# Semaglutide (Ozempic) as a treatment for obesity



## Eddy Edson (Feb 11, 2021)

https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
		


New study just published; weight loss effect looks pretty strong (but note funded by Novo Nordisk, the maker of the drug).
METHODS​In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.

RESULTS​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). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was −15.3 kg in the semaglutide group as compared with −2.6 kg in the placebo group (estimated treatment difference, −12.7 kg; 95% CI, −13.7 to −11.7). 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. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).

CONCLUSIONS​In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.


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## Eddy Edson (Feb 11, 2021)

NY Times story: https://www.nytimes.com/2021/02/10/health/obesity-weight-loss-drug-semaglutide.html

_Those results far exceed the amount of weight loss observed in clinical trials of other obesity medications, experts said. The drug is a “game-changer,” said Dr. Robert F. Kushner, an obesity researcher at Northwestern University Feinberg School of Medicine, who led the study. “This is the start of a new era of effective treatments for obesity.”

Dr. Clifford Rosen of Maine Medical Center Research Institute, who was not involved in the trial, said, “I think it has a huge potential for weight loss.” Gastrointestinal symptoms among the participants were “really marginal — nothing like with weight loss drugs in the past,” added Dr. Rosen, an editor at the New England Journal of Medicine and a co-author of an editorial accompanying the study.

For decades, scientists have searched for ways to help growing numbers of people struggling with obesity. Five currently available anti-obesity drugs have side effects that limit their use. The most effective, phentermine, brings about a 7.5 percent weight loss, on average, and can be taken only for a short time. After it is stopped, even that amount of weight is regained.

...

The semaglutide study confirms what scientists already know, Dr. Kushner said: Willpower is not enough. In the new trial, participants who received the placebo and diet and exercise counseling were unable to see any significant difference in their weight.

Generally, insurers have refused to pay for the weight-loss drugs on the market. Semaglutide is likely to be expensive. The lower dose used to treat diabetes carries an average retail price of nearly $1,000 a month. (Insurers usually pay for diabetes drugs, Dr. Kushner noted.)

Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital and a member of Novo Nordisk’s advisory board, said the effectiveness of semaglutide was “phenomenal” and that the trial results may lead insurers to cover it.

Semaglutide is a synthetic version of a naturally occurring hormone that acts on appetite centers in the brain and in the gut, producing feelings of satiety. A high-dose regimen of the drug has not been studied long enough to know if it has serious long-term consequences.

And it is expected that patients would have to take it for a lifetime to prevent the weight loss from coming back._


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## Lucyr (Feb 11, 2021)

I’ve found that ozempic doesn’t make you magically lose weight without trying, but it does make it possible for you to lose weight if you try. It reduces the physical constant panic levels of hunger that make it hard for me to diet so that I can calorie count and focus on the mental side of dieting.

the last sentence is pretty concerning, implying that the weight will regain if I stop taking it. Though makes sense sadly as I’ll be much hungrier.


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## Eddy Edson (Feb 11, 2021)

Lucyr said:


> I’ve found that ozempic doesn’t make you magically lose weight without trying, but it does make it possible for you to lose weight if you try. It reduces the physical constant panic levels of hunger that make it hard for me to diet so that I can calorie count and focus on the mental side of dieting.
> 
> the last sentence is pretty concerning, implying that the weight will regain if I stop taking it. Though makes sense sadly as I’ll be much hungrier.



I think it's really interesting. 

Research in recent years confirms that it's harder to maintain weight loss than it is to achieve it, because leptin and other hormone feedbacks or whatever increase your hunger levels, more than your activity levels increase. Your body and brain want you to get fat again.  See eg a brief overview of Kevin Hall's excellent research in the area contained in the video here: https://forum.diabetes.org.uk/board...ality-what-matters-most-for-body-weight.91274

That varies a lot between people - I seem to have gotten lucky with my hormones for the moment - but the general point is that behaviour change, food policy change, anything like that just isn't going to cut it, as far as dealing with obesity goes. What we need is a safe, effective, cheap appetite suppressant pill, and this seems to be the closest thing so far (except for the "pill" and "cheap" part, of course).

Also, the 15% average body weight reduction reported in this study is precisely the same as the level Roy Taylor's research indicates as the general target for achieving T2D reversal in many cases for obese/overweight people. His studies show a large - 76% or something - proportion of T2D's getting to remission with his "Newcastle program" with this level of weight loss. But longer term, it doesn't seem like his program has any huge advantage over other behavioural programs for maintaining weight loss.  Stack the weight back on, and all the metabolic syndrome features, including T2D, return. Even the prospect of sustained escape from T2D often isn't enough to keep people's hunger hormones in line. So even more reason for an appetitie suppressant med in the case of T2D.

They should put it in the drinking water! (j/k)


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## Lucyr (Feb 11, 2021)

Eddy Edson said:


> I think it's really interesting.
> 
> Research in recent years confirms that it's harder to maintain weight loss than it is to achieve it, because leptin and other hormone feedbacks or whatever increase your hunger levels, more than your activity levels increase. Your body and brain want you to get fat again.  See eg a brief overview of Kevin Hall's excellent research in the area contained in the video here: https://forum.diabetes.org.uk/board...ality-what-matters-most-for-body-weight.91274
> 
> ...


It sounds like these people were taking higher doses but not sure what dose exactly, would be interested to know. I am taking 0.5 per week and still have 1-2 days a week where I get so hungry that I have to go over my calories. I’ve lost 4.2 kg (3.5%) so far this year but have a lot more to lose. I know you can try a higher 1.0 dose of this so I’m interested in trying that.


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## Robin (Feb 11, 2021)

The BBC have run a story on it this morning and sure enough, the woman interviewed now says she’s putting the weight back on.








						Obesity: Appetite drug could mark 'new era' in tackling condition
					

Some of the people on the 15-month trial lost more than a fifth of their body weight.



					www.bbc.co.uk


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## Lucyr (Feb 11, 2021)

I was hoping that losing weight may somehow help correct the hormones that are out of line in T2, but sounds then that it may be a need to take it for life. It’s a once a week jab though with for me the only side effect is manageable hunger levels, 6 days out of 7 I can now stick to my current calorie goal of around 1650 calories. I hadn’t given any thought to what happens when I stop it before so it has been interesting reading this morning. 

These trial participants seem to have been on 2.4mg, I’ve only been on 0.25 and now 0.5, the maximum at the moment for diabetes is I think 1.0. So going from taking 2.4 down to taking 0 must make you massively more hungry.


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## goodybags (Feb 11, 2021)

I’ve been on Ozempic since beginning of November
I’m surprised to see in the trial the dosage in the trial was as high as 2.4mg ?
I was told to take 0.25 once per week for the first month
then increase that to 0.5 mg once per week ongoing

sometimes I think I could use a higher dose than 0.50 mg, I take this on a Saturday and sometimes by Friday I’m feeling more hungry, but I would struggle to eat a full sized meal, I’m eating reduced size portions now,
this morning it feels like there’s a volcano erupting in my stomach ( I’m finding this occasionally)
maybe that’s the Metformin ? so hopeful i can reduce the dosage of Metformin as currently on maximum dosage of that, having previously had poor control of my sugar, Hba1c due later this month.

In addition to Ozempic, I’m eating a more healthy (less carbs) and testing properly 
just need to up the exercise levels slightly.


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## Lucyr (Feb 11, 2021)

goodybags said:


> I’ve been on Ozempic since beginning of November
> I’m surprised to see in the trial the dosage in the trial was as high as 2.4mg ?
> I was told to take 0.25 once per week for the first month
> then increase that to 0.5 mg once per week ongoing
> ...


I’m probably finding similar to you but maybe with more hunger, it’s helping with appetite but I still have at least one day a week with just unsatiable hunger, and can easily eat full size meals the other days, but the full size meal does then satisfy me and I don’t snack other than the 1 day a week. I have a DSN appointment this morning so I’ll ask about upping the dose.  

I also take mine on a Saturday. Which day do you feel fullest? For me it’s sunday.


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## goodybags (Feb 11, 2021)

Lucyr said:


> I’m probably finding similar to you but maybe with more hunger, it’s helping with appetite but I still have at least one day a week with just unsatiable hunger, and can easily eat full size meals the other days, but the full size meal does then satisfy me and I don’t snack other than the 1 day a week. I have a DSN appointment this morning so I’ll ask about upping the dose.
> 
> I also take mine on a Saturday. Which day do you feel fullest? For me it’s sunday.


I don’t think really feel a lot fuller on a Sunday than any other day (apart from a Frida) if that makes sense,
however am eating considerably less than I was pre Ozempic, and although by the end of the week I might feel more hungry, I would struggle to to eat that big meal or snack that I feel I want,
since I’ve been taking this not snacking so much, which is good for my blood sugars.

good luck at the DSN, your lucky to have one !


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## Eddy Edson (Feb 25, 2021)

Another study just published: https://jamanetwork.com/journals/jama/fullarticle/2777025?alert=article#

After 68 weeks of Ozempic 2.4mg plus intensive counselling, mean body weight reduction of 16%. A pic somebody put together:



Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity. The STEP 3 Randomized Clinical Trial​
*Interventions*_  Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks.

*Main Outcomes and Measures*  The co–primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight.

*Results*  Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was –16.0% for semaglutide vs –5.7% for placebo (difference, −10.3 percentage points [95% CI, −12.0 to −8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants.

*Conclusions and Relevance*  Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings._


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## Eddy Edson (Mar 24, 2021)

Results from the next stage of the study just published, looking at what happens when treatment is continued for 48 weeks after a 20 week initial period, versus moving to a placebo:









						Effect of Weekly Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity
					

This randomized trial compares the effects of continuing weekly treatment with subcutaneous semaglutide vs switching to placebo on change in body weight over 48 weeks among adults with overweight or obesity who completed a 20-week run-in period with semaglutide.




					jamanetwork.com
				






People who continued on the drug continued to lose weight; people who moved to a placebo put weight back on.


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## Lucyr (Mar 25, 2021)

The participants regaining the weight when moved onto placebo is a concern, but makes sense. They would suddenly be much more hungry so struggle to keep it off.


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## Eddy Edson (Mar 26, 2021)

Lucyr said:


> The participants regaining the weight when moved onto placebo is a concern, but makes sense. They would suddenly be much more hungry so struggle to keep it off.


Interesting thread: 



__ https://twitter.com/i/web/status/1374742273305366528


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