A single dose trial of mizagliflozin for the treatment of postbariatric hypoglycemia.

CONTEXT: Postbariatric hypoglycemia (PBH) is a complication of bariatric surgery characterized by severe postprandial hypoglycemia for which there is no approved therapy. OBJECTIVE: To evaluate efficacy and safety of mizagliflozin, a sodium glucose cotransporter 1 inhibitor, for treatment of PBH. METHODS: This was a phase 2, open-label, randomized, single-dose, crossover study. Nine participants with PBH were randomized to receive a baseline mixed meal tolerance test (MMTT), and single doses of mizagliflozin before each of 2 additional MMTTs. Doses included a 2.5-mg liquid formulation, and 2.5-, 5-, and 10-mg capsules. The primary outcome was change from baseline in glucose nadir, and the main secondary outcomes were change from baseline peak glucose and peak insulin. RESULTS: Compared to baseline, all individual doses of mizagliflozin raised the glucose nadir: 6.2 mg/dL (2.5-mg capsule), 17.5 md/dL (2.5-mg liquid), 4.0 mg/dL (5-mg capsule) and 31.5 mg/dL (10-mg capsule). In a post hoc analysis of participants that exhibited hypoglycemia (<70 mg/dL) during the baseline MMTT, mizagliflozin (all capsule doses combined) raised the glucose nadir by 38% (P = .03). Treatment with mizagliflozin also lowered both peak glucose by 21% (P = .03) and peak insulin by 53% (P = .016). Glucose-dependent insulinotropic peptide area under the curve0-3h was reduced by 45% from baseline (P = .048). CONCLUSION: Mizagliflozin resulted in improved glucose nadir, reduction in both postprandial peak glucose and peak insulin, and reduction in postprandial glucose-dependent insulinotropic polypeptide. The results from this proof-of-concept study suggest mizagliflozin represents a promising novel oral treatment for PBH that warrants further clinical development.