AimsTo investigate the effects of exercise in combination with a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), liraglutide, or placebo for the treatment of type 2 diabetes.MethodsThirty‐three overweight, dysregulated and sedentary patients with type 2 diabetes were randomly allocated to 16 weeks of either exercise and liraglutide or exercise and placebo. Both groups had three supervised 60‐minute training sessions per week including spinning and resistance training.ResultsGlycated haemoglobin (HbA1c) levels dropped by a mean ± standard deviation of 2.0% ± 1.2% (from 8.2% ± 1.4%) in the exercise plus liraglutide group vs 0.3% ± 0.9% (from 8.0% ± 1.2%) in the exercise plus placebo group ( P < .001), and body weight was reduced more with liraglutide (−3.4 ± 2.9 kg vs −1.6 ± 2.3 kg; P < .001). Compared with baseline, similar reductions were seen in body fat (exercise plus liraglutide: −2.5% ± 1.4% [ P < .001]; exercise plus placebo: −2.2% ± 1.9% [ P < .001]) and similar increases were observed in maximum oxygen uptake (exercise plus liraglutide: 0.5 ± 0.5 L O2/min [ P < .001]; exercise plus placebo: 0.4 ± 0.4 L O2/min [ P = .002]). Greater reductions in fasting plasma glucose (−3.4 ± 2.3 mM vs −0.3 ± 2.6 mM, P < .001) and systolic blood pressure (−5.4 ± 7.4 mm Hg vs −0.6 ± 11.1 mm Hg, P < .01) were seen with exercise plus liraglutide vs exercise plus placebo. The two groups experienced similar increases in quality of life during the intervention.ConclusionsIn obese patients with type 2 diabetes, exercise combined with GLP‐1RA treatment near‐normalized HbA1c levels and caused a robust weight loss when compared with placebo. These results suggest that a combination of exercise and GLP‐1RA treatment is effective in type 2 diabetes.

In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP-1RA liraglutide or placebo, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean AE standard deviation [s.d.] −7.1 AE 1.6 to −7.7 AE 1.8 cm/s, P = .01), but not in the liraglutide group (−7.1 AE 1.4 to −7.0 AE 1.4 cm/s, P = .60; between groups, P = .02). Similarly, the mean AE s.d. ratio of early and atrial mitral annular tissue velocities improved in the placebo group (1.0 AE 0.4 to 1.2 AE 0.4, P = .003), but not in the liraglutide group (1.0 AE 0.3 to 1.0 AE 0.3, P = .87; between groups, P = .03). We found no significant differences in heart rate, left ventricular (LV) structure or function within or between the groups.In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect of exercise on LV diastolic function. K E Y W O R D Scardiovascular disease, exercise, liraglutide | INTRODUCTIONIn patients with type 2 diabetes, studies examining the effect of exercise on cardiac function have had conflicting results, and the effect of exercise intervention seems to be related to the type, duration and intensity of the exercise. Accordingly, in a study in 223 patients undergoing a 12-month exercise intervention, myocardial function was only improved in response to moderate and vigorous exercise. 2 Both exercise and liraglutide have a complex interaction with the cardiovascular system, affecting both blood pressure and heart rate, 3 and it is unknown how cardiac function is affected by the combination of exercise and liraglutide. We recently reported that treatment with the GLP-1RA liraglutide in addition to exercise was superior to placebo in terms of glycaemic control and body weight loss in dysregulated patients with type 2 diabetes on