Blockbuster weight-loss shots are undergoing a major makeover.
Drugs like Zepbound and Wegovy have already taken the US by storm — with the number of Americans using them to slim down more than doubling over the past 18 months.
And Big Pharma’s not done cashing in on the weight-loss boom. Drugmakers are readying a new wave of next-level GLP-1 treatments, with several promising candidates in the pipeline.
These experimental treatments — which have yet to be approved by the US Food and Drug Administration — aim to address some of the biggest gripes about today’s injections.
And with more options hitting the market, experts say those sky-high price tags that have kept many Americans from accessing them might finally start to drop.
“With this newer generation of medications, we’re not just focusing on weight loss,” David Lau, an endocrinologist and professor emeritus at the University of Calgary Cumming School of Medicine, told The Washington Post this week. “We’re talking about changes beyond what you see on the scale.”
But make no mistake — drugmakers are aiming to help people shed even more pounds with these new iterations.
Current GLP-1s mimic one or two hormones naturally produced by the body that curb appetite, slow digestion and lower blood sugar, helping people stay fuller for longer.
Eli Lilly wants to take that even further with a new medication that targets three hormones — earning it the nickname “triple G.”
In a mid-stage clinical trial, obese adults receiving the weekly injection, called retatrutide, lost up to 22% of their body weight in 11 months — compared to 14% over 15 months for semaglutide, the active ingredient in Ozempic and Wegovy.
Phase 3 trials are set to run until January 2026, meaning FDA approval is still a ways off.
In the meantime, Lilly is readying other contenders, including eloralintide, a once-weekly injection that targets amylin, a hormone released by the pancreas during meals.
“We’ve been studying amylin for weight loss for over 20 years,” Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine, told the Washington Post.
“In certain ways, it may be a better compound,” he said, adding that it appears to cause less lean muscle loss and fewer stomach-related side effects.
In a phase 2 clinical trial, eloralintide patients lost an average of 9% to 20% of their body weight — and didn’t hit a plateau, suggesting they might’ve kept dropping pounds if the study ran longer.
“The weight loss we saw in the study is clinically impactful,” Liana K. Billings, the lead author of the trial, told Medical News Today.
“With this degree of weight loss in only 48 weeks, we see people having improvement or resolution in other conditions like hypertension, hyperlipidemia, osteoarthritis, sleep apnea and more weight-related conditions.”
Novo Nordisk is developing its own amylin-targeting drug that also includes semaglutide, giving it an added punch.
A clinical trial found the combo delivered around 20% weight loss, roughly 5% more than semaglutide alone.
The drug, called CagriSema, was generally safe, with nausea, vomiting, diarrhea and constipation among the most common side effects — similar to those seen with other GLP-1 treatments already on the market.
A post hoc analysis of the trial also found that CagriSema significantly lowered blood pressure and inflammation — two major drivers of heart disease.
“If we can lower inflammation, bring blood pressure to more normal levels, and help people lose weight at the same time, there’s potential for holistic improvement in overall health,” Professor Subodh Verma, a cardiac surgeon and lead author of the analysis, said in a statement.
Nordisk expects to seek FDA approval for CagriSema next year.
Drugmakers aren’t just focusing on injectables.
Lilly and Nordisk are racing to release oral medications that could give patients who are squeamish around needles an alternative to the dreaded jab.
A daily pill from Lilly, known as orforglipron, helped patients lose an average of 10.5% of their body weight — nearly 23 pounds — over 16 months in a late-stage trial. Patients also saw improvements in their cholesterol, blood sugar, blood pressure and triglyceride levels.
Nordisk’s daily pill containing semaglutide, meanwhile, helped people shed 13.6% of their body weight over 64 weeks in a phase 3 study.
Both pills came with some gastrointestinal side effects — and they didn’t deliver the same dramatic results as the injectables — but drugmakers say the potential is still huge.
On top of ditching the needles, the pills don’t need to be refrigerated like other GLP-1s, making them far easier to store and ship.
Nordisk expects to launch its pill in early 2026, with an FDA decision likely by year’s end.
Lilly expects approval for its oral obesity drug by March 2026.
“If approved, we are ready to offer a convenient, once-daily pill that can be scaled globally — removing barriers and redefining how obesity is treated around the world,” Kenneth Custer, Lilly executive vice president and president of Lilly Cardiometabolic Health, said in August.