Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune diseases: a population-based cohort study

Ann Rheum Dis. 2015 Nov;74(11):1968-75. doi: 10.1136/annrheumdis-2014-205216. Epub 2014 Jun 11.


Objective: Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a transmembrane glycoprotein that has a costimulatory function in the immune response. DPP4 inhibitors (DPP4i) are oral glucose-lowering drugs for type 2 diabetes mellitus (T2DM). This study evaluated the risk of incident rheumatoid arthritis (RA) and other autoimmune diseases (AD) such as systemic lupus erythematosus, psoriasis, multiple sclerosis and inflammatory bowel disease, associated with DPP4i in patients with T2DM.

Methods: Using US insurance claims data (2005-2012), we conducted a population-based cohort study that included initiators of combination therapy with DPP4i (DPP4i plus metformin) and non-DPP4i (non-DPP4i plus metformin). RA and other AD were identified with ≥2 diagnoses and ≥1 dispensing for AD-specific immunomodulating drugs or steroids. Composite AD includes RA or other AD. Propensity score (PS)-stratified Cox proportional hazards models compared the risk of AD in DPP4i initiators versus non-DPP4i, controlling for potential confounders.

Results: After asymmetric trimming on the PS, 73 928 patients with T2DM starting DPP4i combination therapy and 163 062 starting non-DPP4i combination therapy were selected. Risks of incident RA and composite AD were lower in the DPP4i group versus non-DPP4i with the PS-stratified HR of 0.66 (95% CI 0.44 to 0.99) for RA, 0.73 (0.51 to 1.03) for other AD and 0.68 (95% CI 0.52 to 0.89) for composite AD.

Conclusions: In this large cohort of diabetic patients, those initiating DPP4i combination therapy appear to have a decreased risk of incident AD including RA compared with those initiating non-DPP4i combination therapy. These results may suggest possible pharmacological pathways for prevention or treatment of AD.

Keywords: Autoimmune Diseases; Epidemiology; Rheumatoid Arthritis; Systemic Lupus Erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / epidemiology
  • Autoimmune Diseases / epidemiology*
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Inflammatory Bowel Diseases / epidemiology
  • Lupus Erythematosus, Systemic / epidemiology
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Multiple Sclerosis / epidemiology
  • Proportional Hazards Models
  • Protective Factors
  • Psoriasis / epidemiology
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use
  • United States / epidemiology


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • Metformin