BOSTON (FRONTLINE MEDICAL NEWS)– Liraglutide in combination with metformin reduced epicardial adipose tissue by nearly half within 6 months of treatment in people with type 2 diabetes, an effect independent of either body weight loss or glycemic control, according to a new study.

Epicardial adipose tissue (EAT) is the fat depot around the heart. While EAT has many cardioprotective properties, increased or excess EAT – seen more frequently in people with type 2 diabetes – has been linked to coronary artery disease, metabolic syndrome, diabetes, insulin resistance, and liver disease, according to a review by Gianluca Iacobellis, M.D., Ph.D., professor of clinical medicine in the division of endocrinology, diabetes and metabolism at the University of Miami ( Nat. Rev. Endocrinol. 2015;11: 363-71 ).

More than a decade ago, Dr. Iacobellis proposed and validated ultrasound measurement of EAT thickness as marker of visceral fat and a therapeutic target ( J. Clin. Endocrinol. Metab. 2003;88: 5163-8 ).

At the annual scientific sessions of the American Diabetes Association, Dr. Iacobellis presented preliminary findings from a case-control study in 35 patients with type 2 diabetes with body mass indexes greater than 27 kg/m2 and hemoglobin A1c levels no greater than 8% on metformin monotherapy.

Patients were randomized to remain on metformin or metformin plus the glucagon-like peptide-1 (GLP-1) analogue liraglutide subcutaneously up to 1.8 mg once daily for 6 months. EAT thickness was measured by ultrasound at baseline, 3 months, and 6 months, along with HbA1c and BMI measures. In the liraglutide group (20 patients), EAT decreased significantly from 10.2 mm to 6.9 mm and 5.8 mm (P < 0.001) after 3 months and 6 months, respectively, for a 42% reduction at 6 months. The metformin-only group (15 patients) saw no reduction in EAT.

The EAT reduction seen in the intervention group was much greater than, and independent of, reductions in body weight or HbA1c. Average BMI fell from 33 kg/m2 at baseline to 31.8 kg/m2 and 31.7 kg/m2 at 3 months and 6 months, respectively, while HbA1c declined 18% among patients on liraglutide.

The findings have important clinical and research implications, Dr. Iacobellis said in an interview. “Emerging evidence is pointing out that EAT as measured with reliable, safe, and cheap ultrasound can be a therapeutic target for medications directly or indirectly targeting the adipose tissue,” he said. And EAT can be measured in clinical settings, he added.

Moreover, there is a strong likelihood that further studies will show cardiovascular benefit associated with reductions in EAT, Dr. Iacobellis predicted.

“There is a direct cross-talk between the cardiac fat and the heart,” he said. “If you target the fat, if you’re able to modulate or to reduce the adipose tissue of the heart, you can directly modulate the myocardium and improve cardiovascular performance.”

Dr. Iacobellis’ study on liraglutide is ongoing, and the investigators are examining the effects of other classes of drugs, including the sodium-glucose cotransporter-2 (SLGT-2) inhibitors, on EAT in people with type 2 diabetes. Dr. Iacobellis said he did not know whether to consider the EAT reduction a likely class effect of GLP-1 analogue medications. It is biologically plausible, he added, because human adipose tissues express GLP-1 receptors.

Other studies are showing that exenatide may have some beneficial cardiovascular effect in patients with coronary artery disease, he said. “However, liraglutide seems to be the most effective in targeting the adipose tissue. There may be a class effect, but one drug could have a more prominent effect compared to others.”

It is possible that liraglutide’s metabolic and weight-loss benefits are in some way mediated by its effect on EAT and other visceral fat depots, Dr. Iacobellis observed, although further research will be needed to show that.

“We know that people lose weight on liraglutide, and we know they have an improvement in glucose control. But what we don’t know is whether the metabolic improvement is actually driven by an effect of the medication on the organ-specific fat depot,” he said.

Novo Nordisk and the University of Miami sponsored the study. Neither Dr. Iacobellis nor his coauthors disclosed conflicts of interest.