Combination of Sodium-glucose Co-transporter 2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitor: A Complementary Approach to Diabetes Management

Abstract

Diabetes mellitus is a consequence of multiple underlying pathophysiologies. India ranks second in the world with 77 million diagnosed with type 2 diabetes mellitus (T2DM). The unmet need of achieving the targeted glycated hemoglobin (HbA1c) goal along with increased patient compliance is associated with development of novel treatment options, for the diabetes care on individual basis. Diabetes being multifaceted disorder, combination therapy becomes key option either at initiation or later part of the treatment. A “pathophysiological approach” using combination therapy with agents addressing the known defects in T2DM seems more rational. A synergistic and rational fixed dose combination of a Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and a dipeptidyl peptidase-4 inhibitor (DPP4i), may address these unmet needs. SGLT2i by increasing glucose excretion through urine reduces reduce hyperglycemia. SGLT2i works independent of insulin secretion or action. DPP4i improves glucose homeostasis by inhibiting the breakdown of active incretin hormones, increasing insulin secretion and decreasing hepatic glucose production in a glucose-dependent manner. Moreover, the combination is safe and effective with reduced side-effects such as genito-urinary tract infection. DPP-4i and SGLT2i fulfill provides corresponding mechanism of action when combined can achieve significant glycemic control in patients with T2DM, with a reduced adverse events and cardiovascular protection. The current review provides insights on this combination along with clinical evidences for safety and efficacy and guidance on the use of the combination.