Mechanism of Semaglutide (ozempic/wegovy) for weight loss

[pumpkinhead]

Trying to figure out the exact mechanism of how semaglutide works for weight loss. What I have found so far is that it is a great appetite suppressor , but not much other than that. As some of you know when some of us older gays and gals do our yearly diets, our body likes to hit more and more stale points and hold on to weight. I am curious if there would be any benefit to this drug, IF we are not cheating on our diets, if our calories are already low.... something to break thru the platue's. Sometimes I get stuck for 7-8 weeks at a time, no matter how much cardio or calorie reduction I throw at my body...would love to find something to keep it going....as I know the older I get the harder and harder it is going to get.

 

[Palifter]

You almost answered your own question in regards to how the drug(s) work. In your case, it sounds like something more in line with T3, Clen, DNP, ECA etc would work better - true thermogenics, if you will. Also monitoring BG.

In my eyes these GLP-1 agonists will be a godsend for individuals who really struggle with food noise or just adhering to a “stricter” diet. Think of your average joe that is used to eating whatever, whenever with snacking in between - this is the demographic that will benefit the most imo. I also see it making a contest prep setting “easier”. A competitor is less likely to go through with cheating on their diet but that doesn’t mean the cravings aren’t there and annoying to say the least. I’m excited to see the long term and down stream effects of this class of drug in the years to come.

 

[pumpkinhead]

You almost answered your own question in regards to how the drug(s) work. In your case, it sounds like something more in line with T3, Clen, DNP, ECA etc would work better - true thermogenics, if you will. Also monitoring BG.

In my eyes these GLP-1 agonists will be a godsend for individuals who really struggle with food noise or just adhering to a “stricter” diet. Think of your average joe that is used to eating whatever, whenever with snacking in between - this is the demographic that will benefit the most imo. I also see it making a contest prep setting “easier”. A competitor is less likely to go through with cheating on their diet but that doesn’t mean the cravings aren’t there and annoying to say the least. I’m excited to see the long term and down stream effects of this class of drug in the years to come.

yea I was just confirming that was the only mechanism at work...appetite.... did not know if some other thing was causing weight loss in the test groups, i.e. lower blood sugar levels or something. I feel bad for my wife as she reallys struggles with the platue each year, we even have her on hormone pellets from doctor, thyroid from doctor, etc..etc.. but ever since she reached her mid 40's, her body has really been giving her problems. At some points we have even taken her calories as low as 1350-1400 and her body won't budge. Was hoping ozempic would have some magic ingrediant in it. lol. thanks for the reply.

 

[stackdizzy]

Semaglutide, sold under the brand names Ozempic, Wegovy and Rybelsus, is an antidiabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management, developed by Novo Nordisk in 2012.[17][18][19]

Semaglutide is a GLP-1 receptor agonist, meaning that it mimics the action of the human incretin glucagon-like peptide-1 (GLP-1), thereby increasing insulin secretion and increasing blood sugar disposal and improving glycemic control.

and

Pharmacology[edit]​

Semaglutide is chemically similar to human GLP-1, with 94% similarity. The only differences are two amino acid substitutions at positions 8 and 34, where alanine and lysine are replaced by 2-aminoisobutyric acid and arginine, respectively.[34] Amino-acid substitution at position 8 prevents chemical breakdown by dipeptidyl peptidase-4. In addition, the lysine at position 26 is in its derivative form (acylated with stearic diacid). Acylation with a spacer and C-18 fatty diacid chain increases the drug's binding to blood protein (albumin), which enables longer presence in the blood circulation.[35]

Semaglutide's half-life in the blood is about seven days (165–184 hours).[28][36] It can be administered by subcutaneous injection once weekly or once-daily by mouth. Based on its half-life and dosing frequency, it can be expected to accumulate more after each injection of the same dose or increasing dose. For this reason, patients may experience an increase in adverse effects throughout each 4-week phase of the same dose, and a possible increase in the satiety-inducing activity over the 4-week period.


Semaglutide subcutaneous injection predicted plasma concentration-vs-time curve for a 2.0 mg once weekly dose.
For a given dose of semaglutide subcutaneous injection, the drug will accumulate in the blood more after each injection until steady-state is reached. Steady-state is expected to occur between 28 and 35 days of repeat weekly dosing of the same dose. This is directly related to the absorption and elimination rate constants, which are reported to be 0.0286 and 0.00413 (fraction/hour), respectively. The peak and trough plasma concentrations are expected to vary by 30% during steady state (a 30% reduction from peak to trough). Note: the steady-state concentration will vary based on patient-specific factors. No significant difference in the decrease from baseline body weight was observed between groups taking it orally (20 mg and 40-mg) or subcutaneously.[37]

cut and paste from WIKI https://en.wikipedia.org/wiki/Semaglutide

 

[Black Beard]

Trying to figure out the exact mechanism of how semaglutide works for weight loss. What I have found so far is that it is a great appetite suppressor , but not much other than that. As some of you know when some of us older gays and gals do our yearly diets, our body likes to hit more and more stale points and hold on to weight. I am curious if there would be any benefit to this drug, IF we are not cheating on our diets, if our calories are already low.... something to break thru the platue's. Sometimes I get stuck for 7-8 weeks at a time, no matter how much cardio or calorie reduction I throw at my body...would love to find something to keep it going....as I know the older I get the harder and harder it is going to get.

Are you using any GH?

 

[slesh]

Semaglutide, sold under the brand names Ozempic, Wegovy and Rybelsus, is an antidiabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management, developed by Novo Nordisk in 2012.[17][18][19]

Semaglutide is a GLP-1 receptor agonist, meaning that it mimics the action of the human incretin glucagon-like peptide-1 (GLP-1), thereby increasing insulin secretion and increasing blood sugar disposal and improving glycemic control.

This is what confuses me. If it’s increasing insulin secretion then then the blood sugar disposal should be delivered into cells which then should cause weight gain, no? I thought these drugs were doing it without the insulin secretion and that’s what was helping with the weight loss? Maybe I’m way off here. Someone smarter than me please explain…

 

[cmryan]

This is what confuses me. If it’s increasing insulin secretion then then the blood sugar disposal should be delivered into cells which then should cause weight gain, no? I thought these drugs were doing it without the insulin secretion and that’s what was helping with the weight loss? Maybe I’m way off here. Someone smarter than me please explain…

Not if you’re taking in fewer overall calories due to the appetite suppression.

They also suppress (to a degree) gluconeogenesis in addition to the increased insulin secretion per unit of blood glucose. Net overall effect of lower of blood glucose. I suspect that’s also why some people complain of lethargy while using.

 

[stackdizzy]

MOA

Semaglutide is a glucagon-like peptide-1 receptor agonist. By mimicking the action of the incretin glucagon-like peptide-1 (GLP-1), it increases the production of insulin, the hormone that lowers the blood sugar level.[27] It also appears to enhance growth of pancreatic beta cells, which are responsible for insulin production and release.[28][29] Additionally, it inhibits the production of glucagon, the hormone that increases glycogenolysis (release of stored carbohydrate from the liver) and gluconeogenesis (synthesis of new glucose). It reduces food intake by lowering appetite and slowing down digestion in the stomach,[30] helping reduce body fat.[31] It reduces hunger, food craving, and body fat.[32][33]

Lowering Glucagon

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body.[3] It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose.[4] It is produced from proglucagon, encoded by the GCG gene

It also increases glycemic control in type 1 diabetics. which you would normally do through insulin injections.

"Perfect glycemic control" would mean that glucose levels were always normal (70–130 mg/dL, or 3.9–7.2 mmol/L) and indistinguishable from a person without diabetes. In reality, because of the imperfections of treatment measures, even "good glycemic control" describes blood glucose levels that average somewhat higher than normal much of the time. In addition, one survey of type 2 diabetics found that they rated the harm to their quality of life from intensive interventions to control their blood sugar to be just as severe as the harm resulting from intermediate levels of diabetic complications

Hope this answered your question. All of this was taken from wiki so I just didn't have to type all of it.

 

[stackdizzy]

Would it be as good as injections for BB purposes in lowering blood sugar...I don't know. Also does the inhibition of glucagon out weigh the slowing digestion. Another question.

 

[pumpkinhead]

Are you using any GH?

lets assume the person is using gh in our hypothetical model

 

[slesh]

Not if you’re taking in fewer overall calories due to the appetite suppression.

They also suppress (to a degree) gluconeogenesis in addition to the increased insulin secretion per unit of blood glucose. Net overall effect of lower of blood glucose. I suspect that’s also why some people complain of lethargy while using.

Even if all their calories are garbage - especially sugar?

 

[stackdizzy]

Rules applying to increased insulin < calorie deficit

 

[Durro]

Here’s a recent video on semaglutide

 

[cmryan]

Even if all their calories are garbage - especially sugar?

Of course. Why wouldn't it so long as the calorie deficit is maintained? Eating mostly garbage almost always makes it tougher to maintain a calorie deficit but that's where the drugs make up the for that. Maybe I'm missing what you're asking but the basic "cals in cals out" is the bottom line when it comes to these drugs. How the drugs accomplish it is the thing that is unique to them.

Many of the people prescribed this drug go from a generic American diet of a calorie surplus with ultra processed food and zero to little exercise to moderate (or even severe) calorie deficit diets. And studies keep showing that calorie content (for the vast majority) doesn't matter for weight loss. Going from 10% to 5% is a different matter, but energy balance is still a primary determinant. Could it be improved by eating a much "better" diet (basic level of protein, fiber and minimally processed foods)? It would certainly be better for overall health but perhaps not for weight loss.

Now, there's a crap ton of detail that comes along with that. In one of the studies of semaglutide, about 100 of the 2000 participants underwent dexa scans to examine lean body mass vs fat mass lost. That particular group dropped an avg of 30 lbs but 38% was lean body mass. Granted, no there details were recorded so their diets might have been 50g of protein per day and no exercise. Or they might have underwent the body transformation challenge type of thing. We don't have access to that information.

Anecdotally, I can say I've seen probably 12-20 people lose a fair bit to an obscene amount of weight using one of these drugs. Most of the people don't exercise and some retain the same eating habits as they previously had, which were garbage foods but less of them. Again, all of them lose weight and a few are downright concerning to me.

 

[need4tren]

It may work through other mechanisms but my personal experience it comes through appetite suppressant. I found myself even using higher doses after 3 or 4 days my body metabolizes the drug and I go back to being hungr, I have started pinning my dose every 3 days

Starting is rough

 

[xpoc]

My wife is on her 2nd bottle of it. She was not obese before...she was actually in decent shape, 30% bodyfat but overall very toned. She is just finishing her 2nd bottle and she is now down 30 lbs., bodyfat is at 16% (almost half) and she gained 3 lbs. of muscle. Keep in mind, she is over 50, has been working out for 10+ years...the only change was the addition of semiglutide. She looks better now at 50+ than she did in her 20's!

 

[stackdizzy]

I think on this board its just common knowledge that proper diet still needs to be maintained. People who don't lift and just cut out calories without regard to macros are not going to maintain muscle. Its beyond me how anyone on this board could not know that? I think Derek does a good job of explaining the drug pros and cons while still maintaining to plug his business. I have heard of people halving the dose twice a week and am considering doing it myself with Tirzepatide but that is only becuase I get hungrier more towards the 5th and 6th day after the shot.

 

[pumpkinhead]

My wife is on her 2nd bottle of it. She was not obese before...she was actually in decent shape, 30% bodyfat but overall very toned. She is just finishing her 2nd bottle and she is now down 30 lbs., bodyfat is at 16% (almost half) and she gained 3 lbs. of muscle. Keep in mind, she is over 50, has been working out for 10+ years...the only change was the addition of semiglutide. She looks better now at 50+ than she did in her 20's!

Does your wife already have a good diet? My wifes diet is always spot on, when dieting, but suffers from the platue's.... do you think if someones diet is already spot on, it could help them push thru the platues faster...she always has trouble dropping the last 10. She is 158lbs in this pic (from last year) , never hit her goal of 150 , her her body would not let it go and her bottom half needed to tighten up more.

 

[xpoc]

Does your wife already have a good diet? My wifes diet is always spot on, when dieting, but suffers from the platue's.... do you think if someones diet is already spot on, it could help them push thru the platues faster...she always has trouble dropping the last 10. She is 158lbs in this pic (from last year) , never hit her goal of 150 , her her body would not let it go and her bottom half needed to tighten up more.

your wife looks great! mine is not a competitor, she just wants to look better naked. and for that, the drug worked very well. i would speculate that even if you have a spot on diet, this stuff will still shed pounds. i don't know how or why exactly. the appetite suppressing aspect is very strong as it was a challenge for her to even get one meal down per day. as far as regulating blood sugar and insulin, i don't know, but it seems to make sense.

 

[pumpkinhead]

your wife looks great! mine is not a competitor, she just wants to look better naked. and for that, the drug worked very well. i would speculate that even if you have a spot on diet, this stuff will still shed pounds. i don't know how or why exactly. the appetite suppressing aspect is very strong as it was a challenge for her to even get one meal down per day. as far as regulating blood sugar and insulin, i don't know, but it seems to make sense.

good to know, I think she is going to give it a try, will report back results if she has any. As this year on her diet she is stuck again, right about the same weight.... never thought our bodies would change so much in our 40's lol. I guess this will be a good test if it works on someone with already a good diet, fairly lean, cardio and weights 5-6x per week. keeping fingers crossed.