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. 2019 Jul;8(8):3918-3927.
doi: 10.1002/cam4.2278. Epub 2019 May 23.

Dipeptidyl peptidase 4 inhibitors as novel agents in improving survival in diabetic patients with colorectal cancer and lung cancer: A Surveillance Epidemiology and Endpoint Research Medicare study

Rohit Bishnoi  1 , Young-Rock Hong  2 , Chintan Shah  1 , Azka Ali  1 , William P Skelton 4th  1 , Jinhai Huo  2 , Nam H Dang  1 , Long H Dang  1
Affiliations

Dipeptidyl peptidase 4 inhibitors as novel agents in improving survival in diabetic patients with colorectal cancer and lung cancer: A Surveillance Epidemiology and Endpoint Research Medicare study

Rohit Bishnoi et al. Cancer Med. 2019 Jul.

Abstract

Background: Dipeptidyl peptidase 4 (DPP4) is a cell surface protein that can act as a tumor suppressor or activator, depending upon the level of expression and interaction with the microenvironment and chemokines. DPP4 inhibitors are used to treat diabetes.

Methods: We conducted this Surveillance Epidemiology and Endpoint Research-Medicare database study to evaluate the role of DPP4 inhibitors on the overall survival (OS) of diabetic patients diagnosed with colorectal (CRC) and lung cancers.

Results: Diabetic patients with CRC or lung cancer who were treated with DPP4 inhibitors exhibited a statistically significant survival advantage (hazard ratio [HR] of 0.89; CI: 0.82-0.97, P = 0.007) that remained significant after controlling for all other confounders. When DPP4 inhibitors were used in combination of metformin which is known to suppress cancer, the survival advantage was even more pronounced (HR of 0.83; CI: 0.77-0.90, P < 0.0001). Data were then analyzed separately for two cancer types. In the CRC-only cohort, the use of DPP4 inhibitors alone had a positive trend but did not meet statistically significant threshold (HR of 0.87; CI: 0.75-1.00, P = 0.055), while the combined use of DPP4 inhibitors and metformin was associated with statistically significant survival advantage (HR of 0.77; CI: 0.67-0.89, P = 0.003). Similarly, for the lung cancer cohort, use of DPP4 alone was not found to be statistically significant (HR of 0.93; CI: 0.83-1.03, P = 0.153), whereas lung cancer patients treated with the combination of DPP4 inhibitors and metformin showed statistically significant survival advantage (HR of 0.88; CI: 0.80-0.97, P = 0.010).

Conclusions: DPP4 inhibition in CRC and lung cancer is associated with improved OS, which possibly may be due to the effect of DPP4 inhibition on immunoregulation of cancer.

Keywords: CD26; DPP4 inhibitors; SEER-Medicare; colorectal cancer; lung cancer.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
This shows the criteria and the flowchart used to identify study cohort
Figure 2
Figure 2
HR of patients using DPP4 inhibitor only (n = 775) in interaction with other variables in the study population after excluding patients treated with metformin (n = 17 517). DPP4, dipeptidyl peptidase 4; HR, hazard ratio
Figure 3
Figure 3
HR of patients using DPP4 inhibitor only (n = 356) in interaction with other variables in CRC cohort (n = 7573). DPP4, dipeptidyl peptidase 4; HR, hazard ratio
Figure 4
Figure 4
HR of patients using DPP4 inhibitor only (n = 419) in interaction with other variables in Lung cancer cohort (n = 9944). DPP4, dipeptidyl peptidase 4; HR, hazard ratio
Figure 5
Figure 5
This shows the multivariable analysis of combined cohort, CRC, and lung cancer patients. CRC, colorectal cancer
See this image and copyright information in PMC

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