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How Effective Are Ozempic, Wegovy, Rebelsus for Weight Loss? Examine the Data!

Social Media Weight Loss Success Stories Are Not Borne Out By the Study Data


The actual response people make to all GLP-1 drugs lies along a huge curve. In their studies, the drug companies must report the average response, not just the wonderful "I lost 100 pounds in three months" success stories. And the average weight loss result reported for all these drugs, compared to what you are seeing in social media, is very modest. 


A Two Year Study Shows the Real Impact

To give you an example, I will use the data from a major study published in Nature. 

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.

This study involved 304 people who passed through an initial screening process and took what sounds like Wegovy, the brand of semaglutide that Novo Nordisk has gotten approved for weight loss in healthy people.

Note that the screening process in the Nature study was specifically for people looking to attain weight loss. It eliminated anyone from the study group who had either a pre-diabetic or diabetic blood sugar. These were supposedly normal, healthy people. 

Semaglutide Caused Underwhelming Weight Loss For Many Who Took It

Of those who passed the initial screening, 13.2% did not stay  on the drug for 2 years, despite the fact that they were getting the drug for free. You have to assume that these people did not experience miracle weight loss. 


Of those who continued on with the study, 77.6% were female. 93% were White. The average weight of participants at the start of the study was 233 pounds and their average BMI was 38.5. (Obesity is defined as BMI over 30). The range of the starting weight of those in the study varied by almost 50 pounds from that 233 pound average.


Interestingly, the men in the study weighed on average only 1 lb more than the women, which I find surprising. But since almost 4 out of 5 participants were women, you have to assume that, as usual, it was mainly women concerned about their appearance who joined the study, along with a much smaller number of health-conscious men who were probably less obese than the average seriously overweight middle-aged American. 

After 2 full years on the drug, the average weight loss within the group who persisted was 15.2% of their starting weight. Simple arithmetic tells us that this works out to an average of 35 lbs lost. This leaves the group weighing on  average weight 198lbs. That is an improvement, yes, but far from miracle weight loss. 

Weight loss plateaued after 16 Months: Observe that if these people continued to take semaglutide after the two years were complete they would likely not have lost any more weight. This figure published with the Nature article shows that their weight loss had plateaued after 68 weeks  (16 months) and that their weight was actually starting to trend upwards at the end of the study. 


The Average Weight Loss is Skewed By Outliers.  Many Subjects Lost Little 

In the abstract of the Nature article is this statistic: 

More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001).

This actually means that almost 23% of the group--nearly a quarter--did not lose even 5% of their starting weight though they continued on in the study, taking the drug for two full years. This also means that the average 233 lb participant achieved a loss of less than 12 pounds. 

The drug also caused unpleasant side effects in 82% of those who took it, most notably vomiting and diarrhea. 

But what about those who lost significant weight?  The study tells us:

Weight loss of ≥5%, a threshold widely used to indicate a clinically meaningful response to therapy, was achieved by >75% of participants in the semaglutide group at week 104. Moreover, 61.8% of participants on semaglutide lost ≥10% of baseline weight, and over a third of participants had achieved at least 20% weight loss at week 104 in the semaglutide group. 

Applying this to the data we were shown, we see that though over three quarters of participants appear to have lost at least 5% of their starting weight--that 11 pounds on the 233 lb average starting weight, only 61.8% of participants lost 10% or more of their starting body weight. That implies that 38.2%, or roughly 4 out of 10 people in the study lost an average of only 23 pounds on an average starting weight of 233 lbs after 2 years on the drug. This likely still left them clinically obese.

And finally, we are told that only "over a third", an interestingly imprecise number which probably means 34%, achieved a weight loss of 20% of their starting weight. That represents a loss of 47 pounds on a starting weight of 233.

Missing Information Is Required to Understand that 34% 

As there was a near 50 pound range of weights in those who were included in the study, we have to wonder whether those who lost the greater amount of weight were those who started out with the highest weights of those included in the study. We also have to wonder what their sex was as it is very well known to anyone involved in dietary studies that men lose weight far easier than do women, especially middle aged women.

Unfortunately, the published study, apparently sponsored by Novo Nordisk, gives us no insight into how the percentages of weight loss broke down across the demographics of those participating.   

So  how Common Are Those who Lose 100 lbs We see On Social Media?

We can only assume they are a very small part of those "greater than a third" who lost more than 20% of their starting weight. Had the percentage been impressive, the authors of the study would have broken out that number and not included it in the 20% or more category.

A cure for the obesity epidemic? Sadly, No.

The Oral Version of Semaglutide, Rebelsus, Has Garnered Similar Effectiveness Statistics

Rebelsus is Novo Nordisk's oral pill version of semaglutide. Novo Nordisk has begun advertising it heavily on TV as you will have noticed if you are watching the MLB playoffs. As you can see from this review or the actual phase 3 study published August 26, 2023 in the Lancet, Rebelsus' efficacy and incidence of side effects as reported in this study is almost identical to that of the injectable versions of semaglutide.

Tirzepatide is yet another new GLP-1 drug just approved to be prescribed for weight loss. It is supposedly more effective, but you will have to wait to see the published long-term studies to see if it is any more effective in the long-term than the drugs we have just explored. Given that all the previous drugs are effective only in about 1/3 of those who take them and that they plateau after a year or two, I doubt you will see a different outcome. 

And, of course, with this latest drug, which unlike the semaglutide drugs prescribed for weight loss have no previous track record as diabetes medication,  you have no idea what the long term side effects will be. 

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