Tirzepatide

Tirzepatide is a peptide that has shown promise in the treatment of Type 2 diabetes. It works by increasing the release of insulin from the pancreas, leading to improved glucose control. Research has indicated that Tirzepatide can significantly reduce hemoglobin A1c (HbA1c) levels, a marker of long-term blood sugar control, by 2.4% after six months of use in individuals with Type 2 diabetes. Additionally, Tirzepatide has been associated with weight loss, with a dose-dependent relationship, and some individuals experiencing a weight loss of up to 11 kg (25 lbs) over six months.

Tirzepatide not only increases insulin levels but also appears to enhance the function of pancreatic beta cells, the cells responsible for producing and releasing insulin. This improvement in beta cell function can reduce stress on these cells and potentially slow the progression of Type 2 diabetes.

Interestingly, Tirzepatide acts in response to increased blood glucose levels. When blood glucose is elevated, Tirzepatide increases insulin levels, but it reduces insulin levels during fasting, thereby improving insulin sensitivity over time. It also decreases fasting levels of glucagon, which can exacerbate hyperglycemia by interfering with liver glucose metabolism. These combined effects contribute to Tirzepatide’s significant impact on glucose control and HbA1c levels.

Tirzepatide is a dual agonist of the gastric inhibitory polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R). GIPR and GLP-1R stimulation have synergistic effects that make Tirzepatide more effective than strict GLP-1 agonists in treating Type 2 diabetes. Tirzepatide has a higher affinity for the GIP receptor compared to the GLP-1 receptor. GIPR stimulation primarily leads to insulin release after meals, while GLP-1R stimulation not only promotes insulin synthesis and release but also increases beta cell density in the pancreas, promoting beta cell survival and insulin production.

Tirzepatide also appears to raise adiponectin levels, a peptide hormone associated with fat metabolism. Increased adiponectin levels reduce fat cell differentiation and enhance energy expenditure by making mitochondria less efficient. This can improve insulin sensitivity and help mitigate conditions such as Type 2 diabetes, atherosclerosis, and non-alcoholic fatty liver disease.

In terms of hunger regulation, Tirzepatide initially delays gastric emptying, leading to increased feelings of satiety and reduced hunger and food cravings. However, this effect diminishes over time due to tachyphylaxis. To address this, a low-dose start with a gradual escalation has been shown to prolong the gastric emptying delay, helping to alter eating patterns over time.

Tirzepatide is also associated with substantial weight loss over six months, which is in contrast to some other GLP-1 analogues that may cause weight gain. The GIP agonism of Tirzepatide appears to play a significant role in its long-term effects on weight. GIP activates receptors in fat cells, increasing insulin sensitivity, reducing adipose inflammation, and increasing adiponectin levels. Additionally, GIP signaling in the central nervous system regulates feeding centers in the hypothalamus, leading to decreased food intake and improved glucose handling, ultimately contributing to weight loss.

Overall, Tirzepatide’s multifaceted actions on insulin release, beta cell function, insulin sensitivity, hunger regulation, and weight loss make it a promising candidate for the treatment of Type 2 diabetes.