No SGLT-2 Inhibitor Reverse Remodeling Seen in Preserved-EF HF With Diabetes

September 24, 2019

PHILADELPHIA — Whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve cardiac structure in patients with both diabetes and heart failure may depend on the type of heart failure.

In an observational study, treatment of type 2 diabetes using these drugs did not appear to reverse or slow the process of adverse ventricular remodeling in patients who also had heart failure with preserved ejection fraction (HFpEF).

Nolberto Hernandez

"In fact, they might worsen cardiac remodeling" in such patients, Nolberto Hernandez, MD, Bronx Care Health System, New York, said when presenting the single-center, retrospective study here at the Heart Failure Society of America 23rd Annual Scientific Meeting.

In 141 patients with diabetes and HFpEF who underwent echocardiography about a year before and at least a year after initiation of SGLT-2 inhibitors, he told | Medscape Cardiology, the measured cardiac structural changes were "all consistent and in the same direction."

They showed modest but statistically significant average increases in left-ventricular (LV) mass, LV end-systolic and -diastolic volumes, left atrial (LA) volume, and other markers associated with diastolic function. Left ventricular ejection fraction (LVEF), on average, did not increase or fall significantly.

The potential reverse-remodeling effects of SGLT-2 treatment for diabetes has been little studied specifically in HFpEF. Pending more definitive randomized trials, the current study suggests that some of the benefits of SGLT-2 inhibitors in diabetes with heart failure in general may not necessarily apply to HFpEF, Hernandez said.

However, a 1-year follow-up after initiation of the drugs might not have been sufficient to see beneficial echocardiographic effects, he said. "Maybe 2 to 3 years, ideally, would be better for seeing reverse remodeling."

The current study isn't enough to cast doubt on a clinical role for SGLT-2 inhibitors in patients with diabetes and heart failure, even with preserved LVEF, Javed Butler, MD, MPH, MBA, University of Mississippi Medical Center, Jackson, told | Medscape Cardiology.

Reverse remodeling "has a very good positive predictive value for improving clinical outcomes," Butler observed. But it has "a very poor negative predictive value that, in these short-term studies, if reverse remodeling did not occur, does not give any indication whether the drug's other effects are not going to make you live longer."

Of 241 patients with diabetes and HFpEF who underwent echocardiography about a year before the initiation of SGLT-2 inhibitors, 141 had echocardiography repeated at least a year after starting on the drugs. Of the latter group, 69% were women (not unusual for a HFpEF population) and about 62% were Hispanic. Their mean age was about 63 years.

Echocardiographic Changes Before and After Initiation of SGLT-2 Inhibitors in Patients With Diabetes and HFpEF
Echo Measurement Pretreatment ≥1 Year After Treatment Initiation P Value
LVEF (%) 62.51 61.70 .79
LV mass (g)* 185.9 201.4 .001
LV mass index* 94.5 101.7 .003
LVDD (cm) 4.58 4.73 .001
LVSD (cm) 3.00 3.15 .001
LVEDV (mL) 70.96 81.78 .001
LVESV (mL) 27.88 32.52 .001
LA dimension (cm) 3.91 3.98 .08
LA volume (mL) 51.8 63.5 .001
LVDD, Left ventricular diastolic dimension; LVSD, left ventricular systolic dimension; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume


*Primary end points

There are no drug therapies specially indicated for HFpEF, but in practice many patients receive meds indicated for heart failure with reduced ejection fraction. In this study, 56% were taking beta blockers, 75% were on ACE inhibitors or angiotensin receptor blockers, 18% were on diuretics, and 4% were taking spironolactone.

Hernandez referred to several ongoing randomized trials of SGLT-2 inhibitors in patients with HFpEF for more definitive answers; they include the DELIVER, PRESERVED-HF, and EMPEROR-Preserved trials.

Hernandez had no disclosures. Butler disclosed that he is on the steering committee for the EMPEROR trial program and has served as a consultant or on an advisory board for Amgen, Array, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, G3 Pharmaceutical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, Stealth Peptide SC Pharma, and Vifor.

Heart Failure Society of America (HFSA) 23rd Annual Scientific Meeting 2019: Abstract 31. Presented September 13, 2019.

Follow Steve Stiles on Twitter: @SteveStiles2. For more from | Medscape Cardiology, follow us on Twitter and Facebook.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: