Incretin Based Drugs and Risk of Pancreatitis in T2DM
Incretin Based Drugs and Risk of Pancreatitis in T2DM
Objectives. To determine whether the use of incretin based drugs, compared with sulfonylureas, is associated with an increased risk of acute pancreatitis.
Design. Population based cohort study.
Setting. 680 general practices in the United Kingdom contributing to the Clinical Practice Research Datalink.
Participants. From 1 January 2007 to 31 March 2012, 20,748 new users of incretin based drugs were compared with 51,712 users of sulfonylureas and followed up until 31 March 2013.
Main Outcome Measures. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for acute pancreatitis in users of incretin based drugs compared with users of sulfonylureas. Models were adjusted for tenths of high dimensional propensity score (hdPS).
Results. The crude incidence rate for acute pancreatitis was 1.45 per 1000 patients per year (95% confidence interval 0.99 to 2.11) for incretin based drug users and 1.47 (1.23 to 1.76) for sulfonylurea users. The rate of acute pancreatitis associated with the use of incretin based drugs was not increased (hdPS adjusted hazard ratio: 1.00, 95% confidence interval 0.59 to 1.70) relative to sulfonylurea use.
Conclusions. Compared with use of sulfonylureas, the use of incretin based drugs is not associated with an increased risk of acute pancreatitis. While this study is reassuring, it does not preclude a modest increased risk, and thus additional studies are needed to confirm these findings.
Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors are new classes of antidiabetes drugs. These drugs stimulate insulin secretion according to glucose concentration and inhibit glucagon secretion by either direct binding to the GLP-1 receptor or by inhibiting the degradation of endogenous GLP-1. While these drugs have been shown to have a modest effect on haemoglobin A1c (HbA1c), with favourable effects on weight and a reduced risk of hypoglycaemia, there have been safety concerns regarding their effects on the pancreas. Specifically, analyses of adverse event databases have associated incretin based drugs with acute pancreatitis, resulting in pharmacovigilance alerts and the addition of this possible adverse event on product monographs. Currently, there are continued concerns, partly due to the conflicting results of the observational studies conducted to date. As a result, the European Medicines Agency and the US Food and Drug Administration have called for additional studies to assess this potential risk.
Given the increasing number of patients being prescribed incretin based drugs and concerns regarding their safety, we conducted a large population based study to determine whether the use of GLP-1 analogues and DPP-4 inhibitors, when compared with sulfonylureas, a second line treatment for type 2 diabetes, is associated with an increased risk of acute pancreatitis.
Abstract and Introduction
Abstract
Objectives. To determine whether the use of incretin based drugs, compared with sulfonylureas, is associated with an increased risk of acute pancreatitis.
Design. Population based cohort study.
Setting. 680 general practices in the United Kingdom contributing to the Clinical Practice Research Datalink.
Participants. From 1 January 2007 to 31 March 2012, 20,748 new users of incretin based drugs were compared with 51,712 users of sulfonylureas and followed up until 31 March 2013.
Main Outcome Measures. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for acute pancreatitis in users of incretin based drugs compared with users of sulfonylureas. Models were adjusted for tenths of high dimensional propensity score (hdPS).
Results. The crude incidence rate for acute pancreatitis was 1.45 per 1000 patients per year (95% confidence interval 0.99 to 2.11) for incretin based drug users and 1.47 (1.23 to 1.76) for sulfonylurea users. The rate of acute pancreatitis associated with the use of incretin based drugs was not increased (hdPS adjusted hazard ratio: 1.00, 95% confidence interval 0.59 to 1.70) relative to sulfonylurea use.
Conclusions. Compared with use of sulfonylureas, the use of incretin based drugs is not associated with an increased risk of acute pancreatitis. While this study is reassuring, it does not preclude a modest increased risk, and thus additional studies are needed to confirm these findings.
Introduction
Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors are new classes of antidiabetes drugs. These drugs stimulate insulin secretion according to glucose concentration and inhibit glucagon secretion by either direct binding to the GLP-1 receptor or by inhibiting the degradation of endogenous GLP-1. While these drugs have been shown to have a modest effect on haemoglobin A1c (HbA1c), with favourable effects on weight and a reduced risk of hypoglycaemia, there have been safety concerns regarding their effects on the pancreas. Specifically, analyses of adverse event databases have associated incretin based drugs with acute pancreatitis, resulting in pharmacovigilance alerts and the addition of this possible adverse event on product monographs. Currently, there are continued concerns, partly due to the conflicting results of the observational studies conducted to date. As a result, the European Medicines Agency and the US Food and Drug Administration have called for additional studies to assess this potential risk.
Given the increasing number of patients being prescribed incretin based drugs and concerns regarding their safety, we conducted a large population based study to determine whether the use of GLP-1 analogues and DPP-4 inhibitors, when compared with sulfonylureas, a second line treatment for type 2 diabetes, is associated with an increased risk of acute pancreatitis.
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