Additive effects of metformin on glucose homeostasis after metabolic-bariatric surgery in non-obese insulin-deficient diabetic rats.

Authors

Mélanie Hirlemann, Mélanie Garmon, Lara Ribeiro-Parenti, Danielle Bailbe, Alexandra Willemetz, Hounayda El-Jindi Shahrour, Jamileh Movassat, Claire Carette, Maude Le Gall

Published in

American journal of physiology. Endocrinology and metabolism. Sep 03, 2026. Epub Sep 03, 2026.

Abstract

This study investigates the individual and combined effects of Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and metformin on glucose regulation in a non-obese, insulin-deficient model of type 2 diabetes. Female Goto-Kakizaki (GK) rats underwent RYGB, SG, or sham surgery. Three weeks postoperatively, animals received metformin (50 mg/kg/day, 5 days/week) or vehicle for three additional weeks. Glucose tolerance was assessed using a standardized meal test, and insulin sensitivity was evaluated by insulin tolerance test. Plasma levels of GLP-1, GIP, insulin, and leptin were measured. RYGB and SG reduced body weight, food intake, and leptin levels, and improved fasting glucose, glucose tolerance, insulin sensitivity, and postprandial incretin and insulin secretion. Metformin alone improved glucose tolerance and insulin sensitivity independently of incretin or insulin changes. When combined with surgery, metformin further reduced postprandial glycemic excursions but did not enhance insulin sensitivity or hormone secretion beyond surgery alone. In conclusion, metabolic-bariatric surgery and metformin independently improve glucose regulation in non-obese diabetic GK rats. Their combination provides additional benefits on postprandial glucose control, despite no additional effects on insulin sensitivity or hormone levels. These findings support the use of metformin as an adjunct to metabolic-bariatric surgery in insulin-deficient diabetes and highlight the need for longer-term, sex-inclusive studies to enhance translational relevance.

PMID:
42691476
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.

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