Novo begins a Phase 3 comparing two injectable cagrilintide presentations

Novo Nordisk's Phase 3 study comparing two different injectable presentations of cagrilintide against placebo has moved from "not yet recruiting" to "recruiting," according to trial registry tracking ^[1]. The study is testing cagrilintide, an amylin analog, in people carrying excess body weight, and is part of Novo's effort to build out a full clinical program for the drug on its own, separate from CagriSema, the combination of cagrilintide and semaglutide ^[1][2].

The interest in cagrilintide as a standalone treatment traces back to a September 2025 sub-analysis of the Phase 3 REDEFINE 1 trial. In that analysis, adults with obesity or overweight and a weight-related health condition, but without diabetes, lost an average of 11.8% of their body weight on once-weekly cagrilintide 2.4 mg over 68 weeks, compared with 2.3% on placebo, assuming full adherence to treatment ^[2]. About 1 in 3 participants on cagrilintide, 31.6%, lost at least 15% of their body weight, versus roughly 1 in 20, or 4.7%, on placebo ^[2]. When researchers counted everyone regardless of how consistently they took the drug, average weight loss was 11.5% with cagrilintide versus 3.0% with placebo ^[2].

Cagrilintide was described as generally well tolerated. The most common side effects were gastrointestinal, including nausea, vomiting, diarrhea and constipation, and these were mostly temporary and mild to moderate ^[2]. Nausea led 1.0% of people on cagrilintide to stop the drug permanently, compared with 0.1% on placebo ^[2]. Based on these results, Novo said it would move cagrilintide into a dedicated Phase 3 program, called RENEW, starting in the fourth quarter of 2025 ^[2]. Trial tracking now shows a related Phase 3 study, comparing two injectable versions of the drug, actively recruiting participants ^[1].

Cagrilintide works differently than approved GLP-1 obesity drugs. It mimics amylin, a hormone made in the pancreas, rather than the GLP-1 hormone that semaglutide and tirzepatide target ^[2]. Novo has framed this mechanism as a way to offer people another option if their response to GLP-1-based treatment is limited ^[2].

Why it matters for patients

For people currently on Wegovy, Ozempic, or considering CagriSema, this trial does not change what is available today. Cagrilintide as a standalone injectable is still investigational and not FDA-approved. But the size of the weight loss signal in the REDEFINE 1 sub-analysis, nearly 12% body weight reduction against about 2% for placebo, has raised the possibility that amylin-based drugs could eventually compete with or complement GLP-1 medications ^[2].

The reason this program matters strategically is also worth understanding. CagriSema, Novo's combination drug, has so far not matched the weight loss seen with Eli Lilly's tirzepatide (Zepbound/Mounjaro) in head-to-head comparisons discussed in the broader GLP-1 field. Cagrilintide alone is described as Novo's hedge, a separate path forward in case the combination does not close that gap. Patients weighing their options between companies and drug classes may see more choices in coming years, but nothing here changes prescribing today.

Any new drug also comes with new safety questions. The gastrointestinal side effects reported for cagrilintide so far look similar in kind, though not necessarily in degree, to those already known for semaglutide and tirzepatide ^[2]. Longer-term safety and comparative effectiveness data are not yet available.

What happens next

The newly recruiting trial comparing two cagrilintide injectable presentations is now enrolling participants, though a completion date was not available in the sources reviewed ^[1]. Novo's broader RENEW Phase 3 program for cagrilintide monotherapy was slated to begin in the fourth quarter of 2025 ^[2]. Results from these later-stage trials, and any regulatory filings that might follow, are not yet known.