Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: A double-blind, randomised controlled clinical trial of efficacy and safety

Abstract

Aims/hypothesis The aim of this study was to determine whether exenatide improves haemodynamic function in patients with type 2 diabetes with congestive heart failure (CHF). Methods The main eligibility criteria for inclusion were: male/female (18-80 years) with type 2 diabetes and CHF (ejection fraction ≤35%, and New York Heart Association functional class III or IV). Out of 237 patients screened, 20 male type 2 diabetic patients participated in this crossover trial design and were allocated (sequentially numbered) to i. v. infusions during two consecutive days with (1) exenatide (0.12 pmol/kg/min); and (2) placebo for 6 h followed by a washout period for 18 h, at Stockholm South Hospital, Sweden. Patients and researchers were blinded to the assignment. Cardiac haemodynamic variables were determined by right heart catheterisation. The primary endpoint was defined as an increase in cardiac index (CI) or a decrease in pulmonary capillary wedge pressure (PCWP) of ≥20%. Secondary endpoints were tolerability and safety of exenatide infusion. Results CI increased at 3 and 6 h by 0.4±0.1 (23%) and 0.33±0.1 (17%) l min -1 m -2, during exenatide infusion vs-0.02±0.1 (-1%) and-0.08±0.1 (-5%) l min -1 m -2 during placebo (p=0.003); and heart rate (HR) increased at 1, 3 and 6 h by 8±3 (11%), 15±4 (21%) and 21±5 (29%) beats per min (bpm), during exenatide infusion vs-1±2 (-2%), 1±1 (2%) and 6±2 (8%) bpm, during placebo (p=0.006); and PCWP decreased at 1, 3 and 6 h by-1.3±0.8 (-8%),-1.2± 1 (-8%) and-2.2±0.9 (-15%) mmHg, during exenatide infusion vs 0.3±0.5 (2%), 1±0.6 (6%) and 1.4±0.7 (8%) mmHg, during placebo (p=0.001). No serious adverse event was observed. Adverse events were reported in nine patients (six, nausea; two, increased HR; one, increased systolic blood pressure). Conclusions/interpretation Infusion of exenatide in male type 2 diabetic patients with CHF increased the CI as a result of chronotropy, with concomitant favourable effects on PCWP and reasonable tolerability of the drug. The clinical implications of using exenatide in patients with CHF are still not clear and further studies are warranted. Trial registration: www.isrctn.org/ISRCTN47533126 Funding: This study was funded through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institute, by the Swedish Society for Medical Research, the Swedish Society of Medicine, Stiftelsen Serafimerlasarettet, the Swedish Heart and Lung foundation, Eli Lilly Amylin Alliance, the European Foundation for the Study of Diabetes, Karolinska Institutet Foundations, and Stiftelsen Olle Engkvist Byggmastare. © 2012 Springer-Verlag.