Background
While novel antidiabetic medications like glucagon like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated weight loss in the general population, data on their impact on weight loss in PWH remains limited.
Methods
We identified adult PWH in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort who initiated GLP-1RAs, SGLT2is, dipeptidyl peptidase-4 inhibitors (DPP4is), or sulfonylureas between 1996-2023 who had ≥2 weight measurements available, including 1 prior to and ≥1 post medication initiation. The primary outcome evaluated was percent weight change at 1 year, analyzed using a linear mixed model. We also assessed whether the effect of GLP-1RAs and SGLT2is on weight change varied by diabetes status. The secondary outcome evaluated, time to ≥5% weight loss, was analyzed using a Cox proportional hazards model. Both models were adjusted for relevant demographic and clinical characteristics.
Results
Overall, 2086 patients met inclusion criteria, with 638 on GLP1-RA, 295 on SGLT2i, 219 on DPP4i, and 934 on sulfonylureas. Mean age at baseline was 52 years (SD: 10), 25% were female, and 47% were Black. At baseline, average weight was 98 kg (SD:25), 83% had diabetes, and 92% were on antiretroviral therapy. In adjusted analyses, percent weight change was significantly greater for GLP-1RAs (-4.13; 95%CI: -4.99, -3.28) compared to SGLT2is (-2.50; 95%CI: -3.72, -1.28), DPP4is (-0.57; 95%CI: -1.49,0.35), and sulfonylureas (-0.49; 95%CI: -1.11,0.13) (interaction p values all <0.05; see Figure). Among PWH on GLP-1RAs, those without diabetes experienced greater percent weight loss (-5.39; 95%CI: -7.20, -3.58) compared to those with diabetes (-3.56; 95%CI: -4.50, -2.62), although the interaction p-value was not significant (p=0.08). Conversely, SGLT2is trended towards a greater percent weight loss for those with diabetes (-3.23; 95%CI: -4.45, -2.00) compared to those without (-0.86; 95%CI: -3.53,1.80), however this interaction p-value was also non-significant (p=0.1). New users of GLP-1RAs were significantly more likely to achieve ≥5% weight loss compared to sulfonylureas (adjusted hazard ratio [aHR]=2.06; 95%CI: 1.69–2.52) and DPP-4i (aHR=1.64; 95%CI: 1.25–2.14), but not compared to SGLT2is (aHR=1.09; 95%CI: 0.86–1.38).
Conclusions
Among PWH, both GLP-1RAs and SGLT2is significantly reduced weight, with GLP-1RAs showing the greatest percent change overall compared to other antidiabetic medications.
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