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No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.
To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.
The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.
The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])
Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).
In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.
The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.
Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.
Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.
The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.
Key clinical point: Neither GLP-1 receptor agonists nor DPP-4 inhibitors increase the risk of acute pancreatitis in type 2 diabetes patients.
Major finding: The risk of acute pancreatitis was not increased among Danes who had been treated with an incretin drug (odds ratio, 0.95), after adjustment for comorbidities and medications that can increase risk.
Data source: A population-based case-control study in 12,868 patients hospitalized for the first time with acute pancreatitis between 2005 and 2012, matched with 128,680 controls, from national medical databases.
Disclosures: The study was supported by the Clinical Epidemiological Research Foundation in Denmark. Most of the authors are at Danish institutions that receive funding and grants from Novo-Nordisk.