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Semaglutide in JAMA Again: Maintaining a Benefit

If you had any doubt about prior reports that semaglutide is likely to be a “game changer” for obesity care, perhaps you should look at JAMA today. Just one month after another paper in JAMA, semaglutide is back in the journal. This time, it is a 68-week study that shows the value of maintaining therapy with semaglutide. In this placebo-controlled, randomized study, patients getting a once-weekly injection of semaglutide lost an average of 17.4 percent of their starting weight after 68 weeks.

Even more impressive is the large proportion – almost 40 percent – who lost 20 percent or more. These results were simultaneously published in JAMA and presented at the annual meeting of the Endocrine Society.

A Crossover to Placebo

The design of this study is somewhat different from the prior pivotal studies. This was a study where all 902 patients started out on the active drug. For patients who completed that 20 week start, the study randomized patients to either continue on the drug or switch to a placebo. The randomization was two to one, meaning that twice as many patients stayed on the active drug versus switching to placebo.

The point here is that obesity is a chronic condition and if a drug is working, continued treatment is necessary to maintain the benefit. Lead author Domenica Rubino explained:

“The message here is twofold. One, for the patient and the doctor, there is hope for the medical treatment of obesity. The results of this study also show us that continued use – chronic treatment for obesity – could be helpful. People not only lost a significant amount of weight with semaglutide from a clinical perspective, but we saw the continuance of weight loss, and those that continued did not experience regain. That is refreshing and hopeful, because the reality is not everyone with obesity can have, or wants, bariatric surgery.”

Other benefits were a reduction in waist circumference, lower blood pressure, and improved physical functioning.

Chronic Therapy for a Chronic Disease

The folks who switched over to placebo had lost about 11 percent of their body weight in the 20 weeks they received semaglutide. But by the end of the study, they had regained all but five percent of it.

This makes a key point. Obesity is not so different from hypertension, high cholesterol, or diabetes. The drugs to treat it don’t work if you don’t keep taking them. This is why it is a chronic disease. Maintaining therapy with semaglutide serves to maintain the benefit. And in fact, most patients continued to get additional benefits for the first year of therapy.

Results Will Vary

As the authors note, this is a well-controlled clinical study. Real world results will undoubtedly be a bit different – and every patient will have a different experience.

But this appears to be an option that will provide some patients a benefit comparable to bariatric surgery. That may wind up being a small number. Or it may be a number approaching 40 percent of the patients who try it.

If so, this will indeed be a big step forward.

Click here for the study, here, here, and here for further reporting.

Lamp Standards Along the Boardwalk, photograph © Bill Barber / flickr

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March 24, 2021

2 Responses to “Semaglutide in JAMA Again: Maintaining a Benefit”

  1. March 24, 2021 at 7:54 am, Allen Browne said:


    More good news.

    This brings up many questions:
    1)The usual group of 5% lost >20% without pharmacotherapy. Who are they? They are a bargain.
    2)70% lost >10% with pharmacotherapy- shown to have excellent health benefits
    3)about 80% lost > 5% with pharmacotherapy – even that amount of weight loss is beneficial.
    4)What is the benefit of weight loss over 10% – I.e. is it worth the cost?
    5)Who are those that lost <5% with pharmacotherapy – they need to be studied.
    6)Was the study carried out beyond 68 weeks – obesity is a chronic, lifelong disease.
    7)What is the projected cost over 10-20 years?

    • March 25, 2021 at 4:51 am, Ted said:

      All these are good questions, Allen, especially on the diversity of responses. For every treatment, there is a range of responses and that range likely reflects the tremendous variation in underlying factors causing obesity in different individuals. Regarding the long-term study, a five-year study of cardiovascular outcomes with semaglutide in obesity is ongoing. Results are due in 2023.