Choosing a diabetes drug? This might help you find the best antidiabetic medication to prevent the risk for adverse cardiovascular events (heart attack, stroke, or cardiovascular death) and heart failure hospitalization.

According to a recent report published in the Annals of Internal Medicine, GLP1 receptor agonists, a group of diabetes medications, have been found to be associated with fewer major adverse cardiovascular events such as heart attack, stroke, or cardiovascular death and heart failure hospitalization, compared to another type of diabetes drug called DPP4 inhibitors in elderly veterans with no previous history of heart disease.

The study’s findings are expected to provide valuable guidance to healthcare practitioners when selecting diabetes drug regimens for older patients.

Over 30 million adults in the United States are living with diabetes mellitus, also known as Type 2 Diabetes, a condition that raises their chances of experiencing cardiovascular complications such as heart attacks, strokes, cardiovascular-related deaths, and hospitalizations due to heart failure.

According to first author Lee Richardson, they aimed to fill in two gaps in knowledge. The first gap is that many recently developed diabetes medications were compared to a placebo during testing, which makes it challenging to determine if any particular type of medication offers an advantage over others. The second gap is that the clinical trials that demonstrated the cardiovascular benefits of these drugs were conducted exclusively on individuals who had pre-existing heart disease.

“We wanted to see if there were differences in MACE — major adverse cardiovascular events — when comparing two commonly used drug classes, GLP1 receptor agonists and SGLT2 inhibitors, versus an active comparator, DPP4 inhibitors, in people without heart disease,” Richardson adds.

DPP4 inhibitors are still commonly used and are thought to have little effect on cardiovascular events.

According to a recent retrospective cohort study conducted on American veterans, the inclusion of a GLP1 receptor agonist in the treatment regimen of Type 2 diabetes patients without prior heart disease was found to be linked to a reduced risk of approximately 20% for MACE and hospitalization due to heart failure, as compared to treatment with a DPP4 inhibitor.

Senior author Christianne Roumie added that this translates to a reduction of about three heart failure, death, heart attack, or stroke events per 1,000 individuals using the medication for a year. 

According to the study conducted on almost 100,000 veterans who were initially prescribed antidiabetic medication (such as metformin, insulin or sulfonylurea) between 2001 and 2016, the addition of a GLP1 receptor agonist, SGLT2 inhibitor or DPP4 inhibitor did not result in reduced MACE (major adverse cardiovascular events) or a decrease in hospitalization due to heart failure when compared to treatment with DPP4 inhibitors for primary prevention of heart disease. The follow-up data for this study was collected up until 2019.

As per the study findings, the median age of patients was 67 years, and the median duration of diabetes was 8.5 years. To conduct the statistical analysis, the researchers considered various factors such as age, gender, race, body mass index, blood pressure, hemoglobin A1c levels, and previous medical conditions.

However, the study did not investigate the effectiveness of GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors as the initial treatment options for Type 2 diabetes.

“Diabetes and its complications represent an enormous health care burden and result in nearly 200,000 deaths annually, often due to heart disease,” Roumie adds. “Doctors, scientists and patients want to do our best to prevent heart disease for those who are at highest risk. We believe that future primary prevention trials with these antidiabetic medications are needed. For some patients, these medications cost a lot, but if they prevent heart disease, then there would be a great return on investment.” 

Richardson pointed out that one limitation of the present study is that the majority of the participants were white males.

“The hope for future primary prevention trials is that they would enroll a diverse cohort of participants who represent the patients we see in our clinics on a day-to-day basis,” he adds.

GLP1 receptor agonists consist of drugs such as exenatide, liraglutide, semaglutide, among others. SGLT2 inhibitors, on the other hand, include medications like empagliflozin, dapagliflozin, and canagliflozin. Finally, DPP4 inhibitors comprise alogliptin, linagliptin, saxagliptin, and sitagliptin.

Source: 10.7326/M22-2751

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