Article 93: Classification of Weight Loss Drugs and Appetite Suppressants

Existing weight-loss drugs use various ingredients, but can be broadly categorized as follows: ① Food suppressants: These include: a. Amphetamines (serotonergic drugs); b. Central appetite suppressants (amphetamine, phentermine, masindole); c. Monoamine reuptake inhibitors (sibutramine). They primarily achieve weight loss by reducing appetite, but some are stimulants that also reduce sleep and appetite. Long-term use can lead to addiction and adverse symptoms such as anxiety, insomnia, high blood pressure, and vomiting.

② Energy-consuming agents: These drugs achieve weight loss by accelerating energy consumption, but due to significant side effects, they have been gradually phased out in other countries. These drugs include: a. thyroid hormones; b. hypoglycemic agents (biguanides); c. β₂adrenergic agonists; d. mixtures of ephedrine and caffeine; e. other hormones. ③ Absorption inhibitors: These drugs are basically divided into two categories. One type inhibits fat absorption, such as lipase inhibitors (orlistat). The other type uses a sham diet, allowing non-caloric, indigestible substances to remain in the stomach, thus eliminating hunger and achieving weight loss, such as fat substitutes. ④ Others: melanocortin receptor agonists, leptin, glycopyrrolidone, orexin, and glucagon-like peptide-1.

Among the emerging pharmaceutical products, some new drugs with good efficacy and few side effects have appeared. These are generally classified into the following categories: ① Drugs affecting lipid metabolism: These hinder lipid metabolism and reduce the accumulation of adipose tissue. Insulin secretion inhibitors: These inhibit excessive insulin secretion, reducing glucose production and fat synthesis. ② Laxatives and diuretics: These increase excretion, reduce intestinal absorption of fat, and excrete water. However, they can cause the body to lose a significant amount of inorganic salts and vitamins, and have some side effects. ③ Naloxone: This reduces appetite, but as a psychotropic drug, it can damage the liver.

While the aforementioned weight-loss products, whether traditional Chinese medicine or Western medicine, can achieve weight loss, obese individuals should only use them under the guidance of a doctor. The choice of Western medicine should be especially cautious, as drugs have multiple effects and side effects. Long-term use of any particular drug can easily lead to disorders of the endocrine, cardiovascular, digestive, and respiratory systems, causing drug-induced diseases and affecting health. Furthermore, the main weight-loss methods of Western medicine are through suppressing appetite, increasing energy expenditure, hindering absorption, and affecting metabolism. Once medication is stopped, weight is likely to rebound, at which point drug resistance develops, making subsequent weight loss more difficult. Traditional Chinese medicine for weight loss is slower to take effect, making it difficult for some obese individuals to adhere to the regimen. Some traditional Chinese medicines have strong laxative effects; if the laxative effect is too strong, it can easily cause dehydration and other illnesses.

Drugs that can decrease appetite are called appetite suppressants. Human appetite is regulated by the feeding and satiety centers in the hypothalamus. Excitation of the feeding center leads to overeating, while inhibition of the feeding center leads to anorexia. Conversely, excitation of the satiety center leads to food refusal, while inhibition of the satiety center leads to overeating. Most appetite suppressants affect both the feeding and satiety centers, thus inhibiting appetite.

Amphetamine-type drugs were discovered in the 1930s to have appetite-suppressing effects and were used for weight loss in the treatment of narcolepsy. The main mechanisms of action of these drugs are: ① promoting the release of dopamine and norepinephrine while blocking the reuptake of catecholamines at nerve endings, thereby suppressing appetite. ② affecting the central nervous system, promoting metabolism, increasing thermogenesis, and thus promoting energy consumption. ③ affecting fat metabolism and promoting fat breakdown. The main side effects of this class of drugs include: nervousness, irritability, palpitations, headache, dizziness, excessive sweating, dry mouth, tremors, insomnia, increased blood pressure, nausea, and vomiting.

Contraindications for amphetamine-type drugs include: ① Hyperthyroidism and glaucoma. ② Hypersensitivity to sympathetic amines. ③ Use of monoamine oxidase inhibitors. ④ Pregnancy and occupations involving hazardous substances.

The main amphetamine drugs include: dextroamphetamine, tolueneamphetamine, benzyl tolueneamphetamine, chlorobenzylamphetamine, chloropropylamphetamine, cyanoethylamphetamine, nicotinamide, phenylbutanylamine, chlorophenylbutanylamine, chlorophenylbutanylamine ester, o-amphetamine, fenfluramine (fluoroamphetamine), fluoroamphetamine phenyl ester, and benzyl phenylbutanylamine.

Fenfluramine is an amphetamine-type appetite suppressant. It has a weak central nervous system stimulant effect. It can lower blood pressure, increase peripheral tissue glucose utilization to lower blood sugar, and also reduce triglycerides, cholesterol, and total plasma lipids. It is well absorbed orally, reaching peak plasma concentration in 2–4 hours, with effects lasting 6–8 hours. Its half-life is 18–30 hours, and steady-state plasma levels are reached after 3–4 days, producing therapeutic effects. Most of it is slowly excreted in the urine as metabolites. It can be used for simple obesity and obese patients with diabetes, hypertension, cardiovascular disease, or anxiety. Each tablet contains 20 mg and is taken orally. During the first week, take 20 mg twice daily, 30–60 minutes before breakfast and dinner. During the second and third weeks, take 20 mg three times daily, 30–60 minutes before breakfast, lunch, and dinner. Thereafter, depending on efficacy and tolerability, the original dose can be maintained or increased to 80–100 mg daily, but 100 mg daily is limited to severely obese individuals. A course of treatment lasts 8–12 weeks. Common adverse reactions include increased non-diarrheal bowel movements, dizziness, drowsiness, dry mouth, abdominal discomfort, nausea, increased nocturia, and depression. However, these symptoms are generally well-tolerated and gradually disappear with continued use. For those who cannot tolerate the symptoms, dose reduction will eliminate them. Contraindicated in patients with depression, epilepsy, and pregnant women. Use with caution in individuals with severe arrhythmias, those working at heights, and drivers. Do not take medication intermittently during treatment. Gradually reduce the dose over the last 4–6 weeks of the course of treatment until discontinuation; abrupt discontinuation is not recommended. Continuous use should not exceed 6 months, otherwise drug tolerance and psychological dependence may develop. Contraindicated in pregnant women. Avoid concurrent use with monoamine oxidase preparations. In obese patients with hypertension and diabetes, synergistic effects may occur when used in combination with antihypertensive or hypoglycemic drugs; therefore, the dosage should be appropriately reduced.

From 1996 to 1997, fenfluramine was widely used in combination with other weight-loss drugs for weight loss in Europe and the United States. However, after large-scale clinical application, it was found that this drug could increase the incidence of valvular degeneration and pulmonary hypertension, so the U.S. Food and Drug Administration banned it in 1997. However, research on its side effects has continued, and the debate over whether to use this drug for weight loss has persisted.

Some American scholars have suggested that when using fenfluramine as a weight-loss drug, the dosage should be small, it should be used alone, and the duration of use should generally be 3 months, and should not exceed 6 months.

These drugs include amphetamine, phentermine, and masindole. They act directly on the central nervous system, inhibiting appetite by suppressing the hypothalamic feeding center and stimulating the satiety center. Masindole can also promote systemic metabolism and glucose uptake by skeletal muscle, increasing energy expenditure and reducing weight.

Dosage: Amfepramone 75 mg, once daily, orally; Phentermine 15 mg, orally half an hour before breakfast, after 3-5 days, reduce to 15 mg, once before breakfast and dinner; Maindo 1 mg, orally before lunch, after 1 week, can be increased to 1 mg, once before breakfast, lunch and dinner.

Side effects: thirst, constipation, stomach upset, nausea, vomiting, insomnia, headache, etc. High doses may cause auditory and visual hallucinations. Contraindicated in patients with schizophrenia and those already using monoamine oxidase inhibitors.

Some studies suggest that this drug has significant addictive properties, rebound effects upon withdrawal, and a significant central nervous system stimulant effect, and it is becoming obsolete.

The imported brand name for this drug is Nometrine, and the domestic brand name is Qumei. This drug can significantly increase satiety and suppress appetite; it can also increase glucose utilization, thus promoting weight loss. With the development of the world economy, obesity, a threat to human health, has attracted the attention of the medical community worldwide. Besides affecting physical and mental health, obesity also increases the incidence and mortality of hypertension, hyperlipidemia, diabetes, and arteriosclerosis. What worries medical experts most is that obesity is gradually spreading to adolescents. While one-third of obese patients have genetic factors, the majority of obese individuals are related to food.

In 1997, the World Health Organization (WHO) established Body Mass Index (BMI) as the standard for judging obesity: a BMI less than 18.5 is considered underweight, 18.5–24.9 is considered normal, 25–29.5 is considered overweight, and greater than 30 is considered obese. Treatment for obesity generally involves three methods: dietary restriction, exercise, and medication. Currently, the U.S. Food and Drug Administration (FDA) has approved two weight-loss drugs for clinical use: sibutramine and orlistat, with sibutramine being more commonly used. Sibutramine is an appetite suppressant, a monoamine neurotransmitter reuptake inhibitor, which reduces food intake and thermogenesis, thus lowering weight.