Glycemic Variability in Youth Prescribed Obesity Pharmacotherapy: A Prospective Case Series with Continuous Glucose Monitoring

Background: The effects of obesity pharmacotherapy on glycemic variability in youth with obesity remain insufficiently explored. Objective: This prospective case series aimed to explore glycemic variability patterns in youth with obesity prescribed obesity pharmacothreapy as part of standard clinical care. Methods: This 12-week case series enrolled youth, ages 7–17 years, with obesity from a comprehensive obesity program at a tertiary children’s hospital. Participants, prescribed an obesity pharmacotherapy, wore an unmasked continuous glucose monitor (CGM) for 14 days at baseline and at 4-week intervals for a total of three sessions. The primary outcome was glycemic variability, measured by standard deviation, coefficient of variation, and modified percent time in range (70–140 mg/dL) from CGM data. Demographic and medical data were also collected. Data were analyzed using EasyGV and R with repeated measures to assess changes in glycemic variability over time and across obesity pharmacotherapy. Results: Sixteen youth consented to participate (56% female, 69% Hispanic, mean age 14.1 ± 1.2 years, 62% publicly insured), with 6 completing the 12-week CGM data collection (44% retention). Medications included topiramate ( n = 1), phentermine/topiramate ( n = 1), liraglutide ( n = 2), semaglutide ( n = 1), and tirzepatide ( n = 1). Participants wore the CGM for an average of 6.3 ± 1.2 days per 14-day period. Medication-specific changes in glycemic variability were observed: topiramate monotherapy showed a 2.8% increase in modified percent time in range (%mTIR), a 6.4% reduction in standard deviation (SD), and a 0.06 decrease in the coefficient of variation (CV). The phentermine/topiramate combination had a 0.8% decrease in %mTIR, a 4.1% increase in SD, and a 0.02 increase in CV. Liraglutide Case 1 saw a 12.5% decrease in %mTIR, a 4.1% increase in SD, and a 0.07 increase in CV, while Liraglutide Case 2 exhibited a 9.2% decrease in %mTIR, a 25.6% reduction in SD, and a 0.25 decrease in CV. Semaglutide resulted in a 1.1% increase in %mTIR, a 6.6% reduction in SD, and a 0.05 decrease in CV. Tirzepatide showed a 0.5% increase in %mTIR, a 4.7% reduction in SD, and a 0.05 decrease in CV. Conclusion: This exploratory case series suggests that obesity pharmacotherapy may have varying effects on glycemic variability in youth with obesity. While most medications demonstrated improvements in standard deviation and modified percent time in range, the magnitude of changes varied across agents. Impact: These findings highlight the potential for obesity optimizing medications to influence glycemic control in this population, warranting further investigation in larger, controlled studies to confirm these effects and understand their long-term implications.