6 New Weight Loss Drugs That Could Dethrone Ozempic

A new wave of treatments for obesity is emerging, building on the recent arrival of medications like semaglutide. These drugs, which work by mimicking the GLP-1 hormone, are demonstrating significantly greater weight loss results compared to traditional diet and exercise alone.

The Changing Landscape of Obesity Treatment

Semaglutide, originally developed by Novo Nordisk, is currently available as a weekly injection under the names Ozempic – a type 2 diabetes medication – and Wegovy, specifically approved for obesity. While Wegovy holds the official approval for weight management, Ozempic has become widely recognized as the standard for GLP-1 therapies, and is often prescribed off-label for weight loss. However, competition is increasing, and Ozempic’s dominance may be waning.

Did You Know? Eli Lilly submitted orforglipron to the FDA for approval as an obesity treatment, with a decision anticipated this spring.

Eli Lilly’s tirzepatide (Zepbound and Mounjaro) represents a step forward, combining GLP-1 with another hunger-regulating hormone, GIP, and achieving greater average weight loss than semaglutide. Furthermore, numerous other GLP-1-based drugs are in development, with potential approvals expected this year. Novo Nordisk is also innovating, having received FDA approval last December for a once-daily pill version of Wegovy.

Emerging Contenders

1. Orforglipron

Developed by Eli Lilly, orforglipron is a once-daily pill that mimics the GLP-1 hormone. In Phase III clinical trials, participants taking the highest dose of orforglipron lost an average of 10% of their initial body weight, compared to 2.5% for those taking a placebo. Further studies suggest it may help maintain weight loss achieved with other GLP-1 drugs like semaglutide or tirzepatide.

Despite potential advantages like the convenience of a daily pill and the flexibility of not requiring food restrictions, orforglipron may face challenges. Its effectiveness could be lower than other options, including Novo Nordisk’s oral Wegovy.

2. CagriSema

Novo Nordisk is also developing CagriSema, a weekly injectable that combines semaglutide with cagrilintide, mimicking the amylin hormone. Clinical trials have shown weight loss of up to 22.7% of baseline weight over a year. The drug was submitted to the FDA for approval in late December, with a decision expected this year.

If approved, CagriSema could become the most effective GLP-1 drug available, and highlight the potential of amylin-based treatments. However, trial results didn’t quite reach Novo Nordisk’s initial expectations of 25% or greater weight loss, and it will compete with Eli Lilly’s tirzepatide.

3. VK2735

Viking Therapeutics is challenging the dominance of Eli Lilly and Novo Nordisk with VK2735, which combines GLP-1 and GIP, available in both injectable and oral forms. Phase II data indicates that individuals taking oral VK2735 lost up to 12% of their body weight over 13 weeks. While peak effectiveness typically takes six to twelve months, the drug had a relatively high dropout rate of 28% due to gastrointestinal issues.

4. MariTide

Amgen’s MariTide offers a different approach, designed as a monthly injection. It mimics GLP-1 activity while blocking the GIP hormone. Phase II trials showed weight loss of up to 20% over a year, and up to 17% in individuals with type 2 diabetes – a population that typically experiences less weight loss with GLP-1 therapy. Phase III trials are currently underway.

Expert Insight: The development of multiple GLP-1 based therapies, each with slightly different mechanisms and delivery methods, suggests a growing understanding of the complex hormonal regulation of appetite and metabolism. This diversification could lead to more personalized treatment approaches for obesity.

5. Retatrutide

Retatrutide, developed by Eli Lilly, is generating significant excitement. Clinical trial data shows individuals with obesity and knee osteoarthritis lost up to 71 pounds, or nearly 30% of their baseline weight, over 68 weeks. This level of weight loss is comparable to that achieved with bariatric surgery, and users also reported reduced knee pain. Retatrutide works by mimicking three hormones: GLP-1, GIP, and glucagon.

While highly effective, retatrutide may not be suitable for everyone, and early evidence suggests potential side effects. Phase III trial results are expected in 2026, with FDA approval potentially following soon after.

6. Rejuva

Fractyl Health’s Rejuva represents a more futuristic approach. This injectable gene therapy aims to permanently boost the body’s own GLP-1 production. Early studies in mice suggest it could match the benefits of existing GLP-1 drugs, with potentially improved tolerability. The company is developing Rejuva for both type 2 diabetes and obesity, and plans to begin its first human trial for diabetes this year.

Frequently Asked Questions

What is GLP-1?

GLP-1 is a hormone that mimics the natural processes in the body that regulate hunger and metabolism, helping people lose weight.

Are these drugs only for people with diabetes?

While some, like Ozempic, were initially developed for type 2 diabetes, others, like Wegovy, are specifically approved for obesity. Ozempic is also frequently prescribed off-label for weight loss.

What are the potential side effects of these drugs?

Gastrointestinal events like vomiting are a common side effect of GLP-1 therapy. VK2735 had a relatively high dropout rate of 28% related to these events.

As research continues and more options become available, how do you envision the future of obesity treatment evolving to meet individual needs?