Given the lack of clarity regarding the benefits of metformin in patients with type 2 diabetes mellitus who were prescribed DPP-4 inhibitors (DPP-4is), we compared KL-6 levels in patients who were prescribed DPP-4is and in patients who were prescribed both DPP-4is and metformin. 54 patients were prescribed DPP-4is and KL-6 levels were measured in all of these patients. 25 patients were prescribed metformin. Thus, the patients were categorized into two groups: DPP-4i (DPP-4i without metformin; N = 29) and DPP-4i and met (DPP-4i with metformin; N = 25). The KL-6 levels in the DPP-4i was significantly higher than that of DPP-4i and met groups (300.76 ±155.39 vs223.96 ±73.83 U/mL, mean ±standard deviation, reference range: <500 U/mL, p= 0.0281). Transient elevation in KL-6 levels beyond the upper limit of normal range was observed in four patients in the DPP-4i group only. KL-6 levels were not elevated in any patients in the DPP-4i and met group. Despite the small sample size, this clinical study provides important information. One strength of the current study is that the KL-6 level was measured in all patients with type 2 diabetes mellitus who were prescribed DPP-4is. We confirmed that KL-6 levels were in the normal range before initiating DPP-4i administration. Moreover, KL-6 levels were transiently elevated and normalized after DPP-4i termination. The frequency of KL-6 level elevation due to DPP-4i administration was 7.4% although all of participated patients showed normal study on chest X-ray examination. This incidence was higher than that of statin-induced interstitial pneumonia. Metformin may prevent or delay interstitial lung diseases due to DPP-4i administration. However, KL-6 level in patients with metformin alone needs to be estimated.


Y. Shimoda: None. J. Okada: None. E. Yamada: None. S. Okada: None. M. Yamada: None.

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