Description
Orsotene Pharmacodynamics
The drug Orsothen is a powerful, specific and reversible inhibitor of gastrointestinal lipases, which has a long action. Its therapeutic effect is carried out in the lumen of the stomach and small intestine and consists in formation of a covalent bond with the active serine site of gastric and pancreatic lipases. The inactivated enzyme loses its ability to break down food fats that come in the form of triglycerides into absorbable free fatty acids and monoglycerides. Since unchecked triglycerides are not absorbed, the resulting decrease in the intake of calories into the body leads to a decrease in body weight. Thus, the therapeutic effect of the drug is carried out without absorption into the systemic bloodstream.
Judging by the results of fecal fat content, the action of orlistag starts 24-48 hours after intake. After withdrawal of orlistat, the content of fat in feces usually returns to the level before the beginning of therapy in 48-72 hours.
Efficacy
Obese patients.
In clinical trials, patients taking orlistat showed greater weight loss compared to patients on diet therapy. Weight loss began within the first 2 weeks of starting treatment and continued for 6 to 12 months, even in patients with a negative response to diet therapy. Over 2 years, there was a statistically significant improvement in the profile of metabolic risk factors associated with obesity. In addition, there was a significant reduction in body fat compared to placebo administration. Orlistat is effective in preventing weight gain again. Re-gain of weight, not more than 25% of the lost weight, was observed in about half of the patients, and in half of these patients re-gain of weight was not observed or even a further decrease was noted.
Patients with obesity and type 2 diabetes mellitus
In clinical trials lasting 6 months to 1 year, patients with overweight or obesity and type 2 diabetes taking orlistat showed greater weight loss compared to patients treated with diet therapy alone. The weight loss was mainly due to a decrease in body fat. It should be noted that prior to the study, despite taking hypoglycemic agents, patients often had insufficient glycemic control. However, statistically and clinically significant improvements in glycemic control were observed with orlistat therapy. In addition, orlistat therapy resulted in decreased doses of hypoglycemic agents, plasma insulin concentrations, and decreased insulin resistance.
Reduced risk of type 2 diabetes in obese patients In a 4-year clinical study it was shown that orlistat significantly reduces the risk of developing type 2 diabetes (about 37% compared to placebo). The degree of risk reduction was even greater in patients with baseline impaired glucose tolerance (approximately 45%). There was greater weight loss in the orlistat therapy group compared to the placebo group. Weight maintenance was observed throughout the study period. Moreover, compared to placebo, patients treated with orlistat showed a significant improvement in the profile of metabolic risk factors.
Pubertal Obesity.
In a 1-year clinical study in obese adolescents, a decrease in body mass index was observed while taking orlistat compared to the placebo group, where even an increase in body mass index was noted. In addition, patients in the orlistat group showed decreases in fat mass and waist and hip circumference compared to the placebo group. Patients treated with orlistat also had a significant decrease in diastolic blood pressure compared to the placebo group.
- Long-term therapy in obese or overweight patients with obesity-associated risk factors, in combination with a moderate hypocaloric diet:
- In adults and children over 12 years of age, the recommended dose of orlistat is 1 capsule of 120 mg with each main meal (immediately before a meal, during a meal, or no later than 1 hour after a meal).
- In combination with hypoglycemic drugs (metformin, sulfonoplurea derivatives and/or insulin) and/or moderately hypocaloric diet in patients with type 2 diabetes mellitus with excessive body weight or obesity: in adults, the recommended dose of orlistat is 1 capsule 120 mg with each main meal (immediately before a meal, at meal time or not later than 1 hour after a meal).
- If meals are skipped, or if the food does not contain fat, the drug Orsothen can also be skipped.
- The drug Orsothen should be taken in conjunction with a balanced, moderately hypocaloric diet containing no more than 30% of calories in the form of fat.
- Daily intake of fats, carbohydrates and proteins should be divided into three main meals.
- Increasing orlistat dose beyond recommended (120 mg 3 times daily) does not increase its therapeutic effect.
- Efficacy and safety of orlistat in patients with hepatic and/or renal dysfunction, as well as in elderly and pediatric patients (younger than 12 years) have not been studied.
