Introduction

Obesity, characterised by excessive body fat accumulation, not only undermines physical health but also poses significant risks to mental well-being. Recent evidence has demonstrated the substantial benefits of Semaglutide in promoting weight loss among individuals with diabetes. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, not only aids in glycaemic control but has also shown remarkable efficacy in reducing body weight. Therefore, in this study, we investigated the effect of oral Semaglutide on weight loss in individuals with overweight or obesity but without diabetes mellitus.

Aims & Methods

The aim of the study was to evaluate the effectiveness and safety of oral Semaglutide when combined with dietary and lifestyle modifications, compared to dietary and lifestyle modifications alone, for the treatment of overweight or obesity in adults without type 2 diabetes. This randomized controlled trial was conducted in the department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad from June 2022 to December 2023. Consecutive consenting patients of both genders aged 18 years or older with either a BMI of 30 or greater or a BMI of 27 or greater with one or more treated or untreated weight-related coexisting conditions (i.e., prediabetes, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease). All the eligible participants after screening were randomized into two groups (Group 1 and 2) by block randomization (block size of 4 and 6) using computer generated random number. Participants in both groups received individual counselling sessions to help them adhere to a reduced-calorie diet (500- kcal deficit per day relative to the energy expenditure estimated at the time) and increased physical activity (with 150 minutes per week of physical activity, such as walking). Participants in group 1 also received oral Semaglutide along with diet and exercise. Treatment was initiated with the 3 mg once-daily dose. The dose was increased to 7 mg and then maximum of 14mg per day in 2-4 weeks interval based on patient tolerance. Participants were assessed for gastrointestinal complaints (nausea, vomiting) during escalation and follow-up. (ClinicalTrials.gov ID: NCT05442450)

Results

A total of 116 (58 per each group) individuals were recruited into the study. Mean percentage(SD) change in body weight from baseline to week 28 was - 10.47% (SD 5.3) with Oral Semaglutide versus 2.4 (SD 4.5) with dietary and lifestyle changes alone (p < 0.001). The mean weightloss noted with Semaglutide was 9.19kg (SD 4.7) compared to 2.3kg (SD 4.5) with dietary and lifestyle measures alone. Subjects who received oral Semaglutide have reported >5%, >10%, >15% and >20% weightloss in 51/58 (87%), 28/58 (48%), 13/58 (22.4%) and 4/58 (6.9%) respectively. Subjects received only dietary and lifestyle changes have lost >5% of baseline weight in 14/58 (24%), >10% in 6/58 (10.34%) and none lost more than 15% of baseline weight. Similarly, body mass index, waist circumference, HbA1C, fasting insulin and CRP were significantly improved with combination of Semaglutide with lifestyle measures. (p<0.001). Body composition analysis revealed a significant change in body fat mass of -7.3 kg (4.8%) with maintained muscle mass in patients who received oral Semaglutide compared to those who underwent diet alone. Adverse events include severe nausea and vomiting noted in the three patients receiving the oral Semaglutide requiring discontinuation of the drug.

Conclusion

In adults with overweight or obesity but without type 2 diabetes, oral Semaglutide combined with dietary and lifestyle modifications resulted in a significant and clinically meaningful reduction in body weight compared to dietary and lifestyle modifications alone.