GLP-1s Help Lower Risk in People With Diabetes

• Researchers say GLP-1 drugs prescribed for weight loss, like Ozempic and Mounjaro, are more effective at reducing heart health risks in people with type 2 diabetes than other types of glucose-lowering medications.
• Experts say this class of medications is effective because it helps with weight loss, blood pressure, and other cardiovascular risk factors in various ways.
• People taking these medications still need to maintain a healthy diet and stick to a regular exercise regimen.

GLP-1 medications commonly prescribed for weight loss, like Ozempic and Mounjaro, significantly reduce cardiovascular risks in people with type 2 diabetes, according to a new study.

The research, published on October 15 in JAMA Network Open, concluded that GLP-1RA drugs were significantly more effective in lowering cardiovascular risks than three other types of glucose-lowering medications.

Rita Kalyani, MD, the chief scientific and medical officer at the American Diabetes Association (ADA), said the research touches upon an important medical topic. Kalyani wasn’t involved in the study.

The researchers focused on three types of heart-related events: nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. Here’s what they found.

The researchers looked at more than 240,000 adults with type 2 diabetes from six healthcare delivery systems in the United States. The average age of the participants was 57, and 54% of the subjects were males.

The participants were prescribed one of four classes of glucose-lowering medications between 2014 and 2021. Those drugs included:

• Sulfonylureas — A group of oral medications first used in the 1950s to help treat diabetes by stimulating the pancreas to release more insulin. Brand names include Glucotrol and Diabeta.
• Dipeptidyl peptidase-4 inhibitors (DPP4s) — A class of oral medications that help manage type 2 diabetes by increasing the levels of incretin hormones, which stimulate insulin secretion and lower blood sugar levels. Brand names include Januvia and Nesina.
• Sodium-glucose cotransporter-2 inhibitors (SGLT2s) — A group of oral medications that help treat type 2 diabetes by inhibiting the reabsorption of glucose in the kidneys. Brand names include Invokana and Jardiance.
• Glucagon-like peptide-1 receptor agonists (GLP-1RAs) — A group of injectable medications used to treat type 2 diabetes whose primary purpose is helping people lose weight. They include medications with the active ingredient semaglutide, such as Ozempic and Wegovy, as well as medications with the active ingredient tirzepatide like Zepbound and Mounjaro.

Metformin, a widely used oral medication that helps manage blood sugar levels in people with type 2 diabetes, was not studied in this particular research analysis.

In their study, researchers noted that major cardiovascular adverse events are “the leading cause of excess mortality in adults with type 2 diabetes.”

The goal of their study was to determine which medications are most beneficial in lowering the risk of these events.

In their findings, they reported that cardiovascular event risk “varied significantly by medication class, with most protection achieved with sustained treatment with GLP-1RAs followed by SGLT2s, sulfonylureas, and DPP4s.”

Cheng-Han Chen, MD, an interventional cardiologist and the medical director of the Structural Heart Program at Saddleback Medical Center in California, said the study reaffirms the effectiveness of these weight loss drugs.

“These results add to our growing body of knowledge on the significant benefits that this class of medications has on our treatment of cardiometabolic conditions and cardiovascular disease,” Chen, who wasn’t involved in the study, told Healthline.

Marilyn Tan, MD, a clinical professor of medicine at Stanford University in California, agreed, saying a wide array of research has shown GLP-1RA drugs to be beneficial for heart health. Tan was likewise not involved in the study.

“All of the studies were slightly different in design and participant demographics, but overall, these newer medications have been promising for not only glucose control but also cardiovascular risk reduction and kidney protection, among other benefits,” she told Healthline.

Mir Ali, MD, a bariatric surgeon and the medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in California, noted that the benefits may help some people more than others. Ali wasn’t involved in the study.

“The overall takeaway is that, given the right patient, the GLP1-RA may provide the most effective treatment to lower cardiovascular risk,” Ali told Healthline. “The most benefit seemed to be in those patients that were older than 65 and had more medical issues.”

Experts say the effectiveness of GLP-1RA drugs may be due to the variety of ways in which they work.

“GLP-1RAs work by mimicking a natural hormone that regulates blood sugar and appetite, leading to weight loss, improved glucose control, and better blood pressure and cholesterol levels,” Katherine DiPalo, PharmD, an associate professor of medicine at the Albert Einstein College of Medicine in New York, told Healthline. DiPalo wasn’t involved in the study.

“They may also have direct protective effects on the blood vessels and heart. Newer agents, such as tirzepatide, combine GLP-1 and GIP receptor activity, resulting in even greater weight loss and metabolic benefits,” added DiPalo, who was the co-author of an American Heart Association (AHA) statement on cardiovascular risk factors in adults with type 2 diabetes.

“There are GLP1 receptors all over the body, including in the heart,” Tan added. “The benefit of GLP-1 agonists seems to be multifactorial, including direct GLP-1 effects, improved glucose control, but also notably, weight loss.”

She added that other research has shown GLP-1RA drugs to be beneficial in reducing cardiovascular risks in people with obesity who don’t have diabetes.

However, all these experts did caution there can be serious side effects to the GLP-1RA medications.

“Tolerability (GI side effects, etc), excessive weight loss (not all patients with diabetes need to or want to lose weight), potential loss of muscle mass, and cost remain limiting factors with GLP-1 receptor agonists,” Tan said.

“Like all medications, there are side effects,” Ali added. “Most commonly, patients experience GI type side effects such as nausea, diarrhea, or constipation; however, more serious side effects such as inflammation of the pancreas and gallbladder have been seen. Also, people with certain familial types of thyroid cancer should not take these medications.”

The Centers for Disease Control and Prevention (CDC) estimates that 38 million people in the United States have diabetes. More than 90% of them have type 2 diabetes. The remainder have type 1 diabetes.

Type 2 diabetes is typically diagnosed in people 45 years and older, but the CDC reports that diagnoses are rising in children, teens, and young adults.

It is also more common in Black, Hispanic, American Indian, Pacific Islander, and Asian American populations.

Type 2 diabetes generally occurs when the body has difficulty managing blood sugar levels due to an inability to properly use the hormone insulin.

• obesity
• lack of physical exercise
• high blood pressure
• high cholesterol levels
• high triglyceride levels

If untreated, type 2 diabetes can lead to serious complications such as cardiovascular disease as well as eye disease, nerve damage, kidney disease, hearing damage, and an increased risk of stroke.

Ali noted that the ramifications of diabetes make it vital that people with the condition get treated.

“The goal with diabetes treatment is to maintain blood glucose in a healthy range,” he said.

“Medications are an important part of treatment; however, a healthy diet and lifestyle are also very important. If a patient takes medications but does not eat the right foods and leads an unhealthy lifestyle, they will likely see progression of the diabetes and all the complications associated with this severe disease.”

The American Heart Association (AHA) has developed a list of eight lifestyle choices called Life’s Essential 8 that can help improve cardiovascular health. These include:

Experts say maintaining good cardiovascular health as well as overall health is crucial for people with diabetes.

“It is important for people with type 2 diabetes to maintain good health by eating a balanced diet low in saturated fat and excess carbohydrates, getting regular physical activity, avoiding tobacco and alcohol, getting regular medical check-ups, getting an adequate amount of quality sleep, managing their blood pressure and cholesterol levels, and controlling their stress levels,” said Chen.

“[Treatment] must be done in conjunction with other lifestyle changes such as regular exercise, interrupting sedentary time, improved sleep, stress reduction, avoiding excessive carbohydrates, [and] avoiding excess sugar,” added Tan.