Rates of Major Adverse Cardiovascular (CV) Events (MACE) and Mortality with Basal Insulin by Liraglutide Use—A DEVOTE Subanalysis

Abstract

CV safety profiles for insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100) were established by the DEVOTE and ORIGIN trials. In the LEADER trial, the GLP-1 analog liraglutide significantly reduced risks of MACE and mortality vs. placebo in patients with type 2 diabetes (T2D) and high CV risk. This post-hoc analysis compared effects of concomitant liraglutide vs. no liraglutide use on MACE and mortality in 7637 patients with T2D and high CV risk randomized 1:1 to degludec/glargine U100 in DEVOTE (NCT01959529). Hazard ratios (HRs) for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time-varying liraglutide use at any time in the trial, without interaction. Sensitivity analyses adjusted for baseline covariates including age, sex, smoking, T2D duration, CV risk, insulin therapy, A1C, LDL, HDL and liver/kidney function. At baseline, 436 (5.7%) patients were on liraglutide: 187 (2.4%) started and 210 (2.7%) stopped liraglutide thereafter. Mean liraglutide exposure from randomization was 731 days. Liraglutide use was associated with significantly lower HRs for MACE and mortality vs. no liraglutide use (Table). HRs from sensitivity analyses were consistent with these results. Thus, liraglutide was associated with significantly lower MACE and mortality rates in basal insulin users. Disclosure K. Brown-Frandsen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. S.S. Emerson: Consultant; Self; Bayer AG, CTI BioPharma, Arena Pharmaceuticals, SFJ Pharmaceuticals Group, Genentech, Inc., GlaxoSmithKline plc., Janssen Research & Development, Novartis AG, Novo Nordisk A/S, Pfizer Inc., Roche Pharma, Allergan, AstraZeneca, Coherus Biosciences Inc, Emmaus Life Sciences Inc., Indivior, Sandoz, Seattle Genetics. Research Support; Self; National Heart, Lung, and Blood Institute. S.P. Marso: Consultant; Self; Abbott Vascular, Novo Nordisk A/S, University of Oxford, AstraZeneca, Bristol-Myers Squibb Company. Research Support; Self; Novo Nordisk A/S, The Medicines Company, Terumo Medical Corporation. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. R. Grøn: Employee; Self; Novo Nordisk A/S. M. Lange: Board Member; Self; Beta Bionics. Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Spouse/Partner; Takeda Pharmaceuticals U.S.A., Inc. A.C. Moses: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P. Örsy: Employee; Self; Novo Nordisk A/S. M.F. Ranthe: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc..