New Delhi: An experimental weight-loss medicine being developed by Eli Lilly has shown promising results in a large international clinical trial. Retatrutide was associated with significant weight loss, improved blood sugar control and changes in several measures linked to cardiovascular and metabolic health.
The drug has not yet been approved by any regulatory authority. However, results from a phase 3 trial suggest that retatrutide could potentially become a treatment option for people with obesity and type 2 diabetes if further research confirms its effectiveness and safety.
The findings were published in The Lancet and presented at the annual meeting of the European Association for the Study of Diabetes in Milan, Italy. Eli Lilly, which is developing the drug, funded the study.
How Does Retatrutide Work?
Retatrutide differs from currently available weight-management medicines because it targets three hormone pathways involved in appetite, blood sugar regulation and metabolism.
The medicine acts on GLP-1 and GIP, two pathways already targeted by some diabetes and weight-management drugs. It also activates the glucagon receptor. This additional mechanism may increase energy expenditure and could contribute to greater weight loss.
For comparison, Mounjaro acts on GLP-1 and GIP pathways, while medicines such as Wegovy work through the GLP-1 pathway. Retatrutide’s three-pathway approach has therefore attracted significant interest in research.
The researchers reported that the drug produced substantial reductions in body weight alongside improved glycaemic control and cardiometabolic measures. They also said its overall safety profile was broadly similar to other medicines with GLP-1 receptor agonist activity.
What Did the Phase 3 Trial Find?
The international study included 2,047 adults from eight countries, including India, the United States, Australia, Argentina, Brazil, Mexico, Romania and Spain.
All participants had a BMI of at least 27 and type 2 diabetes. Their average age was 55, with women accounting for 48% of the participants and men 52%.
For the 80-week phase 3 part of the study, 1,152 participants were assigned to receive either a placebo or one of three weekly retatrutide doses: 4mg, 9mg or 12mg. Participants also received dietary advice and guidance on physical activity.
Weight loss increased with the dose. Participants taking 4mg lost an average of 11.9% of their starting body weight, while those receiving 9mg recorded an average reduction of 16.8%. The 12mg group had an average weight reduction of 18.8%.
By comparison, the placebo group recorded an average weight loss of 5.1%.
The highest dose also helped a substantial proportion of participants reach larger weight-loss milestones. Nearly half of those taking 12mg lost at least 20% of their initial body weight, while around 31% achieved a reduction of at least 25%.
Among participants receiving placebo, 6% lost at least 20% of their body weight and 3% reached a reduction of at least 25%.
Blood Sugar and Other Health Measures Also Improved
The study found that the potential effects of retatrutide extended beyond weight reduction. About 72% of participants receiving the 12mg dose reached an HbA1c level of 6.5% or lower, compared with 29% in the placebo group.
HbA1c is a measure used to reflect average blood glucose levels over approximately the previous two to three months.
Researchers also reported improvements in several cardiometabolic risk factors, including blood pressure and lipid levels. Retatrutide was also associated with lower levels of high-sensitivity C-reactive protein (hsCRP), a blood marker associated with inflammation.
The researchers concluded that retatrutide delivered substantial weight loss while also improving blood sugar control and several cardiometabolic risk factors. Its overall safety profile was broadly consistent with other medicines that have GLP-1 receptor activity.
Side Effects and Pregnancy-Related Research
Gastrointestinal problems were the most frequently reported side effects during the trial. Diarrhoea occurred in 27% to 34% of participants receiving retatrutide, compared with 13% among those taking placebo. Nausea was reported by 14% to 28% of participants in the retatrutide groups and 8% in the placebo group.
Seven participants died during the study. Two deaths occurred in the 4mg group, three in the 9mg group, one in the 12mg group and one in the placebo group. Investigators determined that the deaths were not related to the study treatment.
Because retatrutide has not received regulatory approval, the trial results do not mean that the medicine is currently available as an approved treatment. Further research and regulatory evaluation will be required before its potential use in routine medical care can be determined.
Separate research presented at the same conference examined weight-loss medicines among women with type 2 diabetes. Published in The Lancet Obstetrics, Gynaecology & Women’s Health, the study found that these medicines were not associated with adverse pregnancy outcomes in most cases. However, researchers noted that significant gaps remain in the available evidence and said additional research is needed, particularly as the use of weight-loss medicines increases among women of reproductive age.
Disclaimer: This article is for general informational purposes and summarises findings from the reported clinical research. Retatrutide is an experimental medicine and has not been approved by regulatory authorities. Clinical trial results do not establish that a medicine is suitable for individual treatment. Readers should consult a qualified healthcare professional before making decisions about weight-loss medicines or diabetes treatment.