Effect of exercise combined with glucagon‐like peptide‐1 receptor agonist treatment on cardiac function: A randomized double‐blind placebo‐controlled clinical trial

Abstract

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

Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open Parallel-Group Study

“…Recent large well-conducted randomized studies have demonstrated neutral effect with GLP-1RA on stabile heart failure ( 7 ), or advanced heart failure ( 34 ), in patients with and without diabetes. Among patients hospitalized with heart failure, liraglutide treatment did not lead to greater clinical stability ( 6 ), a finding concordant with some other small clinical studies showing no beneficial effects from GLP-1RA on heart failure ( 8 , 35 ). A recent double-blind placebo-controlled crossover study, which used dobutamine stress TDE, to investigate changes in systolic heart function in newly diagnosed T2D patients with coronary artery disease, also failed to show any beneficial action from liraglutide treatment compared with placebo treatment ( 14 ).…”

“…Our study results contrast with a recent study where 33 T2D patients were treated with liraglutide for 16 weeks compared with placebo add on to supervised exercise. In that study, there was no change in HR between groups; however diastolic function upon supervised exercise was improved in the placebo group and blunted in the liraglutide treated T2D patients ( 8 ). In our study, we used bicycle ergometer exercise to sharp the sensitivity of our method, and not for the treatment of diastolic function, therefore studies are not easy to compare.…”

“…Several small clinical studies have shown beneficial action on systolic heart function after GLP-1 treatment ( 4 , 5 ); however, recent studies have not been conclusive ( 6 , 7 ). Notwithstanding this, studies on the treatment of GLP-1RA in T2D patients with subclinical heart failure are scarce ( 8 , 9 ).…”

Critical role of the epicardium in mediating cardiac inflammation and fibrosis in patients with type 2 diabetes

“…Although incretin‐based agents reduce epicardial fat volume, glucagon‐like peptide‐1 receptor agonism promotes adverse change in the biology of adipose tissue, and dipeptidyl peptidase‐4 inhibitors can potentiate the actions of proinflammatory chemokines . Perhaps for these reasons, in the clinical setting, incretin‐based drugs have not improved ventricular diastolic filling dynamics or reduced the risk of heart failure …”

Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-Associated Complications: A Systematic Review of Preclinical Studies

“…Resveratrol (PubChem CID: 445154) can be found in several food sources including grapes and red wine [21]. Interestingly, experimental evidence reporting on the comparative or combination use of metformin (PubChem CID: 4091) with well-known bioactive compounds like resveratrol has become of great interest [22][23][24][25][26][27]. Although metformin is a commonly used antidiabetic drug, information on its comparative or combination use with resveratrol has not been assessed to understand the potential synergistic or combination advantages of such a therapy in managing metabolic complications.…”