November 19, 2018
4 min read

EMPA-HEART: Empagliflozin reduces LV mass in type 2 diabetes

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Elliott M. Antman

CHICAGO — New data show that empagliflozin promotes reverse remodeling in patients with diabetes, which may explain the CV and HF benefits previously seen in the large EMPA-REG Outcome clinical trial.

In the EMPA-HEART CardioLink-6 study, presented at the American Heart Association Scientific Sessions, patients treated with empagliflozin 10 mg (Jardiance, Boehringer Ingelheim) for 6 months experienced a greater reduction in LV mass indexed to baseline body surface area than those treated with placebo (–2.6 g/m2 vs. –0.01 g/m2; adjusted difference, –3.35 g/m2; P = .01).

The results remained consistent in a sensitivity analysis in which LV mass was indexed to height (P = .03), LV mass indexed to height1.7 (P = .02), LV mass indexed to height2.7 (P = .01) and LV mass indexed to weight (P = .005), according to researcher Subodh Verma, MD, PhD, FRCSC, from the division of cardiac surgery at St. Michael’s Hospital, University of Toronto.

“No matter how we looked at it, the P value remained statistically significantly in favor of empagliflozin vs. placebo,” he said during his presentation of the data.

Lower BP, increased hematocrit

In the large, randomized EMPA-REG Outcome trial, empagliflozin was associated with a decrease in major adverse CV outcomes, CV death, all-cause mortality and hospitalization for HF.

LV mass is a strong and independent predictor of major adverse CV events and the magnitude of LV mass regression correlates with the extent of clinical outcome benefit seen with pharmacological and device therapies, according to Verma. However, it remains unknown whether sodium-glucose cotransporter 2 (SGLT) inhibitors lead to cardiac reverse remodeling. The EMPA-HEART study, he said, sought to answer this question.

Ninety-seven patients were randomly assigned treatment with placebo (n = 48) or empagliflozin 10 mg (n = 49) for 6 months. Baseline cardiac MRI and biomarkers were evaluated at baseline and 6 months after treatment.

Besides the greater overall reduction in LV mass in the empagliflozin group vs. the placebo group, the drug was associated with a greater reduction in LV mass indices in patients with baseline LV mass greater than 60 m/g2 vs. less than 60 m/g2 (P for interaction = .007).

Moreover, after 6 months of treatment, empagliflozin was associated with a greater decrease in ambulatory systolic BP (–7.9 mm Hg vs. –0.7 mm Hg; adjusted difference, –6.78 mm Hg; P = .003) and a nonsignificantly greater decrease in diastolic BP compared with placebo (–2 mm Hg vs. 0.8 mm Hg; adjusted difference, –2.07; P = .22). Treatment also resulted in a greater increase in hematocrit (2.4% vs. 0.4%; adjusted difference, 1.91; P = .006).

On cardiac MRI, the researchers did not find significant differences between groups in LV end-systolic volume (P = .36) or LV end-diastolic volume indexed to body surface area (P = .55), but LV ejection fraction increased by 2.21% more in the empagliflozin group than in the placebo group (P = .07).

There were also no differences between groups in N-terminal pro-B-type natriuretic peptide (P = .28), troponin I (P = .38) or soluble ST2 (P = .53) during the study.

The drug was also extremely well-tolerated, with no significant differences in adverse events between groups.


Baseline characteristics were well-matched between groups, according to Verma. Patients were predominantly men, had a mean age of about 60 years and had a BMI of about 27 kg/m2. Duration of diabetes was approximately 10 years, very few patients had a history of HF and most had been treated for hypertension. Nearly all patients were on background metformin and one-quarter were on insulin, 96% on statins and 85% on ACE inhibitors or angiotensin receptor blockers.

“The study was representative of the EMPA-REG Outcome population, used the gold standard of cardiac MRI with blinded cardiac MRI assessment and included physiologic and biologic evaluations,” Verma said when noting the study’s strengths and limitations. “However, the study had a small sample size, short follow-up and included a stable and well-treated CAD population without marked LV hypertrophy at baseline.”

During a discussion of the findings, Elliott M. Antman, MD, professor of medicine at Brigham and Women’s Hospital and Harvard Medical School and past president of the American Heart Association, said it is important to note the relatively low-risk population with type 2 diabetes in the study. The change in LV mass, he added, was also robust and held up to an array of statistical adjustments.

“This reduction in LV mass is an important observation because it is an independent predictor of CV events, including incident HF,” Antman said.

In determining the drivers for this reduction in LV mass, he said empagliflozin was associated with lower systolic BP and higher hematocrit at 6 months.

“These surrogates suggest that our traditional concepts of afterload and preload appear to be favorably affected by SGLT2 inhibitors as a mechanism for lower LV mass,” Antman said.

The EMPA-HEART study is another notch in the win column for SGLT2 inhibitors with respect to CV benefits, according to Antman, as it joins the ranks of other studies, including DECLARE-TIMI 58 and a subsequent meta-analysis, which were also presented at the AHA Scientific Sessions, supporting the CV benefits of SGLT2 inhibitors, particularly with regard to HF.

Taken together, Antman added, these studies have the potential to change practice.

“As I leave Chicago, I plan to increase the use of SGLT2 inhibitors in my patients, especially if they have HF,” he said. – by Melissa Foster


Verma S. LBS.05 – Late Breaking Clinical Trial: Hot News in HF. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.

Disclosures: The EMPA-HEART CardioLink-6 trial was supported through an unrestricted, investigator-initiated grant from Boehringer Ingelheim. Verma reports he receives research grants and honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novartis, Novo Nordisk, Sanofi and Valeant. Antman reports no relevant financial disclosures.