sign of pre-T1DM – had smaller pancreas volumes than controls.
“This suggests there’s a stepwise reduction in volume that may help us understand risk better for certain patients,” Dr. Haller said.
In the future, he said, physicians may be able to use pancreas volume to distinguish between patients who otherwise appear to face the same T1DM risk. As a result, he said, they could adjust treatment accordingly.
“The datasets still need to become more robust, but it’s a really translatable kind of research,” he said, especially since it relies on MRIs “that you could use at any hospital.”
Funding for the Vanderbilt/UT study is not reported, and its authors report no relevant disclosures. Funding for the University of Florida study is not reported, and its authors report no disclosures except for one who reports a patent issued.
SOURCE: Campbell-Thompson ML et al. ADA 2018. Abstract 1816-P; Virostko J et al. ADA 2018. Abstract 233-OR.
ORLANDO – The pancreas is drawing wider interest among scientists: In one study, researchers report that already-shrunken organs keep atrophying in young people with recently diagnosed type 1 diabetes mellitus (T1DM) even as they go through adolescent growth. And another study finds that the pancreas is smaller in first-degree relatives of people with T1DM, especially relatives with pre-T1DM.
“Pancreas volume is a really exciting area of research because it may tell us something about diabetes that we just didn’t understand before,” said pediatric endocrinologist Michael J. Haller, MD, of the University of Florida, Gainesville, in an interview. Dr. Haller is coauthor of the study into pancreas volume in first-degree relatives. That study’s findings, along with the results of a Vanderbilt University/University of Texas study into pancreas volume in early T1DM, were presented at the annual meeting of the American Diabetes Association.
Scientists already know that the pancreas is 40% smaller in people who have lived with T1DM, Dr. Haller said, and “we now know that occurs long before the clinical diagnosis has been made.”
The pancreas volume mystery, he said, revolves around the fact that only 2%-3% of the organ is made up of beta cells, which make insulin. So why is there a 40% reduction in the pancreas overall? “It tells you the other parts of the pancreas are experiencing considerable damage because of the process,” he said.
In the Vanderbilt/UT study, led by Jack Virostko, PhD, at Vanderbilt University, Nashville, Tenn., researchers examined pancreas volume via MRI in patients with recent-onset T1DM (n = 51; mean age = 14 years, range 8-24 years).
The patients had a smaller median pancreas volume (29.6 mL) than similarly aged controls (49.6 mL; n = 51; P less than .001), and the gap held up after adjustment for factors like age, weight, and body mass index.
Pancreas volumes increased in controls over time as the subjects grew, but shrank even more in those with T1DM over the next year (P less than .001).
“Their research suggests there is a bit of ongoing reduction in volume,” Dr. Haller said. “That’s an area of debate in the literature, and additional larger datasets are being collected to prove or disprove that.”
For his study, Dr. Haller and University of Florida colleagues examined pancreas volume in 223 subjects (average age = 20 years; 45% males).
They found that relative pancreas volume was significantly lower vs. age-matched controls in subjects with recent-onset T1DM and in their first-degree relatives, regardless of their T1DM-related autoantibody status. First-degree relatives whose T1DM-related autoantibody status was positive – a sign of pre-T1DM – had smaller pancreas volumes than controls.
“This suggests there’s a stepwise reduction in volume that may help us understand risk better for certain patients,” Dr. Haller said.
In the future, he said, physicians may be able to use pancreas volume to distinguish between patients who otherwise appear to face the same T1DM risk. As a result, he said, they could adjust treatment accordingly.
“The datasets still need to become more robust, but it’s a really translatable kind of research,” he said, especially since it relies on MRIs “that you could use at any hospital.”
Funding for the Vanderbilt/UT study is not reported, and its authors report no relevant disclosures. Funding for the University of Florida study is not reported, and its authors report no disclosures except for one who reports a patent issued.
SOURCE: Campbell-Thompson ML et al. ADA 2018. Abstract 1816-P; Virostko J et al. ADA 2018. Abstract 233-OR.
ORLANDO – The pancreas is drawing wider interest among scientists: In one study, researchers report that already-shrunken organs keep atrophying in young people with recently diagnosed type 1 diabetes mellitus (T1DM) even as they go through adolescent growth. And another study finds that the pancreas is smaller in first-degree relatives of people with T1DM, especially relatives with pre-T1DM.
“Pancreas volume is a really exciting area of research because it may tell us something about diabetes that we just didn’t understand before,” said pediatric endocrinologist Michael J. Haller, MD, of the University of Florida, Gainesville, in an interview. Dr. Haller is coauthor of the study into pancreas volume in first-degree relatives. That study’s findings, along with the results of a Vanderbilt University/University of Texas study into pancreas volume in early T1DM, were presented at the annual meeting of the American Diabetes Association.
Scientists already know that the pancreas is 40% smaller in people who have lived with T1DM, Dr. Haller said, and “we now know that occurs long before the clinical diagnosis has been made.”
The pancreas volume mystery, he said, revolves around the fact that only 2%-3% of the organ is made up of beta cells, which make insulin. So why is there a 40% reduction in the pancreas overall? “It tells you the other parts of the pancreas are experiencing considerable damage because of the process,” he said.
In the Vanderbilt/UT study, led by Jack Virostko, PhD, at Vanderbilt University, Nashville, Tenn., researchers examined pancreas volume via MRI in patients with recent-onset T1DM (n = 51; mean age = 14 years, range 8-24 years).
The patients had a smaller median pancreas volume (29.6 mL) than similarly aged controls (49.6 mL; n = 51; P less than .001), and the gap held up after adjustment for factors like age, weight, and body mass index.
Pancreas volumes increased in controls over time as the subjects grew, but shrank even more in those with T1DM over the next year (P less than .001).
“Their research suggests there is a bit of ongoing reduction in volume,” Dr. Haller said. “That’s an area of debate in the literature, and additional larger datasets are being collected to prove or disprove that.”
For his study, Dr. Haller and University of Florida colleagues examined pancreas volume in 223 subjects (average age = 20 years; 45% males).
They found that relative pancreas volume was significantly lower vs. age-matched controls in subjects with recent-onset T1DM and in their first-degree relatives, regardless of their T1DM-related autoantibody status. First-degree relatives whose T1DM-related autoantibody status was positive – a sign of pre-T1DM – had smaller pancreas volumes than controls.
“This suggests there’s a stepwise reduction in volume that may help us understand risk better for certain patients,” Dr. Haller said.
In the future, he said, physicians may be able to use pancreas volume to distinguish between patients who otherwise appear to face the same T1DM risk. As a result, he said, they could adjust treatment accordingly.
“The datasets still need to become more robust, but it’s a really translatable kind of research,” he said, especially since it relies on MRIs “that you could use at any hospital.”
Funding for the Vanderbilt/UT study is not reported, and its authors report no relevant disclosures. Funding for the University of Florida study is not reported, and its authors report no disclosures except for one who reports a patent issued.
SOURCE: Campbell-Thompson ML et al. ADA 2018. Abstract 1816-P; Virostko J et al. ADA 2018. Abstract 233-OR.
REPORTING FROM ADA 2018
Alirocumab’s benefit greater in diabetes patients: ODYSSEY Outcomes
ORLANDO – Higher risk translates to higher benefits. That’s the message of a new analysis of the ODYSSEY Outcomes trial in the PCSK9-inhibitor alirocumab that finds people with diabetes gained about twice the reduction in risk of major adverse cardiac events as their non-diabetic counterparts.
“Patients with diabetes and a recent heart attack are at double the risk of a cardiovascular event in the next 3 years as are nondiabetics, despite guideline-based care,” said study presenting author Kausik Ray, MD, ChB, of the School of Public Health of Imperial College London, in an interview. “These patients in our study had LDL of around 89 mg/dL despite high-intensity statins. Current guidelines recommend a goal of LDL of 55 mg/dL in this group. We brought LDL down to around 38 mg/ dL, and showed that by doing this, diabetics derived a greater reduction in the risk of major cardiovascular events. A greater absolute benefit was observed, and a smaller number needed to treat.”
Dr. Ray presented the study findings, a prespecified analysis of results of ODYSSEY Outcomes, at the annual scientific sessions of the American Diabetes Association.
The trial randomly assigned 18,924 patients with recent acute coronary syndrome and LDL cholesterol of at least 70 mg/dL, despite maximum statin therapy, to 75 mg of alirocumab every 2 weeks or placebo. Doses of alirocumab were increased blindly, to 150 mg, to reach LDL cholesterol levels of 25-50 mg/dL.
During a median 2.8 years of follow-up, the overall cumulative rate of major cardiac adverse events (coronary heart disease death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina) occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for an absolute risk reduction of 1.6% and a statistically significant and clinically meaningful 15% reduction in relative risk. The results were presented at the annual scientific sessions of the American College of Cardiology in March.
In the current analysis, in patients with diabetes, the cumulative rate of incidents was 14.1% (380 of 2,693) with alirocumab and 16.4% (452 of 2,751) with placebo, for an ARR of 2.3%.
The ARRs for the prediabetes and normoglycemia groups were both 1.2%.
Dr. Ray noted that there’s no sign that the drug works differently in patients with diabetes. “The drug works in the same way and as effectively in everyone: LDL came down by 64% at 16 weeks in everyone. But absolute risk depends upon absolute risk to start with. So, in higher-risk patients, the absolute benefit is greater.”
According to Dr. Ray, the number needed to treat is 43 over 30 months for people with diabetes and 73 over 30 months for people without diabetes.
Prediman K. Shah, MD, director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai Medical Center and professor of medicine at the University of California, Los Angeles, questioned the cost effectiveness of the medication in an interview.
“Even among the diabetics, the absolute risk reduction is about 2%, which is underwhelming considering the high cost,” he said. “If the cost were to drop to levels closer to cost of statins, such a small risk reduction may be worth the expense.”
Insurers have been skeptical of covering alirocumab because of its $14,000/year cost. However, Sanofi and Regeneron, which jointly market alirocumab, announced in March 2018 that they “will offer U.S. payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price for Praluent Injection (alirocumab) in alignment with a new value assessment for high-risk patients from the [United States].”
In response, Dr. Ray said “the benefits quoted are time-to-first-event, and these are modest. But if you look at recurrent events, which represent the natural course of disease, then the benefits and absolute benefits are greater. These are add-on therapies and will never be used in every single patient at current cost.”
Glen J. Pearson, PharmD, of the University of Alberta, Edmonton, said in an interview that, “while these absolute numbers do seem relatively small, it must be remembered that these patients are already receiving very effective therapies to reduce their risk of future cardiovascular outcomes.”
ODYSSEY Outcomes was funded by Sanofi and Regeneron. The presenter reports various disclosures including consulting and research support relationships with Sanofi and Regeneron. The other study authors report various disclosures. Dr. Pearson reports no relevant disclosures. Dr. Shah reports receiving grant support from Sanofi Regeneron.
SOURCE: Ray K et al. ADA 2018, Abstract 6-LB.
ORLANDO – Higher risk translates to higher benefits. That’s the message of a new analysis of the ODYSSEY Outcomes trial in the PCSK9-inhibitor alirocumab that finds people with diabetes gained about twice the reduction in risk of major adverse cardiac events as their non-diabetic counterparts.
“Patients with diabetes and a recent heart attack are at double the risk of a cardiovascular event in the next 3 years as are nondiabetics, despite guideline-based care,” said study presenting author Kausik Ray, MD, ChB, of the School of Public Health of Imperial College London, in an interview. “These patients in our study had LDL of around 89 mg/dL despite high-intensity statins. Current guidelines recommend a goal of LDL of 55 mg/dL in this group. We brought LDL down to around 38 mg/ dL, and showed that by doing this, diabetics derived a greater reduction in the risk of major cardiovascular events. A greater absolute benefit was observed, and a smaller number needed to treat.”
Dr. Ray presented the study findings, a prespecified analysis of results of ODYSSEY Outcomes, at the annual scientific sessions of the American Diabetes Association.
The trial randomly assigned 18,924 patients with recent acute coronary syndrome and LDL cholesterol of at least 70 mg/dL, despite maximum statin therapy, to 75 mg of alirocumab every 2 weeks or placebo. Doses of alirocumab were increased blindly, to 150 mg, to reach LDL cholesterol levels of 25-50 mg/dL.
During a median 2.8 years of follow-up, the overall cumulative rate of major cardiac adverse events (coronary heart disease death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina) occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for an absolute risk reduction of 1.6% and a statistically significant and clinically meaningful 15% reduction in relative risk. The results were presented at the annual scientific sessions of the American College of Cardiology in March.
In the current analysis, in patients with diabetes, the cumulative rate of incidents was 14.1% (380 of 2,693) with alirocumab and 16.4% (452 of 2,751) with placebo, for an ARR of 2.3%.
The ARRs for the prediabetes and normoglycemia groups were both 1.2%.
Dr. Ray noted that there’s no sign that the drug works differently in patients with diabetes. “The drug works in the same way and as effectively in everyone: LDL came down by 64% at 16 weeks in everyone. But absolute risk depends upon absolute risk to start with. So, in higher-risk patients, the absolute benefit is greater.”
According to Dr. Ray, the number needed to treat is 43 over 30 months for people with diabetes and 73 over 30 months for people without diabetes.
Prediman K. Shah, MD, director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai Medical Center and professor of medicine at the University of California, Los Angeles, questioned the cost effectiveness of the medication in an interview.
“Even among the diabetics, the absolute risk reduction is about 2%, which is underwhelming considering the high cost,” he said. “If the cost were to drop to levels closer to cost of statins, such a small risk reduction may be worth the expense.”
Insurers have been skeptical of covering alirocumab because of its $14,000/year cost. However, Sanofi and Regeneron, which jointly market alirocumab, announced in March 2018 that they “will offer U.S. payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price for Praluent Injection (alirocumab) in alignment with a new value assessment for high-risk patients from the [United States].”
In response, Dr. Ray said “the benefits quoted are time-to-first-event, and these are modest. But if you look at recurrent events, which represent the natural course of disease, then the benefits and absolute benefits are greater. These are add-on therapies and will never be used in every single patient at current cost.”
Glen J. Pearson, PharmD, of the University of Alberta, Edmonton, said in an interview that, “while these absolute numbers do seem relatively small, it must be remembered that these patients are already receiving very effective therapies to reduce their risk of future cardiovascular outcomes.”
ODYSSEY Outcomes was funded by Sanofi and Regeneron. The presenter reports various disclosures including consulting and research support relationships with Sanofi and Regeneron. The other study authors report various disclosures. Dr. Pearson reports no relevant disclosures. Dr. Shah reports receiving grant support from Sanofi Regeneron.
SOURCE: Ray K et al. ADA 2018, Abstract 6-LB.
ORLANDO – Higher risk translates to higher benefits. That’s the message of a new analysis of the ODYSSEY Outcomes trial in the PCSK9-inhibitor alirocumab that finds people with diabetes gained about twice the reduction in risk of major adverse cardiac events as their non-diabetic counterparts.
“Patients with diabetes and a recent heart attack are at double the risk of a cardiovascular event in the next 3 years as are nondiabetics, despite guideline-based care,” said study presenting author Kausik Ray, MD, ChB, of the School of Public Health of Imperial College London, in an interview. “These patients in our study had LDL of around 89 mg/dL despite high-intensity statins. Current guidelines recommend a goal of LDL of 55 mg/dL in this group. We brought LDL down to around 38 mg/ dL, and showed that by doing this, diabetics derived a greater reduction in the risk of major cardiovascular events. A greater absolute benefit was observed, and a smaller number needed to treat.”
Dr. Ray presented the study findings, a prespecified analysis of results of ODYSSEY Outcomes, at the annual scientific sessions of the American Diabetes Association.
The trial randomly assigned 18,924 patients with recent acute coronary syndrome and LDL cholesterol of at least 70 mg/dL, despite maximum statin therapy, to 75 mg of alirocumab every 2 weeks or placebo. Doses of alirocumab were increased blindly, to 150 mg, to reach LDL cholesterol levels of 25-50 mg/dL.
During a median 2.8 years of follow-up, the overall cumulative rate of major cardiac adverse events (coronary heart disease death, nonfatal MI, ischemic stroke, or hospitalization for unstable angina) occurred in 9.5% of the overall population randomized to alirocumab and 11.1% of those on placebo, for an absolute risk reduction of 1.6% and a statistically significant and clinically meaningful 15% reduction in relative risk. The results were presented at the annual scientific sessions of the American College of Cardiology in March.
In the current analysis, in patients with diabetes, the cumulative rate of incidents was 14.1% (380 of 2,693) with alirocumab and 16.4% (452 of 2,751) with placebo, for an ARR of 2.3%.
The ARRs for the prediabetes and normoglycemia groups were both 1.2%.
Dr. Ray noted that there’s no sign that the drug works differently in patients with diabetes. “The drug works in the same way and as effectively in everyone: LDL came down by 64% at 16 weeks in everyone. But absolute risk depends upon absolute risk to start with. So, in higher-risk patients, the absolute benefit is greater.”
According to Dr. Ray, the number needed to treat is 43 over 30 months for people with diabetes and 73 over 30 months for people without diabetes.
Prediman K. Shah, MD, director of the Oppenheimer Atherosclerosis Research Center at Cedars-Sinai Medical Center and professor of medicine at the University of California, Los Angeles, questioned the cost effectiveness of the medication in an interview.
“Even among the diabetics, the absolute risk reduction is about 2%, which is underwhelming considering the high cost,” he said. “If the cost were to drop to levels closer to cost of statins, such a small risk reduction may be worth the expense.”
Insurers have been skeptical of covering alirocumab because of its $14,000/year cost. However, Sanofi and Regeneron, which jointly market alirocumab, announced in March 2018 that they “will offer U.S. payers that agree to reduce burdensome access barriers for high-risk patients a further reduced net price for Praluent Injection (alirocumab) in alignment with a new value assessment for high-risk patients from the [United States].”
In response, Dr. Ray said “the benefits quoted are time-to-first-event, and these are modest. But if you look at recurrent events, which represent the natural course of disease, then the benefits and absolute benefits are greater. These are add-on therapies and will never be used in every single patient at current cost.”
Glen J. Pearson, PharmD, of the University of Alberta, Edmonton, said in an interview that, “while these absolute numbers do seem relatively small, it must be remembered that these patients are already receiving very effective therapies to reduce their risk of future cardiovascular outcomes.”
ODYSSEY Outcomes was funded by Sanofi and Regeneron. The presenter reports various disclosures including consulting and research support relationships with Sanofi and Regeneron. The other study authors report various disclosures. Dr. Pearson reports no relevant disclosures. Dr. Shah reports receiving grant support from Sanofi Regeneron.
SOURCE: Ray K et al. ADA 2018, Abstract 6-LB.
REPORTING FROM ADA 2018
Key clinical point:
Major finding: Over a median 34-month period, patients with diabetes who took alirocumab had a 2.3% absolute risk reduction in major cardiac adverse events incidents. Counterparts without diabetes had an ARR of 1.2%.
Study details: ODYSSEY Outcomes, a double-blind, randomized trial of nearly 19,000 patients with a recent acute coronary syndrome and an LDL cholesterol level of 70 mg/dL or more despite intensive statin therapy.
Disclosures: The study was funded by Sanofi and Regeneron Pharmaceuticals, and many study authors disclose financial relationships with the companies.
Source: Ray K et al. ADA 2018, Abstract 6-LB.
Intensive treatment for T2D pays off in the long run
ORLANDO – Intensified multifactorial treatment proved cost effective over time in type 2 diabetes patients in the practice-changing Steno-2 study, according to 21-year follow-up data from the randomized Danish study.
Cumulative direct health care costs from the start of the trial in 1993 through 2014 were about $13 million in 24 patients in the intensive treatment group who were available for follow-up, and about $12.3 million in 42 patients in the conventional treatment group. The difference in costs between the groups was not statistically significant, Joachim Gaede reported at the annual scientific sessions of the American Diabetes Association.
Costs per patient-year during 1996-2014, however, were significantly lower in the intensive treatment group ($9,648 vs. $10, 681, respectively), said Mr. Gaede, a graduate student in the medicine program at the University of Copenhagen.
Furthermore, patients in the intensified treatment group lived a median of 7.9 years longer than did those who were in the conventional treatment group, suggesting that while costs might be higher early on, investing in early intensified treatment of all known modifiable risk factors in high-risk patients will prolong life and still save money over time thanks to reduced complication-related costs, he noted.
Steno-2 was an open, parallel group study initiated in 1993 to compare conventional multifactorial treatment of type 2 diabetes mellitus (T2DM) with an intensified approach over an 8-year period. Enrollment included 160 patients with high-risk type 2 diabetes. After the primary composite cardiovascular endpoint was assessed, the trial continued as an observational study, with all patients given the intensified, multifactorial treatment that consisted of lifestyle measures and medications targeting hyperglycemia, hypertension, hypercholesterolemia, and hypercoagulation.
Reports from the study over the years led to changes in treatment guidelines to promote more intensive multifactorial treatment, Mr. Gaede said. For example, the initial results reported in 1999 showed a 50% relative risk reduction in kidney, eye, and nerve complications after 4 years with intensive versus conventional treatment; a 2003 report showed a 53% relative risk reduction in MI, stroke, and amputation after 8 years; and a 2008 report demonstrated a 46% relative risk reduction in death after 13 years. Finally, in 2016 a 7.9-year gain in lifespan after 21 years with intensive versus conventional treatment was reported.
In this video interview, Mr. Gaede, junior lead study author, discusses the Steno-2 study findings and the current cost analysis data.
“The bottom line is that ... you can actually, as a patient, be treated at a specialized diabetes clinic ... and, in the long run, it doesn’t cost you anything” more, he said, explaining that the up-front costs of intensive treatment are offset by the money saved because of the reduced complications over time.
Mr. Gaede reported having no disclosures.
sworcester@frontlinemedcom.com
SOURCE: Gaede J et al. ADA 2018, Abstract 162-OR.
ORLANDO – Intensified multifactorial treatment proved cost effective over time in type 2 diabetes patients in the practice-changing Steno-2 study, according to 21-year follow-up data from the randomized Danish study.
Cumulative direct health care costs from the start of the trial in 1993 through 2014 were about $13 million in 24 patients in the intensive treatment group who were available for follow-up, and about $12.3 million in 42 patients in the conventional treatment group. The difference in costs between the groups was not statistically significant, Joachim Gaede reported at the annual scientific sessions of the American Diabetes Association.
Costs per patient-year during 1996-2014, however, were significantly lower in the intensive treatment group ($9,648 vs. $10, 681, respectively), said Mr. Gaede, a graduate student in the medicine program at the University of Copenhagen.
Furthermore, patients in the intensified treatment group lived a median of 7.9 years longer than did those who were in the conventional treatment group, suggesting that while costs might be higher early on, investing in early intensified treatment of all known modifiable risk factors in high-risk patients will prolong life and still save money over time thanks to reduced complication-related costs, he noted.
Steno-2 was an open, parallel group study initiated in 1993 to compare conventional multifactorial treatment of type 2 diabetes mellitus (T2DM) with an intensified approach over an 8-year period. Enrollment included 160 patients with high-risk type 2 diabetes. After the primary composite cardiovascular endpoint was assessed, the trial continued as an observational study, with all patients given the intensified, multifactorial treatment that consisted of lifestyle measures and medications targeting hyperglycemia, hypertension, hypercholesterolemia, and hypercoagulation.
Reports from the study over the years led to changes in treatment guidelines to promote more intensive multifactorial treatment, Mr. Gaede said. For example, the initial results reported in 1999 showed a 50% relative risk reduction in kidney, eye, and nerve complications after 4 years with intensive versus conventional treatment; a 2003 report showed a 53% relative risk reduction in MI, stroke, and amputation after 8 years; and a 2008 report demonstrated a 46% relative risk reduction in death after 13 years. Finally, in 2016 a 7.9-year gain in lifespan after 21 years with intensive versus conventional treatment was reported.
In this video interview, Mr. Gaede, junior lead study author, discusses the Steno-2 study findings and the current cost analysis data.
“The bottom line is that ... you can actually, as a patient, be treated at a specialized diabetes clinic ... and, in the long run, it doesn’t cost you anything” more, he said, explaining that the up-front costs of intensive treatment are offset by the money saved because of the reduced complications over time.
Mr. Gaede reported having no disclosures.
sworcester@frontlinemedcom.com
SOURCE: Gaede J et al. ADA 2018, Abstract 162-OR.
ORLANDO – Intensified multifactorial treatment proved cost effective over time in type 2 diabetes patients in the practice-changing Steno-2 study, according to 21-year follow-up data from the randomized Danish study.
Cumulative direct health care costs from the start of the trial in 1993 through 2014 were about $13 million in 24 patients in the intensive treatment group who were available for follow-up, and about $12.3 million in 42 patients in the conventional treatment group. The difference in costs between the groups was not statistically significant, Joachim Gaede reported at the annual scientific sessions of the American Diabetes Association.
Costs per patient-year during 1996-2014, however, were significantly lower in the intensive treatment group ($9,648 vs. $10, 681, respectively), said Mr. Gaede, a graduate student in the medicine program at the University of Copenhagen.
Furthermore, patients in the intensified treatment group lived a median of 7.9 years longer than did those who were in the conventional treatment group, suggesting that while costs might be higher early on, investing in early intensified treatment of all known modifiable risk factors in high-risk patients will prolong life and still save money over time thanks to reduced complication-related costs, he noted.
Steno-2 was an open, parallel group study initiated in 1993 to compare conventional multifactorial treatment of type 2 diabetes mellitus (T2DM) with an intensified approach over an 8-year period. Enrollment included 160 patients with high-risk type 2 diabetes. After the primary composite cardiovascular endpoint was assessed, the trial continued as an observational study, with all patients given the intensified, multifactorial treatment that consisted of lifestyle measures and medications targeting hyperglycemia, hypertension, hypercholesterolemia, and hypercoagulation.
Reports from the study over the years led to changes in treatment guidelines to promote more intensive multifactorial treatment, Mr. Gaede said. For example, the initial results reported in 1999 showed a 50% relative risk reduction in kidney, eye, and nerve complications after 4 years with intensive versus conventional treatment; a 2003 report showed a 53% relative risk reduction in MI, stroke, and amputation after 8 years; and a 2008 report demonstrated a 46% relative risk reduction in death after 13 years. Finally, in 2016 a 7.9-year gain in lifespan after 21 years with intensive versus conventional treatment was reported.
In this video interview, Mr. Gaede, junior lead study author, discusses the Steno-2 study findings and the current cost analysis data.
“The bottom line is that ... you can actually, as a patient, be treated at a specialized diabetes clinic ... and, in the long run, it doesn’t cost you anything” more, he said, explaining that the up-front costs of intensive treatment are offset by the money saved because of the reduced complications over time.
Mr. Gaede reported having no disclosures.
sworcester@frontlinemedcom.com
SOURCE: Gaede J et al. ADA 2018, Abstract 162-OR.
REPORTING FROM ADA 2018
Diabetes patients pushed into high-deductible plans
ORLANDO – The proportion of diabetes patients enrolled in high-deductible health plans jumped from 10% in 2005 to about 50% in 2014, according to a review of insurance data for 63 million Americans under age 65 years.
Diabetes patients often don’t have a choice. To cut costs, high-deductible plans are increasingly the only ones employers offer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
While that may be adequate for healthy people, it’s quite another issue for people with chronic conditions, especially ones with low income. Out-of-pocket expenses can be thousands of dollars more than with traditional health plans, and the extra costs aren’t always offset by lower premiums.
The trend is concerning, said senior investigator J. Frank Wharam, MB, MPH, an associate professor of population medicine at Harvard Medical School, Boston. He explained the problem, and what’s being done about it, in an interview at the annual scientific sessions of the American Diabetes Association.
aotto@mdedge.com
SOURCE: Garabedian LF et al. ADA 2018. Abstract 175-OR.
ORLANDO – The proportion of diabetes patients enrolled in high-deductible health plans jumped from 10% in 2005 to about 50% in 2014, according to a review of insurance data for 63 million Americans under age 65 years.
Diabetes patients often don’t have a choice. To cut costs, high-deductible plans are increasingly the only ones employers offer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
While that may be adequate for healthy people, it’s quite another issue for people with chronic conditions, especially ones with low income. Out-of-pocket expenses can be thousands of dollars more than with traditional health plans, and the extra costs aren’t always offset by lower premiums.
The trend is concerning, said senior investigator J. Frank Wharam, MB, MPH, an associate professor of population medicine at Harvard Medical School, Boston. He explained the problem, and what’s being done about it, in an interview at the annual scientific sessions of the American Diabetes Association.
aotto@mdedge.com
SOURCE: Garabedian LF et al. ADA 2018. Abstract 175-OR.
ORLANDO – The proportion of diabetes patients enrolled in high-deductible health plans jumped from 10% in 2005 to about 50% in 2014, according to a review of insurance data for 63 million Americans under age 65 years.
Diabetes patients often don’t have a choice. To cut costs, high-deductible plans are increasingly the only ones employers offer.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
While that may be adequate for healthy people, it’s quite another issue for people with chronic conditions, especially ones with low income. Out-of-pocket expenses can be thousands of dollars more than with traditional health plans, and the extra costs aren’t always offset by lower premiums.
The trend is concerning, said senior investigator J. Frank Wharam, MB, MPH, an associate professor of population medicine at Harvard Medical School, Boston. He explained the problem, and what’s being done about it, in an interview at the annual scientific sessions of the American Diabetes Association.
aotto@mdedge.com
SOURCE: Garabedian LF et al. ADA 2018. Abstract 175-OR.
REPORTING FROM ADA 2018
Research provides more evidence of a maternal diabetes/autism link
ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.
Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).
Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.
Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).
The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).
Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.
The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)
The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).
In addition, the study doesn’t track maternal glucose levels over time.
Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.
One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.
He also noted that the impact may be reduced when pregnancy is further along, potentially explaining why researchers didn’t connect late-developing gestational diabetes to ASD.
There’s still a “low risk” of ASD even in children born to mothers with diabetes, he said. “You shouldn’t scare anyone with this.”
The study was funded in part by Kaiser Permanente Southern California Direct Community Benefit funds. The study authors and Dr. Damm report no relevant disclosures.
SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.
ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.
Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).
Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.
Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).
The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).
Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.
The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)
The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).
In addition, the study doesn’t track maternal glucose levels over time.
Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.
One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.
He also noted that the impact may be reduced when pregnancy is further along, potentially explaining why researchers didn’t connect late-developing gestational diabetes to ASD.
There’s still a “low risk” of ASD even in children born to mothers with diabetes, he said. “You shouldn’t scare anyone with this.”
The study was funded in part by Kaiser Permanente Southern California Direct Community Benefit funds. The study authors and Dr. Damm report no relevant disclosures.
SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.
ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.
Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).
Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.
Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).
The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).
Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.
The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)
The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).
In addition, the study doesn’t track maternal glucose levels over time.
Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.
One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.
He also noted that the impact may be reduced when pregnancy is further along, potentially explaining why researchers didn’t connect late-developing gestational diabetes to ASD.
There’s still a “low risk” of ASD even in children born to mothers with diabetes, he said. “You shouldn’t scare anyone with this.”
The study was funded in part by Kaiser Permanente Southern California Direct Community Benefit funds. The study authors and Dr. Damm report no relevant disclosures.
SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.
REPORTING FROM ADA 2018
Key clinical point: Children of mothers with various forms of diabetes – including type 1 diabetes (T1D) – could be at higher risk of autism.
Major finding: Autism spectrum disorder (ASD) was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).
Study details: Retrospective analysis of 419,425 children born at Kaiser Permanente Southern California hospitals from 1995-2012 (51% boys).
Disclosures: The study was funded in part by Kaiser Permanente Southern California Direct Community Benefit funds. The study authors report no relevant disclosures.
Source: Xiang A, et al. ADA 2018 Abstract OR-117.