Semaglutide Forum: Game Changer for Weight Loss

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Mark A. Moyad, MD, MPH & Martin M. Miner, MD, discuss the potential benefits of semaglutide, a newly approved weight-loss drug.

Semaglutide is a medication that has been approved by the FDA to treat type 2 diabetes and has also been approved for obesity management under the brand name Wegovy [1][3]. It helps with weight loss by suppressing appetite, which can lead to a reduced intake of food [2].

semaglutide for weight loss.webp


Semaglutide works by mimicking a hormone called glucagon-like peptide-1 (GLP-1), which is naturally produced by the body. GLP-1 plays a role in regulating blood sugar levels and appetite. Semaglutide affects several processes in the body, including increasing the release of insulin, reducing the release of glucagon, and delaying gastric emptying [2].

The increase in insulin helps lower high blood sugar, while the reduction in glucagon release also contributes to better blood sugar control. Delaying gastric emptying means that food stays in the stomach for a longer time, which can help with satiety and decrease appetite [2].

The typical dose of semaglutide for weight loss is 2.4 milligrams, administered weekly as subcutaneous (under the skin) self-injections [3]. While semaglutide has shown promising results in weight loss, it is important to note that its effectiveness is dependent on continued use, and some experts are skeptical about its long-term safety and limitations [1].

In semaglutide studies, participants experienced significant weight loss. In one clinical trial, participants who received semaglutide lost 5% or more, 10% or more, 15% or more, and 20% or more of their baseline body weight at week 68, compared to those who received a placebo [1]. On average, participants taking semaglutide lost 15% of their body weight [2]. Some individuals lost as much as 40 pounds while participating in a clinical trial of the drug [2].

In another study, after 68 weeks of treatment, the semaglutide group lost an average of 16% of their baseline body weight, equal to 37 pounds. This was compared to a 5.7% average weight loss, or 14 pounds, for those assigned to intensive behavioral therapy combined with a placebo [3]. These results demonstrate the significant weight loss potential of semaglutide in clinical trials.

There are a few ways to save on semaglutide for weight loss, which is available as the brand-name medication Wegovy. One option is to use a copay savings card from the manufacturer. If you have commercial insurance, you may be eligible to pay as little as $25 for Wegovy using this savings card [1]. More information about the copay savings card and other coverage options can be found on the Wegovy website [2].

It's important to note that the cost of Wegovy before insurance is around $1,627 per month, and coverage for weight loss drugs like Wegovy can vary widely depending on the type of insurance you have and your location [3]. The $25 copay card provided by the manufacturer may help ease the cost, but only if your insurance plan covers the medication [3].

A more affordable way to get semaglutide when insurance does not pay is to have your doctor fax a prescription to a compounding pharmacy like EmpowerPharmacy.com. Their price runs approximately $350 per month.
 
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Would you people please speak with an endocrinologist and stop the bro science. These medicines can’t be compounded and they have no effect on the leptin production in the body.
 
I read somewhere that Semaglutide produces antibodies which make it less effective as time goes on. I’m concerned about anything that has the potential to form antibodies because we don’t know the long term effects of how this plays out on our bodies. Any thoughts on this?
About 3% will develop antibody titers
 

What is this if it can't be compounded?
I drove by Empower yesterday going out of town its not so far from my house.. They have a huge complex off of Beltway 8 close to the horse racing track. I have to fine the time to go by there and ask for a tour.
 
Here is a link to the patend of semiglutide synthesis

I have two friends that both are very experienced in peptides synthization. Both own their own equipment and have even produced hGH. I promise if you have the knnowledge, thisis not very hard to reproduce with the proper equipment.


Several peptides comprising the amino acid sequence H-His-X-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Y-Glu-Phe-Ile-Ala-Trp-Leu-Val-Z-Gly-Arg-Gly-OH are well known in the art as insulinotropic peptides. These peptides include GLP-1, Liraglutide and Semaglutide.

Human GLP-1 (Glucagon-like peptide-1) has the formula H-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly-OH.

Liraglutide is an Arg20-GLP-1 analogue substituted on the ε-amino group of the lysine in position 20 of the above sequence with a Glu-spaced palmitic acid. Thus, Liraglutide has the formula H-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(Pal-γ-Glu)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (see also FIG. 1, all chiral amino acid residues are L-amino acid residues). In Lys(Pal-γ-Glu) the ε-amino-group of the Lys residue is linked with the γ-Glu carboxylic side-chain and the Glu is N-palmitoylated.

Semaglutide has the formula H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(AEEA-AEEA-γ-Glu-17-carboxyheptadecanoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH. Herein AEEA-AEEA-γ-Glu-17-carboxyheptadecanoyl is N-(17-carboxy-I-oxoheptadecyl)-L-γ-glutamyl-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl (see also FIG. 2, all chiral amino acid residues are L-amino acid residues).

These peptides can, e.g., be used in the treatment of diabetes II. Further, e.g., Liraglutide can be used in the treatment of obesity, as injectable adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients.

Here is another good paper on the current manufacturing of peptides

 
About 3% will develop antibody titers
Here are the results of a step 2 clinical trial using semaglutide on obese adults for a 68 week period. No where did they find patients developed antibody titers.

This is the 2nd time antibody titers has been brought up and no one has bothered posting reference to this despite me asking. I am tying to have an open mind but I hesistate to get too excited over broscience. I prefer scientific data since it is available.


Here is a clinical trial Phase 2 study, no mention of antibody titers. This is a 52 week study.


Am I missing something?
 
What we do know for sure is GLP-1 receptor agonist suppresse the hunger hormone, ghrelin. plasma active ghrelin diminished from 137.0 to 27.7 (pmol/L). The rate of gastrict emptying has a big effect on both leptin and ghrelin.


Gastric emptying


Semaglutide causes a delay of early postprandial gastric emptying, thereby reducing the rate at which glucose appears in the circulation postprandially.

Here is a phase 3 trial.....the evidence is stacking up...68 weeks here.

 
Would you people please speak with an endocrinologist and stop the bro science. These medicines can’t be compounded and they have no effect on the leptin production in the body.
Interesting you mentioned an endocrinologist. Here in Houston we are well known for our good folks in the medical profession, we have a medical center that is one of the best in the world. My wife went to see an endocrinologist for hunger issues. He tested her blood and determined her cholesterol was high and put her on a statin. He never bother asking her what kind of diet she was on.....KETO. . This expert endocrinologist who charged $650 for his time has no clue the effect of a keto diet high in saturated fat on blood cholesterol levels, nor did he everey bother looking into the causeof the hunger issue. There was no need in a statin so we tossed the script in the garbage. Wonder how many endocrinologists have any clue how a peptide is synthesized?

Did you ever read the research paper my send me that is a biochemist and does do work synthesizing peptides, including semaglutide. Are you guilty of passing off bro science? So far you have not backed up and thing you have claimed.

Speaking of medicines.....Oxytocin is a peptide hormone and neuropeptide and was isolated from pituitary tissue in 1920 and 1st synthesized in 1952. This ...a medicine is not new science. Its amino acid sequence is Cys – Tyr – Ile – Gln – Asn – Cys – Pro – Leu – Gly – NH2 or CYIQNCPLG-NH2. Do you honestly believe that this could not be synthesided in a good lab? A good compounding pharmacy like EMPOWER would most likely have solid phase and/or the 3rd gen liquid phase peptide synthesis equipment?

Yes, Semaglutide is also classified as a medicine by also has a amino acid sequence. Once again, the products you claim you sell are reconstituted and must be refridgerated. They do not sell the raw powder form as 99.9% of the population would never be able to reconstitute, even with directions. The raw powder is much more stable since it is not reconstituted. But then I remember pointing that out to you.

Please get off the bro science and start producing some scentific evidence. The onus is on you.

Again
 
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Here are the results of a step 2 clinical trial using semaglutide on obese adults for a 68 week period. No where did they find patients developed antibody titers.

This is the 2nd time antibody titers has been brought up and no one has bothered posting reference to this despite me asking. I am tying to have an open mind but I hesistate to get too excited over broscience. I prefer scientific data since it is available.


Here is a clinical trial Phase 2 study, no mention of antibody titers. This is a 52 week study.


Am I missing something?
Here is one reference from Drugs.com:

Immunologic​

Frequency not reported: Development of anti-semaglutide antibodies

As with other protein and peptide pharmaceuticals, patients receiving this drug have developed anti-semaglutide antibodies. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, as well as other factor in handling of the sample. For these reasons, the incidence of antibodies cannot be directly compared with other products. Anti-drug antibodies to semaglutide have been reported in up to 1% of patients during clinical trials.
 
<1% is pretty rare. Can't see this as a big concern. Too many large subject clinicals trials have show very good success with this stuff in 52-68 weeks. But thank you posting this. I have yet to see this mentioned anywhere in clinical trials.
 
Let's hope it doesn't work as good as fenfluramine.

@BigTex I am holding my nose taking the escitalopram but so far so good.

 
I still remember when fen-phen was sold locally. As soon as that was ended phentermine was took over. My wife used this stuff a few times but it seemed like after a month or so it just quit working.

We still have lots of weight loss clinics using this stuff. Cheap prices and no insurance accepted. $100 for the exam, blood work and 90 day prescription. Of course you have to pay extra to get the prescription filled.
 
My first post from People Mag:


1673394278477.webp



And recent RCT:

Unless you have diabetes I am not sure why you would pull this lever simply to shortcut fat loss. No go. Would one stay on this for life instead of retraining their brain/metabolism/gut with the hard work?
 
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