Using real‐world data to evaluate the association of incretin‐based therapies with risk of acute pancreatitis: a meta‐analysis of 1 324 515 patients from observational studies

Wang, Tao; Wang, F.; Gou, Zhuoyue; Tang, Huilin; Li, C.; Shi, Luwen; Zhai, Suodi

doi:10.1111/dom.12386

Cited by 61 publications

(53 citation statements)

References 47 publications

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“…At present, several meta-analyses have been carried out with regards to the safety of incretin-based therapy [35–49]. It is reported that incretin-based drugs are associated with increased risk of cardiovascular events, acute pancreatitis and several types of neoplasm [35–49].…”

Section: Discussionmentioning

confidence: 99%

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Incretin-Based Therapy and Risk of Pancreatic Cancer in Patients with Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials

et al. 2016

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IntroductionThe present study aims to evaluate the risk of pancreatic cancer with incretin-based therapy among patients with type 2 diabetes mellitus (T2DM).MethodsWe searched EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for eligible studies published up to March 06 2016. This meta-analysis includes all studies reporting adverse events of pancreatic cancer with use of incretin-based therapies compared with placebo or non-incretin anti-diabetic drugs in patients with T2DM. We used fixed-effect model to compare pooled relative risk (RR) with related 95% confidence intervals (CI).ResultsA total of 159 randomized trials were identified. Out of these, 135 studies were excluded as pancreatic cancer occurrence had not been included as an end point. The remaining 24 trials enrolling 47,904 participants were further assessed. Overall, no increased risk of pancreatic cancer were detected in association with incretin-based treatment (RR = 0.7, 95% CI 0.37–1.05). The incidence of pancreatic neoplasm was even lower among incretin-based groups than controls (RR = 0.50, 95% CI 0.29–0.87) in trials with duration more than 104 weeks. There was even decreased risk of pancreatic cancer within groups paralleled by incretin-matched placebos (RR = 0.55, 95% CI 0.32–0.93) than by non-incretin anti-diabetic drugs. Neither monotherapy (RR = 0.62, 95% CI 0.38–1.01) nor combination regimen (RR = 0.92, 95% CI 0.45–1.90) of incretin mimetics increased the risk of pancreatic cancer.ConclusionThis meta-analysis shows that incretin-based therapies are not associated with increase in the risk of pancreatic cancer. Interestingly, subgroup analyses suggested lower risk of pancreatic cancer in incretin groups than placebo in long-term studies (>104 weeks). Considering the inconsistent results among randomized trials and previous epidemiological investigations, more such studies should be conducted to clarify the existence or non-existence of this association.FundingThis work was supported by grants from the National Natural Science Foundation of China (Nos. 81270476 and 81470830).Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0198-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…It is reported that incretin-based drugs are associated with increased risk of cardiovascular events, acute pancreatitis and several types of neoplasm [35–49]. However, some meta-analyses had only focused on evaluation of a single drug classified within the incretin drug category [36, 38, 39, 45, 48].…”

Section: Discussionmentioning

confidence: 99%

Incretin-Based Therapy and Risk of Pancreatic Cancer in Patients with Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials

et al. 2016

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“…Moreover, the analysis of three retrospective cohort studies and two case-control studies (total n = 320,289) did not show an increased risk of pancreatitis with the administration of exenatide or sitagliptin [83]. Likewise, another recent meta-analysis of nine observational studies (n = 1,324,515 patients and 5,195 cases of acute pancreatitis) found no significant association between incretin-based treatment and acute pancreatitis (OR: 1.03, 95% CI: 0.87-1.20) [84]. Furthermore, FDA and European Medicines Agency (EMA) recently reevaluated more than 250 toxicology studies conducted in nearly 18,000 healthy animals and more than 200 trials involving approximately 28,000 patients taking incretin-based drugs.…”

Section: Pancreasmentioning

confidence: 94%

Adverse Effects of GLP-1 Receptor Agonists

2014

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■ AbstractGlucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.

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“…Meta-analyses have shown no significant increase in acute pancreatitis with GLP-1RA treatment in patients with T2DM 179,274,275 . In addition, results from cardiovascular safety trials have not shown a significant increase in pancreatitis with GLP-1RAs 276 .…”

Section: Safety and Adverse Effectsmentioning

confidence: 99%

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

2016

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Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

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Using real‐world data to evaluate the association of incretin‐based therapies with risk of acute pancreatitis: a meta‐analysis of 1 324 515 patients from observational studies

Abstract: The present meta-analysis of real-world data does not suggest that IBT is associated with AP. Although we should continue to remain vigilant, IBTs should be regarded as reasonable options to consider adding to the regimen of a patient with type 2 diabetes.

Cited by 61 publications

References 47 publications

Incretin-Based Therapy and Risk of Pancreatic Cancer in Patients with Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials

Incretin-Based Therapy and Risk of Pancreatic Cancer in Patients with Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Controlled Trials

Adverse Effects of GLP-1 Receptor Agonists

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

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