The Future of Obesity Medicine

Professor Carel le Roux made a statement in front of a group of obesity researchers in late June 2024 inside a conference center in São Paulo, Brazil, that would have seemed unreal ten years ago. He was discussing a medication known as retatrutide, which is a triple agonist that acts on three different hormonal receptors at once. He projected an average weight loss of 25% in a year.

To put things in perspective, that is the domain of bariatric surgery. The kind of result that, until recently, needed a hospital, a surgeon, and a permanently altered digestive system. The current state of obesity medicine, according to Le Roux, is “an incredibly exciting turning point.” Most likely, the scientists in that room concurred. However, there was a subtle understanding that clinical reality and excitement don’t always coincide, even among sincere believers.

It is impossible to tell the story of obesity medicine’s future without first understanding its current state. Semaglutide, marketed as Wegovy and Ozempic, results in a 15–17% average weight loss. In Phase 3 trials, tirzepatide, a dual agonist that targets both GLP-1 and GIP receptors, raises that to 22.5 percent. Millions of prescriptions for both medications have already been written in waiting rooms from Seoul to Chicago, creating shortages, online black markets, and a genuinely changed cultural dialogue about weight. These drugs are not insignificant. They are productive. How much farther this can go is the question currently being asked in labs.

The solution that has received the most attention is retatrutide. The medication seems to increase energy expenditure in ways that dual agonists fall short of by incorporating glucagon receptor activation into the current GLP-1 and GIP combination. According to preliminary data, it might result in weight loss comparable to that of bariatric surgery, but without the operating room, recovery period, or permanent anatomical alterations.

The 25% estimate is still a projection because the Phase 3 trial results are still being developed. There’s a chance that the final figures will be a little lower or that some patient subgroups react very differently than others. Researchers have previously been taken aback by obesity medication trials in both directions.

Another dual agonist that targets GLP-1 and glucagon receptors, survodutide, is also in Phase 3 and is attracting attention for reasons other than weight loss: it seems to have significant effects on reversing liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis, a dangerous liver disease that frequently coexists with severe obesity.

A single medication that simultaneously treats several overlapping conditions, such as fatty liver, high blood sugar, and elevated cardiovascular risk, is truly beneficial for patients. Phase 2 data indicates that Cagrisema, a combination of semaglutide and an amylin analogue, may be the first obesity medication to achieve comparable weight loss in patients with and without Type 2 diabetes. Given how frequently the two conditions coexist, it has always been a frustrating asymmetry that the majority of current medications work better in patients without diabetes.

Observing all of this from a distance, it seems as though the field is getting close to a sort of compression point: a number of potent medications are coming out in quick succession, each with unique profiles, and it’s still unclear how best to combine or sequence them over years of treatment. Le Roux brought up this issue head-on in São Paulo, warning that the current buzz about average weight loss rates of 25% might be detracting from more important issues regarding long-term care. It took fifty years to fully comprehend bariatric surgery.

It took time and money to learn about the complications that arose over those decades, such as nutritional deficiencies, surgical changes, and the psychological complexity of rapid body change. Since obesity medicine is developing much more quickly, it may not have as much time to learn through experience.

Beneath all of it, the access issue remains largely unresolved. Tirzepatide and semaglutide are costly. The patients most impacted by obesity-related complications—who are disproportionately found in lower-income communities—are less likely to receive these treatments because they are still not adequately covered by insurance in many countries.

That is not automatically resolved by a pipeline of even more advanced drugs. It might even make it worse. The genuine scientific success of what is being developed and the distribution system that will eventually allow it to reach patients are at odds, and this tension is still unresolved.

The development of oral GLP-1 receptor agonist formulations is showing early promise for comparable efficacy to injected versions, which is crucial for patients who find weekly injections intimidating. The adoption curve may become much steeper if pills are able to produce similar outcomes. Along with the kind of cautious scientific skepticism that usually accompanies early-phase data on anything that sounds this convenient, that possibility alone is creating genuine commercial anticipation.

The medications are improving. That much seems obvious. There is currently no clear answer to the question of what obesity medicine will do with that improvement, including who gets access, how long they stay on treatment, and what happens to the people the current options still don’t reach.