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 nonobese, 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/wk) or vehicle for three additional weeks. Glucose tolerance was assessed using a standardized meal test, and insulin sensitivity was evaluated by an insulin tolerance test. Plasma levels of glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (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 nonobese 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.
NEW & NOTEWORTHY Metabolic-bariatric surgery and metformin each improved glucose regulation in nonobese, insulin-deficient female GK rats. Their combination further reduced postprandial glycemic excursions without additional effects on insulin sensitivity or incretin/insulin secretion. These findings demonstrate that metformin retains metabolic activity after metabolic-bariatric surgery and improves postprandial glucose control through mechanisms distinct from surgery-induced incretin pathways. This study contributes to the ongoing discussion regarding metformin use after metabolic-bariatric surgery, particularly in insulin-deficient diabetes.