Efpeglenatide lowered the risk of cardiovascular and renal events in patients with type 2 diabetes who have a history of cardiovascular or kidney disease, according to new data published in The New England Journal of Medicine.
"Efpeglenatide, a GLP-1 receptor agonist administered weekly by means of subcutaneous injection, has been shown to lower glucose levels without causing hypoglycemia," wrote lead author Hertzel C. Gerstein, MD, with the department of medicine at McMaster University in Canada, and colleagues. "The drug consists of a modified exendin-4 molecule conjugated with an IgG4 Fc fragment. Its mechanism of action is akin to that of GLP-1 receptor agonists that are structurally similar to human GLP-1, which have been shown to reduce the risk of adverse cardiovascular events. This similarity and an acceptable safety profile suggest that efpeglenatide may also have cardiovascular and renal benefits in patients with diabetes and concomitant cardiovascular disease, kidney disease, or both."
For the AMPLITUDE-trial, researchers evaluated efpeglenatide in patients with type 2 diabetes and a history of cardiovascular disease or current kidney disease at 344 sites in 28 countries. The trial was sponsored by Sanofi.
The analysis included 4,076 patients who were treated from May 11, 2018, to April 25, 2019. Thirty-three percent of patients were female, and the mean patient age was 64.5 years old. Eighty-nine percent had a history of cardiovascular disease.
While 2,717 patients were given weekly, subcutaneous injections of either 4 mg or 6 mg of efpeglenatide, another 1,359 patients received a placebo.
The authors also noted that similar numbers of patients in the efpeglenatide groups and the placebo group were the recipients of glucose-lowering or cardioprotective drugs at baseline.
According to the authors, the study's primary outcome was the first incidence of a major adverse cardiovascular event (MACE), a composite of nonfatal MI, nonfatal stroke, or death from cardiovascular or other unknown causes.
During a median follow-up of 1.81 years, 7% of participants from the efpeglenatide group and 9.2% of patients from the placebo group experienced at least one MACE.
In the analysis, 31.6% of patients had an estimated glomerular filtration rate (eGFR) of less than 60 ml per minute per 1.73 m2, 21.8% had both cardiovascular disease and a low eGFR, and 15.2% were using a SGLT2 inhibitor at baseline.
In addition, a renal outcome event (a decrease in kidney function or macroalbuminuria) occurred in 13% patients who were administered efpeglenatide and in 18.4% of the placebo group. Incidence of diarrhea, constipation, nausea, vomiting, or bloating were all more prevalent with efpeglenatide compared with placebo.
“The results suggest that these cardiovascular and renal benefits occurred independently of the baseline use of SGLT2 inhibitors, the baseline use of metformin, and the baseline eGFR,” the authors wrote. “The participants in the two efpeglenatide groups had gastrointestinal adverse events (as have also been observed in prior trials of other GLP-1 receptor agonists), but there was no evidence of retinal, pancreatic, or thyroid-related events.”
Read the full study here.