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bioRxiv · 10.64898/2026.04.23.720381

Additional effects of bariatric surgery and metformin on glucose regulation in non-obese insulin-deficient diabetic rats

Hirlemann, M.·Garmon, M.·Ribeiro-Parenti, L.·Bailbe, D.·Willemetz, A.·El Jindi Shahrour, H.·Movassat, J.·Carette, C.·LE GALL, M.
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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 and advanced the glycemic peak but did not enhance insulin sensitivity or hormone secretion beyond surgery alone. In conclusion, 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 additive effects on insulin sensitivity or hormone levels. These findings support the use of metformin as an adjunct to bariatric surgery in insulin-deficient diabetes and highlight the need for longer-term, sex-inclusive studies to enhance translational relevance. NEW & NOTEWORTHYBariatric surgery and metformin each improved glucose regulation in non-obese, insulin-deficient female GK rats. Their combination yielded an additional reduction in postprandial glycemic excursions without further enhancing insulin sensitivity or incretin/insulin secretion. These findings reveal that postprandial glucose dynamics can be modulated independently of hormonal or insulin-sensitivity pathways, highlighting distinct and dissociable mechanisms governing glucose homeostasis in an insulin-deficient model.

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Hirlemann, M., Garmon, M., Ribeiro-Parenti, L., Bailbe, D., Willemetz, A., El Jindi Shahrour, H., Movassat, J., Carette, C., LE GALL, M.. 2026-04-27. Additional effects of bariatric surgery and metformin on glucose regulation in non-obese insulin-deficient diabetic rats. https://doi.org/10.64898/2026.04.23.720381

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