Very low-calorie diet bests semaglutide in short-term weight loss, Combination promising for diabetes management: Study

"Future research with extended intervention and follow-up periods is essential to better understand the effects of the Semaglutide-VLCD combination treatment on managing type 2 diabetes (T2D) and obesity," the researchers wrote in Clinical Nutrition. 

Type 2 diabetes is a complex disease marked by elevated blood glucose levels and insulin resistance, with impaired insulin secretion from pancreatic beta cells being the primary cause.

Overweight and obesity are significant risk factors for the development of diabetes, impacting 90% of individuals with type 2 diabetes. Research indicates that obesity can increase the risk of developing diabetes by seven times while being overweight is linked to insulin resistance and dysfunction in beta-cell function.

Very-low calorie diets and the glucagon-like peptide-1 receptor agonist (GLP1RA) semaglutide induce significant weight loss and improve glycaemic control in T2D patients. Oluwaseun Anyiam, University of Nottingham, Derby, UK, and colleagues conducted a pilot study to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition, and metabolic outcomes.

The study included thirty individuals with type 2 diabetes (age 18–75 years, BMI 27–50 kg m−2). They were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks.

Weight and glycated hemoglobin (HbA1c) levels, dual-energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were conducted at baseline and after the intervention. Diet diaries were used to evaluate compliance. The insulin first-phase response during IVGTT served as an indicator of pancreatic beta-cell function, while insulin sensitivity was assessed using HOMA-IR.

The study led to the following findings:

• Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than in SEM.
• VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively.
• HbA1c and fasting glucose reduced significantly in all groups, however, fasting insulin and HOMA-IR improved in VLCD and COMB only.
• Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD.

The findings showed that VLCD elicited greater short-term fat mass and weight losses than Semaglutide. VLCD addition to Semaglutide stimulated further weight loss than Semaglutide alone.

"The combination did not produce additional effects on weight and body composition beyond those achieved with VLCD alone, but it did lead to greater improvements in pancreatic beta-cell function. Thus, further exploration is warranted of the combination of Semaglutide and VLCD warrants as a novel approach to T2D management," the researchers concluded.

Reference:

Anyiam, O., Phillips, B., Quinn, K., Wilkinson, D., Smith, K., Atherton, P., & Idris, I. (2024). Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus. Clinical Nutrition, 43(8), 1907-1913. https://doi.org/10.1016/j.clnu.2024.06.034