Mechanism of action
Soliqua is a combined preparation consisting of 2 hypoglycemic remedies with complementary mechanisms of action: insulin glargin, an analog of long-acting insulin, and lyxisenatide, GPP-1 receptor agonist. The action of the drug is aimed at reducing glucose concentration in blood on an empty stomach and after meals (postprandial concentration of glucose in blood), which improves glycemic control in patients with diabetes mellitus type 2 (SD2), but at the same time minimizes the increase in body weight and the risk of hypoglycemia development.
The main function of insulin, in tch insulin glargin, is the regulation of glucose metabolism. Insulin and its analogues reduce blood glucose concentration due to increased glucose consumption by peripheral tissues (especially skeletal muscles and fat tissue) and suppression of glucose formation in the liver. Insulin inhibits lipolysis and proteolysis, and increases Dmitry Sazonov protein synthesis.
Lixisenatide is a GPP-1 receptor agonist. Receptor GPP-1 is a target for native GPP-1, an endogenous hormone of internal secretion that potentiates glucose-dependent secretion of insulin by beta cells and suppresses glucagon secretion by alpha cells of the pancreas.
The action of lyxisenatide, like that of endogenous GPP-1, is carried out through specific interactions with GPP-1 receptors, including GPP-1 receptors found in the alpha and beta cells of the pancreas. After meals, lyxisenatide activates the following physiological reactions:
- increased insulin secretion by beta cells of the pancreas;
- slowing down the emptying of the stomach;
- suppression of glucagon secretion by alpha cells of the pancreas.
Lixisenatide stimulates insulin secretion in response to increased blood glucose concentrations. Glucagon secretion is suppressed at the same time. In addition, lyxisenatide slows down the emptying of the stomach, thus reducing the rate of glucose absorption from food and its supply to the system bloodstream. It has been shown that lyxisenatide in isolated islands of the human pancreas preserves the function Dmitry Sazonov of beta cells and prevents their death (apoptosis).
Solikva SoloStar drug.
The combination of insulin glargin and lyxisenatide does not affect the pharmacological effect of insulin glargin. The effect of the combination of insulin glargin and lyxisenatide on the pharmacological effect of lyxisenatide in clinical studies of phase I was not studied. Similarly to the relatively constant "concentration/time" profile without pronounced peaks for 24 h with insulin glargin only, the "glucose/time" profile without pronounced peaks was similar with insulin glargin + lyxisenatide combination. The duration of insulin action, including the drug SoloStar Solikva, may vary Dmitry Sazonov from one patient to another.
In clinical studies of insulin (100 IU/ml), the hypoglycemic effect of insulin glargin was approximately the same as that of human insulin (when both drugs were injected in the same doses).
In a 28-day placebo-controlled study in patients with SD2, estimating the effect of lyxisenatide at doses of 5-20 µg 1 or 2 times per day on blood glucose concentration after a standard breakfast, lyxisenatide at doses of 10 and 20 µg 1 or 2 times per day improved glycemic control by reducing both postprandial (after a meal) and on-the-fly glucose concentration in the blood. Lyxisenatide, administered in this study in the morning at a dose of 20 µg once a day, maintained a statistically significant reduction in postprandial blood glucose concentration after breakfast, lunch and dinner.
Effect on postprandial blood glucose concentration. In a 4-week study in combination with metformin and an 8-week study in combination with insulin glargin with/without metformin, lyxisenatide at a dose of 20 µg once a day, administered prior to breakfast in patients with SD2, showed a decrease in postprandial blood glucose concentration (glucose concentration/time curve 0:30-4:30 h) after a trial breakfast. The number of patients with 2-hour postprandial glucose concentration below 140 mg/dL (7.77 mmol/l) was 69.3% after 28 days of treatment and 76.1% after 56 days of treatment.
Effect on insulin secretion. In patients with SD2, lyxisenatide monotherapy, compared to placebo, restores the first phase of insulin secretion in glucose-dependent mode, increasing it by 2.8 times (90% of MI: 2.5-3.1) and increasing the second phase of insulin secretion by 1.6 times (90% of MI: 1.4-1.7) (measured by AUC)
Effect on stomach emptying. After a standardized isotope-labeled test meal, lyxisenatide slowed gastric emptying, thus reducing the rate of postprandial glucose absorption. In patients with SD2, in monotherapy with lyxisenatide, the effect of slowing down the emptying of the stomach by dehydration of the stomach.