Exploring the safety of combination therapy with SGLT-2 and DPP-4 inhibitors in type 2 Diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) presents a complex pathogenesis involving various mechanisms, necessitating multiple therapeutic approaches for effective glycemic control. While metformin remains the first-line therapy, additional agents are often required to maintain optimal glucose levels. The combinatory use of anti-diabetic agents with complementary mechanisms of action, such as sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors, has emerged as a promising strategy. This review explores the safety profile of different combinations of SGLT2 inhibitors and DPP4 inhibitors. SGLT2 inhibitors offer glucose-lowering effects with potential cardiovascular benefits but come with considerations such as the risk of hypoglycemia, urinary tract and genital infections, diabetic ketoacidosis, and fractures and amputations. Conversely, DPP-4 inhibitors provide effective glycemic control with a low risk of hypoglycemia, although concerns exist regarding infections, hypersensitivity reactions, pancreatitis, and cardiovascular safety. Evaluating combination therapies, including Empagliflozin + Linagliptin, Canagliflozin + Teneligliptin, Dapagliflozin + Saxagliptin, and Dapagliflozin + Sitagliptin, reveals a generally favorable safety profile, with manageable risks consistent with individual component therapies. Notably, these combinations mitigate the risk of hypoglycemia while offering efficacy in glycemic control. Further research and monitoring are warranted to fully elucidate the long-term safety and efficacy of these combination therapies in managing T2DM.