The race to develop the next generation of weight loss drugs has taken an interesting new turn. In recent research, Eli Lilly’s experimental treatment aloralintide helped people lose a substantial amount of weight without using the same approach as existing popular drugs like Ozempic.
Earlier this month in The Lancet, Eli Lilly researchers and others published the latest Phase II trial results of aloralintide. Over a 48-week period, people taking aloralintide lost up to 20% of their baseline body weight, which is well above the average weight loss experienced by people taking placebo. Aloralintide’s early success to date is all the more remarkable because it is not a GLP-1 drug.
a different system
Aloralintide mimics the hormone amylin. Our pancreas naturally releases amylin along with insulin into the bloodstream in response to eating food. Once released, amylin helps tell our body that it is full, reduces our appetite, and slows the passage of food through our digestive tract.
The most effective weight loss drugs today, such as semaglutide (the active ingredient in Ozempic and Vegovy), are long-acting mimics of the hormone GLP-1. Like GLP-1, amylin plays a role in regulating our appetite and blood sugar control. Both hormones also share some overlap in how they influence the body to accomplish these functions. But they also have some key differences, and this makes amylin a promising new target for the treatment of obesity.
One existing amylin-based drug is pramlintide, which was first approved as a treatment for diabetes two decades ago. But it’s the newest amylin analogs in development, like aloralintide, that have really excited scientists. These experimental drugs are designed to last longer in the body than natural amylin, ideally enhancing the effects of the hormone to help people lose weight and control their blood sugar. Like semaglutide, aloralintide is intended to be taken once a week via subcutaneous injection.
early promise
Eli Lilly’s Phase II trial included 263 participants without type 2 diabetes who had obesity (body mass index greater than 30) or who were overweight (BMI greater than 27) with weight-related health conditions. They were randomly assigned to receive either placebo or different doses of aloralintide. Some were given the same dose of the drug throughout the study, while others were given gradually increasing doses.
The study showed that people taking aloralintide, regardless of dosing strategy, saw greater weight loss improvements over an average of 48 weeks than the placebo group. People taking the highest weekly dose, nine milligrams, saw the best results, losing an average of 20% weight over the course of the study, as did those who steadily increased their dose from six to nine milligrams.
It appears to be safe and generally well tolerated. The most common drug-related adverse events were gastrointestinal, similar to known side effects of GLP-1 therapy. The most common adverse event was nausea, with about one third of people taking the highest dose reporting the symptom.
“Aloralintide produced clinically meaningful, dose-dependent reductions in body weight over 48 weeks and was generally well tolerated, supporting the potential use of aloralintide for the treatment of obesity,” the study researchers wrote.
What does this mean for the future of weight loss?
GLP-1s have revolutionized the field of obesity therapy in recent years. And although these drugs are not risk-free and can be prohibitively expensive, they have already begun to turn back the clock on obesity. For the first time in years, America’s obesity rates have declined significantly as use of these drugs continues to increase.
There are now a number of obesity drugs in development, many of which are GLP-1 replications. Other drugs are combining GLP-1 with other appetite-related hormones, including amylin. However, the results with aloralintide are particularly surprising, because the drug is dependent only on amylin. This is important because it could mean that aloralintide could eventually become an attractive option for people who have not responded to GLP-1 therapy.
It is too early to know for sure, especially without a trial directly comparing these drugs. But it’s worth noting that in clinical trials, semaglutide helped people lose about 15% of their body weight on average. Eli Lilly’s existing obesity drug tirazeptide, which combines GLP-1 and the hormone GIP, has shown weight loss rates of about 20%.
Of course, these early findings need to be verified by data from larger trials. But if this research continues to prove promising, aloralantide could open a new area of obesity treatment.