Some medications used to treat diabetes also treat conditions that often accompany diabetes. In this category are what are called glucagon-like peptide-1 (GLP-1) receptor agonists. GLP-1 receptor agonists stimulate the pancreas to increase its secretion of insulin, while also decreasing glucagon, a hormone that releases sugar (glucose) from the liver. GLP-1 receptor agonists are often recommended for people with diabetes who have difficulty reaching target blood sugar levels or who have heart failure, hardening of the arteries (atherosclerosis), or kidney disease. Examples of GLP-1 receptor agonists include Trulicity (dulaglutide), Victoza (liraglutide), Byetta and Bydureon (exenatide), Lyxumia (lixisenatide), and Ozempic and Rybelsus (semaglutide).
A new report in The New England Journal of Medicine evaluated the efficacy of a new GLP-1 receptor agonist called efpeglenatide, which is manufactured by Sanofi, a pharmaceutical manufacturer based in Paris, France. The data was presented virtually at the annual meeting of the American Diabetes Association. The study was a truly international one, taking place in 344 sites. Dozens were in the United States, and others were in Argentina, Bulgaria, Canada, Chile, Denmark, Estonia, Finland, Germany, Hungary, Italy, India, Latvia, Lithuania, Mexico, Norway, Peru, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Sweden, Turkey, and Ukraine.
A total of 4,076 subjects were enrolled. They were confirmed diabetes patients who had either had cardiovascular (CV) disease or who were older patients with at least one cardiovascular risk factor. Most were male (67%) and white (87%). They had had diabetes for an average of 15 years and nearly all were taking glucose-lowering medications, while many also used cardiovascular drugs. Of the total, 2,717 were in a group that received efpeglenatide and 1,359 were in a group that received a placebo (an inactive substance). The efpeglenatide group received weekly injections of either 4 milligrams (mg) or 6 mg.
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During a follow-up period of nearly two years, 7% of the efpeglenatide users suffered a major adverse cardiovascular event (MACE), while 9.2% of the placebo users did. As for kidney function, 13% of the efpeglenatide users experienced what the researchers termed a “composite renal outcome event,” which was either a decrease in kidney function or an elevation of albumin in the urine, a troubling condition known as macroalbuminuria, which is considered a predictor of worsening kidney disease and is associated with death from cardiovascular disease in people with diabetes. Among the placebo users, however, the percentage experiencing a renal event was 18.4. There were some side effects apparently related to efpeglenatide but not to placebo — diarrhea, constipation, nausea, vomiting, bloating.
The lead researcher, Hertzel Gerstein, MD, of McMaster University and Hamilton Health Sciences in Ontario, Canada, said that previous large trials have shown the efficacy of GLP-1 receptor agonists on cardiovascular disease, but he noted that these studies demonstrated that the medications are effective for people who didn’t have a history of heart disease. But, he said, “This is a trial done in a different population and with a different sort of drug, efpeglenatide…. This trial recruited a particularly high-risk population of people who had either cardiovascular disease or renal disease, and a significant number had both.”
The results, he told the medical news service Healio, show that efpeglenatide is “comparable” to the other GLP-1 receptor agonists. “This is not a head-to-head study,” he commented. “From a cardioprotective benefit, efpeglenatide is right in line with the class as a whole. We have clear, unambiguous reduction in primary CV outcomes and in secondary CV outcomes and renal outcomes. That is exciting and, to me, the most important message is it provides even more confidence and reassurance about the GLP-1 receptor agonist class. Here is yet another example of the drug that works.”
Want to learn more about keeping your kidneys healthy with diabetes? Read “How to Keep Your Kidneys Healthy,” “Kidney Disease: Your Seven-Step Plan for Prevention” and “Ten Things to Know About Kidney Disease.”
Want to learn more about protecting your heart? Read “Be Heart Smart: Know Your Numbers,” “Does Diabetes Hurt Your Heart?” “Fight Off Heart Disease With These Five Heart-Healthy Foods” and “Lower Your Risk of Heart Disease.”