TY - JOUR

T1 - Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide

T2 - A randomized controlled trial in patients with type 2 diabetes

AU - Nauck, Michael A

AU - Kahle, Melanie

AU - Baranov, Oleg

AU - Deacon, Carolyn F

AU - Holst, Jens J

N1 - This article is protected by copyright. All rights reserved.

PY - 2017/2/6

Y1 - 2017/2/6

N2 - 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.

AB - 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.

U2 - 10.1111/dom.12802

DO - 10.1111/dom.12802

M3 - Journal article

C2 - 27709794

VL - 19

SP - 200

EP - 207

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 2

ER -