Effects of sitagliptin and metformin treatment on incretin hormone and insulin
secretory responses to oral and "isoglycemic" intravenous glucose.
Author(s): Vardarli I(1), Arndt E, Deacon CF, Holst JJ, Nauck MA.
Affiliation(s): Author information:
(1)Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany.
Publication date & source: 2014, Diabetes. , 63(2):663-74
Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent degradation of incretin
hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic
polypeptide [GIP]), whereas metformin may increase GLP-1 levels. We examined, in
a four-period crossover trial, the influence of metformin (2,000 mg/day),
sitagliptin (100 mg/day), or their combination, on GLP-1 responses and on the
incretin effect in 20 patients with type 2 diabetes, comparing an oral glucose
challenge (75 g, day 5) and an "isoglycemic" intravenous glucose infusion (day
6). Fasting total GLP-1 was significantly increased by metformin and not changed
by sitagliptin. After oral glucose, metformin increased and sitagliptin
significantly decreased (by 53%) total GLP-1. Fasting and postload intact GLP-1
increased with sitagliptin but not with metformin. After oral glucose, only
sitagliptin, but not metformin, significantly augmented insulin secretion, in
monotherapy and as an add-on to metformin. The incretin effect was not changed
numerically with any of the treatments. In conclusion, sitagliptin increased
intact GLP-1 and GIP through DPP-4 inhibition but reduced total GLP-1 and GIP
(feedback inhibition) without affecting the numerical contribution of the
incretin effect. Insulin secretion with sitagliptin treatment was similarly
stimulated with oral and "isoglycemic" intravenous glucose. This points to an
important contribution of small changes in incretin concentrations within the
basal range or to additional insulinotropic agents besides GLP mediating the
antidiabetic effects of DPP-4 inhibition.
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