Semaglutide Natural Alternatives | Over-the-Counter Options

When looking to conduct weight loss study, researchers may be wondering if there are any effective semaglutide natural alternatives.

This detailed review will discuss a few popular over-the-counter (OTC) supplements for weight loss and glycemic control and compare them to semaglutide.

In this comprehensive guide, we’ll answer common questions such as:

• Is there a natural alternative to semaglutide for weight loss?
• How do OTC options compare against semaglutide for weight loss?
• What other peptides are alternatives to semaglutide in weight loss trials?

Keep reading to learn about supplements for weight loss and glycemic control and how they stack up against semaglutide's clinical trial record. We will also share our most trusted source for purchasing high-quality semaglutide online.

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What is Semaglutide?

Semaglutide is an anti-diabetic and weight-loss peptide developed by the pharmaceutical company Novo Nordisk. It is a glucagon-like peptide-1 (GLP-1) receptor agonist, mimicking the function of the naturally-occurring GLP-1 hormone [1].

Semaglutide was initially developed for glycemic control and designed to mimic the glucose-lowering effects of GLP-1 through enhanced pharmacokinetics [1]. Its developers achieved this by modifying the hormone's active form GLP-1 (7-37) at several positions, including the addition of an octadecanoic (C-18) diacid moiety [2, 3].

As a result, semaglutide shares 94% homology with the GLP-1 hormone and has similar affinity to the GLP-1 receptors. It has a half-life of about 7 days, allowing for once-weekly administration subcutaneously [3, 4].

In addition to subcutaneous, semaglutide is the only GLP-1 receptor agonist that is available in oral form. Semaglutide tablets have been approved since 2019 by the United States Food and Drug Administration (FDA) as a treatment of type 2 diabetes (T2D) under the brand name Rybelsus [2, 5].

Injectable semaglutide is also approved for a variety of indications. Here’s a timeline of key regulatory milestones:

2017 

Injectable semaglutide is first approved for human use by the FDA as a once-weekly subcutaneous injection at up to 1.0mg/weekly under the brand name Ozempic [6].

2020

Injectable semaglutide (Ozempic) is approved for reducing the risk of major adverse cardiovascular events (MACE) in T2D patients [7].

2021 

Injectable semaglutide is approved in doses of up to 2.4mg/weekly under the brand name Wegovy as a weight loss therapy in adults with a BMI≥27 (and weight-related comorbidities) or BMI≥30 [6].

2022 

Semaglutide (Ozempic) is authorized for T2D management at a higher dose of 2mg/weekly [8].

2023 

Semaglutide (Wegovy) is approved for adolescents aged 12-17 who classify as obese (with a BMI for age and sex at the 95th percentile) [9].

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How Does Semaglutide Work?

Semaglutide works by activating GLP-1 receptors in target organs such as the exocrine pancreas, the brain, the stomach, the intestines, and white adipose tissue [10].

Here is a short guide to the main effects of semaglutide on each organ and the corresponding benefits:

Exocrine pancreas 

Semaglutide interacts with beta cells to stimulate insulin production, which increases uptake of glucose and lowers blood sugar. It also suppresses glucagon production by pancreatic alpha cells, thus reducing gluconeogenesis and glycogenolysis [4].

Stomach

The peptide slows gastric emptying by 38% for a few hours after a meal. This lowers postprandial glucose spikes and may induce early satiety [11].

Small intestine 

GLP-1 agonists like semaglutide stimulate the production of a peptide called Peptide YY (PYY) that acts as a natural appetite-suppressant. PYY is produced by the endocrine cells found in the small intestine to regulate hunger and increase satiety [10].

Adipose tissue

GLP-1 agonists like semaglutide may minimize the reduction of leptin production by fat tissue, which typically occurs during fat loss. Leptin suppresses appetite and high leptin levels are associated with more sustainable weight loss [10].

Brain

GLP-1 agonists like semaglutide interact with neurons found in the hunger center of the brain. Specifically, semaglutide’s activation of proopiomelanocortin/cocaine- and amphetamine-regulated transcript (POMC/CART) neurons is believed to promote feelings of fullness [10, 12].

By diminishing hunger and enhancing feelings of fullness, semaglutide can catalyze considerable weight reduction. For instance, a study in 72 obese subjects demonstrated that 20 weeks on semaglutide 2.4mg/weekly caused a 35% decrease in caloric consumption during a free, unrestricted test meal when compared to placebo [13].

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Semaglutide for Weight Loss

Semaglutide is approved as a weight loss medication thanks to impressive results from phase-3 trials in the STEP clinical development program [14].

STEP stands for “Semaglutide Treatment Effect in People with Obesity” and is an ongoing program initiated by Novo Nordisk that consists of several studies (STEP 1-10, STEP TEENS, STEP UP, etc.) investigating the effect of semaglutide 2.4mg/weekly on chronic weight management [14].

Here’s a quick guide to some of the most notable published and ongoing trials in the STEP series:

• STEP-1 is the first and largest STEP trial, involving 1961 nondiabetic but obese or overweight individuals. The authors reported that semaglutide at 2.4mg/weekly led to an average weight loss of 14.9% compared to 2.4% for placebo over 68 weeks. A substudy of this trial employed DEXA scans on 140 of the participants and reported that the weight loss was primarily due to fat loss rather than lean mass reduction [15, 16].
• STEP-4 included a total of 902 participants at 2.4mg/weekly for an initial period of 20 weeks. The volunteers were then randomly divided to continue the semaglutide regimen or switch to placebo for the remaining 48 weeks. After a total of 68 weeks, the semaglutide group experienced an overall average weight reduction of 17.4%. On the contrary, those transferred to the placebo group regained 6.9% of their body weight for a net mean weight loss of 5.0% [17].
• STEP-5 is the longest of the STEP trials and spanned 104 weeks at 2.4mg/weekly and reported a favorable safety profile with no serious safety concerns. Weight loss occurred progressively during the first 60 weeks, and was maintained for the rest of the trial. The mean placebo-adjusted weight loss was 12.6% [18].
• STEP UP and STEP UP T2D are ongoing trials that aim to evaluate the weight loss potential of semaglutide at a yet-to-be-approved dosage of 7.2mg/weekly, comparing it to the established 2.4mg/weekly dose for weight loss [19, 20].

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Semaglutide Natural Alternatives | Supplements, Diet, and More

Researchers may be wondering if there are natural supplements or OTC options that could match some of the aforementioned semaglutide benefits.

Below, we discuss some of the most potent over-the-counter supplements for glycemic control and weight loss. All in all, they hold some potential as natural alternatives to semaglutide.

Berberine

Berberine is an alkaloid found in plants like barberries and grapes. Berberine appears to workly mainly by stimulating an enzyme called adenosine monophosphate-activated protein kinase (AMPK) [21].

Activation of this enzyme signals to cells that energy reserves are low, forcing them to draw in glucose from the bloodstream, which lowers blood sugar levels. Several meta-analyses, the largest of which included 46 trials, confirm that berberine supplementation effectively reduces fasting blood sugar levels and improves glycemic control as measured via glycated hemoglobin levels in T2D patients [22, 23].
Researchers also report a potential weight loss effect of berberine, leading to a small reduction in BMI [23]. However, the research supporting its weight loss effects is scarce. Moreover, some authors warn that berberine supplementation may have diminishing returns after several months of use [24].

Chromium

Chromium is an essential mineral found in trace amounts inside a variety of plant products, but especially grains. Its main mechanism is directly tied to chromodulin, a chromium-dependent protein that augments the signaling of insulin receptors. Studies show a reduction in glycated hemoglobin following several weeks of chromium supplementation. However, the research is mixed regarding chromium’s potential to lower fasting blood sugar levels [25, 26].

Therefore, chromium's effects may lie primarily in reducing postprandial blood glucose. Two meta-analyses also suggest chromium may induce a small reduction in body weight (1-2lb) after 12 weeks of supplementation. While chromium is thought to reduce cravings, the evidence on this mineral supplement is still limited [27, 28].

5-HTP

5-HTP (5-Hydroxytryptophan) is a precursor to the neurotransmitter serotonin, and it occurs naturally in many plants, notably including the African plant Griffonia simplicifolia. 5-HTP supplementation appears to help improve mood, but it may also work for weight loss. Researchers have observed an increase in satiety and a decrease in binge eating with supplementation [29].

It may be most effective in individuals prone to emotional or binge eating. Studies in overweight subjects with T2D report significantly reduced appetite and energy intake, ultimately leading to weight loss [30].

While berberine, chromium, and 5-HTP may be among the most effective weight loss and glucose-lowering components in OTC supplements, their effects are clearly limited compared to semaglutide.

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Do note…

Moreover, natural options are not necessarily free of side effects or food-drug interactions. For example, berberine can cause gastrointestinal problems such as bloating and constipation. Due to its effect on AMPK, some studies suggest it may also hamper muscle hypertrophy, which is an undesired effect in subjects trying to build muscle [31].

Likewise, 5-HTP containing supplements should not be used alongside antidepressants due to an increased risk of serotonin syndrome [32].

Although semaglutide is not available OTC, qualified researchers can procure it without a prescription from a trusted vendor like our top-rated source for  research purposes.

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Optimizing Diet and Lifestyle

Regardless of whether semaglutide or OTC supplements are used, a weight loss intervention should always include lifestyle changes like implementing a healthy diet and exercise regime.

In fact, semaglutide is recommended for use only in conjunction with a balanced diet and exercise to maximize weight loss and ensure sustainable health benefits [6, 13].

Here are 7 evidence-based tips for researchers looking to design a weight loss intervention:

• Subjects should prioritize low-calorie foods, since maintaining a calorie deficit is essential to successful weight loss interventions. These include foods with low energy density and a low glycemic index, such as non-starchy vegetables, fresh fruits, whole grains, and low fat protein sources [33, 34, 35, 36, 37].
• Sufficient protein should be consumed at every meal to help stabilize blood sugar levels, prevent muscle wasting during weight loss, increase satiety, and boost energy expenditure. Low calorie protein sources include lean meat, seafood, legumes, and low fat dairy [38].
• Fiber consumption at every meal increases satiety while helping stabilize blood sugar levels. The best high fiber foods to include are fresh fruits, non-starchy vegetables, and whole grains. Studies also suggest that consuming fiber first during a meal increases satiety for further weight loss benefits [39, 40].
• Study participants are encouraged to ingest modest meal sizes, maintain consistent meal times, and practice mindful eating. Clinical data indicates a 10% uptick in food intake when meals are consumed amid distractions like electronic devices [41, 42].
• Study participants must ensure they stay well-hydrated throughout the study. Water needs must be adjusted according to physical exertion, surrounding temperature, and body mass. Drinking water prior to meals has been linked to lower subsequent energy consumption [43].
• Physical activity is a key element of any weight reduction program. Regular exercise increases caloric expenditure, benefits cardiovascular health, prevents muscle loss during low calorie dieting, and accelerates metabolism [44]. Participants are advised to include aerobic workouts, strength exercises, or a blend of both.
• Quality sleep is fundamental for weight loss, given its role in managing hormones linked to appetite control and metabolism. Study participants are recommended to strive for a minimum of 7-8 hours of undisturbed sleep per night [45].

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Semaglutide Alternatives | Top 3 Peptides

Several other peptides have also been studied for their anti-diabetic and weight-loss properties.

Like semaglutide, some of these such as the dual GIP/GLP-1 agonist tirzepatide and the GLP-1 agonist liraglutide are FDA-approved for certain uses [9].

Here are the top three peptide-based alternatives to semaglutide for weight loss:

• Tirzepatide works by simultaneously activating the GLP-1 receptors and the receptors for another incretin hormone called GIP (glucose-dependent insulinotropic polypeptide). It has shown superior anti-diabetic and weight-loss properties compared to other incretin mimetics, semaglutide included [46].

  Tirzepatide is already approved for glycemic control in T2D, showing clinically significant reductions in HbA1c from baseline [47, 48]. It is also under active research as a weight loss peptide in phase-3 studies, where it has led to over 20% weight loss within 72 weeks at the full dose of 15mg/weekly [49].

• Liraglutide is another GLP-1 agonist approved for various indications, including T2D management and weight loss [9]. Studies report that it can cause up to a 2.2% reduction in HbA1c from baseline in T2D subjects [50].

  Liraglutide at its maximum dose of 3.0mg/daily has been reported to cause up to 6.4% weight loss in 68 weeks of administration. Yet, this result is lower compared to the 15.8% drop in body weight at semaglutide 2.4mg/weekly [51].

• AOD-9604, also known as LAT 8881 or Tyr-hGH 177-191, is a modified C-terminal fragment of the human growth hormone. It is known as HGH’s lipolytic fragment that stimulates fat loss without counteracting the effects of insulin, stimulating IGF-1 synthesis, or inducing cell proliferation [52].

  Rat studies suggest that this HGH fragment may lead to a 50% weight reduction in obese animals without increasing the risk of insulin resistance [53]. Clinical research reports that the peptide may lead to a significant weight reduction in obese subjects within 12 weeks of administration. However, clinical findings to date on AOD-9604 are inconsistent, with some trials reporting no effect on weight loss [54].

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Is Semaglutide Safe?

Semaglutide is FDA-approved for multiple indications and is considered safe for use in both diabetics and non-diabetics [6, 55].

But like other peptides in its class, semaglutide is not free of side effects. Similar to other GLP-1 receptor agonists, semaglutide is associated with gastrointestinal (GI) complaints [4, 6].

For example, the largest STEP trial published to date reported that GI issues affected 74.2% of volunteers taking semaglutide, as opposed to 47.9% taking placebo. The most common GI side effects reported were [15]:

• Nausea (44.2%)
• Diarrhea (31.5%)
• Vomiting (24.8%)
• Constipation (23.4%)
• Dyspepsia (10.3%)
• Abdominal pain (10.0%)

The trial also reported potentially serious side effects that may occur due to the inhibitory effect of GLP-1 on cholecystokinin synthesis and gallbladder motility, which delays gallbladder emptying [56].

According to the STEP-1 trial, these events were of mild to moderate intensity and resolved without complications. Overall, they affected less than 3% of study volunteers and included [15]:

• Hepatic disorders
• Cholelithiasis
• Acute pancreatitis

Local site reactions following subcutaneous semaglutide may also include redness, swelling, inflammation, bleeding, and pain. These were reported with 5-7% incidence in both the semaglutide and placebo groups.

Researchers should also consider the contraindications for semaglutide, including:

• History of thyroid cancer
• Multiple endocrine neoplasia syndrome type 2 (MEN 2)
• Pregnancy
• Lactation
• Known allergy to semaglutide

Animal studies suggest that GLP-1-RAs, including semaglutide, could lead to reduced embryo size and developmental anomalies. Based on these concerns, pregnant women should be excluded from semaglutide trials [57].

Data from rat studies has likewise demonstrated an increased risk of thyroid C-cell carcinoma at high semaglutide doses. This is why a history of thyroid cancer or MEN 2 (multiple endocrine neoplasia type 2) is contraindicated for semaglutide use. The thyroid C-cell carcinoma risk observed in animal studies has yet to be confirmed in human trials [58].

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Where to Buy Semaglutide Online? | 2024 Edition

Researchers and laboratory specialists in need of semaglutide for scientific investigation are well-advised to carefully choose where to source it online.

We recommend the two following top retailers.

Limitless Life

After reviewing multiple online peptide stores, we recommend Limitless Life as a reliable supplier of research-grade semaglutide, available through their VIP Club.

Here is why we trust this vendor:

• Superior Purity: All peptides from Limitless Life undergo rigorous HPLC-MS testing at an independent laboratory. This meticulous process ensures product purity of 99%.
• Payment Methods: Limitless Life accommodates a wide range of payment methods, including credit cards, cryptocurrencies, and CashApp.
• Service and Support: Limitless Life’s proficient service and support team is available by phone and email to address all queries and concerns.
• Reliable Shipping: Limitless Life provides swift, reliable, and budget-friendly shipping solutions, with the fee waived for domestic orders of $350+.

Click the link below to sign up for the Limitless VIP Club to gain special access to semaglutide and other innovative research chemicals. Sign up is simple and instant:

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Research Chemical

Research Chemical also earns our endorsement as a top online supplier of research-grade semaglutide.

Here’s why they are worthy of consideration:

• Pure Peptides: Research Chemical sources their semaglutide exclusively from accredited American facilities and subjects each batch to rigorous quality testing.
• Easy Checkout: Research Chemical’s website provides a secure shopping experience with a range of payment options on offer, including credit cards, e-checks, and cryptocurrencies.
• Outstanding Support and Service: The vendor’s amiable customer service staff is always on hand to answer any questions about the company’s products.

Get 15% off at Research Chemical by entering the promo code “peptides15” at checkout.

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Natural Alternatives to Semaglutide | Verdict

Semaglutide is a GLP-1 receptor agonist that is FDA-approved for a variety of indications, including glycemic control in T2D and chronic weight management in adolescents and adults.

OTC supplements like berberine, chromium, and 5-HTP may be used as natural alternatives to semaglutide.

However, the weight loss and glucose-lowering potential of these dietary supplements is much lower compared to pharmacological compounds like semaglutide, liraglutide, and tirzepatide.

Scientists who wish to obtain high-quality semaglutide online should buy it strictly from a vetted vendor like our top-rated one here.

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