Exercise improves metformin 72-h glucose control by reducing the frequency of hyperglycemic peaks

Purpose To determine the separated and combined effects of metformin and exercise on insulin sensitivity and free-living glycemic control in overweight individuals with prediabetes/type 2 diabetes (T2DM). Methods We recruited 16 adults with BMI of 32.7 +/- 4.3 kg m(-2) and insulin resistance (HOMA-IR 3.2 +/- 0.4) under chronic metformin treatment (1234 +/- 465 g day(-1)) enrolled in a high-intensity interval training (HIIT) program. Participants underwent four 72-h experimental trials in a random-counterbalanced order: (1) maintaining their habitual metformin treatment (MET); (2) replacing metformin treatment by placebo (CON); (3) placebo plus two HIIT sessions (EX + CON), and (4) metformin plus two HIIT sessions (MET + EX). We used intermittently scanned continuous glucose monitoring (isCGM) during 72 h in every trial to obtain interstitial fluid glucose area under the curve (IFG(AUC)) and the percentage of measurements over 180 mg dL(-1) (% IFG(PEAKS)). Insulin sensitivity was assessed on the last day of each trial with HOMA-IR index and calculated insulin sensitivity (C-SI) from intravenous glucose tolerance test. Results IFG(AUC) was lower in MET + EX and MET than in CON (P = 0.011 and P = 0.025, respectively). In addition, IFG(AUC) was lower in MET + EX than in EX + CON (P = 0.044). %IFG(PEAKS) were only lower in MET + EX in relation to CON (P = 0.028). HOMA-IR and C-SI were higher in CON in comparison with MET + EX (P = 0.011 and P = 0.022, respectively) and MET (P = 0.006 and P < 0.001, respectively). IFG(AUC) showed a significant correlation with HOMA-IR. Conclusion Intense aerobic exercise in patients with diabetes and prediabetes under metformin treatment reduces free-living 72-h blood hyperglycemic peaks. This may help to prevent the development of cardiovascular complications associated with diabetes.