Novel Pharmacological Treatment of Post-prandial Hyperinsulinemic Hypoglycemia

Abstract

Background: Post Roux-en-Y gastric bypass (RYGB) hyperinsulinemia hypoglycemia (HH) is presumably related to enhanced glucagon-like peptide-1 (GLP-1) response with partial pancreatectomy as recommended treatment. A new approach successfully uses short-acting GLP-1 mimetics, challenging assumptions about post-RYGB HH etiology and standard treatment.Case Description: A 61-year-old woman with lifelong obesity leading to RYGB at 304 pounds followed by 10 years of fatigue and weight fluctuation initially lost 100 pounds, regained 80 pounds, then lost 60 pounds with aggressive diet and exercise. Ten years post-RYGB, she presented with extreme fatigue and weight regain. Mixed-meal tolerance testing revealed post prandial HH: 30-minute post-prandial insulin response of 550.8 mU/mL; 60-and 90-minute post-prandial glucose of 48 and 56 mg/dL, respectively; weight of 219 pounds, BMI 36.4. Initial treatment included pre-meal acarbose 50 mg and exenatide 5 µg three times/day, balanced meals and snacks, and no prescribed exercise. Insulin and glucose levels improved immediately accompanied by weight loss. Acarbose and exenatide doses were adjusted until the insulin response stabilized. Zonisamide (50 mg) and naltrexone (25 mg) twice/day were also prescribed after detecting elevated agouti-related peptide. By 12 months, the patient's weight was 157 pounds (28% weight loss) and BMI 26.1. By 18 months, her weight was 140 pounds (36% weight loss) and BMI 23.3. Conclusions:This report is the first to describe effective use of short-acting exenatide combined with an alpha-glucoside inhibitor to regulate post-RYGB post-prandial HH and facilitate concomitant weight loss, and it challenges previous assumptions regarding post-prandial HH etiology and invasive treatment with partial pancreatectomy.