(A-082) Impact of New Antidiabetic Medications on Weight Loss in People with HIV

Background: Obesity is on the rise in People with HIV (PWH), particularly with the use of modern antiretroviral therapies (ART) such as integrase strand transfer inhibitors and tenofovir alafenamide, which may contribute to weight gain. Despite the demonstrated effectiveness of novel antidiabetic medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT2i), in promoting weight loss in the general population, data on their impact in PWH remains limited.

Objectives: To compare the likelihood of achieving ≥5% weight loss among new users of GLP-1RAs, SGLT2i, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas among PWH.

Methods: We conducted an active-comparator, new-user cohort study using data from 9 sites from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) in the U.S. Adult PWH who initiated GLP-1RAs, SGLT2is, DPP-4 inhibitors, or sulfonylureas between 2013 and 2023 with ≥2 weight measurements (≥1 pre- and ≥1 post-initiation) were included. Date of medication initiation was defined as the index date. Patients were followed from index date until the earliest of the following: outcome occurrence, treatment discontinuation or switching, or the end of clinical data. The primary outcome, time to ≥5% weight loss, was analyzed using a Cox proportional hazards model adjusted for baseline age, sex, race/ethnicity, CNICS site, use of ART, antipsychotics, statins, insulin, and metformin, baseline diagnoses of hypertension, chronic kidney disease, and diabetes, baseline weight, CD4 count, and HIV viral load.

Results: A total of 1601 patients met inclusion criteria: 627 on GLP-1RAs, 295 on SGLT2i, 201 on DPP-4 inhibitors, and 478 on sulfonylureas. The mean baseline age was 53 years (SD: 10), with 25% female and 46% Black. Baseline mean BMI was 33 (SD: 8) and 92% had a viral load <200 copies/mL. At 1 year, the probability of achieving ≥5% weight loss was highest with GLP-1RAs (48.7%), followed by SGLT2i (40.4%), DPP-4 inhibitors (34.7%), and sulfonylureas (21.6%). In adjusted analyses, compared to sulfonylureas, new users of GLP-1RAs and SGLT2i were significantly more likely to achieve ≥5% weight loss (aHR = 2.28, 95% CI: 1.81–2.87 and aHR = 2.05, 95% CI: 1.56–2.69, respectively). In contrast, new users of DPP-4 inhibitors did not show a significant difference in achieving ≥5% weight loss compared to sulfonylureas.

Conclusions: Among PWH, both GLP-1RAs and SGLT2 inhibitors lead to clinically significant weight loss compared to traditional antidiabetic medications, offering potential solutions for addressing the growing obesity epidemic in this population.