Bo Ahrén1, Irl B Hirsch2, Thomas R Pieber3, Chantal Mathieu4, Fernando Gómez-Peralta5, Troels Krarup Hansen6, Areti Philotheou7, Sune Birch8, Erik Christiansen8, Thomas Jon Jensen8, John B Buse9. 1. Lund University, Lund, Sweden bo.ahren@med.lu.se. 2. University of Washington, Seattle, WA. 3. Medical University of Graz, Graz, Austria. 4. University of Leuven, Leuven, Belgium. 5. Hospital General de Segovia, Segovia, Spain. 6. Aarhus University Hospital, Aarhus, Denmark. 7. University of Cape Town Private Academic Hospital, Cape Town, South Africa. 8. Novo Nordisk A/S, Bagsvaerd, Denmark. 9. University of North Carolina School of Medicine, Chapel Hill, NC.
Abstract
OBJECTIVE: To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receivingonce-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS:Mean baseline glycated hemoglobin (HbA1c) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6 mmol/mol]; 1.2 mg: -0.22% [2.4 mmol/mol]; 0.6 mg: -0.23% [2.5 mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis >1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS: In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
RCT Entities:
OBJECTIVE: To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS: Mean baseline glycated hemoglobin (HbA1c) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6 mmol/mol]; 1.2 mg: -0.22% [2.4 mmol/mol]; 0.6 mg: -0.23% [2.5 mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis >1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS: In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
Authors: Kevan C Herold; Jesse Reynolds; James Dziura; David Baidal; Jason Gaglia; Stephen E Gitelman; Peter A Gottlieb; Jennifer Marks; Louis H Philipson; Rodica Pop-Busui; Ruth S Weinstock Journal: Diabetes Obes Metab Date: 2020-07-29 Impact factor: 6.577
Authors: Richard I G Holt; J Hans DeVries; Amy Hess-Fischl; Irl B Hirsch; M Sue Kirkman; Tomasz Klupa; Barbara Ludwig; Kirsten Nørgaard; Jeremy Pettus; Eric Renard; Jay S Skyler; Frank J Snoek; Ruth S Weinstock; Anne L Peters Journal: Diabetologia Date: 2021-12 Impact factor: 10.122
Authors: Klara R Klein; Schafer C Boeder; Jennifer L R Freeman; Imogene Dunn; Chris Dvergsten; Supradeep Madduri; Erin R Giovannetti; Carmen Valcarce; John B Buse; Jeremy H Pettus Journal: Diabetes Obes Metab Date: 2022-06-04 Impact factor: 6.408
Authors: Thomas F Dejgaard; Bernt J von Scholten; Erik Christiansen; Frederik F Kreiner; Lars Bardtrum; Matthias von Herrath; Chantal Mathieu; Sten Madsbad Journal: Diabetes Obes Metab Date: 2021-09-28 Impact factor: 6.408