In a randomized crossover trial, researchers found that 16 weeks of treatment with the glucagon-like peptide-1 receptor agonist liraglutide resulted in significant improvements in myocardial perfusion, energetics, and exercise capacity compared with pioglitazone in patients with type 2 diabetes without cardiovascular disease.

In the single-center, open-label study, published in the Journal of the American College of Cardiology, the researchers recruited 41 patients with type 2 diabetes (mean age = 63 years, 66% male, mean body mass index = 27.8) who underwent cardiovascular magnetic resonance imaging and 31 phosphorus magnetic resonance spectroscopy at baseline and after each 16-week treatment period to assess myocardial perfusion, energetics (phosphocreatine to adenosine triphosphate ratio), and left ventricular function. The 6-minute walk test was used to evaluate functional exercise capacity.

Compared with baseline, liraglutide increased stress myocardial blood flow (1.62 mL/g/min vs 2.08 mL/g/min, P = .01), myocardial perfusion reserve (2.40 vs 2.90, P = .01), rest phosphocreatine to adenosine triphosphate ratio (1.47 vs 1.94, P = .00002), stress phosphocreatine to adenosine triphosphate ratio (1.32 vs 1.58, P = .004), and 6-minute walk distance (488 m vs 521 m, P = .009). Pioglitazone treatment did not significantly change these parameters.

Allocation to pioglitazone resulted in significant increases in left ventricular mass (96 g vs 105 g, P = .003) and mitral inflow E/A ratio (1.04 vs 1.34, P = .008) and a significant reduction in left ventricular concentricity index (0.79 mg/mL vs 0.73 mg/mL, P = .04).

The improvements in myocardial perfusion and energetics with liraglutide were accompanied by a mean weight loss of 1.55 kg (P = .008), whereas pioglitazone led to a mean weight gain of 1.74 kg (P = .0008). Liraglutide treatment increased the resting heart rate by a mean of 5.9/min (P = .0002). Both drugs similarly reduced triglyceride index, a marker of insulin resistance.

The researchers noted that although the mechanisms responsible for the cardiovascular benefits of glucagon-like peptide-1 receptor agonists have been unclear, the favorable effects of liraglutide on myocardial perfusion and energetics in this study may provide insights. They called for further research into strategies targeting insulin secretion to determine wider clinical benefits.

Funding support and author disclosures can be found in the study.