Combining GLP-1 and SGLT2 diabetes medications may reduce risk

Nguyen and his team conducted a meta-analysis of 12 randomized, double-blind, placebo-controlled trials, the “gold standard” of research trials. The analysis included data from more than 70,000 patients with diabetes. Of these patients, a small cohort of about 3,000 (4.2%) had been prescribed GLP-1.

The researchers were interested in whether the cardiovascular and renal protective effects of SGLT2 inhibitors persisted across the available data and how those effects might be altered by the addition of GLP-1.

Not only does the protective effect of SGLT2 persist with or without GLP-1, but the effect is even greater when the two are combined.

The study looked at a number of serious health problems known as complications of type 2 diabetes. These outcomes included the risk of major cardiovascular events (heart attack or stroke), hospitalization for heart failure, or death from cardiovascular disease.

The researchers also looked at progression of chronic kidney disease, which they defined as 40% or more. Decreasing eGFR (a standard measure of kidney function), kidney failure, or death due to kidney function.

Compared to placebo, SGLT2 alone reduced the risk of heart attack and stroke by 11%, and reduced hospitalization for heart failure and death from cardiovascular disease by 23%. The effect on kidney disease progression was even more pronounced, with SGLT2 resulting in a 33% risk reduction compared to placebo.

For each outcome, adding GLP-1 further reduced the risk slightly. For cardiovascular-related hospitalization and kidney disease progression, GLP-1 reduced the risk by an additional approximately 2%. For major cardiovascular events, GLP-1 nearly doubled the protective effect, reducing the risk by an additional 10%.

Whether SGLT2s were used alone or in combination with GLP-1s, safety and tolerability were consistent, meaning that combining the drugs did not increase the number of adverse events.

“These data provide the strongest evidence to date that the combination of these two drugs is not only safe but also highly effective, likely to improve clinical outcomes for patients with type 2 diabetes and cardiovascular-renal disease,” Nguyen said.

The study is likely to capture the attention of physicians and health care organizations that are still evaluating and developing guidelines for these two relatively new classes of medications. First FDA-approved SGLT2 inhibitorInvokana (canagliflozin) was launched in 2013. GLP-1 drugs have been on the market for nearly 20 years, but only recently have they taken the industry by storm, thanks to blockbuster drugs such as Ozempic and Zepbound garnering public attention.

“In this new era of diabetes management, with medications such as GLP-1 receptor agonists and SGLT2 inhibitors available, the goal is to understand which patients will benefit most from which treatment or combination of treatments.” Mona Mashayekh, M.D., Ph.D.“These findings suggest that the effects of steroids on the immune system are not yet fully understood,” Dr. Gregory Bryan, assistant professor of diabetes, endocrinology and metabolism at Vanderbilt University Medical Center, who was not involved in the study, told Healthline.

For type 2 diabetes patients who are at risk for or already suffer from complications such as kidney disease, heart failure, and cardiovascular disease, these drugs appear to hold new promise. Even for patients without diabetes, the benefits of GLP-1 and SGLT2 are a promising development.

“These drugs have clear, clinically important benefits in preventing the symptoms of kidney and heart failure and are therefore recommended for patients with heart failure and kidney disease, even if they do not have diabetes,” Nguyen said.

A meta-analysis of more than 70,000 people with diabetes found that SGLT2 inhibitors improved outcomes for cardiovascular events such as heart attack and stroke, hospitalization, and kidney disease progression.

When SGLT2 inhibitors were combined with GLP-1s (a class of drugs that includes Ozempic and Maunjaro), even greater reductions were seen without any additional safety concerns.

Experts told Healthline that the findings could help doctors better inform the treatment of patients with certain comorbidities, such as kidney or heart disease.