Introduction: Large randomized clinical trials have demonstrated that incretin-based therapies provide effective glycemic control in type 2 diabetes. Long-term safety assessments are ongoing.
Methods: This systematic review of incretin-based therapy safety is based on 112 randomized clinical trials of duration ≥26 weeks published between January 2000 and February 2015 in patients with type 2 diabetes.
Results: As expected, hypoglycemia rates were lower with dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus other oral antidiabetic drugs and insulin. The most common adverse events were infection and infestation (DPP-4is) and gastrointestinal (GLP-1 RAs). Pancreatitis cases were rare across all studies and, in the SAVOR-TIMI and EXAMINE trials, pancreatitis rates were similar in DPP-4i- and placebo-treated patients. No thyroid tumors were reported, and increased risk of cardiovascular events was not associated with DPP-4is in SAVOR-TIMI and EXAMINE, albeit over a short follow-up period.
Conclusions: Overall, incretin-based therapies were well tolerated; however, their long-term safety profile should continue to be periodically assessed.
Keywords: Type 2 diabetes (T2D); adverse event; clinical trials; dipeptidyl peptidase (DPP)-4inhibitor; glucagon-like peptide-1 receptor agonist (GLP-1 RA); safety.