SUN-734 - Response to GLP-1 Therapy in Children with Early Onset Obesity

Aim: To characterize response to GLP-1 or GLP-1/GIP agonist medications in pediatric patients with early onset obesity who have had genetic testing.
Result: The study cohort includes patients with early onset obesity prior to age 5 who have had genetic testing through Rhythm Pharmaceuticals Uncovering Rare Obesity sponsored testing. Chart review identified 44 patients who were prescribed GLP-1 or GLP-1/GIP agonists. 34 patients remained on treatment for at least 3 months and were included in this assessment; 28 of them completed at least 6 months, and 15 were treated for 12 months or longer. Average treatment duration was 12.2 months (SD = 6.28) and the longest duration was 24 months. The average age at beginning of treatment was 14.2 years (SD = 2.48). Average BMI at start of treatment was 46.44 kg/m2 (SD = 10.16) and average BMI z-score was 2.622 (SD = 0.245). The average weight loss at follow up visits between 3-5 months after starting treatment was 2.85% of body weight (SD = 5.28%), at visits between 6-8 months on therapy it was 4.15% (SD = 6.52%), between 9-11 months it was 3.76% (SD = 9.54%), and in those who completed 12 or more months of therapy it was 8.39% (SD = 19.82%). When comparing patients with 12 or more months of treatment to those with less than 12 months of treatment there was increased weight loss (8.39% vs 3.19%), BMI decrease (10.58% vs 2.87%), and statistically significantly higher decrease in BMI z-score (loss of 0.34 vs 0.05, p=0.041).
27 of the patients receiving treatment had genetic testing positive for one or more variant. Most variants were classified as variants of uncertain significance (VUS), only 5 patients had variants classified as risk, likely pathogenic, or pathogenic. There were similar rates of weight loss in patients with no variant compared to those with any variant (4.32% weight loss in those with no variant, 7.12% weight loss in those with 1 variant, 4.30% weight loss in those with 2+ variants). Less than half of all patients (47%) had clinical response to therapy (body weight decrease by >/= 5%) and 26.5% had weight gain. No significant differences were seen in response rates when comparing patients with or without detected genetic variants.

Conclusion: We saw variable response to GLP-1 and GLP-1/GIP agonist therapy in pediatric patients with early onset obesity with less than half of patients showing clinical response of >/= 5% weight loss. Longer treatment duration was associated with increased average weight loss and BMI decrease and significant decrease in BMI z-score but was not associated with higher overall rates of response. More research is needed to help determine pre-treatment characteristics that predict clinical response to GLP-1 and GLP-1/GIP agonist therapy.