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.

First published in Diabetes obesity and metabolism on 2017 Apr.
Diabetes Obes Metab. 2017 Apr;19(4):489-495. doi: 10.1111/dom.12838.

Authors: Forst T, Falk A, Andersen G, Fischer A, Weber MM, Voswinkel S, Heise T, Kapitza C, Plum-Mörschel L

Abstract

Aims:

To investigate the effect of sequential treatment escalation with empagliflozin and linagliptin on laboratory markers of α- and β-cell function in people with type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin monotherapy.

RESEARCH DESIGN AND METHODS:

This review provides a comprehensive clinical update for DKD in people with type 2 diabetes, with a special focus on new treatment modalities. The traditional strategies for prevention and treatment of DKD, i.e., glycemic control and blood pressure management, have only modest effects on minimizing glomerular filtration rate decline or progression to end-stage kidney disease. While cardiovascular outcome trials of SGLT-2i show a positive effect of SGLT-2i on several kidney disease-related endpoints, the effect of GLP-1 RA on kidney-disease endpoints other than reduced albuminuria remain to be established. Non-steroidal mineralocorticoid receptor antagonists also evoke cardiovascular and kidney protective effects.

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 (TP1). The addition of linagliptin during TP2 further improved postprandial glucose levels, probably as a result of a marked reduction in postprandial glucagon concentrations (TP2). The insulin response to an i.v. glucose load increased during treatment with empagliflozin (TP1), and further improved after the addition of linagliptin (TP2).

Conclusion:

After metformin failure, sequential treatment escalation with empagliflozin and linagliptin is an attractive treatment option because of the additive effects on postprandial glucose control, probably mediated by complementary effects on α- and β-cell function.

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