Semaglutide

Semaglutide—more commonly known by its brand names Ozempic and Wegovy—is a peptide that was originally designed as an anti-diabetic medication but was later discovered to be highly effective as a weight-loss drug; after some time, Semaglutide was approved as a weight-loss drug under the brand name “Wegovy.”

Semaglutide is classified as a GLP-1 (glucagon-like peptide-1, a hormone naturally produced in the intestines that helps regulate blood sugar and appetite) receptor agonist. If you aren’t familiar with the word “agonist” in this context, it describes a substance that binds to and activates a receptor, producing a biological response; this means that an increase in the body’s GLP-1 levels will trigger the desirable effects of Semaglutide, such as:

Semaglutide dosages generally range from 0.25 mg to 1.0 mg per week via injection into subcutaneous tissue (usually in your belly fat). If you aren’t a fan of needles, an oral version also exists.

I know it’s easy to think “I’ll get better/quicker results if I inject more!” This is flawed logic that doesn’t work with androgenic-anabolic steroids, nor does it work with peptides. My general advice is to use the least amount necessary to stimulate results. Taking too little of a peptide generally results in you wasting money, but taking too much can result in the amplification of negative side effects.

I urge higher caution when dosing Semaglutide (as well as any other GLP peptide) as it has a half-life of 7 days. This means that if you (accidentally or purposefully) take a double dose, you may find yourself in a rough situation for the next week due to exacerbated side effects.

I created the Peptide Dosage Calculator to help confirm your dose. Simply input a few details, such as vial and syringe volumes, and run the numbers.

Consider using the Peptide Dosage Calculator to help calculate your dose.

In the 1970s, scientists Dr. Joel Habener, Dr. Jens Juul Holst, and Dr. Svetlana Mosjov performed groundbreaking research on incretin hormones. Holst discovered that gut hormones affected insulin secretion, while Mojsov and Habener used early DNA technology to identify and characterize GLP-1 (glucagon-like peptide-1). Their research revealed that GLP-1 stimulated insulin secretion but had an incredibly short half-life of just 1-2 minutes (oh, how far we’ve come) in the bloodstream, which limited its potential in therapeutic applications. Nevertheless, these early discoveries were essential in the advancement of medicine.

Building on this foundation, scientists at Novo Nordisk, led by Lotte Bjerre Knudsen, began developing modified versions of GLP-1 with extended half-lives. They first created liraglutide in 1998, then pursued the development of semaglutide as a once-weekly alternative. Semaglutide's design incorporated several critical modifications: an amino acid substitution to prevent enzymatic degradation and a C18 fatty diacid attachment that enhanced albumin binding and reduced renal clearance, extending its half-life to approximately seven days. After extensive testing of roughly 4,000 molecular variations, researchers finalized semaglutide's structure, achieving the optimal balance between potency and extended duration.
Clinical trials for semaglutide began with a Phase II study in 2008, followed by the comprehensive SUSTAIN clinical trial program across multiple countries. The FDA approved injectable semaglutide (Ozempic) for type 2 diabetes in December 2017 based on seven clinical trials involving over 4,000 patients. Further research demonstrated semaglutide's effectiveness for weight management, leading to the approval of a higher-dose formulation (Wegovy) in June 2021—the first new drug approved for chronic weight management since 2014. Subsequent trials showed cardiovascular benefits, resulting in additional FDA approval for reducing cardiovascular risks. Novo Nordisk also developed an oral formulation (Rybelsus), expanding treatment options and making semaglutide one of the most significant therapeutic advances in metabolic health in recent decades.

Semaglutide offers substantial benefits for patients with type 2 diabetes, providing superior glycemic control through its action as a GLP-1 receptor agonist. Clinical trials have demonstrated that it significantly reduces HbA1c levels, with many patients achieving target levels below 7%. Beyond improving blood sugar control, semaglutide promotes significant weight loss, with patients typically losing 5-15% of their body weight depending on the dosage and formulation. This dual action addresses two critical aspects of metabolic health simultaneously. Additionally, semaglutide has shown cardiovascular benefits, reducing the risk of major adverse cardiovascular events like heart attack, stroke, and cardiovascular death in people with established cardiovascular disease. Its once-weekly dosing (for injectable forms) represents a significant convenience advantage over medications requiring daily administration, potentially improving treatment adherence.

The benefits of semaglutide extend beyond glycemic control and weight management. The medication has been shown to reduce blood pressure and improve lipid profiles, contributing to overall cardiometabolic health improvement. For patients with obesity, the substantial weight loss achieved with semaglutide treatment is associated with improvements in obesity-related complications, including sleep apnea, joint pain, and mobility limitations. Research suggests semaglutide may have beneficial effects on non-alcoholic fatty liver disease (NASH), which frequently co-occurs with obesity and diabetes. While gastrointestinal side effects can occur, particularly during initial treatment and dose escalation, these typically diminish over time for most patients. The development of both injectable and oral formulations has expanded treatment options, allowing healthcare providers to tailor therapy to individual patient preferences and needs. For many patients, the comprehensive health benefits and convenience of semaglutide make it a valuable treatment option for managing complex metabolic disorders.

As with any medication, Semaglutide does come with certain risks and potential side effects. Some of these include injection site reactions such as redness, swelling, or itching at the site where the medication is administered. Additionally, there have been rare reports of pancreatitis and medullary thyroid carcinoma (MTC) associated with the use of GLP-1 receptor agonists like Semaglutide.

In clinical trials, patients treated with Semaglutide reported a relatively low rate of adverse events compared to placebo. In most cases, the benefits of using this medication for diabetes management or weight loss outweigh the risks when used under medical supervision and in accordance with prescribed guidelines. However, it is important for individuals considering the use of Semaglutide to discuss their options with healthcare professionals and weigh the potential risks and benefits based on their personal state of health.