Effects of chronic metformin treatment on training adaptations in men and women with hyperglycemia: A prospective study

OBJECTIVE: This study aimed to determine whether chronic metformin use interferes with the improvements in insulin resistance (IR) and cardiorespiratory fitness with aerobic training in people with hyperglycemia and metabolic syndrome (MetS). METHODS: A total of 63 middle‐aged (53 [7] years) individuals with MetS and obesity (BMI = 32.8 [4.5] kg/m(2)) completed 16 weeks of supervised high‐intensity interval training (3 d/wk, 43 min/session). Participants were either taking metformin (EXER+MET; n = 29) or were free of any pharmacological treatment for their MetS factors (EXER; n = 34). Groups were similar in their initial cardiorespiratory fitness (maximal oxygen uptake [VO(2MAX)]), age, percentage of women, BMI, and MetS factors (z score). The effects of exercise training on IR (homeostatic model assessment of insulin resistance [HOMA‐IR]), MetS z score, VO(2MAX), maximal fat oxidation during exercise, and maximal aerobic power output were measured. RESULTS: Fasting insulin and HOMA‐IR decreased similarly in both groups with training (EXER+MET: −4.3% and −10.6%; EXER: −5.3% and −14.5%; p value for time = 0.005). However, metformin use reduced VO(2MAX) improvements by half (i.e., EXER+MET: 12.7%; EXER: 25.3%; p value for time × group = 0.012). Maximal fat oxidation during exercise increased similarly in both groups (EXER+MET: 20.7%; EXER: 25.3%; p value for time = 0.040). VO(2MAX) gains were not associated with HOMA‐IR reductions (EXER+MET: r = −0.098; p = 0.580; EXER: r = −0.255; p = 0.182). CONCLUSIONS: Metformin use was associated with attenuated VO(2MAX) improvements but did not affect fasting IR reductions with aerobic training in individuals with hyperglycemia and high cardiovascular risk (i.e., MetS).