Obesity medications and acquired hypothalamic obesity in adults: A two-case experience

Background: Acquired hypothalamic obesity (HO) lacks well-described adult pharmacotherapy outcomes, creating a unique clinical challenge for providers tasked with the treatment of patients with hypothalamic obesity. Methods: We conducted a retrospective chart review to evaluate clinical outcomes in two patients who developed hypothalamic obesity following treatment for tumors of the central nervous system. Medical records from the research center were systematically examined to identify individuals meeting criteria for acquired hypothalamic obesity, defined by significant weight gain associated with hypothalamic injury secondary to tumor therapy. Results: Two individuals with acquired hypothalamic obesity were identified, both of whom achieved clinically significant weight loss taking tirzepatide with phentermine, and tirzepatide with phentermine/topiramate combination therapy. In case 1, the patient presented with cirrhosis, dyslipidemia, and transaminitis. Tirzepatide was initiated and escalated to 7.5 mg weekly, without weight response, prompting the addition of phentermine 8 mg daily. Dual therapy yielded 12.26 % weight loss over 7 months. In case 2, the patient presented with hypertension and obstructive sleep apnea (OSA). Tirzepatide 2.5 mg weekly combined with phentermine/topiramate was initiated. Tirzepatide was escalated to 5 mg, with phentermine/topiramate subsequently increased to 37.5/50 mg daily, producing 35.10 % weight loss over 11 months. Conclusion: Tirzepatide-based combination therapy was associated with clinically meaningful weight loss and comorbidity improvement in adults with HO. These cases support further study of targeted, multimodal regimens in patients with acquired HO.