The success of GLP-1 receptor agonists like Ozempic and Wegovy has dominated the weight loss landscape, but the future of obesity treatment is evolving fast. With over 100 anti-obesity drugs in development according to an article published in Nature, pharmaceutical companies are exploring new and improved GLP-1s as well as novel biological pathways to enhance efficacy, minimize side effects, and preserve muscle mass - a key challenge with current weight loss medications.

Big Pharma players such as Amgen, AstraZeneca and Roche are investing heavily into these new programs, but some emerging companies are also breaking ground. Just this week Roche entered into the largest obesity deal to date with a collaboration and licensing agreement with Denmark's Zealand Pharma to develop and commercialize petrelintide, in a deal valued at up to $5.3 billion, includes an upfront payment of $1.65 billion to Zealand. Now along with Roche's own CT-388 & CT-996, the company is in a strong position to compete in the burgeoning obesity treatment market, currently dominated by Novo Nordisk and Eli Lilly.

Bloom Science’s microbiome-based BL-001 is also attracting attention after the company released compelling Ph-1 data this March. They are challenging the long-held dominance of GLP-1 injectable therapies by harnessing the gut microbiome to replicate the ketogenic diet and leverage its well-documented metabolic health benefits and weight loss effects - all in a simple oral capsule. But they aren’t alone - companies like Maryland-based Altimmune, Kallyope, Viking Therapeutics, Elevai and others are racing to bring novel solutions to market.

Let’s dive deeper into eight next generation weight-loss drug candidates that could redefine obesity treatment in the coming years.

1. Bloom Science’s BL-001: The Ketogenic Diet in a Pill for Long-Term Weight Loss

Why It’s Exciting: Bloom Science is taking a gut-first approach to weight loss with BL-001, a microbiome-based live biotherapeutic product (LBP) that uses a well-documented clinical intervention.  Bloom targets the root cause of metabolic dysfunction—reprogramming the microbiome to mimic the ketogenic state naturally, n approach that cannot be easily replicated with traditional drug modalities.

How It Works: Unlike GLP-1 drugs, which manipulate hormonal pathways, BL-001 influences the gut microbiome to induce weight loss by mimicking the ketogenic diet. In early clinical data, BL-001 led to a 2.3% reduction in body weight, which was maintained for weeks post-treatment without showing muscle loss.

Why It Matters: This microbiome-based approach offers a hormone-free option in a convenient, easy-to-administer capsule for a sustainable weight loss solution that doesn’t rely on injections - a potential game-changer in obesity medicine and patient experience. While obesity and metabolic health represent vast markets, Bloom’s platform is also well-suited for addressing rare neurological disorders. The ketogenic diet has been widely recognized as an effective treatment for epilepsy, especially in cases resistant to medication.  

 What’s Next? Bloom Science is advancing BL-001 through clinical trials, and if results continue to show sustained weight loss without injections or hormonal side effects,  the validation of this mechanism also enables the company to continue to pursue its epilepsy research and explore broader metabolic applications, including obesity, type 2 diabetes, and metabolic syndrome.  This approach—targeting both high-value rare disease applications and the broader metabolic health sector—establishes multiple pathways for value creation for the company and its investors.

Read more about Bloom Science’s latest data

2. Kallyope’s K-757 & K-833: Nutrient-Based Weight Loss in a Pill

What It Is: Kallyope is developing oral obesity treatments, K-757 and K-833, designed to activate nutrient receptors in the gut to stimulate natural appetite-suppressing hormone release. This mechanism represents an alternative to hormonal therapies like GLP-1 receptor agonists, aiming to achieve weight loss through metabolic signaling.

Latest Clinical Data: Recent mid-stage trial results for K-757 and K-833 showed modest weight-loss benefits, which fell short of expectations. While the approach remains promising, these findings indicate challenges in achieving clinically significant weight reduction through this method alone.

The Shifting Competitive Landscape: Previously, Kallyope’s candidates were the only known oral nutrient receptor agonists for obesity treatment. However, with Bloom Science’s BL-001 demonstrating a microbiome-based alternative that also leverages the gut’s natural processes, Kallyope is now part of an evolving field of non-GLP-1 approaches to obesity treatment.

What’s Next? Kallyope continues to refine its strategy and evaluate how its nutrient receptor activation model can be optimized for better efficacy. Its recent results underscore the complexities of developing oral alternatives to GLP-1 drugs, a challenge that other emerging players in the space are also working to address.

More on Kallyope’s latest trial results

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3. Altimmune’s Pemvidutide: The Next Big Injectable 

What It Is: Pemvidutide is a GLP-1/glucagon receptor dual agonist, currently in Phase 3 trials. Unlike standard GLP-1 drugs, Pemvidutide activates both GLP-1 and glucagon receptors, aiming to enhance weight loss while maintaining metabolic balance.

How It Works: While GLP-1 receptor agonists like semaglutide primarily work by reducing appetite and slowing digestion, Pemvidutide adds a glucagon-activating component, which stimulates fat burning and energy expenditure. This dual mechanism has the potential to accelerate fat loss while preserving muscle mass, a key concern in obesity treatments.

Early Results: In previous clinical trials, Pemvidutide demonstrated significant weight loss effects, with the potential for greater fat reduction compared to traditional GLP-1 drugs. It is also being studied for non-alcoholic fatty liver disease (NAFLD), making it a versatile metabolic therapy.

What’s Next? As Pemvidutide advances through Phase 3 trials, it could become one of the first next-generation injectables to compete head-to-head with semaglutide and tirzepatide. If results remain promising, the drug could be on the market within the next 2-3 years.

4. Amgen’s Maritide: A Bispecific Approach

What It Is: Maritide (formerly AMG133) is a bispecific molecule designed to activate GLP-1 while blocking GIP, another metabolic hormone involved in energy regulation. The GLP-1 activation suppresses appetite, while the GIP blockade is believed to enhance fat loss and improve metabolic efficiency.

Why It’s Different: Unlike existing GLP-1 receptor agonists, Maritide’s dual-action approach is designed to counteract potential weight plateaus and reduce side effects such as nausea and gastrointestinal discomfort.

Clinical Progress: Currently in Phase 3 trials, early data suggests that Maritide could lead to greater weight loss than traditional GLP-1 therapies, potentially requiring fewer injections.

What’s Next? If Maritide continues to show strong efficacy and a better tolerability profile, it could become a leading competitor to existing GLP-1 drugs, expanding patient options for obesity treatment.

5. AstraZeneca’s AZD5004: A Metabolic Modulator with a New Approach

What It Is: AstraZeneca is positioning AZD5004 as a new class of metabolic modulator, currently in Phase 2b trials. Unlike GLP-1-based therapies, AZD5004 is designed to improve glucose regulation and appetite control through a different biological pathway.

How It Works: While GLP-1 drugs slow gastric emptying and suppress appetite, AZD5004 aims to provide a more targeted effect on metabolic balance, reducing hunger signals while maintaining normal digestive function. This could result in fewer side effects, particularly the nausea and digestive issues commonly associated with GLP-1 treatments.

What’s Next? Still in mid-stage trials, AZD5004 is being closely watched due to AstraZeneca’s track record of developing successful metabolic treatments. If proven effective, it could offer a new alternative for obesity patients who struggle with GLP-1 therapy side effects.

6. Roche’s CT-388 & CT-996: Exploring Multiple Pathways to Weight Loss

What They Are: Roche is advancing two separate obesity drug candidates, CT-388 and CT-996, both in Phase 2 trials. These compounds take different approaches to metabolic regulation, increasing Roche’s chances of delivering an innovative obesity treatment.

Why It Matters: Roche’s strategy is to pursue multiple mechanisms of action, allowing for greater flexibility in targeting different patient populations. By testing diverse pathways, the company aims to develop a best-in-class alternative to existing therapies.

Current Status: Although specific efficacy data is still emerging, Roche’s deep expertise in metabolic disease research suggests that one of these candidates could advance to late-stage trials in the near future.

What’s Next? As Phase 2 data becomes available, Roche’s approach could shape the next generation of weight-loss therapies with potentially unique advantages over existing treatments.

7. Viking Therapeutics’ VK2735: The Oral GLP-1 Contender

What It Is: Viking Therapeutics is developing VK2735, an oral version of GLP-1-based therapy, designed to mimic the effects of injectable drugs like semaglutide and tirzepatide.

Why It’s Different: One of the biggest barriers to GLP-1 adoption is the requirement for weekly injections. VK2735 aims to bring comparable weight loss benefits in a pill format, making treatment more convenient and accessible.

The Challenge: Oral weight loss drugs have historically struggled with absorption and bioavailability issues. However, Viking’s next-generation formulation is designed to overcome these hurdles.

What’s Next? Currently in Phase 2 trials, VK2735 has the potential to become the first highly effective oral GLP-1 drug, eliminating the need for injections without sacrificing efficacy.

8. Roche & Zealand Pharma’s Petrelintide: A Next-Generation Amylin Analog for Weight Loss

Why it's Exciting: Roche and Zealand Pharma are advancing Petrelintide, a long-acting amylin analog designed for once-weekly administration. Unlike GLP-1 receptor agonists, petrelintide leverages the satiety-regulating effects of amylin, a hormone naturally co-secreted with insulin. With Roche’s backing, this therapy has the potential to disrupt the metabolic health market and offer an alternative to existing weight loss treatments.

How it Works: Petrelintide mimics amylin’s natural role in appetite regulation by enhancing feelings of fullness and reducing food intake. Early clinical data indicate that weight loss outcomes may be comparable to GLP-1 receptor agonists, but with improved tolerability, potentially leading to better patient adherence. The drug is administered via a once-weekly subcutaneous injection, offering a more targeted and possibly better-tolerated approach to obesity treatment.

Why it Matters: The obesity treatment landscape is expanding beyond GLP-1 receptor agonists, with Petrelintide joining a new wave of non-GLP-1 metabolic therapies. Companies like Bloom Science and others are also developing innovative, non-hormonal treatments that target alternative mechanisms, such as the microbiome, to drive sustainable weight loss. This diversification of obesity drugs is crucial, as some patients experience side effects or resistance to GLP-1-based treatments, highlighting the need for novel, well-tolerated options.

What's Next: Roche’s deal with Zealand Pharma, valued at up to $5.3 billion, reflects the growing appetite for innovative obesity treatments. Petrelintide will advance through further clinical trials, with Roche and Zealand co-developing and co-commercializing the drug, including potential combination therapies with Roche’s dual GLP-1/GIP receptor agonist, CT-388. If successful, this dual-market strategy—targeting obesity and metabolic disorders—could position Petrelintide as a key player in the evolving weight loss market.

Read more about Roche & Zealand Pharma’s latest developments.

The Next Era of Obesity Treatment is Here

While GLP-1 receptor agonists have transformed the weight loss industry, new innovations are expanding the treatment landscape. From microbiome-based therapies like Bloom Science’s BL-001 to nutrient receptor agonists such as Kallyope and muscle-preserving solutions with EL-22, the next generation of obesity treatments is shaping up to be more diverse, effective, and patient-friendly than ever before.

As clinical trials progress, the battle for the best alternative to GLP-1 drugs is heating up, with several strong contenders emerging. The key questions remain: Which of these will provide sustainable weight loss? Which will have the best side-effect profile? And how will they stack up against current available treatments?