BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are burgeoning public health challenges. Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) have gained prominence because they improve glycemic control and aid weight reduction by slowing gastric emptying and promoting satiety. Liraglutide is a once-daily human GLP-1 analogue marketed for T2DM (at 1.8 mg) and weight management (3.0 mg), whereas semaglutide is a more potent GLP-1 RA administered once weekly at doses of 1.0 mg (diabetes) and 2.4 mg (weight management). Randomized controlled trials suggest that semaglutide yields greater weight loss and HbA1c reduction than liraglutide [1, 2], yet comparative data in real-world South Asian populations are limited.
METHODS: We performed a prospective, open-label, randomized study at Lady Reading Hospital, Peshawar, Pakistan. Adults with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with T2DM were randomized (1:1) to once-weekly semaglutide 2.4 mg plus lifestyle counselling or once-daily liraglutide 3.0 mg plus the same counselling. The primary outcome was the percentage change in body weight at 68 weeks. Secondary outcomes included proportions achieving weight-loss thresholds (≥ 5%, ≥ 10 % and ≥ 15 %) [3]; change in HbA1c [4], fasting glucose, waist circumference, blood pressure, lipid profile, patient-reported quality of life, and adverse events. Mean changes were compared using t-tests; categorical outcomes were compared using χ2 tests.
RESULTS: Two hundred forty participants (mean age 45.6 ± 9.8 years, 52 % women) were enrolled. At 68 weeks, semaglutide recipients lost significantly more weight than liraglutide recipients (-14.7 ± 5.8 % vs -6.2 ± 4.9 %; p < 0.001), consistent with STEP 8 trial findings [1]. A greater proportion of semaglutide patients achieved ≥ 10 % and ≥ 15 % weight loss (70.9 % and 55 %) compared with liraglutide (25.6 % and 12 %) [3]. HbA1c decreased by -1.6 ± 0.4 % with semaglutide versus -1.0 ± 0.4 % with liraglutide (p < 0.001), mirroring SUSTAIN-10 differences [5]. Gastrointestinal adverse events were common but similar between groups (83.5 % vs 82.0 %); nausea and vomiting occurred more frequently with semaglutide [6].
CONCLUSIONS: In a real-world Pakistani cohort, once-weekly semaglutide produced substantially greater weight loss and HbA1c reduction than daily liraglutide, with comparable tolerability. These findings support the preferential use of semaglutide for weight management and glycemic control, particularly when once-weekly dosing improves adherence. Further studies should explore long-term sustainability, cardiovascular benefits, cost-effectiveness, and optimal integration with lifestyle interventions.
