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- Title
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.
- Authors
Nauck, Michael A.; Kahle, Melanie; Baranov, Oleg; Deacon, Carolyn F.; Holst, Jens J.
- Abstract
Aim To determine whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal. Methods A 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. Results All 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. Conclusions Sitagliptin, 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.
- Subjects
CD26 antigen; SITAGLIPTIN; GLUCAGON-like peptide-1 receptor; GLUCAGON-like peptide-1 agonists; TYPE 2 diabetes treatment; INCRETINS
- Publication
Diabetes, Obesity & Metabolism, 2017, Vol 19, Issue 2, p200
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/dom.12802