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SAN DIEGO – results from two new phase 3a studies suggest.
Data from Novo Nordisk’s ONWARDS 1, comparing once-weekly icodec with once-daily glargine, and ONWARDS 3, comparing once-weekly icodec with daily degludec (Tresiba, Novo Nordisk), both in insulin-naive patients with type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association.
In both trials, primary endpoints of superiority and noninferiority in A1c reduction were achieved, and in ONWARDS 1, patients spent more time in target blood glucose range.
“I feel that weekly insulins have the potential to become transformational as preferred options for basal insulin replacement in people with type 2 diabetes in need of initiation of insulin therapy,” said Julio Rosenstock, MD, the lead author of ONWARDS 1.
Asked to comment, independent diabetes industry consultant Charles Alexander, MD, said: “The data certainly support approval of Icodec.”
Dr. Alexander said that an ideal candidate for once-weekly insulin “is someone who’s already on once-weekly [glucagon-like peptide-1 (GLP-1) agonist]. Then, taking your GLP-1 [agonist] and your basal insulin at the same time once a week makes a lot of sense ... Since they’re taking a weekly injection anyway, it’s relatively easy for a person to remember ‘When I take my weekly GLP-1 [agonist], I’ll take my weekly basal insulin.’ ”
However, he also pointed out: “Payers may say they don’t care about the convenience of once-weekly and they prefer to pay for the cheaper daily basal [insulin] ... I think a lot of people will continue to use [insulin] glargine because it is cheaper than either degludec or icodec.”
The data from ONWARDS 1 was published in the New England Journal of Medicine, and the data from ONWARDS 3 was published in JAMA.
Six ONWARDS trials make up Novo Nordisk’s phase 3a clinical development program comparing the efficacy and safety of once-weekly insulin icodec with once-daily basal insulin comparators.
Previously, findings from ONWARDS 2, in which patients with type 2 diabetes taking basal insulin had improved A1c after being switched to once-weekly icodec or once-daily degludec, were presented at the annual meeting of the European Association for the Study of Diabetes.
Insulin icodec has been submitted for regulatory review in the United States, Canada, Europe, China, Australia, Switzerland, and Brazil, with decisions anticipated starting in the first half of 2024.
Hypoglycemia: Is the slight increase clinically significant?
One concern about the once-weekly insulins is that they might result in higher rates of hypoglycemia because they stay active in the body for so long.
Differences in rates of combined level 2 (clinically significant) and level 3 (severe) hypoglycemia were increased with borderline significance in ONWARDS 1.
In ONWARDS 3 there was a threefold significant difference, but the overall risk was still low, equating to one episode per patient per 3 years, said Ildiko Lingvay, MD, of University of Texas Southwestern Medical Center, Dallas, who is lead author for ONWARDS 1 and a co-author for ONWARDS 3.
“Insulin is insulin. When we use insulin there will always be hypoglycemia. But we only have less than one event per year,” added Dr. Rosenstock, of Velocity Clinical Research at Medical City, Dallas.
Dr. Alexander pointed out that in ONWARDS 3 just under half of both groups were taking a sulfonylurea, although the trial design allowed for cutting the dose in half when the basal insulin was added.
In ONWARDS 1, in contrast, sulfonylureas and glinides were stopped at the time of randomization. “That’s not definitive, but I would argue that’s the explanation, to be proven by formal testing.”
Indeed, an audience member asked about that during the discussion, and Dr. Lingvay said they were still analyzing those data. “We’re working on that. It’s very important.”
Dr. Alexander noted, “I think the message here is don’t continue sulfonylureas or glinides in someone you’re giving insulin to because you’re going to get hypoglycemia.”
Better glycemic control, with fewer injections
ONWARDS 1 was a 78-week, randomized, open-label, treat-to-target trial, with a main 52-week phase and a 26-week extension phase. A total of 984 patients with type 2 diabetes and A1c 7%-11% with no prior insulin treatment were randomized 1:1 to once-weekly icodec or daily insulin glargine. All baseline medications except sulfonylureas and glinides were continued.
The primary endpoint was change in A1c from baseline to week 52, and this dropped from 8.5% to 6.9% with icodec, versus 8.4% to 7.1% with glargine, a significant difference, confirming both noninferiority (P < .001) and superiority (P = .02) of icodec, Dr. Rosenstock said.
The percentage of time in blood glucose range (70-180 mg/dL) was also significantly higher with icodec than glargine (71.9% vs. 66.9%; P < .001), also confirming superiority.
Rates of combined clinically significant or severe hypoglycemia at 83 weeks were 0.30 versus 0.16 events per person-year of exposure at week 83 (P = .043). No new safety signals were identified, and incidences of adverse events were similar in the two groups.
A significantly higher proportion of participants achieved an A1c of less than 7% without clinically significant or severe hypoglycemia with once-weekly basal insulin icodec versus once-daily basal insulin glargine (52.6% vs. 42.6%).
ONWARDS 3 randomized 588 patients each to once-weekly insulin icodec plus once-weekly placebo or once-daily insulin degludec plus once-weekly placebo. The primary endpoint, change in A1c from baseline to week 26, fell from 8.6% to 7.0% with icodec and from 8.5% to 7.2% with degludec, confirming both noninferiority (P < .001) and superiority (P = .002).
There were no significant differences between the two insulins in change in fasting plasma glucose, mean weekly insulin dose, or body weight.
Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than in the degludec group from week 0 to 31 (0.31 vs. 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs. 0.12 events per patient-year exposure; P = .01).
The percentage of patients achieving an A1c of less than 7% without level 2 or 3 hypoglycemia was 52.1% with icodec versus 39.9% with degludec.
Dr. Lingvay and Dr. Rosenstock have reported financial relationships with multiple companies.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – results from two new phase 3a studies suggest.
Data from Novo Nordisk’s ONWARDS 1, comparing once-weekly icodec with once-daily glargine, and ONWARDS 3, comparing once-weekly icodec with daily degludec (Tresiba, Novo Nordisk), both in insulin-naive patients with type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association.
In both trials, primary endpoints of superiority and noninferiority in A1c reduction were achieved, and in ONWARDS 1, patients spent more time in target blood glucose range.
“I feel that weekly insulins have the potential to become transformational as preferred options for basal insulin replacement in people with type 2 diabetes in need of initiation of insulin therapy,” said Julio Rosenstock, MD, the lead author of ONWARDS 1.
Asked to comment, independent diabetes industry consultant Charles Alexander, MD, said: “The data certainly support approval of Icodec.”
Dr. Alexander said that an ideal candidate for once-weekly insulin “is someone who’s already on once-weekly [glucagon-like peptide-1 (GLP-1) agonist]. Then, taking your GLP-1 [agonist] and your basal insulin at the same time once a week makes a lot of sense ... Since they’re taking a weekly injection anyway, it’s relatively easy for a person to remember ‘When I take my weekly GLP-1 [agonist], I’ll take my weekly basal insulin.’ ”
However, he also pointed out: “Payers may say they don’t care about the convenience of once-weekly and they prefer to pay for the cheaper daily basal [insulin] ... I think a lot of people will continue to use [insulin] glargine because it is cheaper than either degludec or icodec.”
The data from ONWARDS 1 was published in the New England Journal of Medicine, and the data from ONWARDS 3 was published in JAMA.
Six ONWARDS trials make up Novo Nordisk’s phase 3a clinical development program comparing the efficacy and safety of once-weekly insulin icodec with once-daily basal insulin comparators.
Previously, findings from ONWARDS 2, in which patients with type 2 diabetes taking basal insulin had improved A1c after being switched to once-weekly icodec or once-daily degludec, were presented at the annual meeting of the European Association for the Study of Diabetes.
Insulin icodec has been submitted for regulatory review in the United States, Canada, Europe, China, Australia, Switzerland, and Brazil, with decisions anticipated starting in the first half of 2024.
Hypoglycemia: Is the slight increase clinically significant?
One concern about the once-weekly insulins is that they might result in higher rates of hypoglycemia because they stay active in the body for so long.
Differences in rates of combined level 2 (clinically significant) and level 3 (severe) hypoglycemia were increased with borderline significance in ONWARDS 1.
In ONWARDS 3 there was a threefold significant difference, but the overall risk was still low, equating to one episode per patient per 3 years, said Ildiko Lingvay, MD, of University of Texas Southwestern Medical Center, Dallas, who is lead author for ONWARDS 1 and a co-author for ONWARDS 3.
“Insulin is insulin. When we use insulin there will always be hypoglycemia. But we only have less than one event per year,” added Dr. Rosenstock, of Velocity Clinical Research at Medical City, Dallas.
Dr. Alexander pointed out that in ONWARDS 3 just under half of both groups were taking a sulfonylurea, although the trial design allowed for cutting the dose in half when the basal insulin was added.
In ONWARDS 1, in contrast, sulfonylureas and glinides were stopped at the time of randomization. “That’s not definitive, but I would argue that’s the explanation, to be proven by formal testing.”
Indeed, an audience member asked about that during the discussion, and Dr. Lingvay said they were still analyzing those data. “We’re working on that. It’s very important.”
Dr. Alexander noted, “I think the message here is don’t continue sulfonylureas or glinides in someone you’re giving insulin to because you’re going to get hypoglycemia.”
Better glycemic control, with fewer injections
ONWARDS 1 was a 78-week, randomized, open-label, treat-to-target trial, with a main 52-week phase and a 26-week extension phase. A total of 984 patients with type 2 diabetes and A1c 7%-11% with no prior insulin treatment were randomized 1:1 to once-weekly icodec or daily insulin glargine. All baseline medications except sulfonylureas and glinides were continued.
The primary endpoint was change in A1c from baseline to week 52, and this dropped from 8.5% to 6.9% with icodec, versus 8.4% to 7.1% with glargine, a significant difference, confirming both noninferiority (P < .001) and superiority (P = .02) of icodec, Dr. Rosenstock said.
The percentage of time in blood glucose range (70-180 mg/dL) was also significantly higher with icodec than glargine (71.9% vs. 66.9%; P < .001), also confirming superiority.
Rates of combined clinically significant or severe hypoglycemia at 83 weeks were 0.30 versus 0.16 events per person-year of exposure at week 83 (P = .043). No new safety signals were identified, and incidences of adverse events were similar in the two groups.
A significantly higher proportion of participants achieved an A1c of less than 7% without clinically significant or severe hypoglycemia with once-weekly basal insulin icodec versus once-daily basal insulin glargine (52.6% vs. 42.6%).
ONWARDS 3 randomized 588 patients each to once-weekly insulin icodec plus once-weekly placebo or once-daily insulin degludec plus once-weekly placebo. The primary endpoint, change in A1c from baseline to week 26, fell from 8.6% to 7.0% with icodec and from 8.5% to 7.2% with degludec, confirming both noninferiority (P < .001) and superiority (P = .002).
There were no significant differences between the two insulins in change in fasting plasma glucose, mean weekly insulin dose, or body weight.
Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than in the degludec group from week 0 to 31 (0.31 vs. 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs. 0.12 events per patient-year exposure; P = .01).
The percentage of patients achieving an A1c of less than 7% without level 2 or 3 hypoglycemia was 52.1% with icodec versus 39.9% with degludec.
Dr. Lingvay and Dr. Rosenstock have reported financial relationships with multiple companies.
A version of this article originally appeared on Medscape.com.
SAN DIEGO – results from two new phase 3a studies suggest.
Data from Novo Nordisk’s ONWARDS 1, comparing once-weekly icodec with once-daily glargine, and ONWARDS 3, comparing once-weekly icodec with daily degludec (Tresiba, Novo Nordisk), both in insulin-naive patients with type 2 diabetes, were presented at the annual scientific sessions of the American Diabetes Association.
In both trials, primary endpoints of superiority and noninferiority in A1c reduction were achieved, and in ONWARDS 1, patients spent more time in target blood glucose range.
“I feel that weekly insulins have the potential to become transformational as preferred options for basal insulin replacement in people with type 2 diabetes in need of initiation of insulin therapy,” said Julio Rosenstock, MD, the lead author of ONWARDS 1.
Asked to comment, independent diabetes industry consultant Charles Alexander, MD, said: “The data certainly support approval of Icodec.”
Dr. Alexander said that an ideal candidate for once-weekly insulin “is someone who’s already on once-weekly [glucagon-like peptide-1 (GLP-1) agonist]. Then, taking your GLP-1 [agonist] and your basal insulin at the same time once a week makes a lot of sense ... Since they’re taking a weekly injection anyway, it’s relatively easy for a person to remember ‘When I take my weekly GLP-1 [agonist], I’ll take my weekly basal insulin.’ ”
However, he also pointed out: “Payers may say they don’t care about the convenience of once-weekly and they prefer to pay for the cheaper daily basal [insulin] ... I think a lot of people will continue to use [insulin] glargine because it is cheaper than either degludec or icodec.”
The data from ONWARDS 1 was published in the New England Journal of Medicine, and the data from ONWARDS 3 was published in JAMA.
Six ONWARDS trials make up Novo Nordisk’s phase 3a clinical development program comparing the efficacy and safety of once-weekly insulin icodec with once-daily basal insulin comparators.
Previously, findings from ONWARDS 2, in which patients with type 2 diabetes taking basal insulin had improved A1c after being switched to once-weekly icodec or once-daily degludec, were presented at the annual meeting of the European Association for the Study of Diabetes.
Insulin icodec has been submitted for regulatory review in the United States, Canada, Europe, China, Australia, Switzerland, and Brazil, with decisions anticipated starting in the first half of 2024.
Hypoglycemia: Is the slight increase clinically significant?
One concern about the once-weekly insulins is that they might result in higher rates of hypoglycemia because they stay active in the body for so long.
Differences in rates of combined level 2 (clinically significant) and level 3 (severe) hypoglycemia were increased with borderline significance in ONWARDS 1.
In ONWARDS 3 there was a threefold significant difference, but the overall risk was still low, equating to one episode per patient per 3 years, said Ildiko Lingvay, MD, of University of Texas Southwestern Medical Center, Dallas, who is lead author for ONWARDS 1 and a co-author for ONWARDS 3.
“Insulin is insulin. When we use insulin there will always be hypoglycemia. But we only have less than one event per year,” added Dr. Rosenstock, of Velocity Clinical Research at Medical City, Dallas.
Dr. Alexander pointed out that in ONWARDS 3 just under half of both groups were taking a sulfonylurea, although the trial design allowed for cutting the dose in half when the basal insulin was added.
In ONWARDS 1, in contrast, sulfonylureas and glinides were stopped at the time of randomization. “That’s not definitive, but I would argue that’s the explanation, to be proven by formal testing.”
Indeed, an audience member asked about that during the discussion, and Dr. Lingvay said they were still analyzing those data. “We’re working on that. It’s very important.”
Dr. Alexander noted, “I think the message here is don’t continue sulfonylureas or glinides in someone you’re giving insulin to because you’re going to get hypoglycemia.”
Better glycemic control, with fewer injections
ONWARDS 1 was a 78-week, randomized, open-label, treat-to-target trial, with a main 52-week phase and a 26-week extension phase. A total of 984 patients with type 2 diabetes and A1c 7%-11% with no prior insulin treatment were randomized 1:1 to once-weekly icodec or daily insulin glargine. All baseline medications except sulfonylureas and glinides were continued.
The primary endpoint was change in A1c from baseline to week 52, and this dropped from 8.5% to 6.9% with icodec, versus 8.4% to 7.1% with glargine, a significant difference, confirming both noninferiority (P < .001) and superiority (P = .02) of icodec, Dr. Rosenstock said.
The percentage of time in blood glucose range (70-180 mg/dL) was also significantly higher with icodec than glargine (71.9% vs. 66.9%; P < .001), also confirming superiority.
Rates of combined clinically significant or severe hypoglycemia at 83 weeks were 0.30 versus 0.16 events per person-year of exposure at week 83 (P = .043). No new safety signals were identified, and incidences of adverse events were similar in the two groups.
A significantly higher proportion of participants achieved an A1c of less than 7% without clinically significant or severe hypoglycemia with once-weekly basal insulin icodec versus once-daily basal insulin glargine (52.6% vs. 42.6%).
ONWARDS 3 randomized 588 patients each to once-weekly insulin icodec plus once-weekly placebo or once-daily insulin degludec plus once-weekly placebo. The primary endpoint, change in A1c from baseline to week 26, fell from 8.6% to 7.0% with icodec and from 8.5% to 7.2% with degludec, confirming both noninferiority (P < .001) and superiority (P = .002).
There were no significant differences between the two insulins in change in fasting plasma glucose, mean weekly insulin dose, or body weight.
Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than in the degludec group from week 0 to 31 (0.31 vs. 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs. 0.12 events per patient-year exposure; P = .01).
The percentage of patients achieving an A1c of less than 7% without level 2 or 3 hypoglycemia was 52.1% with icodec versus 39.9% with degludec.
Dr. Lingvay and Dr. Rosenstock have reported financial relationships with multiple companies.
A version of this article originally appeared on Medscape.com.
AT ADA 2023