The FDA Pipeline: New GLP-1 Drugs Coming in 2025 and Beyond

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider before making changes to your treatment plan.

What's in the GLP-1 Pipeline

The success of semaglutide and tirzepatide has triggered the largest wave of investment in metabolic drug development in pharmaceutical history. Every major pharmaceutical company and dozens of biotechnology firms are racing to develop the next generation of agents, and the pipeline is remarkably rich. As of early 2025, there are more than 50 compounds in clinical development targeting GLP-1 receptors or related metabolic pathways, at various stages from early Phase 1 to late Phase 3.

The pipeline broadly falls into several categories: oral formulations of existing or novel GLP-1 receptor agonists, multi-receptor agonists that combine GLP-1 activity with targeting of additional receptors (GIP, glucagon, amylin), longer-acting formulations designed to reduce injection frequency to once monthly or quarterly, and entirely new mechanisms of action such as amylin analogs and novel peptide combinations. Each category addresses a different limitation of current standard-of-care treatments.

The most immediately clinically significant programs are those in Phase 3, which means they are in the final stage of large-scale human trials before potential FDA submission. Phase 3 success is not guaranteed — history is filled with drugs that showed promise in earlier phases but failed to meet primary endpoints or had unacceptable safety signals in pivotal trials. But for the programs discussed in this article, Phase 2 data has been sufficiently compelling that Phase 3 trials have been initiated and are well underway.

Competition in this space is also intensifying the focus on differentiation. A "me-too" GLP-1 that offers similar efficacy and safety to existing semaglutide or tirzepatide products has limited commercial appeal in an era when Novo Nordisk and Eli Lilly have established dominant market positions with proven products. The drugs that will succeed commercially must offer something meaningfully better: greater weight loss, oral bioavailability, longer duration of action, an improved side effect profile, or activity in additional disease areas.

Oral GLP-1 Medications in Development

The holy grail of the GLP-1 space has long been an oral small-molecule agent that can match or approach the efficacy of injectable GLP-1 receptor agonists. Injectable medications work extremely well, but the barrier of weekly self-injection — with the accompanying needle phobia, site reactions, and logistical requirements — limits adherence and patient acceptance. An effective oral GLP-1 pill could dramatically expand the population of patients willing and able to use these medications.

Eli Lilly's orforglipron is the most advanced small-molecule oral GLP-1 receptor agonist in development. Unlike Rybelsus (oral semaglutide), which is a large peptide molecule requiring a complex absorption-enhancing formulation and strict administration requirements (taken on an empty stomach with a small amount of water, 30 minutes before any food or drink), orforglipron is a true small-molecule drug that can be taken with food at any time of day. Phase 2 data published in the New England Journal of Medicine showed weight loss of approximately 14.7 percent over 36 weeks at the highest dose — comparable to injectable semaglutide — with a side effect profile consistent with the GLP-1 class.

Phase 3 trials for orforglipron are ongoing across multiple indications, including type 2 diabetes and obesity. Eli Lilly has indicated it expects to have Phase 3 data in 2025, which would position an NDA (New Drug Application) submission to the FDA potentially by late 2025 or early 2026. If approved, orforglipron would be the first once-daily oral GLP-1 pill for obesity — a genuinely transformative development for patient access.

Novo Nordisk is also pursuing oral options, including a next-generation oral semaglutide candidate designed to overcome the absorption limitations of existing Rybelsus. Early data suggests doses higher than the current 14 mg maximum could achieve substantially greater weight loss, potentially closing the gap between oral and injectable semaglutide. Novo Nordisk is also developing oral amycretin — a combination of semaglutide and an amylin analog in a single oral pill — which showed extraordinary early Phase 1 data suggesting weight loss of up to 13 percent in just 12 weeks. If sustained, this could represent the most effective oral agent ever tested.

Several other companies are in earlier stages of oral GLP-1 development, including Pfizer, AstraZeneca, and a number of smaller biotechnology firms. The Pfizer program had early setbacks with liver toxicity signals in one candidate but the company continues to advance alternative molecules. The sheer number of companies pursuing this goal increases the probability that multiple effective oral options will eventually reach patients, which would have significant positive effects on competition and pricing.

Triple Agonists: Beyond GLP-1

If tirzepatide — a dual GLP-1 and GIP receptor agonist — represented a step beyond semaglutide, retatrutide represents the next step beyond tirzepatide. Retatrutide, developed by Eli Lilly, is a triple agonist that activates GLP-1, GIP, and glucagon receptors simultaneously. The addition of glucagon receptor activity is significant because glucagon stimulates fat breakdown (lipolysis) in the liver and adipose tissue and increases energy expenditure — effects that are complementary to the appetite suppression and insulin sensitization provided by GLP-1 and GIP.

Phase 2 data for retatrutide, published in the New England Journal of Medicine in 2023, was remarkable. Participants receiving the highest dose (12 mg) achieved a mean weight loss of 24.2 percent from baseline over 48 weeks — approaching the weight loss previously only achievable through bariatric surgery. The proportion of participants achieving 20 percent or greater weight loss was substantially higher than any previously reported for a pharmacological agent. Equally important, the drug appeared well tolerated, with a side effect profile broadly consistent with the GLP-1 class (predominantly gastrointestinal, dose-dependent, and manageable).

Retatrutide Phase 3 trials (TRIUMPH program) are underway across multiple indications. The cardiovascular outcomes trial is of particular interest given the cardiovascular significance demonstrated by semaglutide's SELECT trial and tirzepatide's SUMMIT trial. If retatrutide demonstrates superior weight loss and comparable or better cardiovascular protection, it could become the dominant agent in the class for patients with both obesity and cardiovascular disease.

Novo Nordisk is pursuing a different approach to combination therapy with CagriSema — a fixed-ratio combination of cagrilintide (an amylin analog) and semaglutide. Amylin is a hormone co-secreted with insulin from pancreatic beta cells that suppresses glucagon, slows gastric emptying, and reduces food intake through complementary mechanisms to GLP-1. Phase 2 data for CagriSema showed weight loss of approximately 15.6 percent over 32 weeks at the highest dose tested — meaningful but less dramatic than retatrutide. However, Phase 3 data at higher doses and longer duration will be the definitive test.

The theoretical ceiling for pharmacological weight loss continues to be pushed upward by these combination approaches. Analysts and researchers who work in obesity medicine now routinely discuss the prospect of drugs that achieve 30 percent or more weight loss — a threshold that for most of medical history has been achievable only through surgical intervention. Whether the safety and tolerability profiles of these agents will be acceptable at doses that produce such extreme weight loss remains to be seen in larger, longer Phase 3 programs.

Once-Monthly Formulations

Adherence to weekly injection regimens is strong compared to daily oral medications for many chronic conditions, but even weekly administration has adherence and convenience limitations for some patients. A substantial pipeline effort is focused on extending the duration of action of GLP-1 medications to allow monthly or even quarterly dosing.

Eli Lilly is developing a once-monthly injectable tirzepatide formulation using a sustained-release polymer technology. Phase 2 data presented in 2024 showed that monthly tirzepatide achieved efficacy comparable to weekly tirzepatide for both glycemic control and weight management. This is a significant technical achievement because sustained-release formulations of large peptides are notoriously difficult to engineer — getting consistent absorption over 30 days while maintaining a stable pharmacokinetic profile requires sophisticated pharmaceutical science.

Novo Nordisk is working on a once-weekly semaglutide using a similar extended-release approach, as well as exploring quarterly depot injections. Amgen's maridebart cafraglutide (formerly AMG 133) is a bispecific antibody approach to GLP-1/GIPR targeting that, due to its antibody structure, has an extremely long half-life — potentially enabling monthly or less frequent dosing. Early data has been promising, though the antibody approach represents a different pharmacological profile than small-molecule or peptide-based GLP-1 agents.

The patient benefit of reduced injection frequency is not trivial. Adherence to chronic disease medications is strongly correlated with dosing frequency — monthly or quarterly regimens have consistently demonstrated better real-world adherence than weekly regimens in other therapeutic areas. For GLP-1 therapy, where long-term maintenance is essential (weight regain after drug discontinuation is well documented and substantial), any improvement in adherence translates directly into better long-term outcomes.

Expected Approval Timelines

Predicting FDA approval timelines with precision is an inherently uncertain exercise — clinical trials encounter unexpected results, regulatory review timelines vary, and companies sometimes choose to delay submissions. That said, based on publicly available trial timelines, the following represents a reasonable view of what to expect over the next two to four years for the most advanced pipeline candidates.

Orforglipron (oral GLP-1, Eli Lilly) is the nearest-term priority. Phase 3 data readouts are expected in 2025, and if successful, an NDA submission could come as early as late 2025 with a potential FDA approval in 2026. The FDA has granted orforglipron Breakthrough Therapy Designation for obesity, which entitles Lilly to enhanced interactions with the agency during the development process and may accelerate the review timeline once an application is submitted.

Retatrutide (triple agonist, Eli Lilly) is in Phase 3 with data readouts anticipated in 2025 and 2026. If pivotal trial results are positive, an NDA submission could be filed in 2026 with potential approval in 2027. Given the extraordinary Phase 2 results, this is one of the most watched programs in the entire pharmaceutical industry.

CagriSema (amylin + semaglutide, Novo Nordisk) has Phase 3 data expected in 2025-2026, with potential submission and approval following. The oral amycretin program is at an earlier stage and, if Phase 2 data supports advancement to Phase 3, could plausibly reach approval in the 2027-2028 timeframe. Monthly tirzepatide (Eli Lilly) is expected to have pivotal data in 2026, with potential regulatory submission thereafter.

Patients should keep in mind that these timelines represent optimistic scenarios in which Phase 3 trials succeed and regulatory reviews proceed smoothly. Historical success rates for drugs in Phase 3 are approximately 50 to 60 percent, and regulatory agencies have become more demanding in their requirements for metabolic drugs since the cardiovascular safety requirements implemented after 2008. However, given that several of these programs are using proven mechanistic targets with established regulatory precedents from semaglutide and tirzepatide, the success probability for the most advanced candidates is generally viewed as above the class average.

What Current Patients Should Know

If you are currently on semaglutide or tirzepatide and doing well, the most important message from the pipeline is simply encouraging: the therapeutic class you are benefiting from is going to continue improving rapidly. Better options are coming. This should reinforce the value of maintaining the treatment approach that is currently working for you — do not abandon an effective regimen in anticipation of future drugs.

For patients who have tried current GLP-1 medications and have been limited by side effects, suboptimal response, or the barrier of weekly injections, the pipeline offers genuine reason for hope. Oral agents like orforglipron could remove the injection barrier entirely. Next-generation agents with more potent weight loss may be better suited for patients with severe obesity who have not achieved adequate results on current options.

The competitive pressure created by this rich pipeline is also likely to affect pricing and access favorably over time. When multiple competing products exist in a therapeutic class, manufacturers typically adjust pricing to compete for formulary placement, and insurance plans gain leverage to negotiate better terms. The era of a single dominant GLP-1 option is ending — within three to five years, patients are likely to have genuinely meaningful choices between oral and injectable options, weekly and monthly dosing, and products with different risk-benefit profiles.

Patients interested in accessing pipeline drugs before approval may be eligible for clinical trials. Clinicaltrials.gov is the authoritative database of ongoing clinical trials in the United States and globally. Searching for the drug name or condition (obesity, type 2 diabetes) will return currently enrolling studies. Clinical trial participation comes with risks — including exposure to experimental agents with incompletely characterized safety profiles — but also potential benefits including access to cutting-edge treatments and close clinical monitoring. Discuss the option with your prescriber if you are interested.

Finally, do not let the excitement of the pipeline distract from the importance of the behavioral and lifestyle changes that make GLP-1 therapy most effective. No matter how powerful the next generation of metabolic medications becomes, they work best in the context of supported behavior change — improved nutrition, regular physical activity, adequate sleep, and stress management. The drugs create the conditions for transformation; the lifestyle work makes it sustainable and maximizes it. That equation is unlikely to change regardless of how the pharmacological options evolve.