Michael A Nauck1, Melanie Kahle1, Oleg Baranov1, Carolyn F Deacon2, Jens J Holst2. 1. Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany. 2. Department of Biomedical Sciences, Panum Institute, NovoNordisk Foundation Center for Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
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 withmetformin 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.
RCT Entities:
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.
Authors: T D Müller; B Finan; S R Bloom; D D'Alessio; D J Drucker; P R Flatt; A Fritsche; F Gribble; H J Grill; J F Habener; J J Holst; W Langhans; J J Meier; M A Nauck; D Perez-Tilve; A Pocai; F Reimann; D A Sandoval; T W Schwartz; R J Seeley; K Stemmer; M Tang-Christensen; S C Woods; R D DiMarchi; M H Tschöp Journal: Mol Metab Date: 2019-09-30 Impact factor: 7.422
Authors: Roopa Mehta; Daniel Pichel; Chih Hao Chen-Ku; Pablo Raffaele; Antonio Méndez Durán; Francisco Padilla; Jose Javier Arango Alvarez; José Esteban Costa Gil; Juan Esteban Gómez Mesa; Mariano Giorgi; Rodolfo Lahsen; Andrei C Sposito Journal: Diabetes Ther Date: 2020-12-15 Impact factor: 2.945
Authors: Stewart Harris; Martin J Abrahamson; Antonio Ceriello; Guillaume Charpentier; Marc Evans; Roger Lehmann; Andreas Liebl; Sultan Linjawi; Richard I G Holt; Nóra Hosszúfalusi; Guy Rutten; Tina Vilsbøll Journal: Drugs Date: 2020-02 Impact factor: 9.546
Authors: Estela Lajthia; John D Bucheit; Pramit A Nadpara; Dave L Dixon; Lauren M Caldas; Michael Murchie; Evan M Sisson Journal: Pharm Pract (Granada) Date: 2019-12-12