The readout
REDEFINE-1, the phase 3 trial of CagriSema in obesity, reported a 22.7% mean weight loss over placebo in participants receiving the max dose over 68 weeks. The cagrilintide monotherapy arm hit 11.5% and the semaglutide arm 16.1%. The combination beat both individual components — but the bar was higher.
Why it disappointed
Novo's management, in investor presentations through 2023 and 2024, had guided the market toward a loss near 25% with max dose aggressively escalated. In reality, only 57% of patients reached the max dose under the flexible protocol — a design detail analysts hadn't priced in and which dragged the mean number down.
Market reaction
Novo Nordisk shares fell roughly 20% on December 20, 2024, the largest daily drop in more than 20 years, wiping out approximately $100 billion in market cap. Eli Lilly rose 4% on the same day. Jefferies analyst Peter Welford wrote that 'CagriSema has gone from a potential threat to tirzepatide to an also-ran'.
What it means for the GLP-1 race
Tirzepatide (Lilly) keeps the efficacy crown at 22.5% in SURMOUNT-1. Retatrutide (also Lilly), in phase 3, has already shown ~24% in phase 2 studies. Novo will pivot to oral Amycretin and the subcutaneous Amycretin branch from 2025-2026, while continuing to squeeze Wegovy with new indications (renal, cardio).
Source: Novo Nordisk press release
