Analysis of the risk of blood sugar or weight rebound after discontinuation of tilpotide/tirsiparatide (Mufenda)

Tirzepatide is a dual-target GIP/GLP-1 receptor agonist that can significantly improve blood sugar levels in patients with type 2 diabetes and help with weight management. Its mechanism of action is mainly achieved by enhancing insulin secretion, inhibiting glucagon release, delaying gastric emptying and reducing appetite. After stopping the drug, these pharmacological effects will gradually disappear, and the blood sugar and weight control effects may also weaken, so there is a certain risk of rebound. For patients who have relied on tilpotide for a long time to maintain metabolic balance, sudden discontinuation may lead to blood sugar fluctuations and weight gain.

In terms of blood sugar, after stopping the drug, the improvement of insulin sensitivity and the promotion of insulin secretion disappear, and the inhibitory effect of glucagon will also be weakened, so that postprandial and fasting blood sugar may gradually rise again. Especially for patients with poor basic blood sugar control or combined with insulin resistance, their blood sugar rebounds to a greater extent after stopping the drug, and they may experience mild to moderate hyperglycemia and even need to readjust other anti-diabetic drugs. To reduce the risk, patients should develop a blood glucose monitoring plan with their doctor before stopping medication, and adjust their diet and drug regimen based on blood glucose changes.

In terms of weight control, tilpotide helps reduce caloric intake by suppressing appetite and delaying gastric emptying. Once the drug is discontinued, these mechanisms no longer continue to work, and patients may experience increased hunger and a return to food intake, leading to weight regain. Studies have shown that some patients may gradually approach their pre-drug weight levels within weeks to months after stopping the drug. If you do not establish reasonable eating and exercise habits before stopping the drug, the risk of weight regain will be higher.

Overall, both blood glucose and weight management after tilpotide discontinuation require attention to transition strategies. Patients should gradually adjust their lifestyle under the guidance of a doctor, such as increasing dietary fiber, controlling calorie intake, maintaining regular exercise, and closely monitoring blood sugar and weight changes. If there is an obvious increase in blood sugar or rapid weight gain, you should communicate with your doctor in time and consider other drug intervention or lifestyle optimization programs to reduce metabolic risks after drug withdrawal and ensure the continuity and safety of long-term health management.

Reference materials:https://pubmed.ncbi.nlm.nih.gov/36251836/