Julie Peck
October 22, 2025
With the supply of GLP-1 medications finally stabilizing as their use skyrocketed 600% among Americans from 2018 to 2024, the pharmaceutical landscape for anti-obesity medications is now poised to undergo another monumental shift.
A rapid proliferation of drugs that show an unprecedented efficacy for treating this disease is expected over the next year. This expansion in available treatments will be made up of a new generation of drugs that build on the success of existing, transformational medications such as semaglutide (Novo Nordisk’s Wegovy) and tirzepatide (Zepbound from Eli Lilly), as well as some that push weight loss further through novel combinations and formulations. Many of these drugs are in late-stage clinical trials, meaning that 2026 should be a busy year for new weight-loss medications.
Nicholas Jones, MD
Dual and triple agonists are also on the rise. Glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonists such as tirzepatide continue to show superior weight-loss outcomes with fewer side effects, while emerging triple agonists aim to address both appetite and metabolic regulation, Nicholas Jones, MD, founder and medical director of Nip & Tuck Plastic Surgery in Atlanta, said, giving an overview of the landscape to come for anti-obesity medication. In addition to GLP-1 pathways, non-GLP mechanisms such as melanocortin-4 receptor agonists, amylin analogs, and mitochondrial uncouplers are gaining traction, he said.
“These medications can be an appealing option for patients that do not respond to GLP-1s or have specific metabolic needs. Oral alternatives targeting similar pathways without requiring injections could further transform accessibility and patient adherence,” Jones said.
Hayley Miller, MD
The early results of some of the forthcoming medications rival, and in some cases, exceed bariatric surgery. While the race to develop the next blockbuster weight-loss drug is likely to augur commercial success, it also represents a significant effort to address the global obesity epidemic and its associated comorbidities. Hayley Miller, MD, medical director for metabolic health at Nurx, said that while GLP-1s marked a turning point in obesity care, the momentum in obesity treatment is just getting started.
“It’s particularly exciting to see the profound, life-changing impact these medications have on patients. What once felt like a breakthrough is now the standard of care,” she said. “We are entering a new phase — one that is progressing more rapidly, becoming more intelligent, and providing care that aligns better with patients’ actual needs.”
Unless otherwise noted, manufacturers expect to apply for regulatory authorization for all medications mentioned in 2026 as of this writing.
Picking Up Where GLP-1s Left Off: The Rise of Multi-Agonists
The first wave of highly effective anti-obesity drugs, such as semaglutide, primarily acted as GLP-1 receptor agonists. GLP-1 is a naturally occurring hormone that helps regulate appetite and blood sugar.The next evolution, tirzepatide, introduced a dual-agonist approach, targeting both the GLP-1 and GIP receptors. This combination proved to be more powerful, leading to even greater weight loss. The current frontier in clinical trials is exploring the potential of triple agonists and other multi-targeted therapies.
The immediate next generation of medications builds on GLP-1s in some new and interesting ways. First and foremost, oral formulations of these medications are completing trials, an exciting prospect to doctors and to patients who have shied away from the injectable version.
Zaid Jabbar, MD
“Oral semaglutide is already approved for use in diabetes and is advancing in higher-dose obesity trials,” said Zaid Jabbar, MD, chair of obesity medicine at Duly Health and Care in Oak Brook. “Recent data is showing weight loss of up to 15.1% at a daily dose of 50 mg. While it requires administration on an empty stomach with a water-only window, it remains a meaningful oral option for patients who prefer non-injectable therapies.”
Many of the current trials are pushing beyond the known mechanisms of GLP-1s, combining them with other medications as tirzepatide did and innovating in other ways to broaden the landscape of anti-obesity medications. Miller took note of the oral, small-molecule, nonpeptide GLP-1 receptor agonist orforglipron, in late-stage trials at Eli Lilly, which she mentioned has already shown clinically meaningful weight loss in early trials, as well as a few other mechanisms that target multiple receptors.
“For example, CagriSema, a combination of semaglutide and amylin agonist cagrilintide, has shown 15%-17% mean weight loss in just 20-32 weeks. Survodutide, which activates both GLP-1 and glucagon receptors, delivered at 14.9% mean weight loss over 49 weeks,” she said.
CagriSema — developed by Novo Nordisk — and survodutide — developed through a collaboration between Boehringer Ingelheim and Zealand Pharma — each have benefits that extend beyond weight loss. CagriSema helps preserve bone mass and lean body mass during weight loss and has demonstrated improvements in several cardiovascular risk factors.
Survodutide’s GLP-1 action curbs appetite and improves glycemic control, whereas its glucagon agonism promotes fat burning and energy expenditure, and it has also demonstrated promise in the treatment of metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease. Clinical data have indicated that a large percentage of patients treated with survodutide showed an improvement in MASH with no worsening of liver fibrosis. Dual benefits could make these medications attractive to a wide range of patients.
Retatrutide: The Triple-Threat Agonist
One of the medications that doctors cited as most promising is retatrutide, developed by Eli Lilly. Now in late-stage clinical trials, this drug activates three different receptors: GLP-1, GIP, and glucagon. By engaging these three key metabolic pathways, retatrutide is designed to provide a more comprehensive approach to weight management.
The mechanism of action for retatrutide is multifaceted. Like other incretin-based therapies, its GLP-1 and GIP agonism helps suppress appetite, enhance insulin sensitivity, and slow gastric emptying, contributing to a feeling of fullness. The addition of glucagon receptor agonism introduces another layer to its effects: Glucagon plays a role in energy expenditure and fat metabolism. By activating this receptor, retatrutide is believed to not only reduce caloric intake but also increase the body’s ability to burn fat, leading to a synergistic effect on weight loss.
In a phase 2 trial, participants with obesity who were treated with the highest dose of the drug experienced an average body weight reduction of up to 24.2% over a 48-week period. These weight-loss results are comparable to those achieved through bariatric surgery and are a significant development in nonsurgical obesity treatment. The drug is now progressing through phase 3 trials, with studies investigating its efficacy and safety in diverse patient populations, including those with conditions such as type 2 diabetes, cardiovascular disease, and obstructive sleep apnea.
“Beyond weight loss, it’s also showing significant metabolic improvements, making it a promising option for patients with more complex needs,” Miller said. “These are unbelievable results that have the chance to dramatically change lives at scale.”
Fernando Ovalle, Jr, MD, an obesity medicine expert with Drugwatch in Orlando, Florida, said retatrutide could prove to be an “even more significant breakthrough” than the treatment of obesity with GLP-1 agonists.
“While GLP-1s were transformative, retatrutide helped patients lose 58 pounds on average (in) less time than semaglutide or tirzepatide,” he said. “This represents an important leap forward that could fundamentally change how we approach severe obesity.”
Novel Mechanisms and Delivery Methods
The new generation of anti-obesity medications is not limited to multi-agonists. Researchers are also exploring entirely new classes of drugs and novel delivery methods to improve patient outcomes and adherence to treatment.
For example, Amgen’s maridebart cafraglutide (MariTide) represents a departure from the traditional incretin-mimetic approach. While it also targets GLP-1 and GIP, its mechanism is unique: It acts as a GLP-1 receptor agonist but also as a GIP receptor antagonist, meaning it blocks the GIP receptor instead of activating it. The rationale behind this dual action is still being studied, but early results suggest it is highly effective.
The most compelling feature of MariTide may be its dosing schedule. In a phase 2 trial, participants with obesity lost up to an average of 20% of their body weight with a once-monthly or even once-every-other-month injection. This less-frequent dosing could increase patient adherence and thus make it easier for individuals to stick with their treatment plan over the long term, complementing the results that rival those of the current market leaders even with more widely spaced dosing.
MariTide is now progressing into phase 3 trials, with a focus on its long-term safety and efficacy. Amgen expects to apply for regulatory approval for this medication in late 2026 to early 2027.
The Future of Obesity Treatment
These advancements in anti-obesity medications are ushering in a new era in the fight against a disease that has long been stigmatized and undertreated. The new classes of drugs in development will make it easier for doctors to help more patients, Ovalle said.
“The diversification of mechanisms is crucial for clinical practice. Not every patient responds optimally to GLP-1 agonism alone, and having multiple pathways — amylin, GIP, glucagon — gives us more tools to personalize treatment,” he noted.
Miller concurred with Ovalle, looking forward to a more personalized approach to offer her patients.
“Obesity isn’t one-size-fits-all, and treatment can’t be either. With a broader range of options, like different mechanisms, side effect profiles, and dosing, we’ll be able to better match the right treatment to the right person,” she said. “GLP-1s quickly demonstrated that safe and sustained weight loss through medication is achievable. The next wave of treatments will just expand on that promise — helping more people access care that works for them.”
