The Anti-Obesity Phase 3 Pipeline: Active Trials and Mechanisms

A ClinicalTrials.gov registry census (snapshot June 10, 2026) identifies 581 Phase 3 obesity and weight-management clinical trials in total, of which 142 are ongoing (recruiting, active-not-recruiting, not-yet-recruiting, enrolling-by-invitation, or suspended) while 335 are completed, 39 terminated, 10 withdrawn, and 55 remain of unknown status. The pipeline is heavily concentrated: Novo Nordisk and Eli Lilly dominate the historical landscape, sponsoring 54 and 45 of all Phase 3 trials respectively. Among the 142 ongoing trials, Eli Lilly leads the industry with 28 active trials, and Novo Nordisk follows with 19 active trials. Together, these two originators sponsor approximately one-third (33.1%) of all active Phase 3 obesity studies.

The mechanism mix among the 142 ongoing trials highlights the dominance of incretin and amylin pathways: approximately 26 reference semaglutide, 22 reference orforglipron or oral small-molecule GLP-1 receptor agonists, 13 reference tirzepatide, 8 reference the tri-agonist retatrutide, and 8 reference amylin or cagrilintide (including the fixed-dose combination cagrilintide/semaglutide, or CagriSema), with the remaining 70 studies split across older mechanisms or novel targets. Several large Phase 3 trials are currently underway to establish long-term clinical utility, including Eli Lilly's tirzepatide SURMOUNT-MMO cardiovascular-outcomes study (NCT05556512) enrolling 15,374 participants, Amgen's maridebart cafraglutide (MariTide) outcomes trial enrolling 12,800, Boehringer Ingelheim's survodutide cardiorenal outcomes trial enrolling 5,531, Viking Therapeutics' VK2735 trial enrolling 4,500, and Novo Nordisk's CagriSema (cagrilintide/semaglutide) REDEFINE-1 obesity study enrolling 3,400.

Across the 577 Phase 3 obesity trials with reported or planned enrollment numbers, the total patient pool reaches approximately 309,096 participants, with the 142 ongoing trials accounting for 129,962 of that total. Beyond the headline successes, the pipeline shows a material attrition signal, with 39 terminated and 10 withdrawn trials, reminding pipeline and market-access teams that clinical risk remains high even in late-stage metabolic portfolios.

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How many Phase 3 obesity trials are active versus completed or terminated?

To understand the development landscape for anti-obesity medications (AOMs), we look to the clinical trials registry. A search of ClinicalTrials.gov across all start-year partitions through mid-2026 reveals a total of 581 Phase 3 trials registered under conditions related to obesity, overweight, weight management, weight loss, or weight reduction.

The distribution of these trials by registry status is detailed in the table below:

This census shows that while more than half of historical Phase 3 obesity trials are completed—representing the evidence base for first-generation therapies like phentermine/topiramate, naltrexone/bupropion, liraglutide (Saxenda), and the initial approvals of semaglutide (Wegovy) and tirzepatide (Zepbound)—the active pipeline remains substantial. The 142 ongoing trials represent the "second wave" of metabolic drug development, focusing on oral small molecules, multi-receptor agonists, and long-term cardiovascular and renal outcome studies, which are analyzed in how to read ClinicalTrials.gov registry counts.

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Who is running the ongoing Phase 3 obesity pipeline (the Novo-Lilly duopoly and challengers)?

The anti-obesity market is commercially characterized by a duopoly between Novo Nordisk A/S and Eli Lilly and Company. This market concentration is reflected in the registry data:

• Total Historical Footprint: Across all 581 registered Phase 3 trials, Novo Nordisk has sponsored 54 trials and Eli Lilly has sponsored 45 trials, representing a combined 17% of all late-stage obesity research.
• Ongoing Pipeline Concentration: Among the 142 ongoing Phase 3 trials, the concentration is even more pronounced. Eli Lilly leads the industry with 28 active trials, while Novo Nordisk holds 19 active trials. Together, the two originators control approximately one-third (33.1%) of all active Phase 3 studies globally.

However, a challenger field is emerging, seeking to break this duopoly with alternative modalities and dosing schedules:

• Amgen: Sponsors 7 active trials, primarily evaluating its dual GLP-1/GIP receptor antagonist maridebart cafraglutide (MariTide), which features a longer half-life allowing for monthly or less frequent dosing.
• Innovent Biologics: Sponsors 6 active trials, largely focused on mazdutide (a GLP-1/glucagon receptor dual agonist) in the Chinese market.
• Rhythm Pharmaceuticals: Manages trials for setmelanotide (Imcivree), targeting rare, genetic MC4R pathway disorders.
• Challenger Pipeline: Companies like Kailera Therapeutics, Pfizer Inc., and Viking Therapeutics (VK2735) have active Phase 3 trials or are transitioning Phase 2 candidates to Phase 3, as detailed in Eli Lilly's obesity portfolio.

Sponsor Class and Academic Involvement

Across all 581 registered Phase 3 obesity trials, the registry records a significant contribution from academic and non-profit institutions. The sponsor class split is:

• Industry Sponsors: 264 trials (45.4% of total). These are commercial trials funded by pharmaceutical developers seeking regulatory approvals.
• Academic and Other Sponsors: 283 trials (48.7% of total). These investigator-initiated trials (IITs) are typically funded by universities, research hospitals, or medical foundations. They focus on comparative effectiveness, dosing adjustments in special populations, and lifestyle co-interventions.
• NIH and Federal Sponsors: 19 trials (3.3% of total). Funded by the National Institutes of Health or other federal agencies to explore public health outcomes.

These three categories account for 566 of the 581 studies; the remaining 15 carry other or unclassified sponsor designations in the registry, which is why the listed percentages sum to roughly 97 percent rather than 100.

While academic sponsors run nearly half of the trials, they typically feature smaller enrollments (average 100-300 patients) compared to the large-scale commercial registries (average 1,000-5,000 patients) required for drug registration.

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What is the mechanism mix: semaglutide, tirzepatide, oral orforglipron, retatrutide, and amylin?

The mechanism of action (MoA) mix in the ongoing pipeline is shifting from simple GLP-1 receptor mono-agonists toward multi-receptor agonists (GIP/GLP-1 and GLP-1/GIP/glucagon tri-agonists) and oral small molecules.

Among the 142 ongoing Phase 3 trials, the primary therapeutic classes are distributed as follows:

1. Semaglutide (26 Ongoing Trials)

Novo Nordisk continues to expand the clinical profile of semaglutide. These trials evaluate higher-dose formulations (such as Wegovy HD 7.2 mg), oral semaglutide tablets (25 mg and 50 mg), and combinations with other molecules (e.g., cagrilintide). The goal is to defend the franchise against generic competition by demonstrating superior efficacy and convenience, a lifecycle strategy discussed in the semaglutide franchise and its patent cliff.

2. Oral Small-Molecule GLP-1s / Orforglipron (22 Ongoing Trials)

The approval of Eli Lilly’s Foundayo (orforglipron) on April 1, 2026, marked the entry of the first oral small-molecule GLP-1 receptor agonist for obesity. Unlike peptide-based pills like Rybelsus, small-molecule GLP-1s do not require strict water or food restrictions. The 22 ongoing trials in this category evaluate orforglipron and competing oral candidates from Pfizer, Kailera, and structures like Innovent's oral programs. These oral agents are expected to improve adherence and reduce manufacturing costs, as detailed in the oral GLP-1 access checklist.

3. Tirzepatide (13 Ongoing Trials)

Eli Lilly is expanding the indications for tirzepatide (Zepbound/Mounjaro), a dual GIP/GLP-1 receptor agonist. Active trials target sleep apnea, cardiovascular outcomes, and metabolic dysfunction-associated steatohepatitis (MASH).

4. Retatrutide (8 Ongoing Trials)

Lilly’s retatrutide is a triple agonist targeting the GIP, GLP-1, and glucagon (GCG) receptors. Phase 2 data showed average weight loss of 24.2% at 48 weeks. The ongoing Phase 3 trials (the TRIUMPH program) are designed to confirm these results and establish retatrutide as a high-efficacy option for patients who do not achieve their weight loss goals on dual- or mono-agonists.

5. Amylin Analogs / Cagrilintide (8 Ongoing Trials)

This class focuses on amylin pathway modulation, which regulates satiety and gastric emptying. The lead candidate is Novo Nordisk's cagrilintide, evaluated as monotherapy and in combination with semaglutide (CagriSema). Blocking both the GLP-1 and amylin pathways represents a dual-mechanism approach to weight loss.

Modality and Manufacturing Differences: Injectables vs Orals

The pipeline is split between two distinct chemical classes:

• Peptide-Based Injectables (Semaglutide, Tirzepatide, Retatrutide, MariTide): These require recombinant DNA technology or complex peptide synthesis. Recombinant manufacturing is capital-intensive and has faced severe capacity bottlenecks, leading to global drug shortages. These drugs must be filled into sterile autoinjector pens, adding supply chain complexity.
• Small-Molecule Orals (Orforglipron/Foundayo): These are produced via standard chemical synthesis, which is significantly cheaper and easier to scale. Small molecules can be manufactured in traditional solid-dose (tablet/capsule) facilities, avoiding sterile fill-finish constraints. This allows developers to ramp up capacity rapidly to meet global demand, providing a cost advantage that will influence PBM negotiations.

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How big are the cardiovascular-outcome mega-trials reshaping the obesity market?

Payer coverage of anti-obesity medications has historically been limited by benefit exclusions for "cosmetic" weight-loss drugs. However, the publication of Novo Nordisk's SELECT trial (showing a 20% reduction in major adverse cardiovascular events [MACE] with Wegovy 2.4 mg) demonstrated that weight loss has direct cardiorenal benefits.

To secure broad insurance coverage, developers are running large cardiovascular-outcome trials (CVOTs). The table below lists the largest ongoing Phase 3 obesity trials by enrollment:

NCT identifiers are listed only where the registry record was independently confirmed at audit (SURMOUNT-MMO). Enrollments reflect registry target or actual enrollment as of the June 10, 2026 snapshot; individual NCT IDs for the remaining programs can be resolved through the ClinicalTrials.gov registry.

These mega-trials require significant investment and patient recruitment. For access teams, the readout dates of these studies (expected between 2026 and 2028) represent the primary triggers for future coverage updates. If tirzepatide or MariTide demonstrate significant cardiovascular benefits, Medicare and commercial plans will face pressure to expand coverage beyond Wegovy.

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What does the terminated-versus-completed attrition rate say about pipeline risk?

While the metabolic pipeline has yielded major commercial successes, the registry census reveals a material attrition rate that is often overlooked in industry roundups. Of the 581 registered Phase 3 trials, 39 have been terminated and 10 have been withdrawn.

An analysis of these terminated trials highlights several pipeline risks:

1. Safety and Tolerability Failures: Several trials evaluating early oral candidates or combination therapies were halted due to gastrointestinal intolerance or liver enzyme elevations. The high doses required for weight loss amplify safety signals. In particular, several early non-peptide small molecules demonstrated liver toxicity, prompting immediate development halts.
2. Strategic Discontinuations: Multi-national developers frequently terminate trials when a competing agent demonstrates superior efficacy. For example, several daily injectable candidates were discontinued after weekly formulations or oral options showed stronger trial results.
3. Commercial Re-evaluation: The rapid pace of innovation has rendered some late-stage candidates obsolete before their trials concluded. Sponsors have shifted resources to multi-receptor agonists rather than completing trials for single-mechanism agents.
4. Manufacturing Constraints: In some cases, sponsors terminated Phase 3 trials because they could not secure sufficient clinical trial supply of sterile fill-finish autoinjector pens. Reallocating commercial capacity to clinical trials is difficult during active product shortages, forcing developers to prioritize specific programs.

This attrition rate of approximately 8.4% (terminated + withdrawn) serves as a reminder to BD and market-access teams that late-stage clinical trials in the obesity space are not guaranteed to succeed, and portfolio diversification remains critical.

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How should BD and access teams read these registry counts without overreading them?

Registry data is a valuable tool for competitive intelligence, but access teams must recognise its limitations:

• Registry Entries are Approximations: Trial protocols and target enrollments listed in ClinicalTrials.gov represent planned designs, not actual completed data. Actual enrollments may vary, and trial completions are subject to delays.
• Intervention Classification: Registry searches rely on text matches within titles and intervention fields. This approach may miss trials where candidate molecules are referred to by developmental codes (e.g., NNC0487-0111) rather than generic names, requiring manual cross-checking.
• Publication Delay: Sponsors are required to update trial status, but there is often a lag of several months between a trial's termination or completion and the registry update.

For business development teams, this census provides a quantitative framework to evaluate target assets. Rather than relying on investor decks, teams can verify sponsor concentration, enrollment scales, and mechanism trends directly from the registry, establishing a baseline for strategic planning.

6. Detailed Profiles of Key Active Pipeline Candidates

Formulary and drug development teams must trace the development pathways of the leading pipeline candidates. Registry entries reveal key characteristics of these agents:

• Retatrutide (Eli Lilly - GIP/GLP-1/glucagon receptor agonist): Evaluated under the TRIUMPH clinical program, retatrutide represents the next efficacy ceiling. In Phase 2 trials, it achieved a mean weight loss of 24.2% at 48 weeks. The TRIUMPH-1 trial evaluates retatrutide in adults with obesity or overweight, while TRIUMPH-2 targets patients with type 2 diabetes. Ongoing trials evaluate its long-term safety, cardiorenal outcomes, and efficacy in patients with osteoarthritis and knee pain, expanding the indications beyond weight management.
• Maridebart Cafraglutide (MariTide, Amgen - GIP antagonist/GLP-1 agonist): Delivered via a weekly or monthly subcutaneous injection, MariTide’s antibody-peptide conjugate design offers a longer half-life than standard peptide agonists. The ongoing Phase 3 program includes a major cardiovascular-outcomes study enrolling 12,800 patients to demonstrate cardiovascular risk reduction. Unlike daily or weekly peptide therapies, Amgen's antibody-peptide conjugate requires less frequent dosing, potentially improving long-term adherence.
• Survodutide (Boehringer Ingelheim/Zealand Pharma - GLP-1/glucagon agonist): In addition to weight management, survodutide is being evaluated for metabolic dysfunction-associated steatohepatitis (MASH), with Phase 2 data showing 83% of patients achieving histological improvement. Its Phase 3 CVOT focuses on long-term cardiorenal safety.
• VK2735 (Viking Therapeutics - GIP/GLP-1 agonist): Viking is advancing both subcutaneous weekly injections and once-daily oral tablet formulations. The subcutaneous pivotal trials target 4,500 patients to match tirzepatide's efficacy profile.
• MET097 (Kailera Therapeutics - GIP/GLP-1 agonist): Formerly developed by Jiangsu Hengrui Pharmaceuticals, MET097 is a once-weekly injectable peptide currently entering Phase 3, representing a strong challenger to the Novo-Lilly incretin dominance.

7. Cardiometabolic Comorbidities and the Expansion of Clinical Utility

The active Phase 3 pipeline is not merely focused on absolute weight reduction; rather, developers are aggressively pursuing label expansions into metabolic and cardiorenal comorbidities. Historically, obesity was viewed as a primary clinical endpoint, but regulatory pathways now require evidence of secondary clinical benefits to secure reimbursement:

• Metabolic Dysfunction-Associated Steatohepatitis (MASH): Both tirzepatide and survodutide are undergoing late-stage trials to evaluate their ability to resolve liver fat accumulation and prevent progression to fibrosis. Phase 2 trials have shown high rates of liver fat clearance, suggesting these agents will compete directly with thyroid hormone receptor-beta agonists (such as resmetirom).
• Obstructive Sleep Apnea (OSA): Lilly's SURMOUNT-OSA trial evaluated tirzepatide in patients with moderate-to-severe sleep apnea and obesity, demonstrating a significant reduction in the Apnea-Hypopnea Index (AHI). This data is the basis for active label expansions, providing a clinical pathway that bypasses traditional cosmetic exclusions.
• Chronic Kidney Disease (CKD) and Heart Failure (HF): The cardiorenal benefits demonstrated by SGLT2 inhibitors are now being targeted by GLP-1s. Novo Nordisk's FLOW trial (evaluating semaglutide in kidney impairment) was stopped early due to clear efficacy signals, and ongoing Phase 3 trials in obesity are integrating composite cardiorenal endpoints to establish a protective profile across the metabolic spectrum.

8. Payer Utilization Management and Pre-Approval Access Readiness

PBMs and commercial health plans do not wait for FDA approvals to begin designing their clinical utilization management programs. For a high-impact class like anti-obesity medications, payer readiness teams engage in pre-approval access modeling (PAAM) up to 12 months before the anticipated launch. Using data from ClinicalTrials.gov, PBM analysts model the potential budget impact by projecting patient uptake across different pricing scenarios. Key components of pre-approval access planning include:

• Step-Therapy Pathway Development: Payers design step-edits requiring patients to try and fail established, lower-cost therapies before gaining access to novel multi-agonists like retatrutide.
• PA Documentation Checklists: Defining the exact body mass index (BMI) thresholds, documentation of lifestyle modification attempts, and comorbidity criteria required for approval.
• Value-Based Contracting Frameworks: Establishing risk-sharing agreements where the manufacturer offsets the plan's cost if patients do not achieve predefined weight loss milestones, minimizing the plan's financial exposure to early treatment discontinuations. These pre-approval framework updates are critical for formulary readiness, enabling rapid integration of clinical outcomes trials once final FDA approval is announced.

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FAQs

How many active Phase 3 obesity trials are there on ClinicalTrials.gov?

As of June 10, 2026, there are 142 ongoing Phase 3 clinical trials evaluating anti-obesity and weight-management medications. This subset includes trials that are currently recruiting, active-not-recruiting, not-yet-recruiting, or suspended.

Do Novo Nordisk and Eli Lilly really dominate the Phase 3 obesity pipeline by trial count?

Yes. Together, Eli Lilly and Novo Nordisk sponsor 47 of the 142 ongoing Phase 3 trials (Lilly has 28 trials, Novo has 19), representing 33.1% of all active late-stage obesity research. Historically, the two companies have sponsored 99 of the 581 registered trials.

How much of the Phase 3 obesity pipeline is oral (orforglipron-class) versus injectable?

Among the 142 ongoing Phase 3 trials, 22 trials evaluate oral small-molecule GLP-1 receptor agonists (such as Eli Lilly's orforglipron/Foundayo, Pfizer's oral candidates, and other small molecules). The remaining trials evaluate peptide-based injectables (like semaglutide, tirzepatide, retatrutide, or MariTide), indicating that while injectables remain the dominant modality, oral small molecules represent a major growth sector.

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Sources

• ClinicalTrials.gov. Phase 3 Obesity and Weight Management Clinical Trials Census (registry records and NCT identifiers independently re-verified at audit). National Institutes of Health / National Library of Medicine. June 10, 2026. ClinicalTrials.gov Registry
• Garvey WT, et al. Tirzepatide for reduction of morbidity and mortality in adults with obesity: rationale and design of the SURMOUNT-MMO trial (NCT05556512; target enrollment ~15,000). Obesity (Silver Spring). 2025. PubMed 40545827
• FDA. Novel Drug Approvals for 2026: Eli Lilly's Foundayo (orforglipron) Approval. U.S. Food and Drug Administration. April 1, 2026. FDA 2026 Approvals
• Evaluate Vantage. Obesity Pipeline Data Insights: The Next Wave of Weight Loss Therapies. Evaluate. 2026. Evaluate Vantage Report
• Endpoints News. Anti-Obesity Drug Pipeline 2026: Named Assets and Clinical Trial Milestones. Endpoints News. 2026. Endpoints News Coverage
• Novo Nordisk A/S. R&D Pipeline and Scientific Disclosures: CagriSema and Semaglutide Development. Novo Nordisk Science. 2026. Novo Nordisk R&D