Introduction
Type 2 diabetes (T2D) is characterised by chronic hyperglycaemia resulting from insulin resistance and pancreatic beta cell failure. Very-low calorie diets (VLCD) are recommended for management of T2D as they improve both of these defects1,2. However, the deleterious consequences of loss of lean body mass (LBM) with VLCD is becoming of increasing concern3. Similarly to VLCD, new anti-diabetic therapies, such as Glucagon-like peptide-1 receptor agonists (GLP1RA), promote weight loss and glycaemic improvements in T2D, and our recent data demonstrated that exogenous GLP-1 infusions enhanced postprandial muscle protein synthesis4. Investigating interactions between anti-diabetic interventions, such as GLP1RA, and VLCD, with body composition is timely, especially since individuals with T2D are vulnerable to accelerated age-related declines in muscle mass. We therefore investigated the effect of the GLP1RA Semaglutide, VLCD or a combination of the two therapies, upon body composition and muscle function outcomes.
Methods
Nineteen people with T2D and BMI >27 kg.m-2 were allocated to receive either 800 kilocalorie/day VLCD (n=7), once weekly Semaglutide titrated up to 1mg (SEM, n=7), or both in combination (COMB, n=5) for 12-weeks. Dual-energy X-ray absorptiometry scanning was performed at baseline and 12-weeks, along with hand grip strength (HGS) and knee-extensor maximal voluntary contraction (MVC) for assessment of strength. Data were analysed with GraphPad Prism 9.5.0 (La Jolla, USA),
Results
Body weight reduced in all groups (VLCD -14.0kg p<0.0001, SEM -6.4kg p<0.01, COMB -14.9kg, p<0.0001), as did fat mass (VLCD -9.43kg p<0.0001, SEM -3.87kg p<0.01, COMB -10.54kg p<0.0001). Reductions in weight and fat mass were significantly lesser in SEM than in VLCD and COMB (p<0.01 for both). LBM significantly reduced in the VLCD (-3.64kg, p<0.01) and COMB (-4.14kg, p<0.01) groups, with no significant change in the SEM group. There was no significant difference in LBM reductions across the groups. HGS and MVC showed no significant change with any intervention.
Conclusion
Reductions in fat mass occurred with all interventions and were significantly greater with VLCD and the combination of SEM and VLCD compared to SEM alone. Whilst LBM reduced with VLCD and the combination, it did not reduce significantly with SEM, which in the context of weight loss was suggestive of muscle mass preservation perhaps owing to lower overall weight loss. There was no benefit to combining SEM with VLCD, where similar reductions in LBM occurred to the VLCD group. These interim results suggest that Semaglutide may preserve muscle mass during weight loss, however, whether there is a benefit to combining this drug with VLCD requires further investigation. Despite these observed changes in LBM, there were no significant decrements in our measures of arm and leg strength, perhaps indicating an improvement in muscle quality owing to weight loss.