Scientists at the University of Nottingham, UK, have conducted a short-term intervention study to explore the effectiveness of a very low-calorie diet and Semaglutide, individually and in combination, in reducing body weight and controlling blood glucose in patients with type 2 diabetes. The findings of this study have been published in the journal Clinical Nutrition.
Study: Metabolic effects of very-low calorie diet, Semaglutide or combination of the two, in individuals with type 2 diabetes mellitus. Image Credit: Caroline Ruda / Shutterstock
Background
Type 2 diabetes is a multifactorial disease characterized by high blood glucose levels and insulin resistance. Impaired insulin secretion from pancreatic beta-cells is the leading cause of type 2 diabetes.
Overweight and obesity are the major risk factors for diabetes development, affecting 90% of type 2 diabetic patients. While obesity has been found to increase the risk of diabetes development by 7-fold, overweight has been found to be associated with insulin resistance and beta-cell dysfunction.
Glucagon-like peptide-1 receptor agonist (GLP1RA) semaglutide is an antidiabetic medication with favorable efficacy in reducing body weight. A very low-calorie diet (VLCD) is another effective weight loss intervention with a promising ability to restore beta-cell function and improve glycemic control in type 2 diabetes.
In this study, scientists have explored the effects of VLCD and Semaglutide, both individually and in combination, on body weight, body composition, and metabolic outcomes in type 2 diabetes patients.
Study design
The study was conducted on 30 adult individuals with type 2 diabetes and a body mass index (BMI) of 27 – 50 kg.m-2. The participants were randomly assigned to three groups: the VLCD group, the Semaglutide group, and the VLCD—Semaglutide combined group.
The VLCD group participants received a diet restricted to 800 kilocalories per day, and the Semaglutide group participants received subcutaneous Semaglutide once weekly, starting at 0.25 milligrams and increasing every two weeks to 1 milligram. The combined group participants received the same interventions in combination. All interventions were continued for 12 weeks.
All participants were subjected to body weight, whole-body composition (fat and lean body mass), glycated hemoglobin measurements, and intravenous glucose tolerance test (beta-cell function and insulin sensitivity) at baseline and post-intervention. To assess dietary compliance, participants also completed diet diaries.
Important observations
Each intervention group saw a significant reduction in body weight. However, the VLCD and combined intervention groups saw a significantly higher percentage body weight and BMI reduction compared to the Semaglutide group. Specifically, weight loss in the VLCD and combined intervention groups was 5.4 and 7 percent higher than in the Semaglutide group.
Regarding fat mass, a reduction of more than two times higher was observed in the VLCD and combined intervention groups than in the Semaglutide group. However, no significant differences in lean body mass reduction were observed between the three groups.
Dietary assessment
The diet analysis showed a significantly smaller reduction in daily energy intake in the Semaglutide group compared to that in the VLCD and combined intervention groups. Overall, good compliance with the VLCD program was observed in both VLCD and combined intervention groups.
The analysis of the macronutrient content of ingested food showed that the percentage of daily energy intake from protein was significantly higher in the VLCD and combined intervention groups. In contrast, the corresponding value from fat was significantly lower in these two groups compared to that in the Semaglutide group.
Glycemic control
A significant reduction in glycated hemoglobin (a measure of glycemic control) was observed in all groups. The reduction was comparatively higher in the combined intervention group.
Post-intervention, fasting insulin levels were significantly reduced in the VLCD and combined intervention groups and slightly increased in the Semaglutide group. However, the reduction in fasting glucose was comparable between the three groups.
A significant increase in the acute insulin response to glucose was observed in the Semaglutide and combined intervention groups. The induction was 9-fold higher in the combined intervention group compared to that in the VLCD group.
The VLCD and combined intervention groups observed significant improvements in insulin sensitivity but not in the Semaglutide group.
Adverse events
The most common adversity in the Semaglutide group was mild nausea, followed by constipation, mild abdominal discomfort, abdominal bloating, and lethargy.
In the VLCD and combined intervention groups, the most common adversity was constipation. Some participants in the combined intervention group experienced mild abdominal discomfort and mild nausea or headache.
Study significance
The study finds that Semaglutide, in combination with VLCD, is more effective than semaglutide alone in improving pancreatic beta-cell function and reducing insulin resistance. Compared to Semaglutide, VLCD exhibits greater efficacy in reducing body weight and fat mass within a short time period.
Future studies with long-term intervention and follow-up periods are needed to more conclusively understand the impact of Semaglutide—VLCD combination treatment on the management of type 2 diabetes and obesity.
Global gap in diabetes prevalence and treatment has widened since 1990