Can tirzepatide (a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist) cause diabetes mellitus?

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From the Guidelines

Tirzepatide does not cause diabetes; in fact, it is a medication specifically approved to treat type 2 diabetes and obesity. Tirzepatide (brand name Mounjaro or Zepbound) is a dual GIP/GLP-1 receptor agonist that helps lower blood sugar levels by enhancing insulin secretion when blood sugar is high, slowing gastric emptying, and reducing appetite. The medication is typically administered as a once-weekly subcutaneous injection, with starting doses of 2.5 mg that can be gradually increased to 5 mg, 10 mg, or 15 mg based on individual response and tolerability. Rather than causing diabetes, clinical trials have shown that tirzepatide significantly improves glycemic control in people with type 2 diabetes, with some patients achieving substantial reductions in HbA1c levels, as reported in a recent study published in the Journal of the American Medical Association (JAMA) 1. The medication works by mimicking the effects of natural incretin hormones in the body that regulate glucose metabolism. Common side effects include nausea, diarrhea, decreased appetite, vomiting, and constipation, but these typically improve over time as the body adjusts to the medication. Some studies have compared tirzepatide to other medications, such as SGLT2 inhibitors and GLP1 agonists, and found that it has a similar efficacy in improving glycemic control, as reported in a systematic review and network meta-analysis published in the Annals of Internal Medicine 1. However, the evidence suggests that tirzepatide does not increase the risk of diabetes, and instead, it is a valuable treatment option for patients with type 2 diabetes and obesity. Key points to consider when prescribing tirzepatide include:

  • Starting dose: 2.5 mg once weekly
  • Titration: gradual increase to 5 mg, 10 mg, or 15 mg based on individual response and tolerability
  • Administration: subcutaneous injection
  • Common side effects: nausea, diarrhea, decreased appetite, vomiting, and constipation
  • Efficacy: significant improvement in glycemic control, with substantial reductions in HbA1c levels in some patients.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Tirzepatide and Diabetes

  • Tirzepatide is a dual GIP/GLP-1 receptor co-agonist approved for the treatment of type 2 diabetes in several countries, including the USA, Europe, and the UAE 2.
  • The medication has been shown to reduce HbA1c and body weight in patients with type 2 diabetes, with a significant proportion of patients achieving normoglycaemia and losing more than 10% of their baseline body weight 2, 3.
  • Tirzepatide has been compared to other anti-diabetes medications, including semaglutide and basal insulin, and has been found to be more effective in reducing HbA1c and body weight 2, 4.

Safety and Efficacy

  • The safety and efficacy of tirzepatide have been evaluated in several clinical trials, including the SURPASS 1-5 trials, which found that the medication was generally well-tolerated and effective in reducing HbA1c and body weight 2, 3, 4.
  • Common adverse events associated with tirzepatide include nausea, vomiting, diarrhea, and constipation, which were more common at higher doses 2, 4.
  • Tirzepatide has been found to improve insulin sensitivity and insulin secretory responses, and to reduce cardiovascular events, including nonfatal myocardial infarction, non-fatal stroke, and cardiovascular death 2, 5.

Mechanism of Action

  • Tirzepatide works by activating the GIP and GLP-1 receptors, which are key mediators of insulin secretion and are also expressed in regions of the brain that regulate food intake 2, 5.
  • The medication has been found to reduce food intake and body weight, and to improve blood pressure and lipid profiles, including reducing LDL cholesterol and triglycerides 5.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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