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Semaglutide Looks Like the First Truly Impressive Weight-Loss Drug

Summary:
A large number of coauthors, with John P. H. Wilding as first author, report in the New England Journal of Medicine remarkable weight-loss results from semaglutide. The New England Journal of Medicine gives you two free articles a month if you sign up, and the article is relatively short, so you can easily read the results yourself. I didn’t find any flaw in this study: “a total of 1961 participants were randomly assigned to receive semaglutide (1306 participants) or placebo (655 participants).” It was a “randomized, double-blind, placebo-controlled trial at 129 sites in 16 countries in Asia, Europe, North America, and South America” based on “68

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Semaglutide Looks Like the First Truly Impressive Weight-Loss Drug

A large number of coauthors, with John P. H. Wilding as first author, report in the New England Journal of Medicine remarkable weight-loss results from semaglutide. The New England Journal of Medicine gives you two free articles a month if you sign up, and the article is relatively short, so you can easily read the results yourself.

I didn’t find any flaw in this study: “a total of 1961 participants were randomly assigned to receive semaglutide (1306 participants) or placebo (655 participants).” It was a “randomized, double-blind, placebo-controlled trial at 129 sites in 16 countries in Asia, Europe, North America, and South America” based on “68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo.”

Here are the bottom-line results of the study, in quotations from the article with bullet points added to distinguish different passages:

  • The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points (95% confidence interval [CI], −13.4 to −11.5; P<0.001).

  • Participants who received semaglutide were more likely to lose 5% or more, 10% or more, 15% or more, and 20% or more of baseline body weight at week 68 than those who received placebo (P<0.001 for the 5%, 10%, and 15% thresholds; the 20% threshold was not part of the statistical testing hierarchy) … Among the participants for whom data were available at the week 68 visit (1212 participants in the semaglutide group and 577 in the placebo group), these thresholds were reached by 86.4% (1047 participants), 69.1% (838 participants), 50.5% (612 participants), and 32.0% (388 participants), respectively, in the semaglutide group, as compared with 31.5% (182 participants), 12.0% (69 participants), 4.9% (28 participants) …

  • Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo.

  • Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time.

  • Similar percentages of participants in the semaglutide and placebo groups reported adverse events (89.7% and 86.4%, respectively) (Table 3). Gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation) were the most frequently reported events and occurred in more participants receiving semaglutide than those receiving placebo (74.2% vs. 47.9%).

To summarize, with one shot a week, participants achieved major weight loss with the kinds of health benefits one might expect from weight loss. Semaglutide did seem to cause gastrointestinal disorders (especially nausea and diarrhea) for many people, so it isn’t for everyone. But for those who don’t have those side effects, or only quite mild side effects, it sounds like a good deal. Note that these side effects are much less serious than the heart problems that can result from taking amphetamines, which do cause weight loss, but at a high cost.

Besides the nausea and diarrhea (which you would soon know whether you suffered from the drug or not), the most important caveat about the study is that its results were for people who had tried to lose weight in the past and were encouraged to eat less and exercise more during the study. Thus, the effects of semaglutide might be somewhat dependent on motivation to lose weight. The mechanism hypothesized by the authors of the study also suggests this as a real possibility. They write:

Weight loss with semaglutide stems from a reduction in energy intake owing to decreased appetite, which is thought to result from direct and indirect effects on the brain.

There are habit patterns and stress-related eating that might make It easy to eat a lot even if you aren’t hungry. The effects of semaglutide may be dependent on making an effort not to eat unless hungry. But that will be unclear until a semaglutide trial is done with less motivated participants.

When I was younger, I thought often that a drug solution to weight loss was only a few years off. That day was delayed long enough that I lost that confidence. But now, close on the heels of my finding the non-drug solution of fasting, perhaps the day of effective and relatively safe weight-loss drugs has arrived. There may come a time when fasting is only for health and not for weight-loss, since weight-loss has become easy.

For annotated links to other posts on diet and health, see:

Miles Kimball
Miles Kimball is Professor of Economics and Survey Research at the University of Michigan. Politically, Miles is an independent who grew up in an apolitical family. He holds many strong opinions—open to revision in response to cogent arguments—that do not line up neatly with either the Republican or Democratic Party.

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