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

• Published in: Diabetes, obesity & metabolism Vol. 19; no. 2; pp. 200 - 207
• Main Authors: Nauck, Michael A., Kahle, Melanie, Baranov, Oleg, Deacon, Carolyn F., Holst, Jens J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2017; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Antidiabetics; Blood Glucose - metabolism; C-Peptide - metabolism; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; dipeptidyl peptidase‐4 inhibitors; Dipeptidyl-peptidase IV; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Drug Therapy, Combination; Evidence-based medicine; Female; Gastric Inhibitory Polypeptide - metabolism; GLP-1 receptor agonists; Glucagon - metabolism; glucagon secretion; Glucagon-Like Peptide 1 - metabolism; Glucagon-Like Peptide-1 Receptor - agonists; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemic Agents - therapeutic use; incretin‐based diabetes medications; Insulin - metabolism; insulin secretion; Liraglutide - therapeutic use; Male; Metformin - therapeutic use; Middle Aged; Peptides; Sitagliptin Phosphate - therapeutic use; Treatment Outcome; dipeptidyl peptidase-4 inhibitors; insulin secretion; incretin-based diabetes medications; GLP-1 receptor agonists; glucagon secretion
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.12802

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.