Medicine FAQ

CagriSema failed to meet its primary endpoint of non-inferiority to Eli Lilly's tirzepatide (Zepbound). CagriSema achieved 23.0% weight loss at 84 weeks versus 25.5% for tirzepatide on the on-treatment estimand, and 20.2% versus 23.6% on intention-to-treat. The 2.5 to 3.4 percentage point gap across both measures establishes clinical inferiority.

The decline compounded across multiple events: a July 2025 guidance cut on US pricing headwinds, 9,000 job cuts announced in September 2025, a February 2026 guidance for the first revenue decline in modern history (adjusted sales down 5-13%), and the CagriSema REDEFINE 4 failure on February 23, 2026. Structural pricing pressure from MFN, IRA negotiations, and international patent expiries drove the fundamental deterioration.

After the CagriSema selloff, Novo trades at roughly 11x forward earnings and roughly 8x EV/EBITDA, cheaper than Pfizer (9x PE), Merck (14x), AstraZeneca (20x), and AbbVie (17x). This represents a nearly 80% PE compression from the 2024 peak of approximately 50x and a roughly 40% discount to the pharma peer average of 19x forward PE.

The FDA decision on Eli Lilly's orforglipron, expected April-May 2026. Orforglipron is an oral non-peptide GLP-1 with no food restrictions or fasting requirements, which directly undercuts the Wegovy pill's brief first-mover advantage. Goldman Sachs projects orforglipron capturing 60% oral GLP-1 market share by 2030.

Likely yes, based on the REDEFINE 1 and 2 placebo-controlled data submitted in December 2025, with a decision expected late 2026. But launching a drug with proven clinical inferiority to the market leader is a very different commercial proposition than launching one with a credible superiority story.

The GLP-1 market is projected to reach $100-150 billion by 2030, and Novo at 11x earnings prices in a catastrophe. But near-term catalysts are thin: orforglipron approval could arrive any day, post-CagriSema analyst downgrades haven't landed yet, and Lilly is pulling ahead on efficacy, pipeline, oral convenience, and manufacturing. The problems are structural, not sentiment-driven.

The Wegovy pill reached over 170,000 patients within four weeks of its January 2026 launch, with weekly prescriptions hitting 50,000 by late January. TD Cowen noted it generated 15x more prescriptions than injectable Wegovy at the same post-launch stage. However, about 90% of prescriptions are self-pay at $149/month due to limited formulary coverage, and the 13.6% weight loss trails injectable Wegovy (15%) and Zepbound (20%+).

Semaglutide's compound patent already lapsed in Canada in January 2026 after Novo missed a maintenance fee. Dr. Reddy's has filed in 87 countries. In the US, a patent thicket of 320 applications (154 granted) and settlements push generic entry to roughly 2031-32. Internationally, erosion is accelerating, with generics in development across China (15+ manufacturers), Brazil, and other markets.

Cornell research shows households with a GLP-1 user cut grocery spending by 5.3% within six months, with high-income households dropping 8.2%. Fast food spending falls 8.0%. These users aren't switching brands; they're simply eating less.

Savory snacks see the largest decline at 10.1%, followed by sweets, baked goods, and cookies. Even staples like meat, eggs, and bread decline. Yogurt is the only category showing a statistically significant increase, with fresh fruit and nutrition bars trending up slightly.

About 34% of users discontinue within the sample period. When they stop, spending doesn't just return to baseline; it becomes less healthy. Candy and chocolate purchases rise 11.4% above pre-adoption levels, suggesting the drugs suppress appetite biologically without teaching new habits.

Higher-income households show even steeper spending declines (8.2% vs 5.3% average) and are more likely to use GLP-1 medications for weight loss rather than diabetes. They're also the most profitable customers for fast food chains, creating a "double whammy" where companies lose their highest-margin customers.

A phase 2 randomized controlled trial published in February 2025 found that low-dose semaglutide reduced alcohol craving, drinks per drinking day, and heavy drinking episodes compared to placebo. Effect sizes for some outcomes exceeded those typically seen with naltrexone, one of the few FDA-approved medications for alcohol use disorder.

The February 2025 UNC trial showed that despite using doses lower than standard weight loss dosing, semaglutide produced effect sizes exceeding those typically seen with naltrexone. Real-world data also found semaglutide associated with significantly lower risk of AUD diagnosis compared to naltrexone. However, naltrexone remains FDA-approved for AUD while semaglutide is not yet approved for this indication.

New therapies for alcohol use disorder have been approved at a rate of roughly one every 25 years. Only three medications (naltrexone, acamprosate, and disulfiram) are currently FDA-approved. This limited pharmacotherapy landscape makes the early GLP-1 research particularly significant for the millions of people with AUD who have few effective treatment options.

No. GLP-1 receptor agonists like semaglutide are currently FDA-approved only for type 2 diabetes, obesity, and obstructive sleep apnea. While early trial results are promising, larger clinical trials are needed before GLP-1 drugs could be approved as an addiction treatment. Phase 3 trials are underway.

In Phase 1b/2a trials published in The Lancet, injectable amycretin delivered 24.3% average weight loss at the highest dose over 36 weeks, compared to 1.1% for placebo. This outperforms both Wegovy (approximately 15% weight loss) and Eli Lilly's Zepbound (approximately 22.5%). The oral version achieved 13.1% weight loss in just 12 weeks, with patients still losing weight when the trial ended.

Amycretin is a dual-pathway drug that combines semaglutide's GLP-1 receptor activation with amylin receptor agonism. While semaglutide alone slows gastric emptying and reduces appetite through GLP-1 signaling, amycretin adds amylin's complementary satiety signals, meaning both the gut and the brain's appetite control center receive simultaneous "stop eating" messages. This dual mechanism explains the greater weight loss observed in trials.

Amycretin's injectable version completed Phase 1b/2a trials in 2025, with Phase 3 trials expected to begin in 2026. Based on typical drug development timelines, FDA approval could come around 2030-2031, aligning with the expiration of Ozempic's core US patent in December 2031. Novo Nordisk has not announced a specific target approval date.

Ozempic's core US patent expires in December 2031, but Novo Nordisk has multiple defenses. Manufacturing GLP-1 compounds requires specialized peptide production capabilities and patented injection devices that create a significant capacity constraint. Even after patent expiration, generic manufacturers would need years to build sufficient manufacturing infrastructure, giving Novo time to transition patients to next-generation drugs like amycretin while potentially lowering prices to maintain market share.