A prospective, claims‐based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs

Abstract

AimWe evaluated the relationship between liraglutide and acute pancreatitis or pancreatic cancer in an ongoing post-marketing safety assessment programme.MethodsInitiators of liraglutide, exenatide, metformin, pioglitazone or groups containing initiators of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US commercial health insurance claims database (1 February 2010 to 31 March 2013) and followed for a median of 15 months. We estimated incidence rates (IR/100 000 person-years), rate ratio (RR) and 95% confidence intervals (CI) of new insurance claims with diagnoses of primary inpatient acute pancreatitis or pancreatic cancer from Poisson regression models.ResultsThe IR for acute pancreatitis for liraglutide was 187.5 compared with 154.4 for all non-glucagon-like peptide-1 (GLP-1)-based therapies (adjusted RR 1.10; CI 0.81–1.49). The IR for pancreatic cancer was 19.9 for liraglutide compared with 33.0 for all non-GLP-1-based therapies (adjusted RR 0.65; 95% CI 0.26–1.60).ConclusionWe did not observe excess risk of either outcome associated with liraglutide relative to individual or pooled comparator drugs.

Adverse Effects of GLP-1 Receptor Agonists

“…In contrast to the above results, several recent studies and meta-analyses failed to show increased risk of pancreatitis with the use of GLP-1 receptor agonists [72][73][74][75][76][77][78][79][80][81][82]. A meta-analysis of 55 randomized controlled trials (n = 33,350) showed no increased risk of pancreatitis with GLP-1 agonists compared with controls (OR: 1.05, 95% CI: 0.37-2.94) [83].…”

“…Furthermore, analyses from adverse reporting systems are useful, but are difficult to control for confounding factors that increase the risk of pancreatitis and cancer, such as obesity, alcohol consumption, smoking, and the use of other drugs. Recent reports and meta-analyses did not show an increased risk of pancreatic cancer with incretin-mimetic drugs [77,166,167]. A meta-analysis of 25 studies showed that the use of exenatide (OR: 0.86, 95% CI: 0.29-2.60) and liraglutide (OR: 1.35, 95% CI: 0.70-2.59) did not significantly increase the risk of pancreatic cancer, independently of the baseline comparator [78].…”

Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients with type 2 diabetes: dose-dependent effects on glycaemic control in a randomised, double-blind, placebo-controlled study

“…Furthermore, changes in enzyme levels were not associated with GI AEs [23][24][25]. Results from meta-analyses and database research have reported that exenatide and liraglutide did not increase pancreatic safety risks [27][28][29][30]. At this time, FDA and EMA agree that concerns regarding a causal association between incretin-based drugs and pancreatitis or pancreatic cancer are inconsistent with the current data, but they will continue to support labeling for the class stating that pancreatitis is a potential risk, and will continue to monitor for any safety signal [26].…”

Combined insulin detemir and liraglutide therapy in type 2 diabetic patients: a base for an alliance

“…Инкретиновая терапия также способна ингибировать апоптоз [14] и улучшать функцию β-клеток [41,42]. Складывается впечатление о том, что гипотеза «отдыха β-клетки», сформулированная на основании данных применения инсулинотерапии в дебюте СД2 [43], приоб-ретает большую актуальность в условиях своевременной комбинации левемира и лираглутида.…”