Editorially reviewed · Last updated September 8, 2026 · How we review
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Dave Knapp on CagriSema vs Tirzepatide, Novo Nordisk’s Triple Agonist UBT-251, and Retatrutide: Fact Check
This review uses the transcript of his February 24, 2026 episode and the underlying trial announcements. His headline figures mostly match the releases, but neither the cross-trial comparison nor speculation about GIP intolerance establishes which treatment is better for an individual.
Novo Nordisk Cuts Semaglutide Prices
Knapp reports that Novo Nordisk is cutting the list prices of Wegovy by 50% and Ozempic by 35%, effective January 1, 2027, bringing all doses to $675 per month. He clarifies this is the wholesale acquisition cost and won’t directly lower cash-pay prices.
| Claim | Published Data | Verdict |
|---|---|---|
| Wegovy list price cut by 50% | Novo Nordisk press release (Feb 24, 2026): Wegovy list price reduced by approximately 50% effective January 1, 2027. | Accurate |
| Ozempic price cut by 35% | Novo Nordisk press release: Ozempic list price reduced by approximately 35%. The announcement covers the listed semaglutide presentations. | Accurate |
| New list price: $675/month for all doses | Novo Nordisk confirmed $675 monthly list price for Wegovy, Ozempic, and Rybelsus. | Accurate |
| This is the wholesale acquisition cost, not what patients pay | Correct. WAC is the price to distributors. Patient out-of-pocket costs depend on insurance plan structure. | Accurate |
| Cash-pay prices are not affected | Novo's self-pay programs (e.g., NovoCare) remain separate from the list price reduction. The company says this announcement does not affect its direct-to-patient self-pay prices. | Accurate |
CagriSema vs Tirzepatide: REDEFINE-4 Weight Loss Results
Knapp covers the REDEFINE-4 trial results, explaining that CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) was tested head-to-head against tirzepatide 15 mg over 84 weeks. He reports that CagriSema missed its non-inferiority endpoint.
| Claim | Published Data | Verdict |
|---|---|---|
| CagriSema: 23% weight loss (efficacy estimand) | REDEFINE-4 topline results: CagriSema achieved 23.0% weight loss under the efficacy estimand (assuming all patients adhered). | Accurate |
| Tirzepatide: 25.5% weight loss (efficacy estimand) | REDEFINE-4: Tirzepatide achieved 25.5% weight loss under the same estimand. | Accurate |
| Treatment regimen estimand: CagriSema 20%, tirzepatide 23.6% | REDEFINE-4: Under the treatment regimen estimand (accounting for discontinuations), CagriSema hit 20.2% and tirzepatide hit 23.6%. | Accurate |
| 809 adults with mean baseline weight of 114.2 kg | REDEFINE-4 enrolled 809 adults with obesity and at least one weight-related comorbidity. Mean baseline body weight was 114.2 kg. | Accurate |
| CagriSema missed non-inferiority | Novo Nordisk confirmed CagriSema did not meet the primary endpoint of non-inferiority to tirzepatide. | Accurate |
| Open-label study for 84 weeks | REDEFINE-4 was an open-label, randomized trial over 84 weeks. | Accurate |
The reported weight-loss figures and missed non-inferiority endpoint match Novo Nordisk’s February 23, 2026 announcement. The efficacy estimand estimates outcomes under continued treatment; it is not a count of participants who reached the highest dose.
Knapp suggests CagriSema could suit people who do not tolerate tirzepatide’s GIP component. The release does not test that selection rule, and symptoms during tirzepatide treatment do not identify which receptor caused them. Nor does the trial establish that the difference in weight loss is clinically unimportant for every patient.
Novo Nordisk Triple Agonist UBT-251: Phase 2 Weight Loss Data
Knapp introduces UBT-251, a triple agonist (GLP-1/GIP/glucagon) being jointly developed by United Biotechnology and Novo Nordisk. He reports 19.7% weight loss at 24 weeks in a Chinese phase 2 trial.
| Claim | Published Data | Verdict |
|---|---|---|
| UBT-251 is a triple agonist from Novo Nordisk | UBT-251 is jointly developed by The United Laboratories (TUL) subsidiary United Biotechnology and Novo Nordisk. It targets GLP-1, GIP, and glucagon receptors. | Accurate |
| 19.7% mean weight loss at 24 weeks | Novo Nordisk/TUL press release (Feb 24, 2026): UBT-251 delivered up to 19.7% mean weight loss after 24 weeks across the trial’s tested doses; the release does not identify a dose-specific breakdown. | Accurate |
| 205 Chinese participants | The primary release reports 205 Chinese participants with overweight or obesity, randomized to 2, 4 or 6 mg UBT251 or placebo. | Accurate |
| Mean body weight of 92.2 kg | Press release confirms mean baseline body weight of approximately 92.2 kg. | Accurate |
| No plateau observed | Novo Nordisk stated the weight loss curve had not plateaued at 24 weeks, suggesting further weight loss possible with longer treatment. | Accurate |
| Placebo group lost 2% | Press release: Placebo group showed approximately 2% weight change. | Accurate |
The headline numbers match the release. UBT251 was developed by United Biotechnology, a subsidiary of The United Laboratories. Under the March 2025 licence, Novo Nordisk holds development and commercialization rights outside Greater China. That partnership matters when describing whose molecule it is.
UBT-251 vs Retatrutide: The Cross-Trial Comparison
Knapp makes the inevitable comparison between UBT-251 and retatrutide at 24 weeks, while repeatedly warning that cross-trial comparisons are fragile.
| Claim | Published Data | Verdict |
|---|---|---|
| Retatrutide achieved up to 17.5% weight loss at 24 weeks (Phase 2) | Jastreboff et al. (2023) NEJM: Retatrutide 12 mg group achieved 17.5% weight loss at 24 weeks in a US population with mean baseline weight of ~107 kg. | Accurate |
| Comparing across trials is not a fair comparison | Correct. Different countries, baseline weights (92.2 vs ~107 kg), populations, dose escalation strategies, and statistical methods make direct comparison unreliable. | Accurate and responsible |
| Novo Nordisk press release vs peer-reviewed data | UBT-251 data is from a topline press release. Retatrutide 24-week data is from a peer-reviewed NEJM publication. This is an important quality-of-evidence distinction. | Accurate |
| HRS-9531 showed 17.2% at 24 weeks in a Chinese population | HRS9531 is a GLP-1/GIP dual agonist. The retrieved 8 mg phase 2 presentation reports 22.8% mean loss versus 1.7% with placebo at 36 weeks. The 17.2% figure at 24 weeks was not verified in that presentation and should not be labelled placebo-adjusted here. | 24-week figure not verified here |
Knapp appropriately warns against ranking these drugs from separate trials. The figures he compares do not establish that UBT251 is better than retatrutide. Different populations, trial designs and reporting methods limit the comparison, even at the same nominal timepoint. The HRS9531 example is also a dual agonist, so it cannot establish a consistent effect of triple agonism.
Saxenda as the Historical Benchmark
Knapp uses Saxenda (liraglutide 3.0 mg) as a historical comparison point to illustrate how far obesity treatments have come.
| Claim | Published Data | Verdict |
|---|---|---|
| Saxenda achieved about 9% weight loss | SCALE Obesity trial (2015): Liraglutide 3.0 mg achieved 8.0% mean weight loss at 56 weeks (vs 2.6% placebo). This supports an approximate historical comparison, not a head-to-head result. | Approximately accurate |
| 23% weight loss is not good enough to win in today's market | CagriSema's 23% (efficacy estimand) failed to meet non-inferiority against tirzepatide's 25.5%. The trial result does not by itself establish market success or failure. | Accurate |
The Strategic Timing
A strategic connection is his interpretation. Neither release establishes that the trial result caused the pricing decision or that the change will secure better formulary access.
Frequently Asked Questions
Who is Dave Knapp from On The Pen?
Dave Knapp hosts On The Pen, which covers GLP-1 medicines and obesity-treatment news. This review concerns his February 24, 2026 episode; it evaluates the reported claims against primary sources rather than treating the programme as medical advice.
Is UBT-251 better than retatrutide?
Will the Wegovy price cut make it cheaper for me?
How much weight loss does CagriSema achieve?
What is CagriSema vs tirzepatide — which is better for weight loss?
Sources
- Knapp, D. (2026). "NEW GLP3 FROM NOVO NORDISK! BETTER THAN RETATRUTIDE?" On The Pen Podcast. Watch on YouTube
- Novo Nordisk A/S. (2026). Novo Nordisk announces significant reduction in US list price for Wegovy, Ozempic and Rybelsus. Press release
- Novo Nordisk / United Biotechnology. (2026). Triple agonist UBT251 delivers up to 19.7% mean weight loss after 24 weeks in phase 2 trial in China. Press release
- Novo Nordisk. (February 23, 2026). REDEFINE 4 topline results. Primary announcement
- Zhou et al. (2025). HRS9531 8 mg phase 2 trial. ADA presentation
- Jastreboff, A.M., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. DOI: 10.1056/NEJMoa2301972
- Pi-Sunyer, X., et al. (2015). A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE). New England Journal of Medicine. DOI: 10.1056/NEJMoa1411892
- What this is
- Educational information, not medical advice. It reports published research — it doesn’t recommend that you use, obtain, or supply anything.
- Regulatory status
- Retatrutide and similar peptides are investigational — not approved by the FDA or any regulator. Semaglutide and tirzepatide are prescription-only medicines, available only through a licensed prescriber.
- Our standard
- Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
- No commercial ties
- We don’t sell, supply, or link to suppliers of any medicine, and aren’t affiliated with any manufacturer.
Do not make decisions about your health without consulting a qualified healthcare provider. For trial enrolment, see ClinicalTrials.gov. More on how we review.
Sources
- NEW GLP3 FROM NOVO NORDISK! (YouTube)
YouTube
- UBT-251 Phase 2 results
GlobeNewsWire
- Phase 2 trial (NEJM)
New England Journal of Medicine
NEJM
The Lancet
JAMA
FDA
ClinicalTrials.govRelated reading
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