Concurrent Use of Tirzepatide and Retatrutide

Pharmacologic Rationale

• Tirzepatide is a dual GLP-1/GIP receptor agonist that provides potent glucose lowering and weight reduction 1
• The American Diabetes Association explicitly states that concurrent use of DPP-4 inhibitors with a GLP-1 RA or dual GIP/GLP-1 RA is not recommended due to lack of additional glucose lowering beyond that of a GLP-1 RA alone 1, 2
• This same principle applies to combining two incretin-based therapies with overlapping receptor targets 3

Clinical Evidence Against Combination

• No trials have studied the cardiovascular or metabolic outcomes of combining different GLP-1-based therapies 4, 5
• The ACC Expert Consensus notes that while SGLT2 inhibitors and GLP-1 RAs can be combined (different mechanisms), this does not extend to combining two agents acting on the same receptors 4, 5

Practical Approach

• Tirzepatide is preferred for type 2 diabetes with cardiovascular disease as it has proven cardiovascular benefits and is guideline-recommended 6, 1
• GLP-1 RAs (including dual GIP/GLP-1 agonists like tirzepatide) are recommended as first-line agents for type 2 diabetes with chronic kidney disease 1, 3