A fresh therapy for obesity is capturing the spotlight following a report by Eli Lilly that its investigational compound retatrutide demonstrated weight loss near bariatric surgery levels in a key Phase 3 trial. The drug could represent a significant breakthrough in the dynamic realm of obesity medicine. Within the phase 3 TRIUMPH-1 study, the group that was administered the highest dose of retatrutide (12 mg) experienced a mean weight reduction of 28.
3% after 80 weeks, equating to an average weight loss of approximately 70.3 lbs for an individual group whose mean initial weight was approximately 248.
5 lbs. The 9 mg dose group experienced a mean weight reduction of 25.9% while the 4 mg dose group experienced a mean weight reduction of 19%. The most dramatic was the percentage of people achieving very large decreases in body weight.
At 80 weeks 45.3% of the 12 mg group achieved at least a 30% loss in body weight, of whom 27.2% achieved at least a 35% loss in body weight. Lilly states that this degree of weight loss has ‘defined or defined as acceptable in the general medical community to be an indication of the need for bariatric surgery’.
Unlike the group of currently available therapies for obesity based on Glucagon-Like-Peptide, retatrutide is aimed at stimulating the three hormone receptors GIP GLP-1 and glucagon. Some say stimulation of multiple pathways could have more significant effects on food intake, metabolism, and weight. Another interesting point is that weight loss still seemed to advance once the 80-week study had finished. Preliminary data from a prespecified extension study in participants with a baseline BMI of at least 35 showed that retatrutide continued to produce a 30.
3% mean weight reduction at 104 weeks at the 12 mg dose. The group escalated from 9 mg to 12 mg reported mean reductions of 29.5%, and the group escalated from 4 mg to 12 mg reported a reduction of 27.9%. For some of these but, the reduction was large enough that they fell below the threshold for clinicaldefinition of obesity. Of those on 12 mg, 65.3% had fallen below the threshold of a BMI of30 points at 80 weeks. In those that began at class 3 obesity (that is a BMI of40points or more), this figure fell to37.5%.
The potential importance of the weight loss though extends well beyond the number on the scales. Retatrutide was also found to improve many other factors that influence cardiovascular risk, like waist circumference, non-HDL cholesterol triglycerides systolic blood pressure, and high-sensitivity C-reactive protein.
These effects might prove to be critical if subsequent research confirms that the weight loss on retatrutide results in diminished cardiovascular morbidity and other long term outcomes. The adverse events in TRIUMPH-1 were gastrointestinal side effects such as nausea diarrhea constipation and vomiting; these increased at the higher dose levels.
There were higher rates of withdrawals due to adverse events in the 12 mg group (11.3%) than in the placebo (4.9%). The comparison with bariatric surgery is because of this only with the amount of weight loss achieved with surgical treatment in the past, rather than a direct clinical trial of retatrutide versus bariatric surgery.
