DPP-4 Inhibitors and GLP-1 Receptor Agonists Combination Therapy

Introduction to Combination Therapy

• The American Diabetes Association recommends against the concurrent use of DPP-4 inhibitors with a GLP-1 receptor agonist due to lack of additional glucose lowering beyond that of a GLP-1 RA alone 1

Mechanism of Action

• When a GLP-1 receptor agonist is already saturating the GLP-1 receptors, preventing breakdown of endogenous GLP-1 adds no meaningful benefit 1

Guideline Recommendations

• The American Diabetes Association explicitly states that treatment with DPP-4 inhibitors should be stopped when GLP-1 receptor agonists are used, as no additional HbA1c reduction occurs when combining these agents and the combination increases medication burden and cost without clinical benefit 1

Alternative Therapies

• If already on a GLP-1 receptor agonist and considering additional therapy, choose from non-incretin options such as SGLT-2 inhibitors, insulin, or metformin 2, 3
• The combination of GLP-1 receptor agonists with SGLT-2 inhibitors has demonstrated HbA1c-lowering and weight-reduction efficacy 3, 4

Clinical Considerations

• GLP-1 receptor agonists provide supraphysiologic receptor activation that makes endogenous GLP-1 preservation irrelevant 1