718-P: A High FODMAP Diet Reduces Glycemic Excursion without Increasing Gastrointestinal Symptoms in Individuals with Prediabetes Treated with Metformin—A Randomized Crossover Controlled-Feeding Trial

Introduction: Diet and gut microbiota interactions may influence efficacy and tolerability of metformin. Pre-treatment with a diet rich in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may improve postprandial plasma glucose (PG) responses in individuals with prediabetes receiving metformin.

Methods: 26 individuals with impaired glucose tolerance (IGT) [age median(IQR) 58(48-60) years, 46% men, and 2-hour plasma glucose (2hPG) mean±SD 9.2±1.0 mmol/L] participated in a double-blinded, randomized, cross-over controlled-feeding trial. All participants received equicaloric, high or low FODMAP diets for 10 days in combination with 5 days of metformin XR 1000mg daily, separated by at least 2 weeks washout. Continuous glucose monitoring (CGM), oral glucose tolerance tests (OGTT) with insulin and glucagon-like peptide 1 (GLP-1), microbiota profiles and gastrointestinal symptoms were assessed at baseline and each study period.

Results: Both interventions with metformin reduced blood glucose and body weight compared with baseline. High FODMAPs, as compared with low FODMAPs with metformin, led to lower total postprandial CGM glucose incremental area-under-the-curve (ppiAUC_0-3h) (891±269 vs 997±307 mmol/L.min-1, p=0.021) and 2h-PG (7.1±1.7 vs. 8.1±1.9 mmol/L, p=0.017). We observed higher 2-hour total GLP-1, lower high-sensitivity C-reactive protein and a higher relative abundance of Bifidobacterium longum after high-FODMAPs with metformin. There were no differences in gastrointestinal symptoms between interventions.

Conclusion: High FODMAPs with metformin improved postprandial PG without increasing gastrointestinal symptoms in people with IGT. Fermentable carbohydrates promote specific short-chain fatty acids-producing bacteria, which may improve glycemic regulation via gut hormones and anti-inflammation.