Metabolic Effects of Very-Low Calorie Diet (VLCD), Semaglutide, or Their Combination in Individuals with Type 2 Diabetes Mellitus

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Citation: Anyiam O, Phillips B, Quinn K, Wilkinson D, Smith K, Atherton P, Idris I. Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus. Clinical Nutrition, Volume 43, Issue 8, 2024, Pages 1907-1913.

Background & Aim

Both Very-Low Calorie Diets (VLCDs) and the GLP-1 receptor agonist Semaglutide have been proven to promote weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D).

This pilot study aimed to compare the short-term effects of:
✔ VLCD alone (800 kcal/day)
✔ Semaglutide alone (SEM)
✔ Combination of VLCD + Semaglutide (COMB)

📌 Primary Focus: Examining changes in weight, body composition, and metabolic outcomes over 12 weeks.

Methods

📊 Participants: 30 individuals with T2D (ages 18–75, BMI 27–50 kg/m²) randomly assigned to one of three groups:
1️⃣ Semaglutide (SEM) Group
2️⃣ VLCD (800 kcal/day) Group
3️⃣ Combination (VLCD + Semaglutide) Group

📌 Key Measurements (Pre & Post-Intervention):
✔ Weight & body composition (via DXA scan)
✔ Glycated haemoglobin (HbA1c)
✔ Fasting glucose & insulin sensitivity (HOMA-IR)
✔ Pancreatic beta-cell function (via IVGTT test)
✔ Diet diaries used to assess adherence

Results

✅ Greater weight & fat mass loss observed in VLCD & COMB groups than SEM alone (p < 0.01).
✅ VLCD resulted in 5.4% greater weight loss than SEM, while COMB led to 7% greater weight loss than SEM.
✅ HbA1c and fasting glucose significantly reduced in all groups.
✅ Fasting insulin & HOMA-IR improved only in VLCD & COMB groups.
✅ Insulin first-phase response increased in SEM & COMB, with significantly greater improvement in COMB vs. VLCD alone (p < 0.01).

Conclusion

📢 VLCD induced greater short-term weight and fat loss than Semaglutide alone.
📢 Adding VLCD to Semaglutide led to enhanced weight loss compared to Semaglutide alone.
📢 While the combination did not provide additional weight loss benefits over VLCD alone, it significantly improved pancreatic beta-cell function.

🔬 Future Research Needed: Further studies should investigate long-term outcomes of combining VLCD and Semaglutide for T2D management.

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