Can New Weight-Loss Drugs Surpass The Current Ones?

Are the weight loss medications currently on the market possibly being overused or not used as intended? Yes and yes. The article published in Axios, “Wegovy and Ozempic stars dim amid overuse concerns,” quotes a few specialists voicing their concern. One of them is Peter Antall, chief medical officer of digital chronic health company Lark. He says,

There is almost like a backlash kind of a sentiment going on… I don’t believe that we’re having second thoughts about the power of the medication. But I think the shine is coming off how they’re being used in real practice… That’s where many of us are concerned.

Another expert is obesity specialist and gastroenterologist Dr. Christopher McGowan, who penned his opinion in MedPage Today. He explained why his “perspective has shifted based on real-world experience.” Dr. McGowan is “deeply concerned about how GLP-1 medications are being used.” He writes:

The benefits of these drugs cannot be denied when they are taken as intended — meaning indefinitely. But what happens to the body and mind when these medications are discontinued? This is where the problem lies…

Noting that “from an efficacy standpoint, these drugs ‘work’,” but only for those who can “afford, tolerate, and sustain GLP-1.” They lose weight and enjoy other benefits such as improvements in various conditions, including kidney disease, sleep apnea, osteoarthritis — the list goes on. However, Dr. McGowan’s parting words send a chill:

 I fear we will look back on this era — after patients have spent tens of thousands of dollars, endured uncomfortable and sometimes serious side effects and experienced recurring weight gain and resurgent food noise — and ask: Even if these drugs ‘work,’ did they really work? Or did they ultimately harm our patients, our society, and our economy? It’s a sobering thought, but one I fear is all too real.

New kids on the block

Pharmaceutical companies are fully aware of current concerns and are actively testing a new wave of weight-loss medications, or planning more trials for the current ones, with a goal of enhancing their effectiveness and offering additional health benefits beyond shedding pounds.

Current treatments like Ozempic and Wegovy, which contain semaglutide — a GLP-1 receptor agonist that helps regulate blood sugar and appetite, are expensive, require weekly injections, and must be taken long-term to prevent weight regain. Drug makers hope that new alternatives will overcome these challenges. Plus, the global market keeps expanding and the demand is surging, so we are sure Big Pharma sees the dollar signs as well.

Let’s take a quick look at what medications we should expect to improve, and what the manufacturers and the researchers plan for them in 2025, as outlined in a recent article published in Nature.

Tirzepatide

Tirzepatide, marketed as Mounjaro and Zepbound, activates both GLP-1 and another hormone, GIP, which plays a role in fat metabolism. In clinical trials, it helped participants lose up to 20% of their body weight over 72 weeks, outperforming semaglutide, which leads to about 15% weight loss in a similar timeframe. Additionally, tirzepatide reduced heart weight, lowered fat around the heart, improved mobility, and decreased blood pressure and inflammation.

A major trial set to conclude in 2025 will explore its impact on heart disease in people with obesity and diabetes.

Retatrutide

Developed by Eli Lilly, retatrutide stimulates GLP-1, GIP, and glucagon receptors, showing even greater potential than existing drugs. In trials, participants lost an average of 24% of their body weight over 11 months. This medication also helped regulate blood sugar in diabetics and is now in phase III trials, expected to conclude by 2026.

Experts believe that combination therapies like retatrutide could be particularly effective, as obesity is a complex condition that benefits from targeting multiple biological pathways.

Orforglipron

Unlike Ozempic, which requires injection, orforglipron is a daily pill that mimics GLP-1’s effects. In early trials, it led to a 10% weight loss over 26 weeks while improving blood pressure and reducing circulating fat molecules.

Eli Lilly anticipates completing phase III trials in 2025, with potential U.S. regulatory approval in 2026. Experts suggest that if oral drugs like orforglipron prove effective, they could disrupt the market by offering a more convenient and cost-effective option.

MariTide

Amgen’s experimental drug MariTide, which stimulates GLP-1 while inhibiting GIP activity, is designed to be taken via monthly injections. In a 52-week study, it resulted in up to 20% weight loss. Unlike other treatments, MariTide appears to help maintain weight loss for months after stopping the medication, an issue seen with semaglutide and tirzepatide.

This potential for sustained results could make it a more attractive option for patients reluctant to commit to lifelong treatment.

CagriSema

Novo Nordisk’s CagriSema, a blend of semaglutide and cagrilintide, has shown superior weight-loss outcomes compared to its individual components. A 68-week study saw participants lose approximately 23% of their body weight.

Muscle preservation and metabolic treatments

Several companies are exploring synthetic amylin-based therapies, which help regulate appetite and blood sugar while preserving muscle mass — an advantage over GLP-1 drugs, which can lead to muscle loss. Novo Nordisk’s amycretin, a combination of GLP-1 and amylin, led to a 22% weight reduction in just 36 weeks.

Another experimental drug, enobosarm, developed by Veru, was found to preserve muscle in older adults with obesity when combined with Wegovy. Future studies may investigate how to help older or frail individuals lose weight while maintaining muscle strength and preventing osteoporosis.

Emerging therapies targeting cannabinoid receptors, which influence hunger, have shown early promise, with more research expected in 2025.

The bottom line

Looking ahead, researchers hope to shift the focus from simple weight loss to a broader understanding of obesity as a metabolic disease. Some believe that the next major breakthrough could come from a treatment that addresses inflammation, a key factor in obesity — though results from human trials are still a long way off.

Even if these new treatments aren’t widely available in 2025, researchers believe that the coming year will provide key insights into which therapies will be most effective and accessible in the near future.

Your responses and feedback are welcome!

Source: “The weight-loss drugs being tested in 2025: will they beat Ozempic?,” Nature, 2/6/25
Source: “Wegovy and Ozempic stars dim amid overuse concerns,” Axios, 2/11/25
Source: “I No Longer Think GLP-1s Are the Answer,” MedPage Today, 1/30/25
Image by Chokniti Khongchum/Pexels

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OVERWEIGHT: What Kids Say explores the obesity problem from the often-overlooked perspective of children struggling with being overweight.

About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
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Presentations

Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

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