Efficacy and Safety of Semaglutide in Weight Reduction in Overweight or Obese Bangladeshi Adults With or Without Type 2 Diabetes Mellitus

Background and Rationale Obesity has emerged as a significant global health challenge, with its prevalence increasing rapidly across various demographics. Estimates suggest that nearly half of the world's population could be classified as overweight by the year 2030. The ramifications of this trend are profound, leading to increased risk for a variety of chronic diseases, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and several cardiovascular diseases. In fact, obesity is estimated to be responsible for approximately five million deaths globally each year, with a notable mortality rate of 62.6 deaths per 100,000 individuals suffering from obesity. Although the mortality rates in low- and middle-income countries are lower than in developed regions, trends indicate a concerning increase in obesity-related mortality in these areas.

Even modest weight loss (5-10% of body weight) can lead to significant health benefits, such as slowing the progression of T2DM and reducing cardiovascular risks. Moreover, evidence indicates that weight reduction can correlate with an 18% reduction in premature mortality. Traditional weight management strategies primarily involve lifestyle modifications such as dietary changes and increased physical activity; however, many individuals find it difficult to achieve and sustain these changes.

While surgical options are available for severe cases of obesity, they come with inherent risks and complications that necessitate ongoing follow-up care. In this context, pharmacotherapy offers a valuable adjunct to lifestyle interventions, helping individuals achieve and maintain clinically relevant weight loss while potentially improving coexisting health conditions.

Currently, there are limited anti-obesity medications available; thus, there is a pressing need for more effective therapeutic options that can aid in weight maintenance and comorbidity prevention. Among the medications approved for long-term use is semaglutide, a glucagon-like peptide-1 receptor agonist initially developed for the treatment of T2DM. Recent studies have demonstrated its effectiveness in promoting weight loss, particularly in Caucasian populations.

However, existing trials primarily include participants from Europe and North America. This raises questions about the applicability of these findings in Asian populations, such as those in Bangladesh, where genetic and environmental factors can influence obesity outcomes significantly. Morphological differences exist between populations; for instance, central obesity is more prevalent among Caucasians, while subcutaneous fat accumulation is common in Asians.