"Drugs for weight loss": a guide to the original

A review of drugs for the treatment of obesity with a credible evidence base

"Drugs for weight loss": a guide to the original

Excess body weight is a serious problem. According to WHO estimates, the proportion of overweight adults in the world reaches 55%, and with obesity - an average of 15–20% [1]. These data indicate that every second visitor to the pharmacy has "extra pounds", and every fifth is already obese. It is natural that the demand for weight loss drugs is traditionally high, especially in spring, when there are a lot of people who want to quickly get in shape after winter. However, the range of weight loss products is quite specific: most of the positions in it relate to dietary supplements and, accordingly, do not have an evidence base. However, there are several drugs that are used in evidence-based medicine. About them - our new material.

From indications to classification

First of all, it is important to understand that, as such, drugs "for weight loss" do not exist. Drug therapy is prescribed only for the treatment of obesity. The minimum body mass index at which drugs are already indicated is 27 kg / m 2 (recall, BMI is the ratio of body weight in kilograms to height in meters, raised to a square power).

For BMI ≥ 27 kg/m 2 , drug therapy is prescribed in cases where the patient has other risk factors (eg diabetes mellitus), and also to maintain the achieved weight loss. But with a BMI ≥30 kg/m2 , drugs for the treatment of obesity are indicated for all patients without exception [2]. In all other cases, that is, with a BMI less than 27 kg/m2, pharmacotherapy is prescribed if, against the background of non-drug methods (hypocaloric diet, lifestyle changes), a 5% decrease in body weight is not achieved within three months [3].

All drugs that are used to treat obesity are divided into two groups according to the mechanism of action:

  • drugs of central action that suppress appetite due to the effect on monoamine neurotransmitters in the central nervous system (sibutramine);
  • drugs of peripheral action that limit the absorption of essential nutrients (in particular, fats) in the gastrointestinal tract (orlistat).

It is immediately worth noting that there are two key principles for successful pharmacotherapy of obesity [3]:

  1. Drugs for weight loss are used for a long time.
  2. To achieve a good therapeutic response, drugs of central and peripheral action are combined, and in smaller doses than in the case of monotherapy. This tactic allows you to achieve higher efficiency with fewer side effects.

Now let's take a closer look at the drugs that are registered for the treatment of metabolic syndrome and obesity.

Centrally acting drugs

Sibutramine

Sibutramine was approved for use in the US in 1997 and in Europe two years later. According to clinical studies, sibutramine reduces weight by 1.5 times more effectively than orlistat [3].

Mechanism of action

Sibutramine inhibits the reuptake of serotonin in the nuclei of the hypothalamus. Serotonin influences the regulation of eating behavior. The drug reduces the need for food, increasing the feeling of fullness, and is especially effective in cases where it is difficult for the patient to limit himself to food. It is in such situations that it is very difficult to achieve weight loss only through diet and physical activity: people with such eating habits, even achieving certain results, as a rule, cannot maintain them.

Along with increasing the feeling of satiety, sibutramine increases energy consumption, stimulates the breakdown of fats in tissues and maintains an optimal basal metabolic rate. At the same time, energy costs increase by an average of 0.15 kJ / min for 5.5 hours. Due to this effect, the effect of sibutramine is preserved in the long-term period.

It is important to note that sibutramine has a positive effect on the quality of life, psycho-emotional state and erectile function in men [3].

Evidence base

The effectiveness of sibutramine has been proven in many clinical studies. So, in the well-known double-blind, placebo-controlled study STORM, it was shown that the use of the drug for 6 months provided a decrease in body weight by an average of 10.2 kg, a decrease in waist circumference by 9.2 cm and a ratio of waist circumference to hip circumference by 10 %. The achieved results were able to keep (by ≥ 80%) in the next 18 months 43% of patients.

What to warn the client about?

In the treatment of sibutramine, side effects may occur, usually in the first 4 weeks of therapy. Over time, their severity and frequency decrease, and in general, side effects are not severe. The most common adverse reactions include dry mouth, insomnia, headache, taste changes, and constipation.

When using sibutramine, blood pressure and pulse should be monitored. According to studies, they can increase: pressure - by 1-4 mm Hg. Art., and the heart rate - 3-7 beats per minute.

Along with monopreparations of sibutramine, several combinations with it are registered in the Russian Federation.

Sibutramine + MCC

Microcrystalline cellulose is included in combined preparations for the treatment of obesity as an enterosorbent, which has sorption properties and exhibits a detoxifying effect. MCC binds and removes opportunistic and pathogenic microorganisms, their metabolic products, toxins, allergens, xenobiotics, some metabolic products and metabolites associated with the development of endogenous toxicosis from the body.

The effectiveness of the combined preparations of sibutramine and MCC has been clinically proven. Thus, the drug was studied in the large-scale domestic program "Spring" with the participation of 34,719 patients. Within its framework, the safety of sibutramine + MCC was monitored for 6 months and its impact on the health status and quality of life of patients was assessed. The results of the program showed that the use of the combination drug provided weight loss to the target in 48% of patients. 44% of study participants got rid of the diagnosis of obesity, and 11.6% reached their ideal body weight. In addition, it was shown that the use of sibutramine + MCC made it possible to improve the indicators of fat and carbohydrate metabolism by 7–15% and to consolidate the correct eating behavior, which significantly contributes to the retention of the achieved results [4].

Safety indicators, according to the program "Spring", corresponded to the favorable tolerability of the drug: the frequency of adverse events was only 2.8% [4].

Sibutramine + Metformin

Metformin  is a first-line drug for the treatment of type 2 diabetes. It has been proven that, in addition to the hypoglycemic effect, it exhibits a number of pleiotropic effects that allow the drug to be used in metabolic syndrome and obesity and to optimize the treatment of the latter. In visceral adipose tissue, metformin inhibits the formation of mature fat cells from progenitor cells (adipogenesis), resulting in a reduction in visceral fat volume. The drug also suppresses the production of the hormone ghrelin, which stimulates appetite, and increases the content of glucagon-like peptide-1, which exhibits an anorexigenic effect.

Combination preparations containing sibutramine and metformin, acting on various links in the regulation of carbohydrate metabolism and eating behavior, can provide an intensification of weight loss, improve cardiometabolic parameters and reduce the risk of complications [5]. Their main indication is the reduction of increased body weight in patients with a BMI of 27 kg/m 2 or more in combination with type 2 diabetes mellitus and dyslipidemia.

Peripherally acting drugs

Orlistat

Orlistat  is currently the only representative of a subgroup of peripheral drugs for the treatment of obesity.

Mechanism of action

It is a powerful long-acting inhibitor of gastric and pancreatic lipases, reducing the breakdown and subsequent absorption of dietary fats by about 30%. Along with this, the drug reduces the amount of monoglycerides and free fatty acids in the intestinal lumen, which reduces the solubility and absorption of cholesterol, helping to reduce its level in the blood.

An important feature of orlistat is its high selectivity: it acts only on lipases, without affecting the absorption of carbohydrates, proteins and phospholipids. In addition, the drug has a peripheral effect only within the digestive tract and does not show systemic effects (6).

Evidence base

The effectiveness of orlistat has been demonstrated in numerous randomized placebo-controlled trials. Weight loss during 6–9 months of treatment averaged 10.8 kg. In 87% of patients treated with orlistat, a decrease in body weight of 5% or more was recorded, and in 50% of patients - by 10% or more. On average, weight loss during treatment for 6–9 months was 10.7% [7].

Along with a decrease in body weight with long-term use of orlistat, the waist circumference decreases (by 4.5 cm after 6 months of use), the concentration of total cholesterol (on average by 2.4%) and low-density lipoproteins (by 3.5%) [8] .

The results of the studies showed that a decrease in body weight while taking the drug, including the mass of visceral adipose tissue, had a positive effect on cardiometabolic risk factors: it led to a significant decrease in systolic and diastolic blood pressure, and this effect after a year of orlistat therapy persisted for 4 years [7]. When treated with orlistat in patients with obesity, the risk of cardiovascular events decreased by 2 times, the progression of type 2 diabetes mellitus slowed down, and the need for oral hypoglycemic, antihypertensive and lipid-lowering drugs decreased [7].

What to warn the client about?

It is important to tell the customer that when taking orlistat, a moderately low-calorie diet containing no more than 30% of daily calories in the form of fat should be followed. If a meal is skipped or the food does not contain fat, the drug can also be skipped.

If after 12 weeks of taking the drug body weight does not decrease (or the decrease is less than 5% of the initial weight), you should consult your doctor about further treatment tactics and the advisability of using orlistat.

Also, when releasing orlistat, it is important to draw the client's attention to the fact that against the background of the use of the drug, gastrointestinal side effects very often occur, in particular, soft stools, flatulence, fatty oily stools, and so on. To reduce their severity, you should control the amount of fat in the diet. And, of course, continue to take the drug - the course of treatment can last up to 6 months.