GLP-1 Update: Oral Semaglutide Shows Heart Benefits

Introduction

Type 2 diabetes is not just a matter of managing blood sugar—it's also linked to serious complications like heart attacks, strokes, and kidney failure. In fact, cardiovascular disease is the leading cause of death in people with type 2 diabetes. That’s why doctors are increasingly looking for treatments that offer more than just glucose control.

Glucagon-like peptide-1 (GLP-1) receptor agonists have gained attention for their ability to reduce both blood sugar and cardiovascular risks. Injectable semaglutide has already proven effective in this area. But many patients prefer pills over injections, raising a key question: can the oral version of semaglutide offer the same protection for the heart?

A new study—the SOUL trial—provides a clear answer.

The New Study

The SOUL trial was designed to test whether daily oral semaglutide can reduce major heart-related events in people with type 2 diabetes who already have cardiovascular disease, kidney disease, or both.

Methods

Researchers enrolled 9,650 adults over age 50 from 33 countries. All had type 2 diabetes and existing cardiovascular or kidney disease. Participants were randomly assigned to take either oral semaglutide (up to 14 mg daily) or a placebo, alongside their usual care. The study tracked major cardiovascular events—like heart attacks, strokes, and cardiovascular deaths—over nearly four years.

Results

The results were impressive:

• 12.0% of the semaglutide group experienced a major cardiovascular event, compared to 13.8% in the placebo group.

• This represents a 14% relative risk reduction (hazard ratio: 0.86; p = 0.006).

• The most significant benefit was seen in nonfatal heart attacks, which dropped by 26%.

Stroke risk and kidney disease events also decreased slightly, but those changes weren’t statistically significant. Importantly, serious side effects were slightly less common with semaglutide than with placebo. However, more people on semaglutide stopped the medication due to gastrointestinal issues.

Discussion

This study confirms that oral semaglutide can do more than manage blood sugar—it can also reduce the risk of serious cardiovascular problems in high-risk individuals. That’s a major win, especially for patients who prefer pills over injections.

The findings align with previous studies of injectable semaglutide and reinforce the broader value of GLP-1 therapies. On top of heart protection, semaglutide also led to lower inflammation (measured by CRP), better blood sugar control, and modest weight loss.

Bottom Line

For people with type 2 diabetes and existing cardiovascular or kidney issues, oral semaglutide offers a powerful, convenient tool to reduce heart risks. While digestive side effects are something to watch for, the benefits of daily oral treatment are clear—especially for those hesitant about needles.

Study Reference: https://www.nejm.org/doi/full/10.1056/NEJMoa2501006