Semaglutide is a synthetic peptide that mimics the function of glucagon-like peptide 1, a naturally occurring hormone that plays a major role in regulating insulin levels and appetite.
As a result, semaglutide has potent effects on insulin production, glycemic control, and satiety levels, combined with improved pharmacokinetics allowing for once-weekly administration.
Moreover, the peptide is currently approved by the United States Food and Drug Administration (FDA) for a numerous uses, which include:
Type 2 diabetes management
Lowering cardiovascular risk in type 2 diabetes
Chronic weight management issues in adolescents and adults
For scientists looking to incorporate semaglutide into research, this guide will provide up-to-date information on the peptide’s efficacy, safety, dosage, and reconstitution process.
What is Semaglutide?
Semaglutide is a synthetic peptide analog of the naturally occurring glucagon-like peptide-1 (GLP-1) hormone. As an incretin, GLP-1 triggers the release of pancreatic hormones like insulin in the human body, aiding in the regulation of blood sugar levels after meals [1].
Semaglutide was discovered in 2012 by the Danish pharmaceutical company Novo Nordisk. It has similar effects on blood sugar as GLP-1, as it shares 94% homology with the active form of the hormone [2]. This allows semaglutide to bind to GLP-1 receptors throughout the body.
The chain of semaglutide is also made of 31 amino acids, but it is modified compared to GLP-1 (7-37) for enhanced stability and a prolonged half-life in the body [3].
The modifications include aminoisobutyric acid replacing alanine at position 8, an arginine substitution at position 34, and the addition of octadecanoic (C-18) diacid moiety at position 26 [4].
These changes make semaglutide more resistant to degradation by enzymes like DPP-4 compared to other GLP-1 receptor agonists such as liraglutide. This results in a prolonged plasma half-life that allows for once-weekly dosing.
Due to its potent effects and superior pharmacokinetics, semaglutide has been approved by the FDA for a variety of indications. Specifically, the peptide received its first regulatory approval in 2017 at the dose of 1mg/week for the treatment of type 2 diabetes (T2D) under the brand name Ozempic [5].
In 2020, 1mg/weekly injectable semaglutide was also approved for reducing major adverse cardiovascular events (MACE) in diabetics [6]. Further, the FDA-approved a higher dose (2mg/weekly) of semaglutide for these two indications in 2022.
Additionally, a maximum of 2.4 mg/weekly dose of injectable semaglutide has been approved for chronic weight management in adults since 2021 and in adolescents since 2023 under the brand name Wegovy (trade name by Novo Nordisk) [5, 7].
Researchers should also note that semaglutide is the first and only GLP-1 receptor agonist to have been developed and approved by the FDA in an oral form (brand name Rybelsus), and is indicated for T2D management since 2019 [8].
(Peptides.org, sponsored) Semaglutide peptide therapy: uses, dosage, and safety.
What Does Semaglutide Do?
Semaglutide works by activating the GLP-1 receptors throughout the body, which results in various therapeutic effects.
One of the peptide’s most notable effects is improved glycemic control. The peptide achieves this by interacting with the GLP-1 receptors in the pancreas, which stimulates insulin production by pancreatic beta cells and suppresses glucagon production by pancreatic alpha cells in a glucose-dependent manner [3].
The peptide may also help lower the postprandial glucose spike, which occurs right after a meal, and has been shown to slow gastric emptying by up to 38% within the first few hours after a meal [9].
Studies suggest that activation of the GLP-1 receptors in the central nervous system, particularly in reward-related brain areas, is the main mechanism via which GLP-1 receptor agonists modulate appetite [10].
More specifically, scientists suggest that GLP-1 receptor agonists interact with the neurons in the arcuate nucleus in the hypothalamus, which regulates appetite and hunger. These neurons express the so-called proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART).
Semaglutide directly activates POMC/CART neurons, which are known to induce satiety and indirectly suppress the release of two hunger-promoting peptides called neuropeptide Y (NPY) and agouti-related peptide (AgRP).
Studies also suggest that GLP-1 receptor agonists like semaglutide may help minimize the decrease in free leptin and induce higher levels of PYY3-36 during weight loss. This may also help sustain Semaglutide weight loss in the long term [11].
One study has reported that 2.4mg/weekly of semaglutide may result in a 35% reduction of ad libitum (unrestricted) mean energy intake after just 20 weeks of therapy compared to placebo (1736kJ vs. 2676kJ). The subjects in this study also lost 9.9% of their body weight, compared with 0.4% of the placebo group [12].
Semaglutide Benefits | Clinical Trials
Extensive clinical research has demonstrated the pleiotropic benefits of semaglutide. Here, we will explore the most notable semaglutide benefits documented to date, such as for weight loss, metabolic health, and glycemic control.
Semaglutide and Obesity
Semaglutide was approved for weight loss and chronic weight management in patients with or without T2D based on the results of phase-3 trials conducted as a part of the ongoing Semaglutide Treatment Effect in People with Obesity (STEP) program.
STEP is sponsored by Novo Nordisk and consists of ten phase-3 trials (STEP 1-10) geared toward exploring the utility of once-weekly 2.4mg semaglutide as a pharmacologic agent for obese patients.
As of writing, the STEP 1-6 trials, as well as the STEP-8 trial, are already published in peer-reviewed scientific journals. The largest of these trials was STEP-1, which included 1961 obese or overweight patients with related comorbidities but not diabetes [13].
The findings of STEP-1 revealed an average 14.9% reduction in body weight from baseline during 68 weeks of treatment with semaglutide 2.4 mg, compared with just a 2.4% reduction in the placebo group. Both groups also involved lifestyle intervention [14].
On the other hand, STEP-5 was the longest trial and lasted for two full years at 2.4mg semaglutide. The data revealed that the participants progressively lost weight over the first 60 weeks, after which they maintained their progress over the total 104-week study period. The total placebo-corrected weight loss with semaglutide was 12.6% [15].
Further, the STEP-8 trial compared the weight loss effects of 2.4mg/weekly semaglutide to 3.0mg/daily liraglutide over 68 weeks and revealed a significantly greater average body weight reduction of 15.8% with semaglutide, compared with 6.4% with liraglutide. The scientists reported that this equated to an average respective weight loss of 33.7lb and 15lb weight loss [16].
Apart from STEP 1-10, there are also ongoing STEP UP and STEP UP T2D trials, which aim to assess the weight loss effects of a not yet approved 7.2mg/weekly semaglutide dose vs. 2.4mg/weekly semaglutide in patients with and without T2D. These are estimated to conclude by the end of 2024 [17, 18].
Semaglutide for Fat Loss
Although semaglutide appears to induce potent weight loss effects, researchers may wonder if the weight reduction is primarily due to fat loss or if lean body mass is also significantly affected.
One of the largest studies investigating the effects of semaglutide on fat loss and body composition was a substudy of a phase-3 trial that compared 1.0mg semaglutide to 300mg canagliflozin in T2D patients.
A subset of 178 participants underwent a whole-body dual-energy x-ray absorptiometry (DXA) scan after 52 weeks of therapy. The total fat mass decreased by 7.5lb with semaglutide. Further, the total lean mass decreased by 5lb and the proportion of lean mass increased by 1.2%, suggesting improved body composition in the semaglutide group [19].
The STEP-1 trial also employed DXA scans on 140 participants taking 2.4mg/weekly semaglutide. This subgroup experienced a 15% reduction in body weight from baseline to week 68, whereas the placebo group showed just a 3.6% reduction.
By week 68, the semaglutide group had lost 18.41lb of total fat mass and 11.58lb of total lean body mass, compared to the placebo group, which had lost 3.03lb of total fat mass and 4.04lb of total lean body mass [14, 20].
Semaglutide for Type 2 Diabetes
Semaglutide is already approved as a medication for glycemic control in T2D patients. The approval was based on the favorable results of the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) clinical trial program.
SUSTAIN is a series of trials initiated by Novo Nordisk and conducted to evaluate the safety and effectiveness of the peptide in patients with T2D. The program consists of several trials, the latest of which (SUSTAIN-11) was published in 2022 [21].
The trials pitted 1mg/weekly semaglutide against placebo and various medications for glycemic control in T2D patients. The comparators included oral antidiabetics, injectable insulin, and other GLP-1 receptor agonists such as exenatide, dulaglutide, and liraglutide [22, 23, 24, 25, 26, 27].
Semaglutide showed superior effectiveness against all comparators in lowering glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels reduction. The trials also reported a favorable safety profile and a significantly greater body weight reduction with semaglutide therapy [22, 23, 24, 25, 26, 27].
Semaglutide Side Effects
Researchers should note that GLP-1 receptor agonists are linked to potential side effects, primarily related to gastrointestinal (GI) disturbances, and semaglutide is no exception [28].
According to the STEP-1 phase-3 trials, which involved almost 2000 volunteers taking 2.4mg/weekly semaglutide, the most common GI adverse reactions were [14]:
nausea
diarrhea
vomiting
constipation
Overall, these side effects affected 74.2% of the semaglutide group, compared to 47.9% of the placebo group participants, who also experienced GI discomfort.
Most gastrointestinal events were mild-to-moderate in severity, transient, and resolved without permanent discontinuation of the regimen. Nevertheless, 7% of participants in the semaglutide group discontinued treatment due to adverse events, compared to 3.1% of the placebo group.
Serious adverse events were reported in 9.8% of semaglutide participants and 6.4% of placebo participants. The difference was primarily due to a higher incidence of serious gastrointestinal and hepatobiliary disorders in the semaglutide group.
Gallbladder-related disorders, mostly cholelithiasis (gallstones), were reported in 2.6% of the semaglutide group and 1.2% of the placebo group.
Three participants in the semaglutide group experienced mild acute pancreatitis, but they all recovered during the trial period. The researchers also reported no significant difference between the groups in the incidence of benign and malignant neoplasms [14].
Researchers administering semaglutide injections to test subjects should also watch out for the following injection-related side effects around the site of injection:
pain
Itching
swelling
redness
(Peptides.org, sponsored) Semaglutide peptide therapy: uses, dosage, and safety.
Is Semaglutide Safe?
As mentioned, semaglutide is FDA-approved for various indications based on the effectiveness and favorable safety profile demonstrated by numerous phase-3 trials.
Nevertheless, researchers should be aware of the peptide’s contraindications before incorporating it into their studies.
For example, semaglutide is contraindicated in pregnant and breastfeeding women, as safety in these populations has not been investigated.
Animal studies also suggest semaglutide may increase the risk of thyroid C-cell carcinoma. Yet, these risks have not been confirmed in human trials. For the time being, semaglutide is thus contraindicated in patients with a history of thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN 2) [28].
Semaglutide Dosage Calculator and Guide
Semaglutide is marketed in both subcutaneous and oral formulations for therapy in T2D patients.
Scientists should note that the peptide is available for research purposes only as a powder that must be reconstituted and dosed properly in experimental settings.
The most appropriate dosing protocol for semaglutide research will depend on factors like research objective and study duration.
When conducting weight loss research with semaglutide, scientists can refer to available data from phase-3 trials on individuals with T2D and chronic weight management issues.
According to the data, injectable semaglutide should be applied via subcutaneous injection once weekly on the same day.
Each study should be initiated with a low starting dose of 0.25mg, which should be gradually increased every four weeks up to a maintenance dose of 2.4mg, depending on the subject’s tolerability.
Further, the published research suggests that semaglutide can be administered at 2.4mg/weekly doses for extended periods, and the peptide should not be cycled. In fact, the most common dosing protocols have a duration of 52-104 weeks and report that it may take 60 weeks until maximum effectiveness is achieved [15].
Here is a sample weight loss protocol for injectable semaglutide based on the scientific data:
Semaglutide Dose: 0.25mg/weekly for the first four weeks of the study period, followed by an increase to 0.5mg/weekly in weeks 5-8, 1mg/weekly in weeks 9-12, 1.7mg/weekly in weeks 13-16 and 2.4mg in weeks 17 and beyond.
Frequency: Once weekly at the same time every week.
Study Duration: 52-104 weeks.
Notes: Missed doses should be administered within five days, with the following dose delivered according to schedule. Do not exceed the maximum dose of 2.4mg/weekly.
Where to Buy Semaglutide Online?
For educational purposes, qualified researchers can obtain semaglutide without a prescription. However, it is important to exercise caution to avoid purchasing low-quality peptide products, which can have harmful side effects and may not be effective for research purposes.
To ensure that researchers are purchasing high-quality semaglutide, it is recommended to use a trusted source.
Here’s our recommendation for that:
The above link gives access to the Limitless Life VIP club, which gives advance notice of peptide sales and discounts on compounds like semaglutide.
Researchers will be thrilled to discover that purchasing from this vendor also offers the following benefits:
Reasonable Pricing: Limitless Life offers reasonably priced semaglutide and other peptides specifically designed for weight loss research.
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Flexible Payment Options: To provide convenience and flexibility, Limitless Life accepts various secure payment methods, including select cryptocurrencies and options such as Revolut, Cash App, and Zelle.
We highly recommend sourcing semaglutide from one of the reputable vendors above.
(Peptides.org, sponsored) Semaglutide peptide therapy: uses, dosage, and safety.
How to Reconstitute Semaglutide
For research purposes, semaglutide is supplied as a lyophilized powder that requires reconstitution with an appropriate solvent, be it bacteriostatic or sterile water. The choice of solvent is crucial as it determines the peptide’s shelf-life.
We highly recommend using bacteriostatic water, as sterile water does not inhibit microbial growth, making the peptide unsuitable for use within 24 hours—even if it’s refrigerated.
On the other hand, bacteriostatic water allows reconstituted semaglutide to remain viable for up to four weeks when stored correctly within a temperature range of 36 to 46 degrees Fahrenheit (2 to 8 degrees Celsius).
In addition, researchers will also need alcohol swabs, sterile syringes of at least 3cc, and sterile 1″ 20-gauge needles for proper reconstitution of semaglutide.
To simplify the process of gathering all necessary lab supplies, the Peptides.org team readily recommends BacteriostaticWater.org as a reliable vendor of research supplies, which are assembled in convenient kits.
Semaglutide Injections | A-Z Guide
Apart from knowing how to reconstitute the peptide, researchers need to be familiar with the proper method of administering a semaglutide injection.
Here’s a concise guide on correctly and safely administering semaglutide injections to test subjects:
Use sterile needles for each injection, and consider applying pain-numbing cream or ice to minimize discomfort.
Disinfect the injection site and pinch the subject’s skin using the non-dominant hand, taking into account variations in subcutaneous fat.
With the dominant hand, insert the insulin needle quickly into the pinched fold of the skin at a 45° angle, ensuring the bevel is facing up to prevent skin tearing.
Slowly push the syringe’s plunger to inject the peptide, allowing a few seconds before withdrawing the needle. Instruct subjects to apply light pressure on the injection site without massaging it.
Dispose of used needles in the sharps container, and always use new sterile needles and syringes for subsequent injections.
By following these guidelines, researchers can safely administer semaglutide injections to their test subjects.
FAQ
How is semaglutide delivered?
Semaglutide as a reference material is shipped as a lyophilized powder. Before subcutaneous delivery, the powder must be reconstituted into a liquid using an appropriate solvent, such as bacteriostatic water.
How to take semaglutide
Following reconstitution, semaglutide is administered as a once-weekly subcutaneous injection, most commonly into the abdominal area, at least two inches away from the belly button.
Is semaglutide a steroid?
Semaglutide does not have a steroid structure and cannot interact with the androgen receptors or other receptors for steroid hormones. Semaglutide is rather a 31-amino-acid peptide that works by activating the GLP-1 receptors in the human body.
Does semaglutide increase testosterone?
No, semaglutide does not appear to affect testosterone production in any way.
Does semaglutide build muscle?
No, semaglutide has not been linked to any muscle-building or anabolic effects.
Does semaglutide cause weight gain?
No, semaglutide is a potent appetite suppressant that usually results in weight loss rather than weight gain.
Semaglutide. Just. Works
In summary, semaglutide is a potent GLP-1 agonist that is suitable for once-weekly administration. It is already FDA-approved for various conditions, including T2D management, reducing MACE risk in diabetics, and chronic weight management in adolescents and adults.
The peptide is also the first and only GLP-1 agonist available in both oral and injectable forms for T2D treatment.
References
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