Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in obesity and type 2 diabetes mellitus (T2DM), but comparative real-world evidence from the Middle East remains limited. We compared the effectiveness, documented adverse events, adherence and persistence of once-weekly semaglutide and once-daily liraglutide in Omani adults. Methods: Retrospective cohort study of adults treated with semaglutide or liraglutide at Sultan Qaboos University Hospital between January 2024 and December 2025. The primary outcome was change in body mass index (BMI) at 3 and 6 months; change in body weight, percentage total body weight loss and the proportions achieving at least 5% and at least 10% weight loss. Because treatment indication and exposure differed markedly between groups, the primary comparison used propensity-score overlap weighting with additional covariate adjustment, implemented in a design-based general linear model. A mixed model for repeated measures supported the primary analysis and handled missing visits under a missing-at-random assumption, with a delta-adjusted pattern-mixture analysis used to test departures from that assumption. Persistence was analysed with Kaplan-Meier estimation and Cox regression adjusted for baseline covariates only. Secondary outcomes were corrected for multiplicity using the Benjamini-Hochberg procedure. Analyses are labelled throughout as primary, prespecified secondary, or post hoc exploratory. No patient received semaglutide 2.4 mg weekly, the dose licenced for chronic weight management, due to unavailability during the study period. Results: Of 287 treatment records supplied, 257 unique patients were analysed (liraglutide n = 135; semaglutide n = 122). Semaglutide was associated with a greater reduction in BMI than liraglutide at 3 months (adjusted difference -0.60 kg/m2, 95% CI -1.12 to -0.07; p = 0.026) and at 6 months (-1.42 kg/m2, 95% CI -2.60 to -0.24; p = 0.019). In clinical units, the adjusted difference in body weight was -1.70 kg at 3 months (95% CI -3.10 to -0.29; p = 0.018) and -3.66 kg at 6 months (95% CI -6.72 to -0.60; p = 0.020). At 6 months, 56.5% of semaglutide-treated and 24.7% of liraglutide-treated patients had lost at least 5% of body weight (p < 0.001), and 30.4% versus 4.9% had lost at least 10% (p < 0.001). The mixed model gave the same conclusion (group-by-time interaction p < 0.001). No statistically detectable difference in glycated hemoglobin HbA1c change was observed at either time point (p = 0.132 and p = 0.158; interaction p = 0.360). Of eight secondary cardiometabolic outcomes, only total cholesterol at 3 months remained significant after correction for multiplicity (adjusted p = 0.024). Documented adverse events were infrequent and did not differ between groups (12.6% versus 8.2%, p = 0.251). Hypoglycaemia occurred in seven liraglutide-treated and one semaglutide-treated patient (p = 0.069 by exact test) and was not significant after weighting and adjustment for background insulin or sulfonylurea use (p = 0.345). Crude discontinuation was 48.9% with liraglutide versus 9.0% with semaglutide, but median exposure was 17 versus 6 months. After accounting for time at risk, no difference in persistence was statistically apparent (log-rank p = 0.328; adjusted hazard ratio for semaglutide 1.60, 95% CI 0.61 to 4.19). Documented adherence was higher with semaglutide (95.9% versus 83.7%, p = 0.001). Conclusions: In this cohort, semaglutide was associated with a modestly greater reduction in BMI and body weight than liraglutide, and with a higher proportion of patients achieving clinically meaningful weight loss. Glycaemic and most cardiometabolic comparisons were inconclusive once confounding, multiplicity and limited precision were accounted for, and the large apparent difference in discontinuation was no longer statistically apparent after allowing for unequal time at risk. These findings are associative. They describe the drugs as prescribed in one health-care setting, at doses that are not pharmacologically equivalent, and should not be read as evidence of comparative causal superiority.
