SUN-655 Weight Loss with Topiramate and Phentermine Combination Therapy in a Patient with Bardet-Biedl Syndrome (BBS)

Abstract Disclosure: D. Hassan: None. M. Salama: None. S. Kumar: None. K. Muthusamy: None. Background: Obesity is prevalent among individuals with Bardet-Biedl Syndrome (BBS), affecting approximately 72%-86% of patients. Setmelanotide, an MC4R agonist, is approved for the treatment of obesity in patients with BBS. It reduces hyperphagia and improves quality of life. However, the high cost of setmelanotide and the need for daily injections limit its use. Affordable and effective alternative pharmacotherapies are needed for managing obesity in patients with BBS. Here, we present a case of an adult with BBS who experienced significant weight loss following treatment with a combination of topiramate and phentermine. Clinical Case: A 29-year-old Hispanic female with BBS due to a homozygous BBS2 mutation (NM_031885.3, c.717+1G>T, GT donor) was evaluated for migraine. BMI was elevated at 42.5 kg/m², and obesity was complicated by obstructive sleep apnea, chronic respiratory failure requiring supplemental oxygen with activity, impaired fasting glucose (101 mg/dL; reference range [RR]: 70-100 mg/dL), and dyslipidemia (triglycerides: 252 mg/dL [RR: 30-150 mg/dL]; very low-density lipoprotein (VLDL): 50.4 mg/dL [RR: 8-30 mg/dL]; total cholesterol: 190 mg/dL [RR: 0-200 mg/dL]; high-density lipoprotein (HDL): 40 mg/dL [RR: 40-60 mg/dL]). She had polydactyly, retinal dystrophy, developmental delay and subclinical hypothyroidism. Topiramate was initiated at 25 mg and subsequently increased to 50 mg. At 31 years of age, BMI was 40.5 kg/m², and weight had decreased by 7.5 kg after two years of therapy with topiramate and lifestyle interventions. Phentermine 30 mg daily was added. She experienced a notable appetite-suppressing effect, reduced nighttime eating, fewer sugar cravings, and decreased stress-related eating. She was able to extend the duration of exercise with improved endurance. She reported constipation as a side effect but had no other intolerances. After three months of phentermine therapy, BMI decreased to 34.96 kg/m². Repeat metabolic profile revealed fasting glucose 70 mg/dL, HbA1c 5.5% (RR: 4.5-5.6%), triglycerides 204 mg/dL, VLDL 40.8 mg/dL, total cholesterol 175 mg/dL, HDL 38 mg/dL, and low-density lipoprotein (LDL) 96 mg/dL (RR: 70-100 mg/dL). Eight months after starting phentermine, BMI further decreased to 32.31 kg/m², reflecting a 25% total weight loss. Conclusion: This case report highlights the excellent weight loss response (25% total weight loss) and significant improvement in metabolic profile with phentermine and topiramate combination therapy in a patient with BBS. The effects of this combination therapy have not been formally studied in BBS, emphasizing the need for further research to evaluate the efficacy of conventional anti-obesity medications—used alone, sequentially, or in combination with setmelanotide—to optimize weight and metabolic outcomes. Keywords: Bardet-Biedl Syndrome, obesity, topiramate, phentermine, weight loss. Presentation: Sunday, July 13, 2025