Short-Acting Exenatide Added Three Times Daily to Insulin Therapy Improves Fatty Liver Index in Type 1 Diabetes

Fatty liver index (FLI), a marker of hepatic fat content, has been reported as an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes. How short-acting glucagon-like peptide 1 receptor agonists (GLP-1RA) influence FLI in type 1 diabetes remains unknown. We analyzed FLI post-hoc in a phase 2, double-blind, randomized (1:1), clinical trial (NCT03017352) that assessed the efficacy of short-acting GLP-1RA exenatide 10 μg added three times daily to insulin therapy as compared with placebo over 26 weeks of treatment in 108 individuals 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 reduced FLI by 23 % (95 % confidence interval -44; -10, P = 0.001) (Table 1) as compared with placebo after 26 weeks’ treatment. In conclusion, short-acting exenatide reduced FLI-assessed hepatic fat content in patients with long-standing type 1 diabetes and inadequate glycemic control, alluding to potential beneficial effects of this GLP-1RA on both morbidity and mortality in type 1 diabetes. Disclosure N.Johansen: Other Relationship; AstraZeneca, Novo Nordisk, Research Support; JDRF. T.F.Dejgaard: Advisory Panel; Novo Nordisk, Research Support; Novo Nordisk, Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk, AstraZeneca. A.Lund: Speaker's Bureau; Novo Nordisk. C.K.Nielsen: None. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. F.K.Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck. Funding AstraZeneca