ADA2025: Is CagriSema Weight Loss Good Enough?

With two new publications in the New England Journal of Medicine, we are thinking that CagriSema has something to teach us about using weight loss outcomes to judge the merits of a new obesity medicine. Is more always better?

Researchers presented the data from these two pivotal clinical trials on CagriSema at the ADA Scientific Sessions yesterday. These are the details of results that underwhelmed investors and led to a drop in the Novo Nordisk stock price back in December when the company announced their toplines.

The problem? Weight loss with CagriSema did not meet an expectation that the bottom line number would be 25% or more. But doctors are saying that investors stuck in obsolete thinking about obesity – only in terms of weight loss.

REDEFINE  1

In this study of about 3,400 subjects without diabetes, CagriSema delivered weight loss of  22.7% in adherent patients (20.4% overall) after 68 weeks. Two things are worth noting. First, this protocol allowed people to stay on less than the full dose of 2.4 mg each of cagrilintide and semaglutide. And many patients did. The researchers note that this may have led to the second important thing. Treatment discontinuation due to adverse events in this trial was low, eight percent.

In short, people did very well with this combination therapy and did not require the highest dose for satisfactory responses.

REDEFINE 2

This trial was a study of 1,206 adults with overweight and obesity and also type 2 diabetes. After 68‑weeks, people achieved a mean weight loss of 13.7%. These results are consistent with the results seen for tirzepatide in this patient population.

Glycemic control improved significantly Almost three-quarters of patients on CagriSema (74%) reached an HbA1c less than 6.5%. On placebo, only vs 16% did. CagriSema also improved blood pressure, lipid inflammation, physical-function scores, and time in glycemic target range.

Bottom Line

So the bottom line for these studies is actually rather simple. While the weight loss numbers may be disappointing to investors, this does not mean that CagriSema is somehow inadequate to meet the the benchmark for weight loss that tirzepatide has set. Endocrinologist Tim Garvey summed it up when he presented the results:

“What the investors want is not what the clinicians want. This is plenty of weight loss.”

In the long run, we need to shift away from a preoccupation with weight loss outcomes and focus more on health gains. But it will take time to see what the health outcomes will be for CagriSema. Until that becomes clear, it will remain uncertain how competitive it will be.

Click here and here for the REDEFINE 1 and REDEFINE 2 trials. For further reporting on this research, click here, here, and here.

A Readout on Body Weight and Composition, photograph by Ted Kyle / ConscienHealth

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June 23, 2025