Tirzepatide was developed to fight type 2 diabetes, but it has also been shown to protect the cardiovascular system and act as a powerful weight-loss agent. Tirzepatide is a synthetic derivative of gastric inhibitory polypeptide (GIP), which also has the simultaneous functionality of glucagon-like peptide-1 (GLP-1). This combination allows Tirzepatide to reduce the level of glucose in the blood, increase sensitivity to insulin, increase the feeling of satiety and accelerate weight loss.
Tirzepatide
Tirzepatide — it is a synthetic analogue of gastric inhibitory polypeptide (GIP), which was developed due to its ability to stimulate insulin release and thus treats both type 2 diabetes and non-alcoholic fatty liver disease. The relatively large tirzepatide, consisting of 39 amino acids, stimulates the release of insulin from the pancreas by binding to GIP and GLP-1 (glucagon-like peptide-1) receptors. With longer administration, tirzepatide also increases the level of adiponectin by as much as 26%. Studies show that Tirzepatide reduces hunger, lowers insulin levels, and increases insulin sensitivity. Combined, these effects lead to a significant weight loss of 11 kg (25 lbs), improved glucose tolerance, reduced adipose tissue, and reduced cardiovascular risk.
What does Tirzepatide do
Simply put, Tirzepatide increases the release of insulin from the pancreas, which leads to improved glucose control. Studies show that in people with type 2 diabetes, tirzepatide reduces hemoglobin A1c (HbA1c) by 2.4% after six months. The peptide also promotes weight loss, demonstrating a dose-dependent relationship and helping people lose up to 11 kg (25 pounds) in six months.
However, it is not only that Tirsepatide increases the release of insulin. Studies show that the peptide actually improves the function of beta cells in the pancreas, the cells that produce and secrete insulin. Studies show that tirzepatide can actually make beta cells more efficient in insulin processing, which leads not only to an increase in the level of insulin in the bloodstream, but also to a decrease in the load on the beta cells themselves. This, in turn, can help slow down the progression of type 2 diabetes.
How Tirsepatid works
The drug activates the receptors of hormones secreted from the intestines (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) to reduce appetite and food consumption. Tirzepatide is administered by injection under the skin once a week and the dose must be increased within 4-20 weeks to reach the target doses of 5 mg, 10 mg or 15 mg once
The initial dosage is 0.5-1 mg per week. The maximum dose of tirzepatide is 15 mg once a week
Tirzepatide is a dual agonist of gastric inhibitory polypeptide receptor and glucagon-like peptide-1 receptor. Action on these receptors, apparently, has a synergistic effect, which makes Tirzepatide more effective than strict GLP-1 agonists, which are already approved for the treatment of type 2 diabetes. The affinity of tirzepatide for the
GIP receptor is higher than its affinity for the GLP-1 receptor.
Gastric inhibitory polypeptide, which is also called glucose-dependent insulinotropic polypeptide, is naturally synthesized in the small intestine. This polypeptide binds to the GIP receptor, inhibiting the secretion of gastric acid and the release of gastrin, while simultaneously stimulating the release of insulin. The latter is the main function of GIP-R and the main reason for the increase in insulin levels after a meal.
Glucagon-like peptide-1 receptors are found on beta cells, as well as in neurons of the brain. Like GIP-R, GLP-1R stimulation stimulates insulin release.
Natural agonists include glucagon and GLP1, but it has also been shown to bind nearly a dozen synthetic agonists, including dulaglutide, lithium, and oxyntomodulin.
GLP-1R activation increases both insulin synthesis and insulin release, factors that have made it a desirable drug target. In the brain, GLP-1R stimulation reduces appetite.
Interestingly, GLP-1R stimulation appears to increase the density of beta cells in the pancreas. GLP-1R stimulation increases the expression of the anti-apoptotic gene bc-2, while simultaneously reducing the expression of the pro-apoptotic genes bax and caspase-3. This leads to an increase in the survival of beta cells and, ultimately, to an increase in the level of insulin.
The combination of GIPR and GLP-1R activity gives Tirzepatide an advantage over strict GLP-1R agonists. Studies show that tirzepatide acts identically to GIP in relation to GIPR, but it favors the production of TsAMP and not the recruitment of 3-arrestin when acting on GLP-1R. These details may seem somewhat esoteric, but this difference in activity from endogenous GLP-1 appears to cause GLP-1R activation without increasing the physiological internalization of the receptor. The final result is an increase in GLP-1R activity when taking tarazepide compared to both endogenous
GLP-1 and other synthetic GLP-1R agonists. These small changes mean that tirzepatide sharply increases insulin secretion, promotes satiety and reduces inflammation in adipose tissue. These combined effects make it a highly effective peptide against diabetes.
Finally, tirzepatide appears to alter adiponectin levels, increasing overall levels of the fat-burning peptide. An elevated level of adiponectin reduces the differentiation of fat cells and increases energy consumption, making mitochondria more ineffective. Low levels of this peptide hormone are associated with diseases such as type 2 diabetes, atherosclerosis, and nonalcoholic fatty liver disease.
It is worth noting that elevated levels of adiponectin increase insulin sensitivity, so tirzepatide appears to modulate insulin sensitivity through several mechanisms.
Tirzepatide and hunger
Studies show that tirzepatide delays gastric emptying at the earliest stages of its administration, but the effect diminishes over time as a result of tachyphylaxis. These effects are similar to those observed with the use of pure GLP-1R agonists, which indicates that this action of tirzepatide is almost completely controlled by its GLP-1 activity, and not by GIP activity.
It seems that the effect of Tirzepatide on gastric emptying can be prolonged if the peptide is taken at a low dose for four weeks, and then the dose is increased. It also helps mitigate the side effects caused by the peptide and creates a real win-win situation for patients. Delayed gastric emptying can help increase satiety and reduce hunger and food cravings. In combination with the effect of Tirsepatide on the level of glucose, it can really help to change the diet in the long term.
Brief description of Tirzepatide
Tirzepatide is a synthetic derivative of gastric inhibitory polypeptide (GIP), which also has the simultaneous functionality of glucagon-like peptide-1 (GLP-1). This combination allows Tirzepatide to lower the level of glucose in the blood, increase sensitivity to insulin, increase the feeling of satiety and accelerate weight loss. Tirzepatide was developed to fight type 2 diabetes, but it has also been shown to protect the cardiovascular system and act as a powerful weight-loss agent.