GLP-1 agonism with VLCD
Research type
Research Study
Full title
The anabolic effects of GLP-1 agonism to prevent lean muscle losses during very-low calorie diets (VLCDs) for weight loss
IRAS ID
297489
Contact name
Iskandar Idris
Contact email
Sponsor organisation
University of Nottingham
Clinicaltrials.gov Identifier
NCT05606471
Duration of Study in the UK
1 years, 11 months, 27 days
Research summary
The very-low calorie diet (VLCD) is highly effective for inducing significant weight loss and substantial improvements in blood glucose levels in people with type 2 diabetes (T2D) living with obesity. A recent series of studies found that VLCD can even induce remission of T2D, and these positive results have led to VLCD being adopted by the NHS as a treatment for T2D in people with obesity.
Unfortunately, weight regain and worsening of diabetes control (leading to relapse of diabetes in those that achieved remission) following VLCD cessation is common, limiting their long-term effectiveness. Furthermore, concerns exist about the amount of skeletal muscle (SM) mass lost during VLCD, accounting for 20-30% of total weight loss. SM is crucial for controlling blood glucose levels and reduced SM mass is linked to higher insulin resistance, and worse glycaemic control. Thus, in the context of weight regain after VLCD, lower SM mass could cause worse diabetes in the long term. Therefore, a way to reduce SM loss during VLCD could be critical to improving the long term effectiveness of VLCD.
Glucagon-like peptide-1 (GLP-1) agonists are medications used to help people with T2D lose weight and improve blood glucose control. Recently, our department showed that the GLP-1 hormone also stimulates SM growth at low levels. Therefore, a GLP-1 agonist could help reduce SM loss if given alongside a VLCD.
The aim of this physiological study is to test this hypothesis by investigating the effect of the GLP-1 agonist Semaglutide on SM turnover, and whether it reduces the loss of SM induced by VLCD. Forty-five people with T2D will receive either Semaglutide only, VLCD only, or both Semaglutide & VLCD, for 12 weeks. Measures of SM turnover, SM mass, body composition and insulin sensitivity will be taken at baseline and during the 12-week intervention period.
Lay summary of study results: This study recruited 32 participants who were randomly allocated to receive a very-low calorie diet (VLCD), the GLP-1 agonist Semaglutide (SEM), or a combination of the two (COMB). Two participants dropped out so there were 10 in each group.
Significantly greater reductions in body weight and fat mass were seen in the VLCD and COMB groups, than the SEM group. HbA1c (a measure of longer term diabetes control) and fasting glucose reduced significantly in all groups, however fasting
insulin and HOMA-IR improved in the VLCD and COMB groups only. Pancreas function increased in SEM and COMB, and the increase in the COMB group was significantly greater than in the VLCD group.Along with the changes in body weight and fat mass, all groups experienced reductions in lean body mass. In accordance with this muscle protein synthesis (a measure of muscle growth) also reduced significantly in all groups, compared to before the intervention. The reduction in muscle protein synthesis was significantly less in the SEM than the VLCD group, which was in keeping with the changes in lean body mass. Muscle breakdown did not differ significantly between the groups. There were no significant differences in protein intake or physical activity levels between the groups. Intriguingly, between 6 and 12 weeks whilst ongoing weight and fat mass reductions were observed, lean body mass remained stable in all groups.
This study provides some useful insights into the potential metabolic benefis of combining VLCD with Semaglutide, as well as the impact of GLP-1 agonists on muscle function, in the context of weight loss.
REC name
East of England - Essex Research Ethics Committee
REC reference
21/EE/0163
Date of REC Opinion
11 Aug 2021
REC opinion
Further Information Favourable Opinion