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11-26-2021 | Efpeglenatide | News

Efpeglenatide CV benefits independent of SGLT-2 inhibitor use

Author: Laura Cowen


medwireNews: The cardiovascular (CV) benefits of the glucagon-like peptide (GLP)-1 receptor agonist efpeglenatide are unrelated to concurrent sodium-glucose cotransporter (SGLT)2 inhibitor use, suggests an exploratory analysis of AMPLITUDE-O trial data.

The primary study findings, previously reported by medwireNews, showed that a once weekly injection of efpeglenatide 4 mg or 6 mg offers significant cardiorenal protection, versus placebo, in people with type 2 diabetes.

The current analysis indicates that “[c]ombined treatment with SGLT2 inhibitors and GLP-1 [receptor agonists] has the potential to yield substantial benefits across a wide range of CV outcomes,” write Carolyn Lam (National Heart Centre Singapore) and co-authors in Circulation.

They explain that the international AMPLTIUDE-O study included 4076 participants with type 2 diabetes who were at high risk for cardiorenal events. Of these, 618 (15.2%) were receiving an SGLT2 inhibitor at baseline.

In the absence of SGLT2 inhibitors, the researchers found that the risk for major adverse CV events (MACE; nonfatal myocardial infarction, nonfatal stroke, or death from CV or undetermined causes) was significantly lower among the 2305 participants randomly assigned to receive efpeglenatide relative to the 1153 given placebo, at an adjusted hazard ratio (aHR) of 0.74.

This was not significantly different from the aHR of 0.70 for MACE observed in the presence of baseline SGLT2 inhibitor use when the 412 participants who received efpeglenatide in this group were compared with the 206 who received placebo.

There was also no significant difference in aHRs without and with baseline SGLT2 inhibitor use in the risk for expanded MACE (MACE, coronary revascularization, or unstable angina hospitalization, aHRs=0.77 and 0.87), and MACE or non-CV death (aHRs=0.74 and 0.65).

Lam and team note that there was a suggestion in the Kaplan–Meier curves of larger effects among patients who were versus were not receiving SGLT2 inhibitors at baseline for the renal composite outcome (aHRs=0.70 and 0.52) and for heart failure hospitalization (aHRs=0.70 and 0.23). These differences were not significantly different, possibly due to a small number of events within the subgroup of baseline SGLT2 inhibitor users, they say.

Improvements in clinical variables such as blood pressure, bodyweight, low-density lipoprotein cholesterol, and urinary albumin:creatinine ratio with efpeglenatide versus placebo were also independent of concurrent SGLT2 inhibitor use, and use of both drug types did not impact adverse event rates relative to efpeglenatide monotherapy.

Lam et al comment that although “guidelines and societies recommend the addition of SGLT2 inhibitors after a GLP-1 [receptor agonist] or vice versa for patients with diabetes, with or at high risk of atherosclerotic CV disease or chronic kidney disease,” there is a lack of evidence to back up these recommendations.

They say that their “data support combined SGLT2 inhibitor and GLP-1 [receptor agonist] therapy in type 2 diabetes,” but acknowledge that “more data are needed to confirm both the efficacy and tolerability of this combination of treatments.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

Circulation 2021; doi:10.1161/CIRCULATIONAHA.121.057934


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