Tirzepatide: New kid on the block for obesity and heart failure with preserved ejection fraction
20 January 2025
Tirzepatide: New kid on the block for obesity and heart failure with preserved ejection fraction
- Tirzepatide is a novel medication approved by the US Food and Drug Administration (FDA) in May 2022 for treating type 2 diabetes mellitus (T2DM).
- Tirzepatide is a synthetic polypeptide and dual agonist for the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. Tirzepatide, “twincretin,” exhibits distinct characteristics from GLP-1 receptor agonists. Functionally, tirzepatide stimulates insulin release from the pancreas and reduces hyperglycemia. In addition, tirzepatide also increases the levels of adiponectin. The dual agonism ability decreases hyperglycemia significantly more than GLP-1 agonist agents and reduces the patient’s appetite
- The drug leads to significantly improved glycemic control and weight reduction in patients with T2DM, maximizing benefits similar to GLP-1 medications such as semaglutide. Tirzepatide is currently utilized as a second-line diabetes medication akin to GLP-1 drugs, such as semaglutide, and is administered once weekly via subcutaneous (SQ) injection with incremental dosage adjustments.
- Tirzepatide is not approved for the treatment of type 1 diabetes mellitus (T1DM) and has not undergone studies in patients with pancreatitis. Tirzepatide can also demonstrate efficacy in weight loss, leading to its off-label use for obesity treatment.
- The initial dosage of tirzepatide for treatment initiation is 2.5 mg administered SQ once weekly, with the primary goal of initiation rather than glycemic control. After 4 weeks, increase to 5 mg SQ once weekly. For additional glycemic control, escalate the dosage by 2.5 mg after at least 4 weeks on the current dose. The maximum tirzepatide dosage is 15 mg SQ once weekly.
- The primary adverse effects are gastrointestinal-related, but other side effects have also been infrequently reported. Decreased appetite is frequently reported, though this is a potential contributory etiology of intentional weight loss.Other less common side effects includes sinus tachycardia, acute kidney injury secondary to dehydration , hypersensitivity reactions , cholelithiasis and cholecystitis , worsening of pre existing retinopathy and hypoglycemia.
- Patients using other GLP-1 agents, such as semaglutide or liraglutide, should not be prescribed tirzepatide. Patients on insulin therapy can be initiated on tirzepatide therapy and cautiously have the insulin dose decreased to minimize the risk of hypoglycemia.
- Tirzepatide is contraindicated in patients with medullary thyroid cancer. Tirzepatide is also contraindicated in multiple endocrine neoplasia syndrome type-2 (MEN-2).
- The SURMOUNT-4 trial results emphasize the need to continue pharmacotherapy to prevent weight regain and ensure the maintenance of weight reduction and its associated cardiometabolic benefits.
- The SUMMIT trial showed that treatment with tirzepatide led to a lower risk of a composite of death from cardiovascular causes or worsening heart failure than placebo and improved health status in patients with heart failure with preserved ejection fraction and obesity
