According to the WHO, the prevalence of obesity has tripled in the last half century. And when it comes to children and adolescents, it has risen from 15 to 7 percent. It is a paradox, but today more people die from extra pounds than from hunger. Obesity provokes the development of chronic pathologies: diabetes, dyslipidemia, hypertension, which increase the risk of disability and death.
Obesity reduces life expectancy by an average of 15 years. In addition, the diseases of obesity increase the costs of the health system, because it is necessary to correct not only the weight of the body, but also the metabolic disorders, homeostasis system. In other words, all this should be taken into account when choosing medications. From this article you will learn about the possibilities of modern pharmacology for weight loss.
- General information.
- Medical problem.
- How to arrange treatment for obesity.
- Medications for treating obesity.
- Leptin and ghrelin.
- Other Drugs.
The problem of obesity has been considered in medical (and not only) literature since the beginning of the 17th century. It was logically thought that fat in reasonable amounts promotes beauty, but in excess it is transformed into disease. People suffering from obesity, according to the author of “Notes of the Pickwick Club” become lethargic, sleepy, lethargic.
Contribute to the development of obesity bad habits, stressful situations, lack of exercise and immoderate eating. An increase in the number of patients associated with a predominance of carbohydrates in food, as well as the consumption of foods with a high concentration of fat, sugar and salt. In other words, with high energy density and a minimum of micronutrients.
Such a diet is cheaper, but has a low nutritional value. Combined with little physical activity, this gives a dramatic increase in the prevalence of obesity, and the problem of malnutrition itself remains unresolved. Obesity is an age-related problem, it is increasing, affecting children, adolescents and elderly patients alike. in part, this can be explained by low physical activity. According to statistics, obesity is more common among urban residents.
Interestingly, statistics provide reliable data on the affiliation of obesity with depression or anxiety. At least one psychiatric disorder is seen in half of people with an elevated BMI. While in healthy people depressed mood occurs in 15% of the population, in obese patients this figure reaches nearly 60%. Many believe that the rise in the prevalence of obesity is not only due to poor diet, but also to the high stress of modern life. A number of researchers have noted the association of obesity with the metabolic syndrome. For example, waist circumference in men changed from 94 to 102 cm and in women from 80 to 88 cm.
According to WHO, in the last 10 years nearly 2 billion adults over the age of 18 have been overweight and 650 million have become obese. At the same time the frequency of overweight is about 40% and obesity – 13%: in men – 11%, in women – 15%. The number of children and adolescents under 18 years of age who are overweight exceeds 340 million, and almost 40 million under 5 years of age. Egypt has the highest rate of obesity among adults at 35% and the United States has the highest rate among children at 13%. The lowest incidence of obesity among adults is found in Vietnam at 1.5% and among children in Bangladesh at just over 1%.
This situation resembles an epidemic. That is why the WHO has adopted a global strategy on diet, physical activity and health. Not the least of these strategies is the ability to balance adipose tissue hormones, which include leptin.
A medical problem
Obesity is a medical problem because overweight is affiliated with a number of serious pathologies, including not only hypertension and diabetes mellitus 2, but also polycystic ovarian syndrome, osteoarthritis, and nighttime apnea syndrome. The first guideline for the treatment of obesity was developed in the United States by the National Institutes of Health.
It suggested that when examining patients who are overweight, three indices should be evaluated:
- body mass index;
- waist circumference;
- risk of cardiovascular disease.
The criterion for excessive BMI is 30 kg/m2, and obesity is higher than this figure. It is emphasized that patients over 18 years of age with a BMI ≥25 kg/m2 have an increased risk of developing diabetes mellitus 2, heart and vascular disease, respiratory disease, and osteoarthritis. In addition, central obesity is an independent trigger of hypertension and atherosclerosis.
At the same time, it has been proposed to divide patients with high weight into three groups, which are correlated by the risk of cardiovascular disorders:
- Patients with a very high risk of cardiovascular complications and mortality.
- Patients with one of the risk factors: hypertension, dyslipidemia, postmenopause.
- Patients with other pathologies: gynecological, GI, osteoarthritis.
Weight loss is recommended if the patient has two or more risk factors, or for women and men with a waist circumference greater than 88 cm and 102 cm, respectively. In other words, obesity is no longer a purely endocrinological problem. Its correction involves not only general practitioners, but also cardiologists, gastroenterologists, surgeons, rehabilitation therapists, nutritionists and preventive medicine specialists. Most physicians deal with primary obesity.
The indication for pharmacotherapy of obesity is BMI >30 kg/m2 with no effect from diet and lifestyle changes. It also includes BMI up to 30 kg/m2 in the presence of concomitant diseases: hypertension, hyperinsulinemia, dyslipidemia, abdominal obesity with a genetic predisposition to diabetes mellitus 2.
How to arrange treatment for obesity
The WHO approach is based on recognition of the chronic nature of obesity, that is, the need for long-term therapy. One should not use methods of rapid weight loss (more than 5 kg per month). Minimizing leptin levels due to rapid weight loss leads compensatorily to increased food intake and secondary weight gain. The goal of this therapy is a weight loss of 10% of initial body weight in six months.
It is achieved by changing the lifestyle, which includes a diet with a minimum of calories and a maximum of movement. If this is not enough, involve pharmacotherapy. It should not be forgotten that the use of drugs to treat obesity without diet will not give a good effect. Contraindications for medications are children’s age, pregnancy and lactation period.
Drugs for the treatment of obesity
The only drug implicitly approved by the FDA (American Food and Drug Administration) is Orlistat peripherally. The essence of its correction is contact with gastrointestinal lipase to block the absorption of fat from the intestine. Orlistat inhibits a third of the lipids that enter the body with food, reducing body weight by an average of 8%. When taking the drug, additional intake of fat-soluble vitamins A, D, K and E is mandatory to prevent hypovitaminosis.
Correction with this drug provides minimization of cholesterol and triglycerides levels as a result of their hydrolysis. Orlistat is taken during a meal or an hour after a meal. In combination with thyroid medications, an interval of 4 hours is necessary. As side effects, flatulence and diarrhea may be of concern. Cholestasis and malabsorption are contraindications to Orlistat use. The lower the amount of fat in the food, the lower the risk of side effects. The drug is not contraindicated after bariatric surgery and in the elderly.
Another drug against obesity is the centrally acting drug Sibutramine. It selectively blocks norepinephrine and serotonin reuptake in CNS synapses. This lengthens the time that neurotransmitters stay in the synapses and thus neurotransmission. It is not addictive and can be combined with a hypocaloric diet. Despite the weight minimization from taking Sibutramine, there is a risk of cardiovascular complications. Therefore, in the U.S., for example, this drug was banned 12 years ago. But in Russia it is still used, although it is dispensed only with a prescription, that is, with the knowledge of the doctor.
Central sympathomimetic anorectics include Phentermine, which has adrenergic and serotonergic properties. The drug is used continuously or by courses. In combination with a hypocaloric diet, the effect is much better. Phentermine is indicated if BMI>30 kg/m2 or BMI>27 kg/m2, but the patient has provoking factors that can cause exacerbation of concomitant pathology.
Contraindications to the use of the drug are considered pulmonary hypertension, cardiac defects, hyperthyroidism, pregnancy and alcoholism. Side effects are considered tachycardia, hypertension, cephalgia, vertigo, dry mouth and sleep disorders. The dosage of the drug is 15 to 37.5 mg once daily or 8 mg three times daily before meals. The choice of dose is the doctor’s prerogative.
A relatively new treatment for obesity is the combined drug Phentermine/Topiramate. Its administration for one year leads to a decrease in body weight by 7-9%. At first it is taken for two weeks at a dose of 3.75 mg of Topiramate and 23 mg of Phentermine, later the dose is doubled for two more weeks. Hyperthyroidism, taking MAO inhibitors, and pregnancy are considered contraindications to use.
Side effects: impaired concentration, hyperesthesia, depression, cognitive dysfunction. There are cases of congenital malformations like wolf’s mouth in children. Due to the risk of changes in blood sodium concentration, electrolyte metabolism should be constantly monitored.
A combination of Bupropion and Naltrexone is completing clinical trials. The former blocks norepinephrine and dopamine reuptake, while the latter inhibits opioid receptors. This combination is used in the therapy of obese patients who have given up smoking. The effectiveness is a 10% weight loss in a year and a half. Side effects include headaches, dizziness, constipation, dry mouth, nausea and sleep disorders. Contraindications to taking the combination are hypertension, epilepsy, anorexia, and pregnancy. Therapy is not combined with other antidepressants.
A prolonged analogue of glucagon-like peptide 1, Liraglutide, has been recognized as a promising treatment for obesity. It activates pancreatic insulin release, improves glycemic control and stimulates satiety, thus controlling food intake. The drug and was originally used to treat type 2 diabetes. Today, its use guarantees a weight loss of 8% within a year. Contraindications to taking the drug are pregnancy and a history of thyroid cancer. But after bariatric surgery, in elderly and drinking patients the drug is not prohibited.
Another promising drug is Amylin. It supplements insulin in glucose regulation, slows the evacuation of food from the intestine, and minimizes glucagon secretion. The disadvantage of the drug is that it must be taken at every meal. A negative consequence is nausea.
The drugs of central action include the selective serotonin receptor antagonist Lorcaserin. The effect is achieved by blocking the hunger center in the hypothalamus. Its use provides a weight loss of 5% over a year. At the same time, blood sugar and glycated hemoglobin levels are reduced, which has opened up the possibility of its use in food diabetes.
Cephalgia, vertigo, nausea, and drowsiness are considered side effects of taking it. Today, a number of other drugs are in clinical trials. For example, Setilistat, an analogue of Orlistat. But it is contraindicated when treated with Warfarin and thyroid hormones.
Leptin and ghrelin
Leptin also belongs to the group of experimental drugs. It is a peptide chain hormone produced by lipid layers, which circulates in the bloodstream free and in bound form. The serum leptin concentration is the sum of the energy reserve of the fat interlayers, and it changes with short-term disturbances in energy balance and changes in the levels of proinflammatory bioactive substances circulating in the blood.
Binding of the fat cell hormone to receptors in the hypothalamus activates neuropeptides that control the body’s energy balance. This is the main role of leptin in the development of obesity. It is involved in the response to starvation. Today, the hormone is used to correct lipodystrophy. However, after discontinuation of the drug in the body begins to cumulate fat, so prescribe leptin should be with caution and in the absence of an alternative. High doses of the drug do not lead to an increase in body weight.
Ghrelin is an analogue of leptin, which affects the CNS directly. It is considered the most promising in the treatment of obesity because it minimizes the feeling of hunger, blocks the absorption of fat, and prevents the minimization of the body’s energy reserves. The concentration of ghrelin is directly proportional to the level of leptin.
There are also other drugs with a different mechanism of action. For example, Resvatrol activates free fatty acid oxidation, improving insulin sensitivity. Atomoxetine inhibits norepinephrine reuptake, critically reducing appetite and reducing the severity of impulsive behavior – the main mechanism of food addiction. The drug is used in the therapy of concentration disorders with hyperactivity. Velneperine is a powerful yet selective neuropeptide Y receptor antagonist that minimizes the feeling of hunger and controls energy expenditure.
The expansion of the range of medications against obesity gives hope for better results in the fight against the epidemic of overweight. The therapy algorithm includes not only pharmaceuticals, but also diet, exercise, psychological help, and even surgery. Only this approach will achieve weight minimization and provide an improvement in the patient’s health.