In a Scientific Sessions symposium on Monday, June 28, investigators will share findings from the first trial of a glucagon-like peptide-1 (GLP-1) receptor agonist looking at both cardiovascular and renal outcomes in a high-risk population of type 2 diabetes patients. First Results of the Effect of Efpeglenatide on Cardiovascular Outcomes (AMPLITUDE-O) Trial will be presented from 2:15 p.m. – 4:15 p.m. ET.

“To date, there have been seven large GLP-1 receptor agonist cardiovascular outcomes trials that have assessed the effects of various GLP-1 receptor agonists on cardiovascular outcomes in people with diabetes and additional cardiovascular risk factors,” said AMPLITUDE-O Principal Investigator Hertzel C. Gerstein, MD, MSc, FRCPC, Professor of Medicine and Population Health Institute Chair in Diabetes Research at McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.

“A meta-analysis of these seven trials shows that, overall, GLP-1 receptor agonists reduce cardiovascular outcomes in people with and without previous cardiovascular disease—that’s established and already incorporated into guidelines,” Dr. Gerstein continued.

A number of important factors distinguish AMPLITUDE-O from those previous trials, he added.

“This is a trial done in a different population and with a different sort of drug, efpeglenatide, which is an exendin-4-based GLP-1 receptor agonist, not a human-based one,” Dr. Gerstein said. “Additionally, this trial recruited a particularly high-risk population of people who had either cardiovascular disease or renal disease, and a significant number had both.”

In AMPLITUDE-O, 4,076 participants were recruited between May 2018 and April 2019 at 344 sites in 28 countries. Participants included people who were at least 18 years of age with type 2 diabetes, had A1C greater than 7%, and previously had been diagnosed with cardiovascular disease; or people at least 50 years old with chronic kidney disease (CKD) and one or more additional cardiovascular risk factors.

Participants were randomized in a 1:1:1 ratio, stratified by current, intended, or neither current nor intended use of a sodium-glucose cotransporter-2 (SGLT2) inhibitor to receive weekly injections of efpeglenatide (4 mg or 6 mg) or masked placebo. The primary outcome is a major adverse cardiovascular event; secondary outcomes include a composite kidney outcome.

“The other important and unique thing about this trial is we have a significant number of people who are on an SGLT2 inhibitor, approximately 15% of all the participants, which means that this is really the first trial to assess the cardiovascular and renal effects of a combination of a GLP-1 receptor agonist and an SGLT2 inhibitor,” Dr. Gerstein said. “We’re certainly going to be looking very closely at those people on both drug classes to answer the question as to whether there will be any additional effects.”

The results of AMPLITUDE-O will be of great interest to clinicians who care for people with diabetes, as it will inform the use of an exendin-based GLP-1 receptor agonist in people with type 2 diabetes and high cardiovascular risk, with and without CKD, in the presence and absence of an SGLT2 inhibitor, Dr. Gerstein said.

“None of the other trials with exendin-4-based GLP-1 receptor agonists have shown a clear benefit, and we look forward to sharing whether or not this trial has shown a benefit,” Dr. Gerstein said. “Obviously, if it did, it will suggest that GLP-1 receptor agonists derived from various peptides are all beneficial. If it did not, then it will suggest that only human GLP-1 receptor agonists are beneficial.”