Introduction: Dipeptidyl peptidase-4 inhibitors (DPP-4is) are generally considered as glucose-lowering agents with a safe profile in type 2 diabetes.
Areas covered: An updated review of recent safety data from randomised controlled trials, observational studies, meta-analyses, pharmacovigilance reports regarding alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin, with a special focus on risks of hypoglycemia, pancreatitis and pancreatic cancer, major cardiovascular events, hospitalisation for heart failure and other new safety issues, such as bone fractures and arthralgia. The safety of DPP-4i use in special populations, elderly patients, patients with renal impairment, liver disease or heart failure, will also be discussed.
Expert opinion: The good tolerance/safety profile of DPP-4is has been largely confirmed, including in more fragile populations, with no gastrointestinal adverse effects and a minimal risk of hypoglycemia. DPP-4is appear to be associated with a small increased incidence of acute pancreatitis in placebo-controlled trials, although most observational studies are reassuring. Most recent studies with DPP-4is do not confirm the increased risk of hospitalisation for heart failure reported with saxagliptin in SAVOR-TIMI 53, but further post-marketing surveillance is still recommended. New adverse events have been reported such as arthralgia, yet a causal relationship remains unclear.
Keywords: Cardiovascular disease; DPP-4 inhibitor; heart failure; pancreatitis; renal impairment; safety; type 2 diabetes mellitus.