Retatrutide and CagriSema Tracker: Clinical Trials, Weight-Loss Results and FDA Status (2026)
Retatrutide and CagriSema are two closely watched investigational medicines for obesity and metabolic disease, but they work differently and have been tested in different trials. This living page tracks the most important results, trial status, safety findings and regulatory milestones—while keeping the difference between peer-reviewed evidence and company-reported topline data visible.
At a glance: Retatrutide is a single molecule that activates GIP, GLP-1 and glucagon receptors. CagriSema combines semaglutide, a GLP-1 receptor agonist, with cagrilintide, a long-acting amylin analogue. Trial percentages are not directly comparable unless population, dose, duration, comparator and statistical analysis are sufficiently similar.
Retatrutide (LY3437943)
Developer: Eli Lilly
Mechanism: GIP, GLP-1 and glucagon receptor agonist.
Latest major readouts: Positive topline Phase 3 results reported for TRIUMPH-1, -2, -3 and -4.
Regulatory milestone: Lilly stated it planned to submit a US BLA in Q1 2027.
CagriSema
Developer: Novo Nordisk
Mechanism: Fixed-dose combination of cagrilintide and semaglutide.
Latest major readouts: REIMAGINE 5 and REDEFINE 9 topline results announced September 21, 2026.
Regulatory milestone: US NDA submitted December 2025; Novo said an FDA decision was expected in late 2026.
Latest developments
The table below is sorted by announcement date. “Topline” means a company has released summary results; detailed peer-reviewed papers and complete safety tables may still be pending.
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| Date | Programme / trial | Headline finding | Evidence status | Key caveat |
|---|---|---|---|---|
| Sep 21, 2026 | CagriSema · REIMAGINE 5 | At week 60, CagriSema 1.0/1.0 mg was reported to reduce weight by 12.4% versus 9.1% with tirzepatide 5 mg in adults with type 2 diabetes. HbA1c reductions were 1.71% and 1.67%, respectively. | Company topline | This comparison used tirzepatide 5 mg, not 10 mg or 15 mg. It does not establish superiority versus every tirzepatide dose. |
| Sep 21, 2026 | CagriSema · REDEFINE 9 | At week 68, CagriSema 1.0/1.0 mg was reported to reduce weight by 21.0% versus 2.0% with placebo. | Company topline | Check the full report for analysis estimand, confidence intervals, treatment discontinuations and detailed safety results. |
| Jul 23, 2026 | Retatrutide · TRIUMPH-2 and -3 | At week 80, reported mean weight reduction reached 20.8% in adults with type 2 diabetes (TRIUMPH-2) and 22.6% in adults with severe obesity and established cardiovascular disease (TRIUMPH-3). | Company topline | Cardiovascular event estimates in TRIUMPH-3 were imprecise; these results do not prove cardiovascular event reduction. |
| May 21, 2026 | Retatrutide · TRIUMPH-1 | At week 80, weight reduction reached 28.3% with 12 mg. A selected extension subgroup with baseline BMI ≥35 continued to week 104 and reported a 30.3% mean reduction. | Company topline | The 104-week result is from an extension subgroup, not the complete randomized population. |
| Feb 23, 2026 | CagriSema · REDEFINE 4 | At week 84, weight reduction was 23.0% with CagriSema and 25.5% with tirzepatide 15 mg under the efficacy estimand. | Company topline | The primary non-inferiority endpoint versus tirzepatide 15 mg was not met. |
| Dec 18, 2025 | CagriSema · US regulatory filing | Novo announced submission of a US NDA for weight management. | Regulatory filing | An application is not an approval. Verify the current regulator record before updating the status. |
At-a-glance comparison
| Feature | Retatrutide | CagriSema |
|---|---|---|
| Developer | Eli Lilly | Novo Nordisk |
| Drug design | Single investigational molecule | Fixed-dose combination of two active molecules |
| Main pathways | GIP, GLP-1 and glucagon receptors | GLP-1 receptor (semaglutide) and amylin-related pathways (cagrilintide) |
| Administration studied | Once-weekly subcutaneous injection in the Phase 3 trials | Once-weekly subcutaneous injection in the Phase 3 trials |
| Main Phase 3 evidence noted here | TRIUMPH-1 through -4 topline results reported in 2025–2026 | REDEFINE 1 and 2 peer-reviewed; REDEFINE 4, REIMAGINE 5 and REDEFINE 9 results reported by the company |
| US regulatory snapshot | Investigational; Lilly said a BLA submission was planned for Q1 2027 | NDA submitted December 2025; the latest located company update expected an FDA decision in late 2026. Verify whether a later decision has been announced. |
| How to compare efficacy | Do not rank by the highest number alone; trials differ in population, dose, endpoints and duration. | Do not treat placebo-controlled trials and active-comparator trials as interchangeable. |
Interpretation: the maximum reported percentages in this tracker are not a head-to-head ranking. For example, TRIUMPH-4 enrolled people with obesity and knee osteoarthritis without diabetes, while REDEFINE 1 studied people with overweight or obesity without type 2 diabetes. Such differences matter.
Retatrutide clinical-trial tracker
Retatrutide is a triple hormone-receptor agonist being investigated for obesity and related complications. The results below are sponsor-reported efficacy-estimand figures from Phase 3 topline announcements. The efficacy estimand is intended to estimate efficacy under the trial's specified assumptions about continued study treatment; it can differ from a treatment-regimen or treatment-policy estimate.
| Trial | Population and follow-up | Reported body-weight change | Other key finding | Evidence status and caveat |
|---|---|---|---|---|
| TRIUMPH-1 NCT05929066 |
Adults with obesity or overweight plus a weight-related complication, without diabetes; 80 weeks. | 4 mg: −19.0% 9 mg: −25.9% 12 mg: −28.3% Placebo: −2.2% |
In a pre-specified extension subgroup with baseline BMI ≥35, participants continuing into week 104 lost an average of 30.3% with 12 mg / maximum-tolerated-dose strategy. | Topline 104-week figures refer to a subgroup extension; the full peer-reviewed report should be checked for all methods and safety details. |
| TRIUMPH-2 NCT05929079 |
Adults with obesity or overweight and type 2 diabetes; 80 weeks. | 4 mg: −12.7% 9 mg: −19.1% 12 mg: −20.8% Placebo: −4.0% |
HbA1c reductions were 1.4, 1.6 and 1.5 percentage points with 4, 9 and 12 mg, respectively, versus 0.2 points with placebo. | Topline Diabetes affects weight-loss and glycemic outcomes; do not directly compare with non-diabetes trials. |
| TRIUMPH-3 NCT05882045 |
Adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes; 80 weeks. | 9 mg: −21.6% 12 mg: −22.6% Placebo: −3.2% |
For the pre-specified time-to-first MACE-5 analysis, HR 0.82 (95% CI 0.55–1.22); for MACE-3, HR 1.12 (95% CI 0.64–1.96). | Topline Both confidence intervals cross 1.0. Do not describe these data as proving cardiovascular risk reduction. |
| TRIUMPH-4 NCT05931367 |
Adults with obesity or overweight and knee osteoarthritis, without diabetes; 68 weeks. | 9 mg: −26.4% 12 mg: −28.7% Placebo: −2.1% |
The 9 mg dose reduced the WOMAC knee-pain score by 4.5 points (reported 75.8%); the 12 mg dose reduced it by 4.4 points (74.3%). | Topline Some percentage changes in pain/function were post-hoc; consult the final publication for prespecified analyses and multiplicity considerations. |
Retatrutide safety items worth tracking
In the TRIUMPH-1, -2 and -3 company releases, common adverse events included gastrointestinal effects such as nausea, diarrhea, constipation and vomiting. Dysesthesia (abnormal skin sensations) was also reported more often in retatrutide arms than placebo in the announced results. Track the frequency by dose, severity, persistence, discontinuation and the final peer-reviewed safety tables rather than treating all adverse events as equivalent.
- Gastrointestinal adverse events by dose and titration schedule.
- Dysesthesia and other neurologic or sensory symptoms, including duration and resolution.
- Discontinuation rates and whether lower or slower dose escalation affects tolerability.
- Body composition, lean mass, strength, nutrition and functional outcomes—not only scale weight.
- Long-term cardiovascular, renal, liver and other patient-important outcomes in purpose-designed trials.
CagriSema clinical-trial tracker
CagriSema combines cagrilintide, a long-acting amylin analogue, with semaglutide, a GLP-1 receptor agonist. Do not confuse REDEFINE trials with REIMAGINE trials: these are separate studies within the development programme, and their populations, comparators and questions differ.
| Trial | Population / comparison | Key reported result | Evidence status | Interpretation / caveat |
|---|---|---|---|---|
| REDEFINE 1 NCT05567796 |
Adults with overweight or obesity and a weight-related complication, without type 2 diabetes; 68 weeks; placebo and active-control arms. | Body-weight change at week 68: −20.4% with CagriSema versus −3.0% placebo under the treatment-policy estimand; −22.7% versus −2.3% under the trial-product estimand. | Peer-reviewed | Always label which estimand is being quoted. These figures are from a placebo-controlled trial, not a direct comparison with retatrutide or tirzepatide. |
| REDEFINE 2 NCT05394519 |
Adults with type 2 diabetes and overweight or obesity; placebo-controlled; 68 weeks. | Body-weight change: −13.7% with CagriSema versus −3.4% placebo under the treatment-policy estimand; −15.7% versus −3.1% under the trial-product estimand. | Peer-reviewed | Results differ from REDEFINE 1 in part because the population has type 2 diabetes. The two trial numbers and trial registry IDs must not be swapped. |
| REDEFINE 4 | Adults with obesity and at least one comorbidity; open-label active-comparator trial; CagriSema 2.4/2.4 mg versus tirzepatide 15 mg; 84 weeks. | Weight change: −23.0% versus −25.5% under the efficacy estimand; −20.2% versus −23.6% under the treatment-regimen estimand. | Topline | Primary non-inferiority endpoint not met. Keep this negative head-to-head endpoint visible alongside the positive placebo-controlled results. |
| REIMAGINE 5 Registry search |
Adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor or both; CagriSema 1.0/1.0 mg versus tirzepatide 5 mg; 60 weeks. | Weight change: −12.4% versus −9.1%. HbA1c reductions: 1.71 versus 1.67 percentage points; HbA1c result reported as non-inferior. | Sep 2026 topline | The comparator was tirzepatide 5 mg. This does not demonstrate superiority to tirzepatide 10 mg or 15 mg or across all patient groups. |
| REDEFINE 9 Registry search |
Adults with overweight or obesity; CagriSema dose groups versus placebo; 68 weeks. | At the 1.0/1.0 mg dose, Novo reported weight reduction of 21.0% versus 2.0% with placebo. | Sep 2026 topline | Await detailed results for analysis methods, confidence intervals, dose-arm reporting, discontinuations and full safety data. |
| REDEFINE 3 Registry search |
Cardiovascular outcomes study in adults with established cardiovascular disease and overweight or obesity, with or without type 2 diabetes. | Outcome-focused trial; do not infer cardiovascular benefit from weight-loss results alone. | Outcome trial | Follow the registry and final event analyses for cardiovascular outcomes, safety and study completion. |
Important REDEFINE 4 context
REDEFINE 4 was an open-label 84-week comparison of CagriSema 2.4/2.4 mg and tirzepatide 15 mg in 809 randomized participants with obesity and one or more comorbidities. Novo reported that the primary endpoint—non-inferiority of CagriSema for weight loss—was not achieved. The efficacy-estimand percentages (23.0% versus 25.5%) and treatment-regimen percentages (20.2% versus 23.6%) answer slightly different statistical questions; include the estimand in the table or text whenever quoting them.
How to compare the weight-loss figures fairly
A percentage alone is an incomplete summary of a clinical trial. Each comparison should show the population, dose, treatment duration, comparator, statistical estimand and evidence status. This is especially important when comparing an investigational drug across trials or comparing an active-comparator trial with a placebo-controlled trial.
| Field | What the tracker should record | Why it matters |
|---|---|---|
| Population | Diabetes status, baseline BMI or body weight, comorbidities and prior treatments. | Baseline risk and response can differ substantially across trial populations. |
| Treatment | Dose, titration schedule, duration at maintenance dose and concurrent lifestyle support. | The dose named in the headline may not describe the full escalation regimen. |
| Comparator | Placebo, active treatment and exact comparator dose. | A trial versus placebo cannot establish superiority over another drug. |
| Analysis estimand | Treatment-policy, treatment-regimen, efficacy or trial-product estimand, as defined in that trial. | Results can differ depending on how treatment discontinuation, adherence and rescue therapy are handled. |
| Uncertainty | Confidence intervals, statistical test, primary endpoint and whether the study met that endpoint. | Point estimates alone do not establish superiority, non-inferiority or clinical certainty. |
| Evidence maturity | Registry entry, abstract, company topline, full report, peer-reviewed paper or regulator decision. | Topline releases may not include all methods, subgroup caveats and complete adverse-event tables. |
Safety and unanswered questions
Both medicines affect appetite and energy intake, and gastrointestinal adverse events are important to monitor. The current trial programmes cannot by themselves answer every question about rare adverse events, use in all patient groups or long-term outcomes.
| Domain | What to monitor | What would strengthen confidence |
|---|---|---|
| Gastrointestinal tolerability | Nausea, vomiting, diarrhea, constipation, abdominal symptoms and related discontinuation. | Full adverse-event tables by dose, severity, time course and treatment arm. |
| Sensory symptoms | Dysesthesia or other abnormal sensations reported in retatrutide trials. | Incidence by dose, duration, resolution and evaluation of contributing factors. |
| Lean mass and function | Changes in lean mass, muscle strength, physical function, protein intake and nutritional status. | Prespecified body-composition and functional outcomes, not scale weight alone. |
| Gallbladder, pancreas and kidney | Adverse events, dehydration, relevant lab results and safety signals over longer follow-up. | Adjudicated events, exposure-adjusted rates where appropriate and pooled safety data. |
| Glycemia and concomitant treatment | HbA1c, hypoglycemia when other glucose-lowering medicines are used, and rescue therapy. | Results stratified by diabetes status and background medication. |
| Discontinuation and weight regain | Reasons for stopping treatment, durability of weight reduction and outcomes after withdrawal. | Long-term follow-up and well-designed discontinuation or maintenance studies. |
| Cardiovascular and other clinical outcomes | Major cardiovascular events, mortality, kidney/liver outcomes and functional endpoints. | Adequately powered outcome trials; improvements in biomarkers alone are not enough. |
This is an evidence-monitoring checklist, not a complete prescribing label. Patients should consult current official product information and a qualified healthcare professional for individual medical decisions.
Regulatory status and access
| Question | Retatrutide | CagriSema |
|---|---|---|
| US development status | Investigational. Lilly stated it planned a BLA submission in Q1 2027. | Novo announced a US NDA submission in December 2025 and said an FDA decision was expected in late 2026. |
| What should be reported as of Oct 17, 2026? | No approval claim; verify any new FDA or Lilly announcement before changing this status. | In the official company sources reviewed for this page, the stated decision window remained late 2026. No later approval notice was verified for this article; check the FDA database immediately before publication. |
| Does filing equal approval? | No. | No. |
| Does US status determine other countries? | No. Approval and access are jurisdiction-specific. | No. Approval and access are jurisdiction-specific. |
| Where to confirm? | FDA Drugs@FDA and Lilly newsroom. | FDA Drugs@FDA and Novo newsroom. |
Regulatory status is time-sensitive and differs by country. A US submission or decision does not automatically authorize use in the UK, EU, Malaysia or another market. If approval is announced, update the page with the date, official label, approved indication and any limitations—not just a headline saying “approved.”
What to watch next
| Priority | Milestone | Why it matters | Best source |
|---|---|---|---|
| High | Any FDA decision or request for additional information on CagriSema | Could change US regulatory status, label, indication and access. | FDA Drugs@FDA and Novo announcements |
| High | Full peer-reviewed publications for retatrutide TRIUMPH Phase 3 readouts | Needed for detailed methods, uncertainty intervals, subgroup results and complete adverse-event reporting. | ClinicalTrials.gov, Lilly and journals |
| High | Retatrutide BLA submission | Lilly stated Q1 2027 as its intended US submission window; an actual filing should replace the plan once confirmed. | Lilly newsroom and FDA |
| Medium | REDEFINE 11 and the higher-dose CagriSema programme | Could add evidence on weight-loss potential, longer treatment and tolerability. Novo previously expected REDEFINE 11 data in H1 2027 and planned to initiate a higher-dose trial in H2 2026. | ClinicalTrials.gov: CagriSema and Novo pipeline updates |
| Medium | Lean mass, strength, nutrition and body composition | Helps distinguish total weight loss from changes in fat mass, lean mass and physical function. | Full papers, supplements and conference abstracts |
| Medium | Durability, discontinuation and cardiovascular outcomes | Long-term clinical value is not captured by short-term weight change alone. | Outcome trials, registry updates and follow-up publications |
Update log
Tracker reviewed and tables redesigned. Added the September 2026 CagriSema REIMAGINE 5 and REDEFINE 9 topline readouts; incorporated the July 2026 retatrutide TRIUMPH-2/-3 results; retained the negative REDEFINE 4 non-inferiority result; and corrected the registry number for REDEFINE 2 to NCT05394519.
Add a dated entry only when a meaningful development is confirmed. Record the source, trial identifier, population, dose, duration, endpoint, analysis estimand, safety/discontinuation findings, evidence type and regulatory implication. Preserve earlier negative or inconclusive results instead of silently replacing them.
Frequently asked questions
Is retatrutide approved?
In the company sources reviewed for this update, retatrutide remained investigational. Lilly said it planned a US BLA submission in Q1 2027. Check current FDA and Lilly announcements for any change.
Is CagriSema approved?
Novo submitted a US NDA in December 2025 and said in its September 2026 update that an FDA decision was expected in late 2026. Verify the latest FDA Drugs@FDA listing and company newsroom before stating its current status.
Which medicine causes more weight loss?
These trials do not provide a clean head-to-head comparison between retatrutide and CagriSema. Population, dose, trial duration, comparator and estimand differ. Do not rank treatments by comparing the largest percentages across separate studies.
Does CagriSema outperform tirzepatide?
Not universally based on the current evidence summarized here. In REDEFINE 4, CagriSema did not meet the non-inferiority endpoint versus tirzepatide 15 mg. In REIMAGINE 5, CagriSema 1.0/1.0 mg was reported to produce greater weight reduction than tirzepatide 5 mg in adults with type 2 diabetes. These are different comparisons with different doses and contexts.
Are all recent results peer-reviewed?
No. REDEFINE 1 and REDEFINE 2 have peer-reviewed publications in NEJM. The highlighted 2026 Phase 3 findings for retatrutide and the September 2026 CagriSema findings were released as topline company results in the sources cited here. Update this tracker when full papers and supplementary safety tables are available.
Can someone purchase retatrutide or CagriSema online?
Do not assume an online product is approved, authentic, sterile or equivalent to the products used in clinical trials. Products marketed as “research use only” should not be used as self-treatment. Discuss authorized treatment options and clinical-trial eligibility with a licensed healthcare professional.
Primary sources and further reading
- Eli Lilly. Retatrutide Phase 3 TRIUMPH-2 and TRIUMPH-3 topline results, July 23, 2026. Company release.
- Eli Lilly. Retatrutide TRIUMPH-1 topline results, May 21, 2026. Company release.
- Eli Lilly. Retatrutide TRIUMPH-4 topline results, December 11, 2025. Company release.
- Novo Nordisk. CagriSema REIMAGINE 5 and REDEFINE 9 topline results, September 21, 2026. Company release.
- Novo Nordisk. REDEFINE 4 results: CagriSema did not meet non-inferiority versus tirzepatide 15 mg, February 23, 2026. Company release.
- Novo Nordisk. REDEFINE 2 results, March 10, 2025. Company release.
- Garvey WT et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2025;393:635–647. doi:10.1056/NEJMoa2502081.
- Davies M et al. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. New England Journal of Medicine. 2025;393:648–659. doi:10.1056/NEJMoa2502082.
- ClinicalTrials.gov. TRIUMPH-1 (NCT05929066); TRIUMPH-2 (NCT05929079); TRIUMPH-3 (NCT05882045); TRIUMPH-4 (NCT05931367).
- ClinicalTrials.gov. REDEFINE 1 (NCT05567796); REDEFINE 2 (NCT05394519); CagriSema study registry search.
- US Food and Drug Administration. Drugs@FDA database—confirm current US application and approval status.
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