Darwin's Our Take: FDA approves Novo Nordisk’s Wegovy pill

Novo Nordisk received FDA approval on Dec. 22 for its once-daily oral version of Wegovy (semaglutide), making it the first oral GLP-1 receptor agonist approved for weight management.

Approved in a 25 mg dose, the Wegovy pill is indicated for:

• Reducing excess body weight
• Maintaining long-term weight reduction
• Lowering risk of major adverse cardiovascular events

The approval applies to adults only and excludes patients under 18 and those with MASH.

Novo Nordisk is now the first company to bring an oral GLP-1 therapy to market for weight management.

“The pill is here… No other current oral GLP-1 treatment can match the weight loss delivered by the Wegovy pill,” said Novo Nordisk CEO Mike Doustdar.

OASIS 4 Trial Results

The FDA approval was based on the Phase IIIb OASIS 4 trial:

• 307 adults with obesity or excess weight
• At least one weight-related comorbidity
• No diabetes

Results at 64 weeks:

• 13.6% average weight loss (vs. 2.2% placebo)
• ~30% lost at least 20% of body weight

Side effects were similar to injectable Wegovy, primarily gastrointestinal. Discontinuation rates were:

• 6.9% (Wegovy pill)
• 5.9% (placebo)

Dosing and Switching Flexibility

Treatment begins at 1.5 mg and titrates to 25 mg by week 17.

Patients may:

• Switch from injectable Wegovy to the pill for maintenance
• Return to injectable dosing if the 25 mg pill is not tolerated

Novo Nordisk plans to launch the Wegovy pill in early January, with pricing now available for insured and self-pay patients.

Our Take

While the oral format improves convenience, adherence may be challenging. The pill must be taken:

• In the morning
• On an empty stomach
• With water only
• Followed by a 30-minute fasting period

This may limit appeal for some patients.

Eli Lilly’s oral GLP-1 candidate orforglipron does not have these restrictions because it is a small-molecule incretin rather than a peptide.

However, efficacy differences remain:

• Wegovy pill: 13.6% weight loss at 64 weeks
• Orforglipron: 12.4% weight loss at 72 weeks (highest dose)

Manufacturing advantages may favor orforglipron due to simpler production processes.

Prescribing behavior, payer coverage, formulary placement, safety profiles, and pipeline competition from companies such as Amgen, Pfizer, Roche, Viking, Zealand, and Structure Therapeutics will ultimately shape market adoption.

Lilly is also advancing retatrutide, while Novo has filed for approval of CagriSema, a semaglutide + amylin combination injectable.

Disclosure: Novo Nordisk is a client of Darwin Research Group.

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