Safety of Dipeptidylpeptidase-4 Inhibitors in Older Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract BackgroundWe aim to assess the safety of dipeptidylpeptidase-4 inhibitors (DPP4s) in older type 2 diabetes patients with inadequate glycaemic control. MethodsWe included RCTs in older (≥65 years) patients with type 2 diabetes. The intervention group was treated with any DPP4. A systematic search in MEDLINE and EMBASE was performed in December 2020. For assessing risk of bias, the RoB 2 tool was applied. The quality of evidence was assessed using GRADE. We pooled outcomes using random-effects meta-analyses. ResultsWe identified 16 RCTs that included 19,317 patients with a mean age >70 years. The mean HbA1c ranged between 7.1g/dl and 10.0g/dl.Adding DPP4s to standard alone care may increase mortality slightly (RR 1.04; 0.89-1.21). Adding DPP4s to standard care increases the risk for hypoglycaemia (RR 1.08; 95%CI 1.01-1.16), but difference in overall adverse events is negligible.DPP4s added to standard care likely reduce mortality compared to sulfonylureas (RR 0.88; 0.75-1.04). DPP4s probably reduce the risk for hypoglycaemia compared to sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible.There is insufficient evidence on hospitalizations, falls, fractures, renal impairment, and pancreatitis. Conclusion There is no evidence that DPP4s in addition to standard care decrease mortality but DPP4s increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously because even in drugs with a good safety profile like DPP4s. In the case second-line treatment is necessary, DPP4s appear to be superior to sulfonylureas. RegistrationPROSPERO: CRD42020210645