New data shows just how powerful the next weight-loss drugs may be

Business Standard

3 days ago

Doctors call the new weight-loss drugs revolutionary. Game-changing. Unprecedented.
Soon, they may also call them obsolete.
Drugmakers are racing to develop the next wave of obesity and diabetes medications that they hope will be even more powerful than those currently on the market.
'I think what we are going to see very quickly is that Wegovy has received a lot of the press attention, because it got there first,' said Simon Cork, a senior lecturer at Anglia Ruskin University in England who has studied obesity. 'But it will be rapidly overtaken by much more potent medications.'
On Saturday, researchers presented data at an annual meeting of the American Diabetes Association on perhaps the most anticipated of these medications: a daily pill. A late-stage study showed that the drug, called orforglipron, appeared to be about as effective as a weekly Ozempic injection at inducing weight loss and lowering blood sugar. It is just one of over a dozen experimental medications that researchers will share data about at the conference this weekend.
Some of these drugs are still in early trials, but others could hit the market as soon as next year. They include medications that may lead to more weight loss than the roughly 15 to 20 percent body weight people lose on existing drugs. They may also be easier to take than weekly injections and help people shed pounds without dropping as much muscle. More competition — and, in the case of the pill, lower manufacturing costs — might also mean that, eventually, patients pay less.
'A lot of people are like, 'Oh, we have Ozempic, everything's good now,'' said Megan Capozzi, a research assistant professor at the University of Washington Medicine who studies treatments for diabetes and obesity. 'But I think there are so many more things to improve on.'
More convenience, less muscle loss
By some estimates, one in eight adults in the United States has already taken a medication like Wegovy or Zepbound. But researchers believe far more people would use — and stick with — weight-loss drugs that did not require weekly injections.
Simply put, Dr. Capozzi said, 'people would rather takes pills than shots.'
That's why doctors and investors are so excited about orforglipron. Like Ozempic and other drugs on the market, orforglipron mimics a hormone that regulates blood sugar and curbs appetite. In the data presented at the conference, researchers who followed over 500 patients with Type 2 diabetes reported that those who took the highest dose lost an average of around 16 pounds after nine months. Around two-thirds of people who took the drug also saw their blood sugar levels fall to a target range.
If the drug is more broadly used in people with obesity and not just diabetes, those with higher body weights may see even more weight loss, since people with diabetes alone tend to lose less on these kinds of drugs, said Dr. Scott Hagan, an assistant professor of medicine at the University of Washington.
Eli Lilly, the pharmaceutical company that makes the pill, will release data from additional studies in orforglipron in people with obesity later this year. The company will seek regulatory approval for the drug first as an obesity treatment and later for Type 2 diabetes. It could be available as soon as next year.
The company has not said how much orforglipron will cost, but it's generally cheaper to mass-produce pills than shots. If it does have a significantly lower price tag than the currently available drugs, which can cost hundreds or even around a thousand dollars a month, more patients could afford the medication. More insurers might even cover it.
Over the next few days, researchers will also present data on other, earlier-stage drugs that could be more convenient than weekly shots. This includes MariTide, an injectable drug made by the biopharmaceutical company Amgen that patients could take once a month.
Some new medications in development are also trying to solve for a persistent side effect of existing drugs: Patients who lose fat also tend to lose muscle. This can be particularly dangerous for older adults because it makes them more likely to fall and can worsen osteoporosis.
One experimental drug combines the substance in Ozempic and a compound that blocks the receptors that regulate skeletal muscle and fat mass. Several others simulate the hormone amylin, which has been shown in rodent studies to preserve some lean muscle tissue, though more data is needed in humans. Some researchers remain skeptical that any drug can lead to significant weight loss without sacrificing at least some muscle.
Potential for even more weight loss
While the incoming generation of drugs might offer more convenience or help safeguard muscle, it's still unclear whether they would offer significantly greater weight loss.
Investors and doctors had high hopes for a drug called CagriSema, which is a weekly injection that combines the substance in Ozempic with a new compound. Novo Nordisk, the company that makes the drug, had set a goal of 25 percent weight loss, but the early results fell short, showing that people with obesity who took the drug lost nearly 23 percent of their body weight after over a year. That was not enough for analysts to consider the drug a clear winner over Zepbound, which is widely considered the most effective option on the market.
'The threshold for a slam dunk is now getting just higher and higher,' Dr. Hagan said.
But some drugs that are less far along in development look more promising, including retatrutide, a weekly injection that beat the Zepbound results in early trials. That medication is still long away from potential approval, however.
Even if some medications that hit the market soon deliver only equivalent weight loss, or nearly as much, their arrival could have a big impact, for a few reasons. The biggest of these is that a cheaper or more convenient medication could help more patients stay on a weight-loss drug for longer.
People are supposed to stay on weight-loss drugs for the rest of their lives — if patients stop taking a drug, they often regain weight. But by some estimates, over half of patients go off these drugs within a year, sometimes because of insurance issues, side effects or intermittent shortages of the medications. These interruptions help explain why people lose much less weight in the real world than they do in carefully controlled clinical trials.
'We're going to turn around in three to five years and find out that the vast majority of people were only on these drugs for eight or nine months, gone off these drugs and gained back the weight,' said Dr. David Kessler, a former commissioner of the Food and Drug Administration who has written a book about weight-loss drugs.
'We're going to conclude that this has been one big failure — unless we can figure out how to use these drugs in the real world,' he added.
Many of the medications in development also work slightly differently from those currently on the market. This might mean that individual people will respond better to them, Dr. Hagan said. By some estimates, around 15 percent of people do not lose substantial weight on the drugs available now.
The more options there are, the better doctors can make sure patients are getting the drug best suited for them, Dr. Hagan said.
'We're starting to shift out of the initial phase where, 'Oh, wow, we finally have some drugs that are safe and effective,'' he said. 'We have a menu of them.'