In the pursuit of the perfect body, appetite control remains a cornerstone. Fighting hunger is the most difficult stage for anyone who has been on a diet. Appetite blockers come to the rescue, but what is hidden behind this name? How did they evolve from dangerous stimulants to ‘smart’ peptides that trick the brain? Let’s look at the mechanisms, generations, and hidden risks of these powerful drugs.
Not all blockers are the same: 3 strategies to fight hunger
Before we talk about specific substances, it is important to understand how you can affect your appetite in general.
- Mechanical filling. The simplest and oldest way. This includes eating plenty of fiber, bran, or just plain water. The stomach fills up, its walls stretch, and a signal is sent to the brain: ‘I’m full.’ The effect is short-lived and not always effective.
- Central exposure (via the central nervous system). A more powerful, but also riskier path. Substances of this group directly affect neurotransmitters in the brain, which are responsible for the feeling of hunger and satiety. These historically include:
- Amphetamines and Ephedrine: Dramatically increase the level of dopamine and norepinephrine. The result is euphoria, a surge of energy, and a complete loss of appetite. The price is a huge load on the cardiovascular and nervous systems, irritability, tremor, a high risk of addiction and mental disorders.
- Sibutramine: Blocks the reuptake of serotonin and norepinephrine. This creates a persistent feeling of fullness. However, its side effects (tachycardia, increased blood pressure, irritability) led to the drug’s ban in most countries.
- Hormonal effects (peptide agonists). The most modern and physiological approach. These drugs do not’ break ‘the system, but’ deceive ‘ it, imitating the effect of natural satiety hormones that are released after eating.
Revolution: Peptide agonists or ‘Satiety Hormones’ in the syringe
This is the gold standard of modern pharmacology for weight control. Their work is based on the simulation of incretins — hormones of the gastrointestinal tract.
How does it work?
When you eat, your gut releases several hormones, including GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). They perform several tasks:
- They send a signal to the brain (in the hypothalamus) about saturation.
- Slow down the emptying of the stomach, prolonging the feeling of satiety.
- They stimulate the production of insulin in response to food intake.
Peptide agonists are synthetic analogues of these hormones that are resistant to rapid degradation and work for a long time.
Generations of ‘smart’ appetite blockers
Generation 1: GLP-1 agonists (Liraglutide, Semaglutide-Azempic)
- Operating principle: They selectively ‘sit’ on GLP-1 receptors in the small intestine.
- Advantages: Effectively suppress appetite, promote weight loss, improve insulin sensitivity.
- Cons and hidden nuances:
- Signal imbalance. There are also receptors in other parts of the intestine. When the signal comes from only one part of the brain, but not from others, the brain receives conflicting information. This leads to neurological side effects: nausea, irritability, ‘alarm’ in the body.
- Digestive problems. Greatly slows down the motility of the gastrointestinal tract. Meat and solid food are digested for a very long time, causing a ‘brick’ feeling in the stomach. Constipation occurs, and stagnation can form in the biliary system.
Generation 2: Dual Agonists (Tirzepatide-Munjaro)
- Operating principle: They activate two types of receptors at once — GLP-1 and GIP.
- Advantages: A more physiological effect, as the natural work of two hormones is imitated. This results in stronger and more comfortable appetite suppression, fewer side effects, and better weight loss results.
- An important caveat: Munjaro is not just a’ stronger ‘ Azempik. The . old medical tactic of ‘start with Azempic, and when it stops working, switch to Munjaro’ is incorrect. It is more logical to immediately use a more balanced drug.
Generation 3: Triple Agonists (Retatrutide)
- Operating principle: Three receptors are involved-GLP-1, GIP and glucagon. Glucagon is traditionally considered a blood sugar-boosting hormone, but in this bundle it enhances metabolic effects and thermogenesis.
- Advantages: To date, this is the most physiological and promising option. It provides mild but very effective appetite suppression without sudden food withdrawal, while demonstrating better performance in improving insulin sensitivity.
Hidden risks and what they don’t say in advertising
- Azempic-face and sarcopenia. The biggest danger. Drugs do not have the magical ability to burn only fat. On a caloric deficit, the body looks for light energy. And if you don’t consume enough protein, that energy becomes amino acids from your muscles. The result — loss of muscle mass, sagging skin, flabbiness of the face (‘azempik-face’), loss of strength. Solution: Increase protein intake to 2 g per kg of dry weight, use liquid amino acids and proteins that are easier to digest.
- Formation of antibodies. Peptides are proteins that are foreign to the body. Over time, the immune system begins to produce antibodies against them. This leads to tolerance: the dose stops working, and it has to be increased. After a few months at the maximum dose, the effectiveness may disappear. .: Use a course scheme (for example, 3 months of admission / 3 months of break) to allow the body to clear itself of antibodies.
- Psychological dependence. A person gets used to the fact that you can do nothing and not want to eat. After discontinuation of the drug, if the correct eating habits are not formed, the appetite returns with a vengeance, and all the weight is gained back. .: Use the drug as a ‘crutch’ for the duration of active weight loss, while radically changing your diet and lifestyle.
- Lack of vitamins and trace elements. Against the background of reduced appetite and difficult digestion, people begin to eat less not only high-calorie, but also healthy food. There are deficiencies of B vitamins, iron, which leads to hair loss, deterioration of the skin and nails. .: Mandatory intake of vitamin and mineral complexes, especially group B.
Application tactics: How to use wisely
- Don’t chase after speed. Rapid weight loss (more than 4-5 kg per month) is always a disaster for the metabolism and appearance. Tune in for a slow but stable result.
- Start with minimal doses. For sports purposes and comfortable diet compliance, doses 2-3 times lower than the starting ones indicated in the instructions for the treatment of obesity are often sufficient.
- Combine with enzymes and choleretics. To improve digestion, use pancreatic enzymes (such as Creon). Ursosan may be useful for preventing bile congestion.
- Analyze combinations. Do not mix drugs that affect the central nervous system (for example, Tesofensin) with antidepressants — this can lead to dangerous serotonin syndrome.
Of course, here’s a separate paragraph about microdosing for athletes:
Separately, it is worth highlighting the strategy of using microdoses of peptides, which is popular among athletes. Unlike the clinical approach, where the goal is maximum appetite suppression, here the task is different: not to kill the feeling of hunger completely, but only to dull it, making compliance with a strict diet psychologically comfortable..
Athletes use doses that may be 2-3 times lower than the official starting dose — for example, 100 mcg of Azempic instead of 250 mcg or 1 mg of Munjaro instead of 2.5 mg. Such microdosing does not cause complete rejection of food, which is critical for maintaining energy and performance during training, but it effectively removes the painful feeling of hunger, obsessive thoughts about food and helps to control ‘breakdowns’. This makes it easier to tolerate a caloric deficit, more accurately fit into the planned weight indicators and at the same time maintain muscle mass due to the ability to consume enough protein.
Peptides and drugs for controlling appetite and weight:
- Azempic (Semaglutide) – GLP-1 receptor agonist.
- Munjaro (Tirzepatide – is a double agonist of GLP-1 and GIP receptors.
- Retatrutide is a triple agonist (GLP-1, GIP, glucagon).
- Mazudutide is a Chinese analog of Munjaro (GLP-1 + glucagon).
- Liraglutide -GLP-1 agonist
- Sibutramine is a central appetite blocker (banned).
- Tezofensin is a central appetite blocker (triple serotonin, norepinephrine, and dopamine reuptake inhibitor).
- Cahriflutide is an analog of amylin.
Non-peptide substances for fat burning:
- BAM-15 -uncoupler of mitochondrial respiration.
- Metformin / Berberine – increased insulin sensitivity.
