Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: A randomized controlled trial in patients with type 2 diabetes

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Michael A Nauck, Melanie Kahle, Oleg Baranov, Carolyn F Deacon, Jens J Holst

AimTo determine whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal.
MethodsA total of 16 patients with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (1) sitagliptin (100 mg orally) and (2) placebo (patients and care givers blinded) administered 60 minutes before a mixed meal, or vice versa. Glucose excursions (incremental area under the curve [AUC]; primary endpoint) and insulin, C-peptide, glucagon and incretin concentrations were measured. The study setting was a metabolic study unit at a specialized diabetes hospital.
ResultsAll 16 patients completed the study and were analysed. Glucose (AUCglucose 319 ± 30 [placebo] vs 315 ± 18 mmol.L-1.min-1 [sitagliptin], Δ 7 [95% confidence interval −50 to 63] mmol.L-1.min-1), insulin, C-peptide and glucagon concentrations were not affected significantly by sitagliptin treatment ( P = .60-1.00). Intact glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) concentrations were augmented by sitagliptin, by 78.4% and 90.2%, respectively (both P < .0001). The influence of sitagliptin treatment on incretin plasma concentrations was similar to previously published results obtained in patients with type 2 diabetes on metformin treatment only.
ConclusionsSitagliptin, in patients already treated with a GLP-1 receptor agonist (liraglutide), increased intact GLP-1 and GIP concentrations, but with marginal, non-significant effects on glycaemic control. GLP-1 receptors have probably been maximally stimulated by liraglutide. Our findings do not support combination treatment with GLP-1 receptor agonists and DPP-4 inhibitors, but longer-term trials are needed to support clinical recommendations.
Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Issue number2
Pages (from-to)200-207
Number of pages8
Publication statusPublished - 6 Feb 2017

ID: 167474547