Metformin and Exercise in Type 2 Diabetes

Abstract

OBJECTIVETo determine the effect of metformin on the acute metabolic response to submaximal exercise, the effect of exercise on plasma metformin concentrations, and the interaction between metformin and exercise on the subsequent response to a standardized meal.RESEARCH DESIGN AND METHODSTen participants with type 2 diabetes were recruited for this randomized crossover study. Metformin or placebo was given for 28 days, followed by the alternate condition for 28 days. On the last 2 days of each condition, participants were assessed during a nonexercise and a subsequent exercise day. Exercise took place in the morning and involved a total of 35 min performed at three different submaximal intensities.RESULTSMetformin increased heart rate and plasma lactate during exercise (both P ≤ 0.01) but lowered respiratory exchange ratio (P = 0.03) without affecting total energy expenditure, which suggests increased fat oxidation. Metformin plasma concentrations were greater at several, but not all, time points on the exercise day compared with the nonexercise day. The glycemic response to a standardized meal was reduced by metformin, but the reduction was attenuated when exercise was added (metformin × exercise interaction, P = 0.05). Glucagon levels were highest in the combined exercise and metformin condition.CONCLUSIONSThis study reveals several ways by which metformin and exercise therapies can affect each other. By increasing heart rate, metformin could lead to the prescription of lower exercise workloads. Furthermore, under the tested conditions, exercise interfered with the glucose-lowering effect of metformin.

Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both?

“…There are differences between the present study and previous ones [1][2][3] that may help explain the disparate results. The most important differences may relate to the timing and type of measures of glycaemic control or insulin sensitivity.…”

“…This finding is important because it is contrary to recent studies suggesting that the addition of exercise to metformin treatment increased postprandial glucose [1], increased hepatic glucose output [2] and had no additional effect on insulin sensitivity [2,3] compared with metformin treatment alone. The DARE trial represents the largest supervised exercise study examining this issue and is the only study that includes a group dedicated to performing resistance training alone.…”

“…Alternatively, it could be speculated that differences were due to the fact that previous studies were performed in metformin-naive participants [1][2][3] whereas participants in the DARE trial had been taking metformin for a longer time before starting exercise. The previous studies involved randomly assigned participants with better glycaemic control (i.e.…”

“…The most important differences may relate to the timing and type of measures of glycaemic control or insulin sensitivity. In previous studies [1][2][3] meal tolerance tests or hyperinsulinaemiceuglycaemic clamps were performed within 28 h of an exercise session. In contrast, HbA 1c reflects average blood glucose concentration over the previous 2-3 months and fasting glucose measurements in DARE had been taken at least 2 days after the last exercise session.…”

“…Recently, some studies suggested that the glucose-lowering or insulinsensitising effects of exercise may be affected by metformin [1][2][3]. These studies did not examine whether participants already taking metformin would also have attenuated improvements in glycaemic control following exercise training, as reflected in longer-term indicators of glycaemic control such as HbA 1c .…”