278-LB: The Effect of Combining Very-Low-Calorie Diet with Semaglutide on Beta-Cell Function in Individuals with Type 2 Diabetes

Abstract

Type 2 diabetes (T2D) is characterised by the loss of the first phase response of insulin-producing pancreatic beta cells. Recently, Very-low calorie diets (VLCD - defined as less than 800 kilocalories per day) have been shown to restore this first phase response to induce remission of T2D, while Glucagon-like peptide-1 agonists also improve the first phase response by enhancing postprandial insulin secretion. Here, we present interim results of an investigation exploring the effect of combining these two interventions on beta cell function, in individuals with T2D. Eighteen individuals with T2D and body mass index >27kg.m-2 were randomly allocated into 3 groups: i) Semaglutide (S), ii) VLCD (V), and iii) Semaglutide-plus-VLCD (SV). Semaglutide was administered once weekly gradually up titrated to a maximum dose of 1mg and VLCD regime was provided by LighterLife® total meal replacement. Beta cell function was assessed using intravenous glucose tolerance tests (IVGTT) performed at baseline and 12 weeks. First-phase insulin response was calculated as the incremental area under the suprabasal plasma insulin concentration curve during 0-10 minutes of the IVGTT (µU.min.ml-1). Data were analysed using GraphPad Prism 9.5.0 (La Jolla, USA). All groups were equally matched at baseline. Mean weight loss was 6.4, 14.1 and 14.9 kg in S, V and SV, respectively. A significant improvement in first phase response was observed in all groups (S: +398.5; V: +88.4; SV: +547.8 µU.min.ml-1, all p<0.05 vs. baseline). At 12 weeks, first phase response in SV was significantly higher than in V (583.9 vs. 169.2 µU.min.ml-1 respectively, p<0.05). These data suggest that combination of VLCD and Semaglutide results in a significantly greater improvement in first phase response than VLCD alone. This approach could result in a more robust remission of T2D in the longer-term, and may have important implications for the future design of interventions for the clinical management of T2D. Disclosure O. Anyiam: None. B. E. Phillips: None. D. J. Wilkinson: None. K. Smith: None. P. J. Atherton: None. I. R. Idris: None. Funding Medical Research Council Confidence in Concept Scheme