Researchers believe they’ve created a new weight loss medication that may be over twice as effective as Ozempic while presenting fewer adverse effects.
GLP-1 injectable drugs, including Ozempic, Wegovy, and Mounjaro, work by imitating a natural hormone called glucagon-like peptide-1 (GLP-1), which helps control appetite and metabolism.
Depending on the specific medication, these drugs can target one, two, or even three hormones.
They promote insulin production, delay gastric emptying for prolonged fullness, and influence the brain’s satiety centers to lower hunger and cravings.
As a result, they can reduce food intake, aiding in blood sugar management and weight control.
However, these medications can come with serious side effects, some of which can be severe, leading to issues like tooth decay, vision loss, or hearing problems.
A team at Tufts University in Massachusetts has discovered a fourth hormone to target, which they believe could enhance appetite-suppressing effects without the adverse consequences.
They propose that their ‘four-in-one’ hormone treatment is designed for lasting weight loss results similar to bariatric surgery, often seen as the pinnacle of weight loss solutions.
This medication targets multiple biological pathways governing appetite, metabolism, and energy usage, making it purportedly more effective and better tolerated than existing options.
Bariatric surgery is typically regarded as the most successful long-term weight loss option, with data indicating patients shed significantly more weight post-surgery compared to those on weight loss drugs.
For instance, expected weight loss averages around 10-15% for Wegovy and Ozempic, and up to 21% for Zepbound and Mounjaro. In contrast, bariatric surgery may lead to a 25-35% weight loss. Surgery—often costing over $10,000—carries risks such as leaks, bleeding, and severe infections, and can result in long-term complications like nutritional deficiencies and gallstones.
However, the Tufts team is optimistic that their novel drug could replicate surgical weight loss effects.
Distinct from other GLP-1 medications, their new treatment aims to target four ‘dimmer switches’ in the body, impacting appetite, satiety, blood sugar, and energy expenditure.
The four hormones involved include GLP-1, GIP, glucagon, and Peptide YY (PYY).
Lead researcher Tristan Dinsmore, PhD, explained that they have engineered a single experimental peptide that acts like four hormones at once, allowing for a balanced approach rather than pushing one mechanism too hard.
Dinsmore also mentioned they are looking to include PYY, which is released by the gut post-meal and serves to reduce appetite and slow gastric emptying through different mechanisms compared to GLP-1 and GIP.
However, combining these distinct hormones was a complex challenge.
The drug, unfortunately, is still in development and hasn’t yet entered human trials.
Currently, over 15 million adults in the U.S.—about 4.5% of the population—are using weight loss medications like Ozempic and Wegovy.
While these drugs are effective, they have downsides. Discontinuing use can often lead to weight regain, and there are concerns about side effects like osteoporosis and muscle loss. Nausea is also a common challenge, making long-term adherence tough.
Particularly with GLP-1 receptor agonists, there have been reports of severe side effects, including suicidal thoughts and gastrointestinal disorders like gastroparesis. However, evidence is mixed, and agencies such as the FDA haven’t confirmed direct cause-and-effect relationships.
Once patients stop using weight loss drugs, they generally regain about two-thirds of lost weight within a year as hormone levels return to baseline.
Krishna Kumar, a professor of chemistry at Tufts, highlighted the significant issues with GLP-1 drugs, namely the necessity for weekly injections and the intense nausea experienced by some. Up to 40% of users quit after just the first month.
In contrast, Mounjaro and Zepbound exhibit less nausea and operate on both GLP-1 and GIP pathways, making them ‘dual-acting’ medications.
Another drug named retatrutide is currently in trials, targeting three hormone pathways, but the Tufts team believes their ‘four-in-one’ solution could transform weight loss treatment.
Martin Beinborn, a visiting scholar, concluded that by engaging with four hormone receptors simultaneously, they hope to enhance overall treatment efficacy.
The findings from Tufts were published in the Journal of the American Chemical Society.
