Novo Nordisk unveiled the results of a commercially risky study of CagriSema for obesity yesterday and it was another tough break for Novo Nordisk. The study aimed to prove that – at worst – this next generation combination obesity drug is as good as tirzepatide. There was a slim hope was that it might prove to be better. On both counts, CagriSema fell short.

That sparked another sharp drop in the value of Novo Nordisk stock. The 16% decline yesterday brought the cumulative loss in the stock price to 72% since it peaked in 2024.

A Non-Inferiority Trial

The term of art for this type of study is a non-inferiority trial. In such a study, researchers are not trying to prove the new drug is better. The primary objective is to show it is not meaningfully worse than the comparison drug. In this case the comparator was tirzepatide.

It was an 84-week study of adults with obesity but not diabetes. The primary outcome measure was percent weight loss. On tirzepatide, people who stayed on treatment lost 25.5%. On CagriSema, the number was 23.0%.

For each drug in isolation, these clinical results look great. But for CagriSema, it was not close enough to prove that it is no less effective than tirzepatide. “This is something of a swing and a miss,” as financial analyst Søren Løntoft Hansen aptly said.

Wildly Differing Interpretations

These are just topline results. We don’t have any of the details that will be necessary to understand exactly how and when CagriSema will have clinical value. Will it be the next leap ahead in clinical efficacy for obesity, displacing tirzepatide? Probably not. Will it be a solid addition to the currently sparse armamentarium of drugs for treating obesity? Quite possibly. Time will tell.

But financial analysts and business managers cannot wait for that. So in the company’s briefing on this yesterday, we heard sharply different interpretations of events. At one extreme, Emmanuel Papadakis from the research division of Deutsche Bank said to Novo Nordisk CEO Mike Doustdar:

“CagriSema looks somewhat obsolete now as a competitive upgrade to semaglutide, especially with the 7.2 mg semaglutide available, as you mentioned.”

Doustdar took offense and replied:

“I think, Emmanuel, to say it’s obsolete is quite belittling to a fantastic drug in all honesty. Again, when CagriSema will make it to the market early next year as the first amylin-based product, it will have the best weight loss label of any product marketed at that time. Let’s start with that. It will have the best weight loss label of any marketed product at that time.”

This comes close to sounding like some version of a political term of art: alternative facts. Suffice it to say that these results can be described in wildly different terms.

Stuck on Weight Loss

Let’s be frank. The true clinical value of CagriSema will emerge over time. It might prove to be a modest addition to the options clinicians can offer. It might turn out to be very valuable.

Right now, judgments are clouded by a preoccupation with weight loss as the end-all, be-all measure of clinical success. But the truth is that dealing with obesity is a marathon, not a sprint. The outcomes that matter to patients include weight loss, but many more factors come into play. Whether CagriSema is helpful to a large number of patients is something we will have to wait and see.

It will be more that a single measure of weight loss that tells this story.

Click here for the press release from Novo Nordisk on these topline results and here for a transcript of the investor briefing.  For further reporting, click here, here, and here. For perspective on how ever more weight loss cannot continue to be the singular measure of success in obesity care, here is free access to some fine reporting in the New York Times.

Smögen, Sweden, Seen Through an Empty Drinking Glass, photograph by W.carter, licensed under CC BY-SA 4.0