Tirzepatide
Overview
Tirzepatide is a once‑weekly injectable peptide that simultaneously activates the glucose‑dependent insulinotropic polypeptide (GIP) and glucagon‑like peptide‑1 (GLP‑1) receptors. By mimicking both of these incretin hormones, tirzepatide enhances insulin secretion, reduces glucagon release, delays gastric emptying, and increases satiety, thereby helping to control blood sugar and reduce body weight. Because of this dual action, tirzepatide offers a more potent metabolic effect than traditional GLP‑1 agonists, making it an important therapy option for people with type 2 diabetes as well as those seeking chronic weight management.
Background and Date of Approval
Tirzepatide was developed by Eli Lilly as a synthetic, acylated peptide capable of binding both GIP and GLP-1 receptors. Preclinical design incorporated structural modifications, including a fatty acid chain, to allow strong binding to albumin and extend its half-life, enabling once-weekly dosing. Clinical trials known as the SURPASS program demonstrated its efficacy in reducing blood glucose and body weight significantly. The U.S. Food and Drug Administration first approved tirzepatide for the treatment of type 2 diabetes in 2022. Subsequently, it was also approved for chronic weight management in people with obesity or overweight who have related medical conditions.
Uses
Tirzepatide is indicated for adults with type 2 diabetes as an adjunct to diet and exercise to improve glycemic control. It is also approved for chronic weight management in adults with obesity or overweight plus a weight‑related condition, when used alongside reduced-calorie diet and physical activity. In some regions, tirzepatide is considered for additional metabolic‑risk indications, though its use should always follow clinical assessment and monitoring.
Administration
Tirzepatide is administered as a subcutaneous injection once weekly. The initiation typically begins at 2.5 mg per week, and the dose is increased every four weeks in 2.5 mg increments as tolerated, up to a maximum of 15 mg weekly depending on the indication. Treatment continues until the clinical goals of glycemic control or weight reduction are achieved, or until the patient experiences an unacceptable adverse effect.
Side Effects
The most common side effects of tirzepatide are gastrointestinal in nature, including nausea, vomiting, diarrhea, constipation, and abdominal discomfort. These generally emerge during dose escalation and may reduce over time as the patient stabilizes on the target dose.
Warnings
Tirzepatide can lead to more serious adverse effects, including pancreatitis, gallbladder disease, and acute kidney injury. There is also a warning based on preclinical data about potential thyroid C‑cell tumors; thus, it is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in those with Multiple Endocrine Neoplasia syndrome type 2. Hypoglycemia risk is elevated when tirzepatide is used with insulin or insulin secretagogues.
Precautions
Because tirzepatide delays gastric emptying, it may impact the absorption of concomitant oral medications, requiring monitoring or dose adjustments. It should be used cautiously in patients with a history of pancreatitis. Thyroid monitoring may be warranted in patients at risk for thyroid C-cell disease. Regular assessment of renal function is advised, especially in those with preexisting kidney issues, given reported risks of kidney injury.
Expert Tips
Before initiating tirzepatide, evaluate the patient's thyroid history, renal status, and propensity for pancreatitis. Counsel patients that gastrointestinal side effects are common during the early weeks but generally improve with gradual dose escalation. Emphasize adherence to the once-weekly schedule, and instruct them on proper subcutaneous injection technique, including rotating injection sites. When combining with other glucose-lowering therapies, especially insulin or sulfonylureas, carefully monitor blood glucose to adjust doses and reduce hypoglycemia risk. Periodic follow-up is essential to assess both therapeutic benefit and tolerability, and to make dose adjustments as needed.