Obesity has become one of the biggest health challenges in the world. It increases the risk of type 2 diabetes, heart disease, stroke, fatty liver disease, sleep apnea, and several cancers.
While healthy eating, regular exercise, and lifestyle changes remain the foundation of weight management, many people need medication to achieve meaningful long-term weight loss. In recent years, GLP-1 medicines such as semaglutide have changed obesity treatment by helping people lose significant amounts of weight.
However, these medicines are usually given by injection, which can discourage some patients and make treatment less accessible.
Researchers have now developed a new oral GLP-1 medicine called aleniglipron that may overcome some of these barriers. The findings were published in Nature Medicine by researchers from multiple institutions, including Northwestern University, where Professor Emeritus Dr. Robert Kushner was a co-author.
Like injectable GLP-1 medicines, aleniglipron copies the actions of the natural GLP-1 hormone. It helps the body release insulin when needed, reduces appetite, slows stomach emptying, and helps people feel full for longer. These effects can lead to lower calorie intake and gradual weight loss.
Unlike current injectable GLP-1 drugs, aleniglipron is a small-molecule medicine. Small molecules are made through chemical manufacturing rather than as peptide medicines.
This means the drug can be taken as a tablet, does not require injections, can potentially be produced more easily, and may be simpler to store and distribute because refrigeration is not required. It may also become easier to combine with other medicines in the future.
The phase II randomized, double-blind, placebo-controlled clinical trial enrolled 230 adults with obesity or overweight at 38 medical centers across the United States. The average participant was about 50 years old. Volunteers received either placebo or one of three daily doses of aleniglipron for 36 weeks, with the dose increased gradually every four weeks.
By the end of the study, participants taking the highest dose lost an average of 12.1% of their body weight. Those taking the middle dose lost 10.7%, while the lowest dose group lost 9.0%. In comparison, people receiving placebo lost only 0.5%.
Most side effects involved the digestive system, such as nausea or stomach discomfort. These effects were generally mild to moderate and became less common as treatment continued. About 10% of participants stopped treatment, and researchers did not detect drug-induced liver injury.
The results support moving aleniglipron into larger phase III clinical trials. However, this was still a relatively small study lasting only 36 weeks. Researchers will need to confirm long-term safety, effectiveness, and durability of weight loss in much larger and more diverse populations.
Even if future trials are successful, healthy eating and regular physical activity will remain important parts of obesity treatment. Overall, the findings suggest that an effective daily weight-loss pill could greatly improve access to GLP-1 therapy and make treatment easier for many patients.
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Source: Northwestern University.
