Background Incretin-based therapies have emerged as effective strategies for obesity and type 2 diabetes mellitus (T2DM) management. Semaglutide and tirzepatide are among the most promising agents. Real-world data in Bangladesh on their efficacy, lifestyle interactions, and safety profiles remain limited. The objective of the study is to evaluate the associations of tirzepatide and semaglutide with weight reduction and safety in adults with obesity, and to assess the influence of lifestyle factors on treatment outcomes. Methods This retrospective observational study analyzed the electronic medical records of 100 adults with obesity from three tertiary centers in Bangladesh (58 patients treated with tirzepatide, 42 patients treated with semaglutide) over one year. Participants had completed at least three months of therapy. Demographics, clinical parameters, comorbidities, lifestyle adherence, weight change, and adverse events were collected using a structured questionnaire. Results A total of 100 participants (58 tirzepatide, 42 semaglutide; median age 27 years) were included, with 87 (87%) being female. Baseline BMI was higher in the tirzepatide group (36.6±4.77 vs. 32.3±3.55 kg/m²; p<0.001). Both drugs produced significant weight loss, with tirzepatide achieving greater reductions than semaglutide (8.53±4.10 vs. 6.85±3.38 kg; p=0.033). Clinically meaningful weight loss (≥5%) was observed in 89 (89%) of participants, and ≥10% loss in 33 (33%), with higher proportions in the tirzepatide group. Lifestyle interventions further enhanced weight reduction, most notably with tirzepatide. Gastrointestinal adverse events were the most common, occurring more frequently with tirzepatide, while serious events were rare. Overall, tirzepatide was associated with greater weight reduction, especially when combined with lifestyle modification. Conclusion Tirzepatide and semaglutide were both associated with weight reduction in obesity, with greater reductions observed with tirzepatide, particularly when combined with lifestyle interventions, underscoring the importance of combining behavioral and pharmacological strategies.
