Semaglutide

Sermorelin and semaglutide are two well-researched peptides derived from naturally occurring proteins found in most mammals, including humans. Both have shown profound benefits in helping to optimize body composition and both may have additional benefits beyond their most widely touted attributes. Many people are interested in the comparison between sermorelin vs semaglutide and want to know what the research says about these two peptides. The biggest similarity between sermorelin and semaglutide is their ability to alter body composition and promote fat burning. Despite this similarity and their similar relative effectiveness, these peptides promote changes in body composition through drastically different mechanisms.

Their ability to promote body composition change is where the major similarities between sermorelin vs semaglutide end. While they share some other, minor similarities, it is the differences between these two peptides that are of interest and will help determine how they are most effectively applied to a given situation. Here is a look at the differences between sermorelin vs semaglutide and why those differences matter.

What Is Sermorelin?

Sermorelin is a peptide analog of growth hormone-releasing hormone (GHRH). It is used to stimulate the production and release of growth hormone (GH) from the pituitary gland. In the clinical setting, this is primarily done to diagnose and treat growth hormone deficiencies in children and adults. As a prescription medication, sermorelin is primarily used to treat those with growth hormone deficiency as well as those experiencing excessive declines in growth hormone levels with age. As a research peptide, sermorelin has been deeply studied in a variety of animal models and in vitro settings.

What Is Semaglutide?

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It is primarily used for the treatment of type 2 diabetes mellitus, helping to control blood sugar levels by stimulating insulin release. Semaglutide is indicated for adults with type 2 diabetes who require better glycemic control, either as a standalone treatment or in combination with other diabetes medications.

Semaglutide is also used to produce weight loss in those suffering from obesity. Semaglutide works by mimicking the action of GLP-1, a hormone that stimulates the release of insulin from the pancreas, reduces glucagon secretion, slows gastric emptying, and promotes a sense of fullness. These actions help to lower blood sugar levels and reduce appetite[1], [2].

Semaglutide, a GLP-1 agonist and synthetic analogue of human GLP-1, is widely known for its ability to promote weight loss, lower blood sugar levels, and enhance growth of beta cells in the pancreas. Semaglutide produces weight loss in several ways.

• First, it decreases food intake by lowering appetite (a central nervous system effect) and by slowing down digestion in the GI tract.
• Second, it reduces insulin resistance and helps to shift metabolism away from fat storage.
• Third, there is also good evidence to support the ability of semaglutide to reduce cravings and help control feeding behavior.

Research indicates that over a 20-week period, semaglutide can lead to significant weight loss, assuming other factors like exercise and dietary choices remain consistent. One study demonstrated that semaglutide resulted in a weight loss of nearly 8% over 20 weeks, compared to nearly 7% weight gain in the placebo group. In more aggressive weight loss programs, semaglutide can yield a weight reduction of approximately 16% over 2-3 months, as opposed to less than 6% with a placebo[1], [2]. Semaglutide is typically administered as a once-weekly injection when used for weight management, which differs from the twice-weekly injections prescribed for diabetes management.

In recent months, with widespread usage of this peptide to induce weight loss, reporting on a number of off target effects has left people with a lot of questions. What follows is a look at some of these off-target effects and why they occur. Understanding their origin can help individuals to manage or avoid them. In some cases, however, the off-target effects are more important than the intended effects. In fact, there are several research trials investigating the “off-target” effects of semaglutide in the treatment of a variety of conditions such as neurodegenerative diseases and alcohol use disorder. In the future, semaglutide may be thought of less as an anti-obesity peptide and more as an anti-consumption therapeutic, making it easier for people to make healthy lifestyle and consumption choices.

Does Semaglutide Make You Tired?

Research indicates that semaglutide does make you tired, but that the degree to which it causes fatigue varies based on the specific preparation of semaglutide. In some clinical trials, semaglutide was observed to induce fatigue in about 0.4% of its users while in clinical trials for other forms of the peptide, fatigue occurred in as many as 11% of users[3]. Although fatigue is relatively infrequent, it does represent one of the potential off target effects associated with semaglutide. Most people report that the fatigue is self-limiting and generally resolves after a month or two of using the peptide. For others, the fatigue remains but is only a problem on the day that they take the injection. For these people, timing the injection to ensure that fatigue corresponds with their normal sleep cycle alleviates most of the problem.

The primary mechanism through which semaglutide can lead to fatigue is by creating a calorie deficit. It also seems likely that some central mechanism related to GLP-1 signaling may cause some cases of fatigue. After all, GLP-1 is released in response to feeding and is likely to blame for the “postprandial fatigue” we experience after eating. Research suggests that GLP-1 release is biphasic and that the second and longer phase, which occurs 30-60 minutes after eating, may account for the sleepiness many people experience after eating a large meal (e.g. Thanksgiving).

Recently, researchers have been investigating the ability of semaglutide and other GLP-1 receptor agonists to treat some of the symptoms associated with sleep apnea. It was originally thought that the weight loss properties of these peptides were enough to explain their benefit in sleep apnea, but research suggests that they may directly impact the duration of non-rapid eye movement sleep, which is the most restorative type of sleep. These trials are ongoing and few conclusions can be made about them at this time.

Managing the fatigue associated with semaglutide is relatively straightforward. Basically, eat a healthy diet, try to be active, and avoid alcohol. This latter factor is interesting because many people report reduced alcohol cravings after taking semaglutide. As we will see, there is evidence to support this claim. In the end, the fatigue usually resolves on its own with continued use of the peptide. Most people report no fatigue whatsoever with semaglutide and those that do experience find it to be mild.