Background Cardiovascular outcome trials have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular risk in patients with type 2 diabetes (T2D). However, their comparative effectiveness remains uncertain, particularly in South Asian populations. Objective The objective of this study was to compare the effectiveness of SGLT-2i and GLP-1 RA in reducing major adverse cardiovascular events (MACE) and improving cardiometabolic parameters in patients with T2D. Methods This retrospective study was conducted at the Combined Military Hospital, Lahore, Pakistan, over 24 months. A total of 200 patients with T2D were included, with 100 in the SGLT-2i group and 100 in the GLP-1 RA group. Baseline characteristics, including age, sex, duration of diabetes, HbA1c, body mass index (BMI), hypertension, and dyslipidemia, were comparable between groups. The primary outcome was the incidence of MACE, while secondary outcomes included changes in HbA1c, blood pressure, lipid profile, and BMI. Statistical analysis included chi-square tests, independent t-tests, Kaplan-Meier survival curves, and Cox regression. Results Over a mean follow-up of 18.6 ± 3.1 months, MACE occurred in 18% of patients in the SGLT-2i group compared to 30% in the GLP-1 RA group (χ² = 4.26, p = 0.04). Kaplan-Meier analysis showed higher event-free survival with SGLT-2i (log-rank χ² = 4.71, p = 0.03). Cox regression revealed a 42% reduced risk of MACE with SGLT-2i (HR 0.58, 95% CI 0.35-0.95, p = 0.03). Secondary outcomes indicated greater reductions in systolic blood pressure (p = 0.02) and BMI (p = 0.01) with SGLT-2i, while HbA1c reduction was slightly greater with GLP-1 RA but not statistically significant (p = 0.42). Lipid changes favored GLP-1 RA but were not significant. Conclusion SGLT-2 inhibitors demonstrated superior effectiveness compared to GLP-1 receptor agonists in reducing cardiovascular risk, lowering systolic blood pressure, and promoting weight loss in Pakistani patients with T2D. These findings support the preferential use of SGLT-2i in high cardiovascular risk populations.
