745-P: Short-Acting Exenatide Added Three Times Daily to Insulin Therapy Improves Insulin Sensitivity in Type 1 Diabetes

Average life expectancy in type 1 diabetes is reduced by more than a decade due to cardiovascular (CV) disease. Reduced insulin sensitivity as assessed by low values of estimated glucose disposal rate (eGDR) has been observed to correlate with increased risk of CV events. How short-acting glucagon-like peptide 1 receptor agonists (GLP-1RA) influence eGDR in type 1 diabetes remains unknown. We analyzed eGDR post-hoc in a phase 2, double-blind, randomized (1:1) , clinical trial (NCT03017352) that evaluated the short-acting GLP-1RA exenatide μg added three times daily to insulin therapy as compared with placebo over 26 weeks of treatment in 1individuals with type 1 diabetes (76/32 men/women, age 50 (14) years (mean (standard deviation)) , diabetes duration 21 (12) years, BMI 28 (4) kg/m2, glycated hemoglobin A1c 8.2 (0.7) % / 66 (7) mmol/mol) . Exenatide significantly increased eGDR by 0.36 mg/kg/min (95 % confidence interval 0.03; 0.69, P = 0.032) (Table 1) as compared with placebo after 26 weeks’ treatment. Short-acting exenatide apparently improved insulin sensitivity in patients with long-standing type 1 diabetes and inadequate glycemic control, alluding to potential CV benefits of this GLP-1RA in type 1 diabetes. Disclosure N.Johansen: Employee; Novo Nordisk A/S. T.F.Dejgaard: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. A.Lund: Speaker's Bureau; Novo Nordisk A/S. T.Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd. H.U.Andersen: Advisory Panel; Abbott Diabetes, Stock/Shareholder; Novo Nordisk A/S. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. Funding Partly funded by AstraZeneca