Jose Lopez, MD, is a cardiology fellow at the University of Miami JFK Medical Center.

Jose L. Lopez, MD

Leveraging SGLT2 Inhibitors, GLP-1 RAs in Heart Failure, with Jose Lopez, MD

Once viewed solely as glucose-lowering agents for 

, sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as powerful tools in the management of 

Initial skepticism surrounding the cardiovascular safety of these agents limited their early use in this population due to early trials raising concern about potential harm. However, more recent research suggests that these agents are not only safe, but also provide meaningful cardiovascular benefits, marking a turning point in how these therapies are viewed in heart failure care.

“When these trials were first conducted, the main point was to make sure these diabetes medications were not harmful to the heart because of earlier trials that had shown neutral or even harmful effects,” Jose Lopez, MD, a cardiovascular disease fellow at the University of Miami Miller School of Medicine/JFK Medical Center, explained in an interview with HCPLive. “When EMPEROR came out and we showed that there was no harmful effect, but actually a benefit, I think it was a really big turning point and a really big part of that shift because we realized these are not just diabetes medications and they can actually be really big players in the space of heart failure, which they have been.”

Lopez emphasizes that SGLT2 inhibitors and GLP-1 RAs are no longer just diabetes medications, referring to both as being “more heart failure medications than anything” and further suggesting SGLT2 inhibitors should be used in almost every patient with heart failure. For those with persistent symptoms, he says GLP-1 RAs can be added later on.

Acknowledging the lack of data on GLP-1 RAs in patients with heart failure with reduced ejection fraction (HFrEF) compared to heart failure with preserved ejection fraction (HFpEF), Lopez notes that use of these medications in this patient population is controversial. However, he indicates a need for additional research before writing GLP-1 RAs off for HFrEF patients, citing small sample sizes, short follow up, and the use of participants with very advanced heart failure as potential limitations to existing research.

“I feel there's still a lot that we don't know,” Lopez said. “I wouldn't necessarily jump to say that these medications are harmful.”

When confronted with the clinical conundrum of both SGLT2 inhibitors and GLP-1 RAs bring indicated in the same patient—for example, a patient with HFpEF, obesity, and diabetes—Lopez says he prioritizes initiating SGLT2 inhibitors and adding GLP-1 RAs on later if needed, noting that this is “almost an everyday situation nowadays.”

Editors’ note: Lopez has no relevant disclosures to report.

Lopez J, Makuvire T, Davis JD, Carbone S. The Short and Sweet on Sodium-Glucose Cotransporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure. US Cardiol. 

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Lopez discusses the evolving understanding of the utility of SGLT2 inhibitors and GLP-1 RAs in heart failure care, including both HFpEF and HFrEF.

Recognizing Racial, Ethnic Differences in Diabetic Cardiomyopathy, with Jose Lopez, MD

 (DbCM) increases risk of overt heart failure in individuals with diabetes mellitus, but emerging research suggests racial and ethnic differences may cause some patients to experience more severe DbCM risk features than others.

The topic was discussed during a session at the 

 in Philadelphia, Pennsylvania, by Jose Lopez, MD, a cardiovascular disease fellow at the University of Miami Miller School of Medicine/JFK Medical Center, during which he reviewed findings from the ARISE-HF trial assessing the efficacy of an aldose reductase inhibitor for exercise capacity preservation in people with DbCM. Specifically, Lopez discussed racial and ethnic differences in baseline characteristics, echocardiographic parameters, and functional capacity in the ARISE-HF cohort.

“I think we need to be aware that diabetic cardiomyopathy exists, that you can have heart muscle disease from diabetes itself and all the metabolic changes it produces independently of ischemic heart disease,” Lopez explained to HCPLive, noting that although the main trial results did not show a statistically significant difference, he believes this was largely attributable to the trial design and that there may still be benefit with these medications.

In ARISE-HF, among a cohort of 691 individuals with DbCM who were randomized to receive placebo or ascending doses of AT-001 twice daily, peak Vo2 fell in the placebo-treated patients by −0.31 mL/kg/min by 15 months (

 = .005 compared to baseline), whereas in those receiving high-dose AT-001, peak Vo2 fell by −0.01 mL/kg/min (

 = .21); the difference in peak Vo2 between placebo and high-dose AT-001 was 0.30 (

In prespecified subgroup analyses among those not receiving sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists at baseline, the difference between peak Vo2 in placebo vs high-dose AT-001 at 15 months was 0.62 mL/kg/min (

Further analysis stratified by race and ethnicity revealed Black and Hispanic patients had lower use of diabetes mellitus treatments and Black patients had poorer baseline ventricular function and more impaired global longitudinal strain. Health status was preserved, as determined by Kansas City Cardiomyopathy Questionnaire scores, but reduced exercise capacity was present as evidenced by reduced Physical Activity Scale for the Elderly (PASE) scores.

When stratified by race and ethnicity and compared with the entire cohort, Black patients had poorer health status, more reduced physical activity, and a greater impairment in exercise capacity during cardiopulmonary exercise testing, whereas Hispanic patients also displayed compromised cardiopulmonary exercise testing functional capacity. In contrast, White patients demonstrated higher physical activity and functional capacity.

Lopez cautions that the racial differences observed in ARISE-HF should be interpreted as being related to social determinants of health rather than biological factors, noting many of these disparities can be traced back to ones that already exist in patients with diabetes.

“The most important thing to get actionable change would be policy interventions, because there are a lot of things that clinicians can do, but there are a lot of others that are out of their hands,” Lopez explained, describing the importance of things like having an area to walk and access to high-quality, healthy food, as well as medicine.

Lopez J, Liu Y, Butler J, et al. Racial Differences in Diabetic Cardiomyopathy: The ARISE-HF Trial. 

https://doi.org/10.1016/j.jacc.2024.04.053

Januzzi J, Butler J, Del Prato S, et al. Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy. 

https://doi.org/10.1016/j.jacc.2024.03.380

Lopez reviews findings from an analysis of ARISE-HF highlighting racial and ethnic differences in baseline characteristics and diabetic cardiomyopathy disease progression.

An analysis from the ARISE-HF trial is shedding further light on racial and ethnic differences in diabetic 

American College of Cardiology (ACC) 2025 Annual Scientific Sessions

, this secondary analysis provides insight into the differences in baseline characteristics as well as disease progression in both the AT-001 and placebo groups.

The ARISE-HF trial was presented at ACC.24 and concluded use of AT-001, an aldose reductase inhibitor, did not result in significantly better exercise capacity compared with placebo.

Results from the secondary analysis presented at ACC.25 demonstrated that Black and Hispanic patients in the placebo group experienced significantly greater declines in peak VO2 compared to White patients (-0.74 and -1.67 vs. -0.23 mL/kg/min, respectively; 

= .005). Black patients in the placebo arm also had the greatest declines in Kansas City Cardiomyopathy Questionnaire scores, indicating worse symptom burden and quality of life, with similar but less pronounced declines observed in the AT-001 group. Although AT-001 treatment showed a trend toward a 50% slower decline in peak VO2, this effect did not reach statistical significance across racial and ethnic groups.

According to investigators, these findings highlight significant racial and ethnic disparities in DbCM progression, likely driven by differences in baseline disease severity, comorbid conditions, and broader social determinants of health. Although AT-001’s effects on functional capacity were consistent across racial and ethnic groups, further research is needed to address underlying disparities and optimize treatment strategies for high-risk populations.

For more on this study, check out our interview with lead investigator Jose Lopez, MD, of the University of Miami JFK Medical Center, from the conference floor at ACC.25.

Racial and Ethnic Differences in Diabetic Cardiomyopathy from ARISE-HF, with Jose Lopez, MD

Lopez has no relevant disclosures to report.

Lopez JL, Liu Y, Butler J, et al. RACIAL AND ETHNIC DIFFERENCES IN OUTCOMES IN PATIENTS WITH DIABETIC CARDIOMYOPATHY TREATED WITH AN ALDOLASE REDUCTASE INHIBITOR: THE ARISE-HF TRIAL. Presented at: American College of Cardiology (ACC.25) Annual Scientific Session. March 29 – 31, 2025. Chicago, Il.

Januzzi JL Jr, Butler J, Del Prato S, et al. Randomized Trial of a Selective Aldose Reductase Inhibitor in Patients With Diabetic Cardiomyopathy. 

. 2024;84(2):137-148. doi:10.1016/j.jacc.2024.03.380

Jose Lopez, MD, discusses findings and perspective into racial and ethnic differences in DbCM from the ARISE-HF trial. 

Jose L. Lopez, MD

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