Looking Ahead at the Next Generation of Weight-Loss Medications

While current GLP-1s are already game-changers, they’re only the beginning of the weight-loss medication revolution. A handful of similar drugs are in various stages of clinical testing and they’re generating a lot of buzz.

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GLP-1 receptor agonists (GLP-1s) have revolutionized obesity treatment. Though originally developed to treat Type 2 diabetes, GLP-1s subsequently gained traction as weight-loss drugs. About 10 years ago, formulations approved specifically for weight loss began to hit the market.

Currently, three GLP-1s for weight loss are available in the US: Wegovy, which contains semaglutide, the same active ingredient in Ozempic; Saxenda, which contains liraglutide, the same active ingredient in Victoza; and Zepbound, which contains tirzepatide, the same active ingredient in Mounjaro.

While these medications are already game-changers, they’re only the beginning of the GLP-1 revolution. A handful of similar drugs are currently in various stages of clinical testing for patients who have obesity or who are overweight and also have a weight-related health condition, such as high blood pressure. And these next-generation medications are generating buzz for their potential to be even more effective than their forebears. Some might be available to patients as soon as 2025, while others might take two or three more years.

Here’s a preview of some of the new weight-loss medications everyone will be talking about in the next few years. The list includes four drugs that are coming down the pipeline plus Zepbound, which is considered to be one of the first second-generation anti-obesity medications.

Zepbound, from Eli Lilly

Active ingredient(s): Tirzepatide

Drug class: Dual GLP-1/GIP dual agonist

How it’s taken: Once weekly injection

Status: Brand new to the market, though has previously been approved to treat type 2 diabetes under the name Mounjaro 

What else to know: Zepbound was approved in November 2023 to treat chronic weight management. Doctors are starting to write prescriptions for Zepbound, but it’s not widely available yet and supply will likely remain limited for a few months (at least).

Zepbound contains tirzepatide, the same active ingredient in Mounjaro, which was approved by the FDA to treat Type 2 diabetes in 2022. Zepbound and Mounjaro are essentially the same drug; the main difference is that they’re approved to treat different conditions. Tirzepatide is typically described as a GLP-1 drug, but it’s technically a GLP-1/GIP dual agonist. While GLP-1 drugs mimic the effects of a single appetite-regulating hormone, tirzepatide mimics two hormones.

In clinical trials, participants taking the maximum recommended dose of tirzepatide lost 22.5% of their body weight in 72 weeks, on average. By comparison, the average weight loss in trials for semaglutide was 15% over two years, and 4% to 6% over 68 weeks for liraglutide.

CagriSema, from NovoNordisk

Active ingredient(s): Semaglutide and cagrilintide

Drug class: Combo GLP-1/amylin analog

How it’s taken: Once weekly injection

Status: Phase 3 clinical trials

What else to know: CagriSema is the first weight-loss medication of its kind. It combines two drugs: The GLP-1 semaglutide (the same ingredient in Wegovy and Ozempic) and cagrilintide, an amylin analog believed to potentiate the weight-loss effects of semaglutide. 

Cagrilintide is an analog of an appetite-regulating hormone called amylin, which helps to delay gastric emptying, reduce food intake and reduce the secretion of glucagon. Amylin is co-secreted with insulin, and the two hormones work together to control glucose levels after meals. The only amylin analog currently on the market, Symlin, is used to treat diabetes, not obesity, though it can lead to modest weight loss.

NovoNordisk has been testing cagrilintide as a weight-loss treatment both on its own (aka as a “monotherapy”) and as one of two drugs that make up CagriSema. Trial data suggests that cagrilintide causes some weight loss by itself, as patients taking it lost 10.8% of their body weight over 26 weeks. But it appears to be more effective when combined with semaglutide. In phase 1b trials for CagriSema, participants lost an average of 17.1% of their body weight over 32 weeks. Phase 3 trials are evaluating the medication in patients who have obesity, obesity and type 2 diabetes, and obesity and heart disease. The trial for obesity only is estimated to wrap up in 2025.

Survodutide, from Boehringer Ingelheim and Zealand Pharma

Active ingredient(s): Survodutide is the name of the active ingredient; there’s no brand name for the drug yet.

Drug class: Glucagon receptor (GCGR)/GLP-1 dual agonist

How it’s taken: Once weekly injection

Status: Enrollment for phase 3 clinical trials 

What else to know: Glucagon is another hormone produced in the body that complements the actions of GLP-1 and also enhances energy expenditure. Survodutide combines a GLP-1 agonist with a GCGR agonist.

So far, data suggests that survodutide can cause significant weight loss in people who have obesity or are overweight. In phase 2 trials, participants lost up to 18.7% of their body weight over 46 weeks. Researchers are recruiting participants for phase 3 trials, which are estimated to wrap up in 2026. In addition to obesity, survodutide is also being studied for use in people who have a type of liver disease called nonalcoholic steatohepatitis (NASH) as well as liver fibrosis.

While current GLP-1 drugs primarily suppress appetite, survodutide might have the additional effect of improving energy expenditure (the amount of energy a person burns to maintain basic physiological functions), according to the lead researcher for the phase 2 trial. One thing that researchers still hope to learn about survodutide is whether it’s effective for patients who don’t respond to the current GLP-1s. 

Retatrutide (aka “triple G”), from Eli Lilly

Active ingredient(s): Retatrutide is the name of the active ingredient; there’s no brand name yet.

Drug class: GLP-1/GCGR/glucose-dependent insulinotropic polypeptide (GIP) triple agonist 

How it’s taken: Once weekly injection

Status: Phase 3 clinical trials

What else to know: Retatrutide is similar to tirzepatide and survodutide in that tirzepatide and survodutide each mimic GLP-1 and either GIP or GCGR.  But retatrutide is the first drug to mimic three satiety hormones — GLP-1, GIP and GCGR — all of which start with the letter “G,” hence its nickname.

So far, trial results are extremely promising: On average, participants in phase 2 trials lost 24.2% of their body weight in 48 weeks. Women lost more weight than men, on average, and women under 50 with severe obesity saw especially pronounced results. Trial results also showed considerable improvements in non-alcoholic fatty liver disease (NAFLD), which is more common in people with obesity. It is also being studied for the treatment of osteoarthritis and obstructive sleep apnea. Phase 3 trials for the treatment of obesity are estimated to be completed in 2026. Phase 2 trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis are ongoing.

Orforglipron, from Eli Lilly

Active ingredient(s):  Orforglipron is the name of the active ingredient; there’s no brand name yet.

Drug class: GLP-1 receptor agonist

How it’s taken: Once daily oral pill

Status: Phase 3 clinical trials

What else to know: Orforglipron is similar to currently available GLP-1 medications, but it’s taken as a daily pill rather than an injection.

Orforglipron is currently being studied to treat chronic weight management and Type 2 diabetes. In phase 2 trials for obesity, it resulted in up to 12.6% weight loss in 26 weeks, on average, for the highest dose, and almost 15% weight loss in 36 weeks for the same dose. Researchers are currently recruiting participants for phase 3 trials, which are estimated to wrap up in 2025.

Right now, Rybelsus (oral semaglutide, the active ingredient in both Wegovy and Ozempic) is the only oral GLP-1 on the market, and it’s approved for Type 2 diabetes, not weight loss, although Rybelsus is undergoing phase 3 trials at higher doses for the treatment of obesity. All other drugs in the GLP-1 family are taken via weekly or daily injections. If approved, Orforglipron could be an attractive option for patients who prefer to take pills than give themselves shots.

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