Semaglutide SELECT Study: No News Is News

Newspaperman in ParisSometimes the hardest news to digest is no news. This was certainly the case yesterday for Novo Nordisk, the market leader in anti-obesity medicines. Their stock dropped by nearly 13 percent when the company told investors that there would be no news on the semaglutide SELECT study.

So why was no news seemingly such big news? After all, a 13 percent drop in stock price in one day is a pretty big deal.

Expectations for a Landmark

The answer is really quite simple. It’s all about expectations. Analysts are expecting a lot from the SELECT study. The long form of the name for this study is Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity. In short, it is hoped to be a landmark study of major cardiovascular outcomes for patients treated with a highly effective anti-obesity medicine – Wegovy.

If the results were especially strong, an interim analysis with good results in the third quarter of this year (i.e., right now) would have been very big news. Indeed, some analysts had predicted this. Instead, though, the company yesterday announced there would be no such news and the trial would proceed to its planned completion next year.

Hindsight reminds us that these studies don’t care what we’re hoping or expecting. This is an experiment, so nobody knows what the answer will be until the experiment and its analysis are complete.

An Elusive Goal

Make no mistake. If the SELECT trial yields a positive result next year, it will be a big deal.

The goal of showing obesity treatment can prevent strokes, heart attacks, and deaths is something of a holy grail. With bariatric surgery, we have pretty good evidence for this. But the gold standard of evidence – a double-blind randomized, controlled trial – is not very practical in a surgical intervention.

Researchers tried to show that behavioral therapy for weight loss in obesity could prevent heart attacks and deaths with the Look AHEAD study. But that study stopped early because of a futility analysis. In other words, it became apparent that behavioral therapy was not enough to prevent heart attacks and an early death.

Likewise, a CV outcomes study of naltrexone/bupropion (Contrave) fell flat six years ago – in part because a premature release of study data caused the study to be halted early. A similar study of lorcaserin yielded a neutral result.

Inflated Expectations Make No News into Big News

This is why, at the end of the day yesterday, no news was big news for the stock price of Novo Nordisk and more than $20 billion of its market value fell away. For news about cardiovascular outcomes with semaglutide in obesity, we’ll just have to wait another year.

Click here, here, and here for more on the news yesterday for Novo Nordisk and expectations for the SELECT study.

Newspaperman in Paris, painting by Giovanni Boldini / WikiArt

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August 4, 2022

7 Responses to “Semaglutide SELECT Study: No News Is News”

  1. August 04, 2022 at 9:43 am, Allen Browne said:

    Patience is a virtue.


  2. August 04, 2022 at 12:17 pm, Elysia Burns said:

    Interesting that the behavioral therapy study was stopped because it became apparent that behavioral therapy was not enough.

    This seems like yet another data point showing that choice factors in less than we think.


  3. August 08, 2022 at 9:55 pm, Pam said:

    Could it also be an issue that thousands of physicians would love to prescribe Wegovy but have no access to do so due to issues with the pen?

  4. August 12, 2022 at 2:30 pm, Owen J Kelly said:

    Part 1 of my comment (character restrictions):
    I was a little disappointed in this article and its overreaching conclusions about the role of diet and exercise in weight loss, and especially sustained weight loss (Look AHEAD).
    First, let us not forget that all (to my knowledge) semaglutide trials included a reduced-calorie diet and increased physical activity (lifestyle intervention). For better evidence related to a weight loss drug, I expect the drug to have the benefit without any lifestyle intervention or dietary restrictions. I briefly searched the literature to see if SELECT included lifestyle intervention, but I could not find this information.

  5. August 12, 2022 at 2:30 pm, Owen J Kelly said:

    Part 2 of my comment (character restrictions):
    In September 2012, the NIH stopped the Look AHEAD trial, 11 years after it started, as the intervention was not significantly decreasing the occurrence of cardiovascular events (it must be noted that the intervention was considered safe by the independent advisory board).
    Look AHEAD showed an 8.6% weight loss in the first year (versus 0.7% in control). After 4 years the intervention showed a weight loss of 6.15%, showing weight loss was sustained. I stopped at 4-year data as it was close to the 5-year SELECT trial. (Obesity. 2006 May;14(5):737-52 & Diabetes Care. 2007 Jun;30(6):1374-83 & Arch Intern Med. 2010 Sep 27; 170(17): 1566–1575).

  6. August 12, 2022 at 2:30 pm, Owen J Kelly said:

    Part 3 of my comment (character restrictions):
    However, Look AHEAD also focused on good blood sugar control (meal replacements were diabetes friendly and nutrition education also targeted lower glycemic food choices). However, the ACCORD study showed that intensive therapy to control blood glucose increased mortality (N Engl J Med 2008; 358:2545-2559).
    Intentional weight loss, regardless of how it occurred, typically results in lower blood lipids, blood pressure and other CVD risk factors. If anything, all the Look AHEAD data would point to a null effect of sustained weight loss over 11 years on CVD mortality and morbidity, regardless of the intervention. I also did not find (in my brief search) a proposed mechanism of action for lower CVD related events due to semaglutide.

    • August 12, 2022 at 5:15 pm, Ted said:

      Thanks for sharing your thoughts. Yes, intensive diet and exercise programs for weight loss have health benefits, but not a reduction in mortality and major adverse cardiovascular events. For semaglutide, it’s already been shown that there is such a benefit for persons who receive it at the lower dose for type 2 diabetes.

      The open question is whether it delivers such a benefit at the higher dose for for obesity.