Haidar, Lara2026-04-292026-04-292026-04-272026-04-28http://hdl.handle.net/1993/39777Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have proven metabolic and kidney benefits in the general population, but evidence among people with HIV (PWH), a population with high comorbidity burden, is limited. This thesis evaluated their safety and effectiveness in PWH, focusing on bodyweight, glycemic control, kidney function, and depressive symptoms. Methods: Four observational studies were conducted using data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a multicenter cohort of PWH in care across the US (2013–2024). Study 1 assessed one-year changes in bodyweight and hemoglobin A1c (HbA1c) following semaglutide initiation. Study 2 used a new-user, active-comparator design to compare weight outcomes across four antidiabetic classes: GLP-1RAs, SGLT2is, dipeptidyl peptidase-4 inhibitors, and sulfonylureas. Study 3 applied propensity score matching to compare SGLT2is versus other antidiabetic classes on acute estimated glomerular filtration rate (eGFR) decline (≥10% and ≥30% at 6 months) and longer-term eGFR trajectories. Study 4 used a pre-post design to evaluate changes in depressive symptoms (Patient Health Questionnaire-9; PHQ-9) after semaglutide initiation. Continuous outcomes were analyzed using linear mixed models, and time-to-event outcomes using Cox proportional hazards models. Results: In Study 1, semaglutide initiation was associated with a mean weight reduction of 6.47 kg (95% CI: -7.71, -5.23) and an HbA1c reduction of 1.07% (95% CI -1.64, -0.50). In Study 2, GLP-1RAs were associated with the greatest weight loss (4.44%; 95% CI -5.51, -3.36), particularly among individuals without diabetes, with obesity, and those receiving semaglutide. SGLT2is were associated with modest weight loss, while other classes showed minimal changes. In Study 3 (295 matched pairs), SGLT2i use was associated with higher rates of acute eGFR decline (≥10%: aHR 1.79 [95% CI 1.40–2.28]; ≥30%: aHR 1.69 [95% CI 1.05–2.73]), although the mean decline was small (-2.6 mL/min/1.73 m²) and appeared transient over time. In Study 4, semaglutide was not associated with worsening depressive symptoms (mean PHQ-9 change: -0.1; 95% CI: -0.7, 0.5). Conclusion: Among PWH, GLP-1RAs, particularly semaglutide, were associated with clinically meaningful weight and HbA1c reductions without evidence of worsening depressive symptoms, while SGLT2is were associated with modest weight loss and generally favorable kidney outcomes.engAntidiabetic MedicationsPeople with HIV