For patients with Afib and Type 2 diabetes, GLP-1 drugs outperform SGLT-2 drugs

BUFFALO, N.Y. —  Individuals with atrial fibrillation (Afib), or irregular heart rhythm, are at increased risk of stroke, chronic kidney disease and heart failure.

These risks are significantly exacerbated if a Type 2 diabetes diagnosis is added to the mix, says Md Mohaimenul Islam, PhD, research assistant professor in the Department of Pharmacy Practice in the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

In recent years, physicians have prescribed medications in two classes to treat the combined conditions: glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i). While the former includes semaglutide (Ozempic/Wegovy) and liraglutide, the latter includes drugs like empagliflozin (Jardiance) and dapagliflozin (Farxiga).

Islam and Arinze Nkemdirim Okere, PhD, clinical professor and head of the Division of Outcomes and Practice Advancement in the pharmacy school, explored which is the better choice and found GLP-1 drugs to be more effective. They published their findings on May 31 in Diabetes Research and Clinical Practice.

This study, which pulled data from 108 U.S. health systems, marks the largest head-to-head comparison in this exact population. It’s also the first to map how each drug class shapes the natural history of Afib, according to the researchers.

“Type 2 diabetes and atrial fibrillation are a punishing combination, sharply raising the odds of stroke, heart failure and early death,” Islam says. “Yet treatment guidelines have offered no clear direction for choosing between these two leading drug classes, leaving clinicians to make high-stakes decisions on thin evidence.”

Islam and Okere used medical records from a national database to compare 18,035 patients who started on a GLP-1 receptor against an equal number who started on an SGLT-2 inhibitor.

After one year, people taking a GLP-1 drug had better outcomes than those taking an SGLT-2 drug. Specifically, they were 36% less likely to die from any cause, 12% less likely to be hospitalized, 22% less likely to have a heart attack, stroke or other cardiovascular death, and about 20% less likely to need a procedure to treat Afib.

These findings were consistent across age and weight subgroups.

The burden of co-existing atrial fibrillation and Type 2 diabetes is substantial and growing. Islam points to the sobering statistic that between 1999 and 2020, there were 419,036 deaths recorded among U.S. adults age 25 or older who had both conditions. That number has been driven in large part by the obesity epidemic, population aging and improvements in detection, he says.

“Obesity is itself a strong and independent risk factor for both conditions,” Islam says. “It also accelerates the progression of atrial fibrillation through mechanisms involving atrial remodeling, inflammation and metabolic stress.”

This is why finding the most effective treatment is of paramount importance.

“As more patients live with obesity and diabetes, the population at risk for developing concurrent atrial fibrillation continues to grow, which is one of the reasons this combination is increasingly recognized as a distinct clinical phenotype that deserves its own evidence base,” Okere says.

However, the authors emphasize that this study doesn’t mean that everyone should switch to GLP-1 drugs. While GLP-1 inhibitors definitely have their advantages, SGLT-2 drugs have well-established benefits for certain heart and kidney conditions

“For patients with established heart failure or progressive kidney disease, regardless of whether they also have atrial fibrillation, SGLT-2 inhibitors remain a first-line, guideline-recommended therapy and should not be displaced by our findings,” Islam says.

He adds that their study, which compared the two drug classes over a one-year period, was not designed to evaluate the long-term heart failure and kidney trajectories on which SGLT-2 inhibitors have their strongest evidence.

In addition, Islam points out that this was an observational study reviewing patient records, not a clinical trial. Therefore, the findings may be influenced by factors not captured in electronic data.

The two researchers plan to pursue follow-up studies.

For now, Islam says, “The takeaway for clinicians is that class selection between these two therapies should be individualized. The patient’s full clinical picture, including the presence or absence of heart failure, kidney disease, obesity, and atrial fibrillation, should guide the decision.

“Our findings add one more piece of evidence to that decision-making process, particularly for the substantial group of patients with concurrent atrial fibrillation and diabetes who do not yet have established heart failure or advanced chronic kidney disease.”