Two distinct synthetic peptides, AOD 9604 and Semaglutide, have been investigated for their potential to improve weight management. AOD 9604 is a peptide segment originating from human growth hormone (HGH). It is thought to promote weight loss by increasing fat oxidation and stimulating the breakdown of fat cells. An approved medication for type 2 diabetes and, more recently, weight management is Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 agonist). It functions by imitating the actions of GLP-1, a hormone that controls hunger and blood sugar levels. Semaglutide aids in calorie intake reduction, increased sensations of fullness, and decreased hunger. Clinical trials have demonstrated considerable weight loss outcomes with its once-weekly injectable administration.
Although these two peptides function through distinct processes, they have much in common. Additionally, they are conducting the research at various phases. Let’s dive into AOD 9604 vs Semaglutide.
The primary difference between AOD 9604 vs Semaglutide lies in their mechanisms of action and their subsequent effects on the body's systems. AOD 9604 directly targets fat metabolism by mimicking the way natural growth hormone regulates fat breakdown and oxidation without significantly affecting blood sugar levels or promoting muscle growth. In contrast, Semaglutide operates through the endocrine system by mimicking the action of the GLP-1 hormone, which regulates glucose metabolism and decreases appetite. As a result, Semaglutide not only aids in weight loss by reducing hunger and food intake but also helps manage blood glucose levels, making it particularly beneficial for individuals with type 2 diabetes. This fundamental difference in action—AOD 9604's focus on direct fat metabolism versus Semaglutide's broader impact on appetite suppression and glucose regulation—highlights their distinct weight management approaches and potential therapeutic applications.
Weight Loss Peptides
The weight management industry is currently experiencing something of a rebirth, having not seen any significant advancements in almost fifty years. The last truly effective medication in this class, Fen-phen, was taken off the market due to severe adverse effects before its recent comeback. Research into possible weight loss medications has stalled as a result of the negative reputation that fen-phen received. Rather, the majority of attention has been directed at food and exercise, with bariatric surgery being saved for the most severe circumstances.
Scientists have investigated some of the hormonal signals regulating the human body's energy balance in the last few decades. This first prompted research into peptide hormones such as ghrelin, which indicates hunger, and leptin, which indicates satiety. These findings briefly held great scientific acclaim and offered the prospect of straightforward medications to combat the rising obesity crisis. Unfortunately, the excitement was short-lived as researchers soon discovered that although these peptides were crucial for central nervous system signals of hunger and satiety, they were not the main attraction.
Even as interest in lay culture declined, scientists kept working in the background to understand better the intricate brain signaling that determines when and how much to eat by looking into peptide hormone signaling. During that procedure, they discovered that growth hormone, melanocortins such α-MSH, and GLP-1 natural peptide receptors all had significant effects on energy balance.
GLP-1: Semaglutide
Glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) are the two incretin hormones that the body produces. Both have receptors on the pancreas, intestines, vagal nerve, and brain and are generated in the intestines. Synthetic GLP-1 agonists include liraglutide and Semaglutide, among others. They imitate the physiological effects of GLP-1 by binding to the GLP-1 receptor.
Semaglutide stimulates the pancreas' ability to secrete and produce more insulin. For this reason, when the peptide was first created and authorized, it was intended to treat diabetes. Based on scientific evidence, it improves beta cell survival and proliferation, which makes it the first substance to target the fundamental cause of diabetes. It reduces A1c levels, a marker of long-term blood sugar levels, by 1% and all-cause mortality. When compared to baseline, it can boost insulin release up to ten times.
Semaglutide slows down the food's passage through the colon and distal small intestine in the GI tract. Stretch receptors cause the brain to receive signals to cease eating when food transit slows down. Therefore, one way Semaglutide reduces hunger is by shortening the time it takes for food to pass through the intestines.
Semaglutide dramatically reduces the urge to eat and creates feelings of satiety in the brain. Based on available data, it appears that this is most likely how Semaglutide works to cause significant weight loss. Participants dropped 8% of their body weight in a 20-week experiment without altering their diet or degree of exercise. Participants dropped 16% of their body weight when Semaglutide was administered with dietary and exercise changes.
Semaglutide, created in 2012 and given FDA approval for use in humans a few years later, aids in controlling hunger and cravings. Studies show that the peptide can lessen binge-like eating and drinking behaviors in rat and mouse models. These results suggest that the effects of Semaglutide on intake and consumption patterns may be widespread. Research to learn more about how Semaglutide reduces consumption behavior is still happening.
AOD 9604:
Growth hormone (GH) is a complicated hormone that regulates body weight and fat metabolism, among other aspects of body composition. Four factors account for the involvement of growth hormone (GH) in weight management: insulin sensitivity, fat metabolism, muscle growth, and hunger control. A keen reader will immediately be able to compare these characteristics of GH and those of the previously discussed incretins, such as GLP-1.
Growth hormone (GH) improves insulin sensitivity, which facilitates glucose absorption by muscle cells and inhibits the conversion of glucose into fat. This makes sense because growth in muscle and bone is also brought on by GH, which also promotes protein synthesis. Because of these characteristics, growth hormone (GH) is a valuable hormone for promoting an increase in lean body mass.
Furthermore, studies reveal that GH can promote lipolysis—the breakdown of fat that has been stored—by blocking lipoprotein lipase and activating hormone-sensitive lipase (HSL). This causes a shift in the balance of adipose tissue, or fat tissue, from production to breakdown. This might also be involved in how well GH controls appetite, but we'll talk about that at the conclusion of this section.
The GH fragment AOD 9604 is sometimes called the “lipolytic fragment” because to its capacity to promote fat metabolism. The distinct roles of the various parts of the GH peptide are probably due to their varying capacities to bind to receptors. This should not be surprising because many large compounds have many binding domains and multiple activities.
The advantage of focusing only on a portion of the GH molecule is the significant reduction of off-target effects. It seems that AOD 9604 just promotes fat burning, with no discernible impact on insulin resistance, levels of insulin-like growth factor-1, or the development of muscle and bone. This lessens the possibility of unintended side effects from long-term GH treatment. One advantage of AOD 9604 over Semaglutide is its oral activity, meaning it can be administered orally.
AOD 9604 has been shown to almost triple weight reduction in mice compared to a placebo. Nonetheless, there have been significant inconsistencies in clinical studies. AOD 9604 resulted in considerable weight loss in one research study when no dietary adjustments were made, but nearly no weight loss in another study when combined with a low-calorie diet and exercise.
The disparity observed in these outcomes could perhaps be related to the functionality of AOD9604. It binds to beta(3)-adrenergic receptors, which are known to be very changeable based on several circumstances, according to research conducted in mice. Interestingly, AOD 9604 boosts this receptor's levels and accelerates fat burning in obese mice. However, AOD 9604 does not affect beta(3)-adrenergic receptors in mice that are not obese[5]. To understand why these two clinical studies yielded such disparate findings, more study is required to ascertain whether dietary choices and/or physical activity also impact these extremely varied receptors.
Changes in appetite are the last method that GH causes weight loss. But this is a complicated process all around, especially with GH involved. This is complicated because it has been demonstrated that GH can both enhance and decrease hunger. Numerous studies have demonstrated that growth hormone (GH) increases appetite, but only for specific foods that are often lower in fat and sugar. How can a peptide simultaneously increase and decrease appetite?
Research on growth hormone (GH) has shown that it influences appetite via a minimum of four distinct mechanisms: binding to GH in the hypothalamus, controlling the release of ghrelin, encouraging the release of insulin-like growth factor-1, and indirectly by inducing the breakdown of fat.
The primary source of the hormone leptin, which indicates fullness, is adipose tissue. It basically serves as a signal to the body that food is not necessary and that fat is not being broken down. Therefore, it would make sense that AOD 9604's breakdown of fat would increase appetite. Adipose tissue produces other hormones besides leptin, and it's not the most powerful one either.
It is better to see fat as an endocrine organ than as a means of storing energy. This is because adiponectin, resistin, and leptin are just three of the hormones that are produced by adipose tissue. Adiponectin's main function is to enhance the transfer of glucose and free fatty acids into muscle, liver, and fat cells. Its blood concentration is many orders of magnitude higher than that of leptin.
In humans, resistin is predominantly expressed in macrophages and white adipose tissue in mice. Resistin levels are frequently higher in the blood of fat people. Resistin is a chemical that is thought to be pro-inflammatory and has been linked to the onset of diabetes and its consequences. Insulin resistance and compromised glucose homeostasis are thought to be caused by its interference with insulin signaling and glucose metabolism in target tissues. Most notably, resistin is linked to adipocyte proliferation and malfunction in adipose tissue, both of which can result in diabetes. AOD 9604 lowers resistin levels by boosting fat burning. Although it hasn't been shown, this element might be the main way that AOD 9604 encourages fat loss.
AOD 9604 vs Semaglutide: Summary
Up until now, research has indicated that Semaglutide is most likely the most successful peptide for weight loss, but there are other options as well. AOD 9604 has a lot of potential, especially in its capacity to control inflammation in adipose tissue and lower the chance of acquiring diabetes in the first place. AOD 9604 may also be a very good adjuvant to Semaglutide, helping to improve insulin sensitivity by reducing inflammation in adipose tissue, although much more research is needed in this area.
Ultimately, these peptides have provided important insights into the physiology of energy balance and have advanced our understanding of the fight against obesity. They have substantially contributed to the field's advancement and are the cornerstone for creating the following weight loss tools.