Incretin-based therapies and risk of pancreatic cancer in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

Diabetes Obes Metab. 2018 Apr;20(4):910-920. doi: 10.1111/dom.13177. Epub 2018 Jan 3.

Abstract

Aims: To perform a meta-analysis of randomized controlled trials (RCTs), including 6 recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with type 2 diabetes (T2DM).

Materials and methods: For the period January 1, 2007 to May 1, 2017, the PubMed, Embase, Cochrane Central Register and ClininalTrials.gov databases were searched for RCTs in people with T2DM that compared incretin drugs with placebo or other antidiabetic drugs, with treatment and follow-up durations of ≥52 weeks. Two reviewers screened the studies, extracted the data and assessed the risk of bias independently and in duplicate.

Results: A total of 33 studies (n = 79 971), including the 6 CVOTs, with 87 pancreatic cancer events were identified. Overall, the pancreatic cancer risk was not increased in patients administered incretin drugs compared with controls (Peto odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.02). In the 6 CVOTs, 79 pancreatic cancer events were identified in 55 248 participants. Pooled estimates of the 6 CVOTs showed an identical tendency (Peto OR 0.65, 95% CI 0.42-1.01). Notably, in the subgroup of participants who received treatment and follow-up for ≥104 weeks, 84 pancreatic cancer events were identified in 59 919 participants, and a lower risk of pancreatic cancer was associated with incretin-based therapies (Peto OR 0.62, 95% CI 0.41-0.95).

Conclusions: Treatment with incretin drugs was not associated with an increased risk of pancreatic cancer in people with T2DM. Instead, it might protect against pancreatic malignancy in patients treated for ≥104 weeks.

Keywords: GLP-1 analogue; dipeptidyl peptidase-4 inhibitors; incretins; meta-analysis; type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Databases, Factual
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination / adverse effects
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Incretins / administration & dosage
  • Incretins / adverse effects*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / chemically induced*
  • Pancreatic Neoplasms / epidemiology*
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Risk Factors

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Incretins