Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes

Aims: To 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. Methods: Thirty-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. Results: Glycated 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. Conclusions: In 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.