Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Fasting hyperglucagonemia is a key feature of type 2 diabetes (T2D), which leads to increased hepatic glucose production and exacerbates hyperglycemia. Preclinical studies have shown that low concentrations of sulfonylureas can partially restore appropriate glucose-regulated glucagon secretion in islets from donors with T2D. In this pilot clinical trial, sixteen participants with T2D (diet controlled or on metformin alone) underwent a 4-week open-label, non-randomized, dose-titration (0.3-6mg/day) trial of an oral glibenclamide suspension. The dose was increased every 3-4 days and fasting blood samples (for glucagon, glucose, insulin, C-peptide and glibenclamide measurement) were taken prior to each dose change. Masked continuous glucose monitoring (CGM) was used throughout the study. Glibenclamide at 0.3mg/day reduced glucagon by 32% in the four participants with fasting hyperglucagonemia (25.6pmol/L vs 17.4pmol/L; p<0.05) but not in those with normal levels. Fasting insulin and C-peptide were unaffected, and doses ≥3mg/day significantly increased time spent hypoglycemic. Our results suggest that fasting hyperglucagonemia can be reduced by 1/3 in patients with T2D, using <10% the normal glibenclamide starting dose, without causing hypoglycemia or affecting insulin secretion. This article is protected by copyright. All rights reserved.

Original publication




Journal article


Diabetes Obes Metab

Publication Date