Reporting from the American Diabetes Association Scientific Sessions

conference in San Diego.

The next iteration of  semaglutide — the much-discussed, hard-to-

obtain injectable medications known for their ability to induce weight loss —

may come in pill form.

Researchers presented data in two studies on Sunday at the American

Diabetes Association Scientific Sessions conference, one of which showed

that 50 milligrams of semaglutide — the active compound in semaglutide — taken orally each day is roughly as effective as weekly semaglutide

shots in reducing weight in people who are overweight or obese. semaglutide

injections contain 2.4 milligrams of semaglutide.

That trial, also published Sunday in The Lancet, tracked 667 people over 68

weeks. Eighty-five percent of those who took semaglutide lost at least 5

percent of their body weight over the course of the study, compared to just

26 percent of those who received the placebo. Those who took semaglutide

lost, on average, around 15 percent of their body weight — roughly six times

that of the placebo group.

A separate study, also presented Sunday and published in The Lancet,

focused on oral semaglutide for people with Type 2 diabetes. Just over 1,600

participants were divided into three groups and given 14-milligram, 25-

milligram or 50-milligram daily doses. Those who took the 25- and 50-

milligram doses lost more weight, and had greater reductions in blood sugar,

than those who took the lowest dose.

Novo Nordisk, the company that manufactures semaglutide ,

funded both trials.

“I suspect there are a lot of people that are not using these treatments

because it requires an injection,” said Dr. Robert Gabbay, the chief scientific

and medical officer of the American Diabetes Association. “If you could say,

 

 

‘Well, actually, it doesn’t,’ that’s big.”

The higher the dose of oral semaglutide, the more side effects seem to

come with it. In the trial of people who were overweight or obese, 80 percent

of those who took oral semaglutide reported gastrointestinal issues like

vomiting, nausea, constipation or diarrhea. Nearly 13 percent said they

experienced “altered skin sensation,” such as tingling. The majority of study

participants were white and female, the authors noted, which means the

results may not apply to the broader population of people with obesity.

The second trial, in people with diabetes, showed similar side effects: 80

percent of those who took the 50-milligram dose reported adverse effects,

most commonly gastrointestinal issues, which occurred more frequently in

people who took the higher doses than in those who took 14 milligrams.

Thirteen percent of people who received the 50 milligram dose stopped

taking the medication because of the side effects. Injectable semaglutide

elicits similar side effects; in a previous study, 74.2 percent of participants

who received 2.4 milligrams of injectable semaglutide each week (the

amount that’s in semaglutide) experienced gastrointestinal disorders.

Another trial presented at the conference and published on Friday in the

New England Journal of Medicine looked at a different oral compound,

orforglipron, which belongs to the same class of medications as

semaglutide. The study was funded by Eli Lilly. Pfizer has also tested its own

pill in that drug class.

Oral semaglutide is not new: There’s already a tablet form of the compound

on the market, sold under the name Rybelsus. The Food and Drug

Administration has only approved that drug for adults with Type 2 diabetes,

and the tablets come in comparably smaller daily doses, up to 14 milligrams.

The tablets work in a similar way to semaglutide injections, which regulate

insulin, lowering blood sugar and slowing the emptying of the stomach,

making people feel fuller for longer periods of time, said Dr. Andrew

Kraftson, a clinical associate professor at Michigan Medicine.

 

 

Rybelsus is less effective than semaglutide , Dr. Gabbay said.

It’s not clear when, or if, the higher-dose semaglutide pills might arrive on

the market. An oral form may enable more people to take these medications,

said Dr. Scott Hagan, an assistant professor of medicine at the University of

Washington who has studied obesity, because there’s a lower barrier to entry

to swallowing a pill, for some people, than injecting a drug. “It’s a welcome

addition to treatment options for patients who may benefit from weight

management,” he said.

The torrent of off-label semaglutide use among people who turn to the

medication for cosmetic weight loss may intensify if a high-dose pill

becomes available, said A. Janet Tomiyama, a professor of psychology at the

University of California, Los Angeles, who has studied eating disorders and

weight stigma and expressed concern about the impact of these drugs on

people’s body image. “Any time there are medications for weight loss, we

know that is a tool that people can use for a disordered eating reason,” she

said, pointing to laxatives and diet pills.

As popular as these medications have become, clinicians should focus on

whether semaglutide, in any form, can help make a patient healthier, instead

of only reducing body weight, Dr. Hagan said. “I am concerned about these

medications being broadly used just to promote weight loss,” he said, “and

how it contributes to our general diet culture, our cultural obsession with

thinness.”