Eli Lilly’s stock dropped 13% after releasing trial data on its obesity pill, orforglipron, which showed less weight loss and more side effects than analysts expected. Results also trailed Novo Nordisk’s oral semaglutide, which has demonstrated stronger efficacy. Still, shares have rebounded 12% since.
Analysts believe Lilly’s once-daily pill could remain a strong contender in the $95 billion weight-loss drug market, even as the second to launch. Unlike Novo’s peptide-based semaglutide, orforglipron is a small-molecule drug that absorbs more easily, avoids dietary restrictions, and is simpler to manufacture at scale—critical as global demand outpaces supply.
Pricing remains uncertain, but experts suggest Lilly may undercut Novo, an edge given limited U.S. insurance coverage for obesity drugs. Leerink Partners and Goldman Sachs project Lilly could capture 60% of the oral pill segment by 2030, worth an estimated $13.6 billion, while Novo could secure about 21%.
The push for oral obesity drugs is intensifying. While Pfizer abandoned its earlier candidate, companies like Viking Therapeutics, Structure Therapeutics, AstraZeneca, and Roche are advancing new options. Both Lilly and Novo are also testing additional oral treatments.
Industry leaders caution that pricing and insurance coverage will ultimately decide the winner. “Both drugs are going to be gamechangers,” said Dr. Mihail Zilbermint of Johns Hopkins. “But cost is the biggest issue.”
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Weight Loss and Side Effect Comparisons
Comparing Eli Lilly’s orforglipron with Novo Nordisk’s oral semaglutide is tricky since the trials involved different patient groups and no head-to-head study exists. Lilly’s ATTAIN-1 trial followed 3,000 patients, while Novo’s OASIS 4 tested about 300.
Data so far suggests Novo’s pill delivers greater weight loss. At its highest dose, Lilly’s drug reduced body weight by 12.4% at 72 weeks, or 11.2% when including all patients. Investors had hoped for closer to 15%, matching Novo’s injection Wegovy. By contrast, Novo’s 25 mg oral semaglutide cut weight by up to 16.6% at 64 weeks, or 13.6% when accounting for discontinuations. Nearly one-third of patients saw weight loss of 20% or more.
Still, analysts say Lilly’s pill remains competitive. “For many patients, 12% is a really great number,” said BMO’s Evan Seigerman, noting strong demand for alternatives. Bank of America analysts agreed, suggesting physicians are unlikely to shift prescribing decisions based on modest differences.
Side effects for both drugs were mainly gastrointestinal, including nausea and vomiting. In Lilly’s trial, 10.3% of patients on the highest dose discontinued treatment, compared with 2.6% on placebo. About 24% reported vomiting and 33.7% nausea. Novo’s pill showed higher rates, with 30.9% reporting vomiting and 46.6% nausea. Analysts say tolerability looks broadly comparable, though full data will be key.
Johns Hopkins’ Dr. Mihail Zilbermint cautioned that safety comparisons remain premature. Meanwhile, Seigerman emphasized dietary restrictions could become a deciding factor between the two drugs.
Food Requirements, Manufacturing, and Pricing
Novo Nordisk’s oral semaglutide comes with strict rules: patients must take it in the morning on an empty stomach with no more than four ounces of water, then wait 30 minutes before eating, drinking, or taking other medications. Analysts warn this could deter long-term use. “If you’re a busy parent who needs coffee right away, this will be tough,” said BMO’s Evan Seigerman.
Manufacturing costs also differ sharply. Novo’s semaglutide is a peptide drug, making it complex and expensive to produce. Leerink’s David Risinger said this likely means higher prices than Eli Lilly’s orforglipron, a small-molecule drug that is easier and cheaper to scale. Novo has already invested $24 billion in U.S. manufacturing and R&D over the past decade to expand production of both oral and injectable GLP-1 drugs.
Pricing remains unclear. Eli Lilly CEO David Ricks has said orforglipron’s price will reflect its health-care value, including savings from treating obesity-related conditions. Goldman Sachs analysts expect pricing similar to Lilly’s Zepbound injection, which costs just over $1,000 per month. Johns Hopkins’ Dr. Mihail Zilbermint cautioned that while pills are cheaper to make, R&D costs could keep prices high.
Commercialization strategies may also shape the rivalry. Analysts question whether Novo will extend its CVS Caremark deal — which prioritized Wegovy over Lilly’s Zepbound — to cover its oral semaglutide. Meanwhile, Lilly could push orforglipron through LillyDirect, its direct-to-consumer pharmacy that bypasses insurers. Seigerman said these market tactics could prove as important as clinical results: “The go-to-market campaign will matter a lot.”
Other Competitors Lag Behind
Most rival obesity pills remain in early development, making direct comparisons to Eli Lilly and Novo Nordisk difficult until larger, long-term trials are complete. So far, results suggest competitors trail significantly.
Viking Therapeutics’ stock plunged 40% after mid-stage trial data disappointed investors. Its once-daily pill showed up to 12.2% weight loss at three months, but with a 28% discontinuation rate. By contrast, Eli Lilly’s orforglipron showed similar weight loss over a much longer 72-week trial, with fewer discontinuations.
Mizuho strategist Jared Holz said Viking’s results “look inferior” to Lilly’s across nearly all measures. Still, experts note Viking’s data has not yet reached a plateau, meaning weight loss could increase with extended use.
Frequently Asked Questions
How does Eli Lilly’s obesity pill work?
Orforglipron is a small-molecule drug that mimics the GLP-1 hormone to suppress appetite and regulate blood sugar. Unlike Novo Nordisk’s oral semaglutide, it doesn’t require dietary restrictions and is easier to manufacture at scale.
How effective is Eli Lilly’s pill compared to Novo Nordisk’s?
In trials, Lilly’s orforglipron helped patients lose about 12% of body weight at 72 weeks. Novo’s oral semaglutide showed up to 16.6% weight loss at 64 weeks. While Novo’s pill appears more effective, analysts say Lilly’s results are still strong enough to be competitive.
What are the main side effects of these pills?
Both drugs commonly cause gastrointestinal issues, including nausea and vomiting. In Lilly’s trial, 10% of patients on the highest dose stopped treatment due to side effects, compared with about 2.6% on placebo. Novo’s pill showed somewhat higher nausea and vomiting rates.
Will these obesity pills be affordable?
Pricing hasn’t been finalized. Analysts expect Lilly’s pill could be priced around $1,000 per month, similar to its Zepbound injection. Novo’s pill may cost more due to complex manufacturing. Insurance coverage will be a key factor in affordability.
When will these pills be available?
Novo Nordisk expects potential U.S. approval of its oral semaglutide later this year. Eli Lilly aims to launch orforglipron globally by next year, pending regulatory approval.
Are other companies developing obesity pills?
Yes. Viking Therapeutics, Pfizer, AstraZeneca, Roche, and others are testing oral treatments. However, most are still in early trial phases, and current data suggests they lag behind Lilly and Novo.
Conclusion
Eli Lilly and Novo Nordisk are shaping the future of weight loss drugs with daily oral pills that could expand access beyond injections. While Novo’s oral semaglutide shows stronger weight loss results, Lilly’s orforglipron offers advantages in manufacturing, convenience, and potentially pricing. Both face questions around insurance coverage, commercialization strategies, and long-term tolerability, but analysts agree these drugs will be game changers in the $95 billion obesity market.