Novo Nordisk Drops 3.25% as CagriSema Trials Show Mixed Results

On June 23, 2025, Novo Nordisk's stock experienced a 3.25% drop in pre-market trading, reflecting investor sentiment following the release of comprehensive data from two Phase III clinical trials for its novel weight-loss drug, CagriSema.

Novo Nordisk recently disclosed the full results of its Phase III clinical trials for CagriSema, revealing that while the drug showed promising weight loss and metabolic improvements, it also had a higher incidence of gastrointestinal side effects compared to the placebo group. This outcome, while consistent with earlier interim data, fell short of market expectations, contributing to the stock's volatility. Additionally, the company recently underwent a leadership change, with CEO Lars Fruergaard Jorgensen being dismissed last month.

During the American Diabetes Association's annual meeting in Chicago, Novo Nordisk presented detailed findings from a 68-week clinical study. The results indicated that overweight or obese non-diabetic patients treated with CagriSema achieved an average weight loss of approximately 23%, while type 2 diabetic patients with obesity lost around 15.8%. In comparison, Eli Lilly's similar drug, Tirzepatide, marketed as Zepbound, achieved a 22% weight loss in a 72-week trial.

Melanie Davies, co-director of the Leicester Diabetes Centre and principal investigator of the diabetes trial, noted that CagriSema's efficacy data was "comparable to the best-in-class drugs," particularly in blood sugar control. The trial showed that 73.5% of patients in the treatment group achieved HbA1c levels of 6.5% or lower, significantly higher than the 15.9% in the placebo group.

Safety data revealed that 79.6% of CagriSema users experienced gastrointestinal reactions such as nausea, vomiting, and constipation, compared to 39.9% in the placebo group. The incidence of severe adverse events was 9.8% in the treatment group versus 6.1% in the placebo group. However, Novo Nordisk's chief development officer, Martin Holst Lange, emphasized that most side effects were mild to moderate and transient. Notably, 6% of CagriSema participants discontinued treatment due to adverse events, compared to 3.7% in the placebo group.

CagriSema is administered via weekly injections and combines Novo Nordisk's popular GLP-1 agonist Wegovy with the amylin mimetic cagrilintide. Davies highlighted that the lower dose group showed better weight loss outcomes than the higher dose group, suggesting a potential for optimizing dosage schedules to balance efficacy and tolerability. Animal studies suggest that amylin may increase energy expenditure, which, if confirmed in humans, could mitigate metabolic adaptations during weight loss.

Novo Nordisk plans to submit CagriSema for regulatory approval in the first quarter of 2026, with an anticipated approval date in early 2027. Beyond weight loss indications, the company is conducting additional studies on the drug's cardiovascular benefits. Flexible dosing regimens will be a key focus in clinical applications, allowing for controlled weight loss rates and reduced side effect burdens. The global obesity treatment market is highly competitive, and if approved, CagriSema will directly compete with Eli Lilly's GLP-1/GIP dual-target drug.