Efpeglenatide: how it works, trial results and approval status
Clinical review pending
Efpeglenatide is an investigational GLP-1 receptor agonist. What is known about how it works and studies of cardiovascular and kidney events.
Efpeglenatide is an investigational medicine studied as a once-weekly injection for type 2 diabetes. In a large phase 3 trial, major cardiovascular events occurred less often with efpeglenatide than with placebo. That result applies to the adults studied: people with type 2 diabetes and existing cardiovascular or kidney disease. At the stage of development documented here, efpeglenatide is not approved.
What is efpeglenatide?
Efpeglenatide is an investigational GLP-1 receptor agonist: it activates the GLP-1 receptor. It is based on an exendin-derived peptide. Its half-life has been extended through engineering to make once-weekly injections possible. Half-life describes the time it takes for the concentration of a medicine in the body to fall by half.
Hanmi Pharmaceutical developed efpeglenatide and, for a time, licensed it to Sanofi. Sanofi later returned the rights. Researchers studied efpeglenatide in type 2 diabetes and investigated whether it reduces cardiovascular and kidney risks. At the stage documented here, the medicine remains investigational and is not approved in major pharmaceutical markets.
How does efpeglenatide work?
Efpeglenatide activates the GLP-1 receptor 1. This is the receptor to which the gut hormone GLP-1, one of the hormones known as incretins, normally binds. Medicines such as semaglutide and dulaglutide also act at this receptor. Activating it:
- in response to glucose levels, increases the release of insulin,
- suppresses the release of glucagon,
- slows stomach emptying,
- reduces appetite.
These effects lower blood glucose and body weight in people with type 2 diabetes. Studies of GLP-1 receptor agonists have also shown cardiovascular benefits. The effect of efpeglenatide on cardiovascular events was investigated in the AMPLITUDE-O trial.
Is efpeglenatide FDA-approved?
At the stage documented here, efpeglenatide is approved neither by the US FDA nor in the European Union. It remains investigational. After Sanofi returned the development rights, Hanmi continued the program itself and pursued regional licensing agreements. No information about approval in other major pharmaceutical markets is documented here either.
What does the research show?
The main findings come from the phase 3 AMPLITUDE-O trial [2]. More than 4,000 adults with type 2 diabetes and existing cardiovascular or kidney disease took part. The trial examined cardiovascular events; a further analysis compared benefits in participants with and without additional treatment with an SGLT2 inhibitor.
| Endpoint | Result |
|---|---|
| Major adverse cardiovascular events | Occurred less often with efpeglenatide than with placebo (hazard ratio 0.73). |
| Composite kidney endpoint | Events included in the composite kidney endpoint occurred less often with efpeglenatide. |
| Benefit when taking an SGLT2 inhibitor | A prespecified analysis 3 found similar benefits regardless of whether participants were already taking an SGLT2 inhibitor. |
The hazard ratio describes the relative rate of events over the course of the study. The value 0.73 alone does not tell us how many fewer people experienced a cardiovascular event. That also requires the absolute event rates and the follow-up period. The composite kidney endpoint groups several outcomes together; without its exact definition, it remains unclear which changes in kidney health the result includes.
The positive phase 3 results were published in peer-reviewed journals. They concern the group studied: people with type 2 diabetes and existing cardiovascular or kidney disease. At the stage documented here, efpeglenatide had not yet received approval.