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

Diabetes, Obesity and Metabolism - Tập 19 Số 4 - Trang 489-495 - 2017
Thomas Forst1,2, Alexander Falk2, Grit Andersen2, Annelie Fischer2, Matthias M. Weber1, Stephan Voswinkel3, Tim Heise2, Christoph Kapitza2, Leona Plum‐Mörschel4
11st Medical Department, Endocrinology Johannes Gutenberg University Mainz Germany
2Profil, Neuss, Germany
3MLM Medical Laboratories Moenchengladbach Germany
4Profil, Mainz, Germany

Tóm tắt

AimsTo 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 methodsA total of 44 people with T2DM received 25 mg empagliflozin for a duration of 1 month in an open‐label fashion (treatment period 1 [TP1]). Thereafter, they were randomized to a double‐blind add‐on therapy with linagliptin 5 mg or placebo (treatment period 2 [TP2]) for 1 additional month. α‐ and β‐cell function was assessed using a standardized liquid meal test and an intravenous (i.v.) glucose challenge. Efficacy measures comprised the areas under the curve for glucose, insulin, proinsulin and glucagon after the liquid meal test and the assessment of fast and late‐phase insulin release after an i.v. glucose load with a subsequent hyperglycaemic clamp.ResultsEmpagliflozin 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).ConclusionAfter 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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Thông tin xuất bản

Diabetes, Obesity and Metabolism

Tập 19 Số 4

489-495

Thông tin tác giả