What is the effect of Mounjaro (tirzepatide) on the pancreas in patients with type 1 diabetes?

Effects of Tirzepatide (Mounjaro) on the Pancreas in Type 1 Diabetes

Tirzepatide (Mounjaro) is not FDA-approved for use in type 1 diabetes and has limited evidence regarding its effects on the pancreas in this population, though recent observational data shows potential benefits for glycemic control and weight management with careful monitoring for adverse effects.

Mechanism and Pancreatic Effects

• Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, primarily approved for type 2 diabetes 1, 2
• Unlike in type 2 diabetes, the pancreatic beta cells in type 1 diabetes are destroyed by autoimmune processes, limiting tirzepatide's insulin-stimulating effects on the pancreas 3
• The medication does not appear to regenerate or restore pancreatic beta cell function in established type 1 diabetes, though it may have effects on other pancreatic hormones like glucagon 4

Current Evidence in Type 1 Diabetes

• A recent proof-of-concept observational study showed tirzepatide reduced HbA1c by 0.59% and body weight by 10.1% over 8 months in adults with type 1 diabetes 5
• The medication improved time in target glucose range by 12.6% and reduced time above range by 12.6% in type 1 diabetes patients 5
• Unlike pramlintide (the only FDA-approved non-insulin adjunctive therapy for type 1 diabetes), tirzepatide has not completed rigorous clinical trials for safety and efficacy in type 1 diabetes 6

Potential Benefits and Risks

• Tirzepatide may provide benefits in "double diabetes" (type 1 diabetes with features of insulin resistance and/or obesity) through its weight-reducing and insulin-sensitizing effects 3
• Similar to other GLP-1 receptor agonists in type 1 diabetes, tirzepatide may:
  • Reduce insulin requirements 4
  • Promote weight loss 4
  • Improve glycemic control 4
• However, important risks to consider include:
  • Potential increased risk of diabetic ketoacidosis (DKA), including euglycemic DKA, as seen with other incretin-based therapies in type 1 diabetes 4, 6
  • Gastrointestinal side effects (nausea, vomiting, diarrhea) 1, 5
  • Possible hypoglycemia risk if insulin doses aren't appropriately adjusted 6

Clinical Implications and Recommendations

• Insulin remains the cornerstone of therapy for type 1 diabetes, as tirzepatide cannot replace insulin therapy 4, 6
• For patients with type 1 diabetes considering tirzepatide:
  • Close monitoring for ketosis and DKA is essential 4
  • Insulin dose adjustments should be made carefully to prevent hypoglycemia 6
  • Regular assessment of pancreatic function through C-peptide levels may be valuable 4
• The 2025 American Diabetes Association Standards of Care acknowledges that GLP-1 receptor agonists in type 1 diabetes show modest A1C reductions (0.4%), weight decreases (5 kg), and reductions in insulin doses, but are not FDA-approved for this indication 4

Future Directions

• Randomized controlled trials are needed to establish the efficacy and safety of tirzepatide specifically in type 1 diabetes 5
• Research is ongoing to determine if tirzepatide or similar agents might help preserve residual beta cell function in early-onset type 1 diabetes or latent autoimmune diabetes in adults (LADA) 3
• Until more evidence is available, tirzepatide use in type 1 diabetes should be considered experimental and used with caution 4