Empagliflozin may reduce LVM in patients with T2D
Treatment with the SGLT2i* empagliflozin appears to significantly reduce left ventricular mass (LVM) among patients with type 2 diabetes (T2D), according to results of the EMPA-HEART** CardioLink-6 trial presented at AHA 2018.
This trial involved 97 normotensive patients with T2D (HbA1c level ≥6.5 to ≤10 percent, mean age 60 years) and established coronary artery disease (CAD, prior coronary revascularization or history of myocardial infarction [MI]) who had a normal LVM index (LVMI) of 60 g/m2. Patients were randomized to receive either empagliflozin 10 mg (n=49) or placebo (n=48) daily for 6 months. Cardiac MRI, biomarkers (ie, NT-proBNP***, troponin I, and soluble ST2 levels), and ambulatory blood pressure (BP) measurements were evaluated at the initial and final visits. Patients were followed up for 6 months. [AHA 2018, abstract LBS.05-19332]
At 6 months, patients treated with empagliflozin had a significant reduction in LVMI compared with placebo (change from baseline, -2.6 vs -0.01 g/m2, adjusted difference, -3.35; p=0.01).
Subgroup analysis demonstrated a significantly greater reduction in LVMI among patients with higher (>60 g/m2) vs lower (≤60 g/m2) LVMI (adjusted difference, -7.26 vs -0.46; p=0.007).
A lower ambulatory BP was observed among patients in the empagliflozin than the placebo group, though the difference was only significant for systolic BP (change from baseline, -7.9 vs -0.7 mm Hg, adjusted difference, -6.7; p=0.003 for systolic BP and -2.0 vs 0.8 mm Hg, adjusted difference, -2.1; p=0.22 for diastolic BP).
Empagliflozin treatment was also associated with a significantly increased haematocrit level compared with placebo (change from baseline, 2.4 percent vs 0.4 percent, adjusted difference, 1.91; p=0.006).
Of note, an increase in the left ventricular ejection fraction (LVEF) was demonstrated among patients on empagliflozin than those on placebo (change from baseline, 2.2 percent vs -0.01, adjusted difference, 2.21; p=0.07).
“[One should be reminded that] these benefits were seen in a normotensive population, with preserved ejection fraction, without known heart failure (HF), and on top of standard of care therapies (with ≥80 percent on RAS+ blockers), and were greater in those with higher baseline LVMI,” said study lead author Dr Subodh Verma from St. Michael’s Hospital in Toronto, Ontario, Canada. This population had low baseline levels of NT-proBNP, troponin 1, and soluble ST2, and remained unaffected over the treatment period, he said.
The empagliflozin therapy was extremely well tolerated with no significant adverse events.
“LVM is a strong and independent predictor of major cardiovascular (CV) events – including CV and all-cause mortality, MI, and HF,” according to Verma.
“These data suggest that the SGLT2i, empagliflozin, promotes early, statistically, and clinically significant reverse remodelling which may contribute to the cardiovascular and HF benefits observed in the EMPA-REG OUTCOME++ trial and other SGLT2i studies,” he said.
“[EMPA-HEART] is a very important mechanistic study … [it] is an important step along our journey in clinical translational research on our way to our ultimate goal and providing a more precise care for our patients,” said discussant Dr Elliott Antman from Brigham and Women’s Hospital in Boston, Massachusetts, US.
“I plan to further increase the use of SGLT2i in my patients with T2D, especially if they have a history of HF and CAD,” added Antman, who encouraged attendees to consider doing the same. “[C]olleagues in general medicine, endocrinology, and nephrology [may] consider this information as well.”
“Our work is not done [yet], we [still] need to continue to evaluate the physiological effects of SGLT2 inhibition,” Antman noted.
*SGLT2i: Sodium-glucose cotransporter-2 inhibitor
**EMPA-HEART: Effects of empagliflozin on cardiac structure in patients with type 2 diabetes
***NT-proBNP: N-terminal pro-B-type natriuretic peptide
+RAS: Renin-angiotensin system++EMPA-REG OUTCOME: BI 10773 (empagliflozin) cardiovascular outcome event trial in T2DM patients