Powerful weight-loss drugs have become widely known for their ability to reduce appetite and help people lose substantial amounts of weight.
But many of today’s leading treatments require injections, and scientists are racing to create easier pills that could produce similar benefits.
A new drug called aleniglipron has taken an important step toward that goal. In a phase II trial, adults taking the highest tested dose lost an average of 12.1 percent of their body weight after 36 weeks.
The findings were published in Nature Medicine. Robert Kushner of Northwestern University Feinberg School of Medicine was among the study authors, and Structure Therapeutics supported the research.
Aleniglipron targets the GLP-1 system, which has become one of the most important areas of modern obesity treatment. GLP-1 is short for glucagon-like peptide-1, a hormone the gut naturally releases after a meal.
This hormone helps the body respond to food in several ways. It supports insulin release when blood sugar rises and sends signals that reduce hunger and increase feelings of fullness.
Scientists learned that medicines copying or activating this signal could help people eat less without relying entirely on willpower. This led to treatments such as semaglutide and other drugs that have produced major weight loss in clinical trials.
Obesity is now understood as a complex long-term condition influenced by genetics, hormones, brain signals, environment and behavior. For many people, losing weight activates biological responses that increase hunger and encourage weight regain.
GLP-1 medicines can partly counter these responses by changing appetite signals. This is one reason they can produce more weight loss than lifestyle changes alone in many people with obesity.
But current treatments have practical limitations. Many GLP-1 medicines are peptides, which are relatively large molecules that can be broken down in the digestive system and therefore are commonly delivered by injection.
Aleniglipron is different because it is a small molecule. It is chemically produced and designed to activate the GLP-1 receptor while being taken as a daily tablet.
This distinction could matter for patients and manufacturers. Pills may be more acceptable to people who dislike injections, while small molecules may be easier to produce at very large scale.
The experimental drug can also be taken with or without food, according to study co-author Robert Kushner. That could make it more convenient for everyday use if future trials confirm its benefits.
Researchers tested the drug in 230 adults with obesity or overweight. The participants were treated at 38 medical centers across the United States and had an average age of 50.
The study was carefully controlled. Participants were randomly placed into groups receiving one of three aleniglipron doses or a placebo, and the trial was double-blind so expectations were less likely to influence the results.
The doses were 45, 90 and 120 milligrams taken once a day. Researchers gradually raised the dose every four weeks rather than beginning immediately at the full amount.
At the end of 36 weeks, all three aleniglipron groups had lost considerably more weight than the placebo group. Average weight loss was 9 percent with 45 milligrams and 10.7 percent with 90 milligrams.
Participants receiving 120 milligrams lost the most, averaging a 12.1 percent reduction from their starting weight. People receiving placebo lost about 0.5 percent.
The results suggest that stronger doses produced greater average weight loss over the study period. This kind of dose-response pattern is useful evidence when researchers are deciding which doses should move into larger trials.
Like other GLP-1 treatments, aleniglipron commonly caused digestive side effects. The researchers said these problems were generally mild or moderate and tended to become less common as the trial went on.
About 10.4 percent of participants discontinued treatment. No cases of drug-induced liver injury were reported, and the investigators said they did not identify a new safety signal during the trial.
That does not establish that the drug is completely safe. Rare problems may not appear in a study with only a few hundred participants, and some side effects may emerge only after much longer use.
This is especially relevant for obesity medicines because treatment may continue for years. A successful drug must not only produce weight loss but also remain acceptably safe and tolerable during long-term use.
The next major test will be phase III research. These larger studies are intended to confirm effectiveness and gather much more information about safety before regulators consider whether a new medicine should be approved.
The researchers plan to slow the dose increases further in the upcoming phase III program. A gentler increase may reduce nausea and other digestive problems and help more participants remain on treatment.
If aleniglipron succeeds, its biggest advantage may not necessarily be that it produces more weight loss than every existing treatment. Convenience and manufacturing could be just as important.
A chemically manufactured tablet could potentially be easier to distribute than complex injectable medicines. It could also give doctors another option for patients who cannot or do not want to use injections.
However, it is too early to know how aleniglipron will compare directly with established GLP-1 drugs. Different trials include different people and use different methods, so percentages from separate studies should not be treated as head-to-head comparisons.
It is also unknown how well patients will maintain their weight loss over several years. Research with existing obesity medicines has shown that weight regain can occur when treatment is stopped, suggesting that many patients may require ongoing care.
The trial has strong features, including random assignment, placebo comparison and double blinding. The sizable difference between the treatment and placebo groups provides convincing early evidence that the drug has a real effect on body weight.
Its main limitation is that phase II trials are still relatively early in drug development. The number of participants and length of follow-up are not enough to answer all questions about long-term effectiveness, rare side effects or cardiovascular outcomes.
The fact that the study was supported by Structure Therapeutics should also be transparent when interpreting the evidence. Industry funding is common in drug development, but results become more convincing when they are reproduced in larger trials and examined by regulators and independent researchers.
Overall, the Nature Medicine study shows that a non-peptide GLP-1 pill can produce clinically meaningful weight loss in adults with obesity or overweight. Aleniglipron now needs to prove in phase III trials that these encouraging results can be maintained safely on a much larger scale.
If that happens, the next generation of GLP-1 treatment may look much more like an ordinary daily medicine. For patients, that could mean another effective option without the need for regular injections.
If you care about weight, please read studies about diet that can treat fatty liver disease, obesity, and hop extract could reduce belly fat in overweight people.
For more health information, please see recent studies about how to curb your cravings for ready-to-eat foods, and results showing what you can eat to speed your metabolism up.
Source: Northwestern University.
