Novo Nordisk has strengthened its position in the fiercely competitive GLP-1 drug market with new data showing its weight-loss therapy CagriSema delivered superior weight reduction compared to Eli Lilly's Tirzepatide in a head-to-head Phase 3 trial.

On September 21, at its Capital Markets Day investor briefing, Novo Nordisk unveiled top-line results from two Phase 3 clinical trials of CagriSema. The REIMAGINE 5 trial demonstrated that patients with type 2 diabetes receiving CagriSema 1.0 mg/1.0 mg achieved an average weight loss of 12.4%, surpassing the 9.1% seen in the Tirzepatide 5 mg group. Meanwhile, the REDEFINE 9 trial showed that the therapy produced an average weight reduction of 21.0% in adults with overweight or obesity, compared to 2.0% in the placebo group.

Both trials met their primary efficacy endpoints. In REIMAGINE 5, beyond comparing weight-loss effects between the two drugs, CagriSema also met the non-inferiority criterion for HbA1c reduction versus Tirzepatide.

This data release comes at a pivotal moment, as CagriSema is currently navigating the U.S. regulatory approval process. Novo Nordisk submitted a New Drug Application (NDA) for the weight management indication to the FDA in December 2025, with an anticipated regulatory decision in the fourth quarter of 2026. If approved, the drug would directly challenge Tirzepatide in both the weight-loss and diabetes treatment markets.

Impressive Weight-Loss Results Put CagriSema in Direct Competition with Eli Lilly

REIMAGINE 5 was a Phase 3 study directly comparing CagriSema with Tirzepatide in adult patients with type 2 diabetes who had inadequate glycemic control despite treatment with metformin, SGLT2 inhibitors, or a combination of both.

By week 60, the CagriSema 1.0 mg/1.0 mg group showed a mean weight reduction of 12.4%, while the Tirzepatide 5 mg group recorded a 9.1% reduction. HbA1c levels decreased by 1.71% and 1.67% in the respective groups, with CagriSema meeting the non-inferiority threshold. Notably, this trial utilized a relatively lower dose of CagriSema, whereas Tirzepatide 5 mg represents one of its lower dosing regimens.

The separate REDEFINE 9 trial focused on adults with overweight or obesity. At week 68, participants treated with CagriSema 1.0 mg/1.0 mg achieved an average weight loss of 21.0%, compared to just 2.0% in the placebo arm. The therapy also demonstrated improvements in secondary measures, including systolic blood pressure, waist-to-height ratio, and fasting lipid levels.

FDA Decision Looms as Safety Profile Shows No New Signals

CagriSema is a fixed-dose combination therapy administered as a once-weekly subcutaneous injection, combining semaglutide with cagrilintide, a long-acting amylin receptor agonist.

Novo Nordisk submitted the NDA for the weight management indication to the FDA in December 2025, with the agency expected to render a decision in the fourth quarter of 2026. CagriSema has not yet received approval in any market. At the Capital Markets Day, the company also presented initial data on the therapy's use in treating painful diabetic peripheral neuropathy in type 2 diabetes, describing the preliminary results as promising.

Regarding safety, CagriSema was generally well tolerated in both trials, with a safety profile consistent with previous studies and no new safety signals identified. The company has not yet disclosed specific adverse event rates, which will be provided in future detailed disclosures.