The oral diabetes treatment met its cardiovascular safety target while reducing hypoglycaemia and deaths compared with insulin glargine, but caused more gastrointestinal side effects.
A once-daily pill from Eli Lilly has shown cardiovascular safety comparable with insulin glargine in a phase 3 diabetes trial, while also delivering lower rates of hypoglycaemia and fewer deaths, according to a report published in The Lancet to coincide with the European Association for the Study of Diabetes meeting in Milan.
The study, led by Klara R. Klein of the University of North Carolina School of Medicine, compared orforglipron with insulin glargine in 2,749 adults with type 2 diabetes, overweight or obesity, and elevated cardiovascular risk. After a median follow-up of two years, the four-part measure of major adverse cardiovascular events occurred in 4.2% of patients taking orforglipron and 5.0% of those on insulin glargine, meeting the trial’s non-inferiority goal.
That means the tablet was not worse than the injectable insulin on the primary cardiovascular safety measure used in the study. The difference in serious heart-related outcomes was modest, but the results matter because the trial enrolled people already at higher risk of cardiovascular complications, making safety a key concern as new diabetes treatments move into broader use.
The trade-off was a higher rate of gastrointestinal side effects with the pill, which affected 62.1% of patients versus 14.2% of those receiving insulin glargine. By contrast, clinically significant or severe hypoglycaemia was less frequent with orforglipron, at 6.8% compared with 19.2% in the insulin group. Deaths were also less common in the orforglipron arm, though the study said nearly all were judged unrelated to treatment.
In a statement quoted by HealthDay, Klein said the ACHIEVE-4 study confirmed the drug’s safety while also showing meaningful improvements in blood sugar control and weight. She added that the appeal of a shelf-stable, once-daily oral treatment that does not require fasting or water restrictions could help broaden access to diabetes care worldwide.
Orforglipron is being developed by Eli Lilly, which funded the trial. The findings add to interest in oral GLP-1 medicines, a class that could eventually offer some of the benefits of injectable drugs in a simpler form for patients who prefer tablets.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
