Francisco J Tinahones1,2, Baptist Gallwitz3, Matias Nordaby4, Sophia Götz4, Mario Maldonado-Lutomirsky5, Hans J Woerle5, Uli C Broedl5. 1. Department of Diabetes, Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA) Hospital Universitario Virgen de la Victoria, Universidad Málaga, Málaga, Spain. 2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Málaga, Spain. 3. Department of Medicine IV (Endocrinology, Diabetes, Angiology, Nephrology & Clinical Chemistry), Eberhard Karls University, Tübingen, Germany. 4. Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. 5. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Abstract
AIM: To evaluate the efficacy and safety of linagliptin vs placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with inadequate glycaemic control despite stable-dosemetformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (>53 and ≤91 mmol/mol) (N = 482) were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or to linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg (study 1) or metformin and empagliflozin 25 mg (study 2). The primary endpoint was change from baseline (defined as the last value before first intake of randomized, double-blind treatment) in HbA1c at week 24. RESULTS: At week 24, HbA1c (mean baseline 7.82-8.04 [62-64 mmol/mol]) was significantly reduced with linagliptin vs placebo; adjusted mean (SE) differences in change from baseline in HbA1c with linagliptin vs placebo were -.32% (.10) (-3.59 [1.08] mmol/mol) ( P = .001) for patients on empagliflozin 10 mg and metformin, and -0.47% (0.10) (-5.15 [1.04] mmol/mol) ( P < 0.001) for patients on empagliflozin 25 mg and metformin. Adverse events were reported in more patients receiving placebo than in those receiving linagliptin: 55.5% vs 48.4% in study 1 and 58.9% vs 52.7% in study 2. CONCLUSIONS:Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated.
RCT Entities:
AIM: To evaluate the efficacy and safety of linagliptin vs placebo as add-on to empagliflozin and metformin in patients with type 2 diabetes. MATERIALS AND METHODS:Patients with inadequate glycaemic control despite stable-dose metformin received open-label empagliflozin 10 mg (study 1) or 25 mg (study 2) as add-on therapy for 16 weeks. Subsequently, those with HbA1c ≥7.0 and ≤10.5% (>53 and ≤91 mmol/mol) (N = 482) were randomized to 24 weeks' double-blind, double-dummy treatment with linagliptin 5 mg or placebo in study 1, or to linagliptin 5 mg or placebo in study 2; all patients continued treatment with metformin and empagliflozin 10 mg (study 1) or metformin and empagliflozin 25 mg (study 2). The primary endpoint was change from baseline (defined as the last value before first intake of randomized, double-blind treatment) in HbA1c at week 24. RESULTS: At week 24, HbA1c (mean baseline 7.82-8.04 [62-64 mmol/mol]) was significantly reduced with linagliptin vs placebo; adjusted mean (SE) differences in change from baseline in HbA1c with linagliptin vs placebo were -.32% (.10) (-3.59 [1.08] mmol/mol) ( P = .001) for patients on empagliflozin 10 mg and metformin, and -0.47% (0.10) (-5.15 [1.04] mmol/mol) ( P < 0.001) for patients on empagliflozin 25 mg and metformin. Adverse events were reported in more patients receiving placebo than in those receiving linagliptin: 55.5% vs 48.4% in study 1 and 58.9% vs 52.7% in study 2. CONCLUSIONS:Linagliptin as add-on to empagliflozin and metformin for 24 weeks improved glycaemic control vs placebo, and was well tolerated.
Authors: Sushrima Gan; Adem Y Dawed; Louise A Donnelly; Anand T N Nair; Colin N A Palmer; Viswanathan Mohan; Ewan R Pearson Journal: Diabetes Care Date: 2020-08 Impact factor: 19.112