This was a pilot evaluation involving the SLIM LIVER Study to assess changes in weight, waist circumference, lipids and glucose 24 weeks after discontinuation of low-dose semaglutide among adults with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD) who had received 24 weeks of semaglutide.  51 participants were initially enrolled and 47 remained on study at week 48.  Participants maintained their same ART regimen throughout follow-up: 82% were on INSTI-based ART and all were virologically suppressed < 40 copies/mL.  Between weeks 24 and 48, the absolute mean weight regain among participants was +2.9 kg [95% CI 1.5, 4.3]: although over half of participants regained at least 2.27 kg, 60% maintained an overall mean weight loss of at least 2.27 kg by week 48 compared to baseline.  Semaglutide treatment cessation was also associated with increases in mean waist circumference (2.0 cm), fasting glucose (5.1 mg/dL), and A1c (0.2).  No significant changes were observed in fasting serum total cholesterol, LDL, HDL, triglycerides, systolic blood pressure, or metabolic syndrome – although trends were generally towards reversal of the initial beneficial effects of semaglutide.  Among 34 participants who had a > 2.27 kg initial decrease followed by either significant regain or maintained, 59% regained > 2.27 kg and 41% did not.

Similar to the general population, semaglutide discontinuation was associated with rapid weight regain [of over 5 pounds] and the reversal of many weight loss-associated cardiometabolic benefits in this population of people with HIV and MASLD.  Although a small subset of participants did not experience full weight regain, sample sizes precluded robust comparison, and authors note that the incorporation of lifestyle changes including sustainable changes in physical activity and healthy nutrition remains essential in ongoing weight maintenance.  Additionally, research on long-term therapeutic approaches to maintain beneficial GLP-1 RA effects are needed.