6533b7cffe1ef96bd125848b

RESEARCH PRODUCT

Effects on α- and β-cell function of sequentially adding empagliflozin and linagliptin to therapy in people with type 2 diabetes previously receiving metformin: An exploratory mechanistic study.

subject

description

Aims The aim of the study was to investigate the effect of sequential treatment escalation with empagliflozin and linagliptin on laboratory markers of alpha- and beta cell function in patients with type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin monotherapy. Methods Forty-four patients with T2DM received 25 mg empagliflozin for a duration of one month in an open-label fashion (treatment period (TP 1). Thereafter, patients were randomised to a double-blind add-on therapy with linagliptin 5 mg or placebo (TP 2) for one additional month. Alpha- and beta cell function were assessed with a standardised liquid meal test (LMT) and an intravenous (iv.) glucose challenge. Efficacy parameters comprised of the area under the curve (AUC) for glucose, insulin, proinsulin and glucagon after the LMT and the assessment of fast- and late-phase insulin release after an intravenous glucose load with a subsequent hyperglycaemic clamp. Results Empagliflozin reduced fasting and postprandial plasma glucose levels associated with a significant reduction in postprandial insulin levels, and an improvement in the conversion rate of proinsulin (TP 1). Addition of linagliptin during TP 2 further improved postprandial glucose levels most probably due to a marked reduction in postprandial glucagon concentrations (TP 2). The insulin response to an intravenous glucose load increased during treatment with empagliflozin (TP 1), and further improved after the addition of linagliptin (TP 2). Conclusion After metformin failure, sequential treatment escalation with empagliflozin and linagliptin is an attractive treatment option due to additive effects on postprandial glucose control, most probably mediated by complementary effects on alpha- and beta cell function.