Empagliflozin Significantly Reduced Myocardial Glucose Metabolic Rate in T2D Treatment

Elena Succurro, MD

Treatment with empagliflozin was linked to a significant reduction in the myocardial glucose metabolic rate in patients with type 2 diabetes (T2D) without coronary artery disease, according to recent findings.

Study data from the prospective, randomized FIORE trial suggest treatment with empagliflozin reduced the myocardial glucose metabolic rate in patients by 45.1% after 26 weeks of trial, compared with glimepiride treatment.

“This effect appears specific for SGLT2 inhibition because treatment with glimepiride increased myocardial [glucose metabolic rate] by 33.9%, despite no differences in metabolic control being observed between the two treatments,” wrote study author Elena Succurro, MD, Department of Medicaland Surgical Sciences, University Magna Graecia of Catanzaro.

Determining whether previous research observations on observed reduction in myocardial glucose uptake oxidation from SGLT2 inhibitor treatment is a transient phenomenon or a long-term adaptive remains to be seen. Succurro and colleagues’ primary aim was to determine whether empagliflozin treatment was able to modify myocardial glucose metabolic rate as measured by cardiodynamic 18F-FDG-PET and euglycemic-hyperinsulinemic clamp compared with glimepiride from baseline to 26 weeks.

The trial was conducted at a single center in Italy and included patients with T2D in monotherapy treatment with a stable dose of metformin, age 40 - 69 years, and HbA1c 6.5% –9%. Patients were randomly assigned 1:1 to receive empagliflozin 10 mg or glimepiride 2 mg daily for 26 weeks and then crossed over to the opposite treatment for another 26 weeks.

From a total of 50 screened individuals, 26 met the inclusion criteria and were randomized equally to each cohort. Investigators noted the evaluable study cohort was 23 patients as 3 participants withdrew prematurely from the trial.

Patients randomized to empagliflozin showed greater reduction in myocardial glucose metabolic rate after 26 weeks (14.4 ± 9 vs. 7.9 ± 8 μmol/min/100 g, P < .0001) compared with patients randomized to glimepiride (10.3 ± 9 vs. 13.8 ± 10 μmol/min/100 g, P = .01). The adjusted difference between groups was 6.07 μmol/min/100 g (P< .0001).

After 26 weeks of treatment, patients randomized to empagliflozin exhibited a greater reduction in the following:

• Body mass index (adjusted difference, 0.93 kg/m²; P =.01)
• Waist circumference (adjusted difference, 1.94 cm; P = .001)
• Systolic blood pressure (adjusted difference, 11.94 mmHg; P <.001)
• Diastolic blood pressure (adjusted difference, 5.33 mmHg; P = .007)
• Resting heart rate (adjusted difference, 9.55 bpm; P <.0001)

Moreover, patients randomized to empagliflozin had greater reduction at 26 weeks in left atrial diameter (P <.0001), left ventricular end-systolic volume (P <.0001), left ventricular end-diastolic volume (P = .02), interventricular septum thickness (P = .01), and systolic pulmonary arterial pressure (P <.0001).

“Further randomized clinical trials of adequate duration carried out in larger cohorts of patients with type 2 diabetes, and including patients with HF, are required to confirm the observed changes in cardiac geometry and function,” Succurro noted.

The study, “Effects of 26 weeks of treatment with empagliflozin vs glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open-label, crossover, active-comparator FIORE trial,” was published in Diabetes, Obesity and Metabolism.