Oncotarget

Clinical Research Papers:

Meglitinides increase the risk of hypoglycemia in diabetic patients with advanced chronic kidney disease: a nationwide, population-based study

Pei-Chen Wu _, Vin-Cent Wu, Cheng-Jui Lin, Chi-Feng Pan, Chih-Yang Chen, Tao-Min Huang, Che-Hsiung Wu, Likwang Chen, Chih-Jen Wu and The NRPB Kidney Consortium

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Oncotarget. 2017; 8:78086-78095. https://doi.org/10.18632/oncotarget.17475

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Abstract

Pei-Chen Wu1,2,*, Vin-Cent Wu3,*, Cheng-Jui Lin1,4,5, Chi-Feng Pan1, Chih-Yang Chen1, Tao-Min Huang6, Che-Hsiung Wu7, Likwang Chen8, Chih-Jen Wu1,4,9,10 and The NRPB Kidney Consortium11

1 Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

2 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

3 Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

4 Department of Medicine, Mackay Medical College, Taipei, Taiwan

5 Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan

6 Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Douliou, Taiwan

7 Division of Nephrology, Taipei Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi University, Taipei, Taiwan

8 Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan

9 Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan

10 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

11 NRPB, National Research Program for Biopharmaceuticals, ROC, Taiwan

* These authors have contributed equally to this work

Correspondence to:

Chih-Jen Wu, email:

Keywords: meglitinide, diabetes mellitus, hypoglycemia, chronic kidney disease, mortality

Received: January 21, 2017 Accepted: April 14, 2017 Published: April 27, 2017

Abstract

The safety of short-acting meglitinides in diabetic patients with advanced chronic kidney disease (CKD) has not been widely reported.

Diabetic patients with advanced CKD who had a serum creatinine level of > 6 mg/dL a hematocrit level of ≦ 28% and received erythropoiesis-stimulating agent treatment between 2000 and 2010, were included in this nationwide study in Taiwan.

The outcomes of interest were defined as hypoglycemia and long-term mortality. The risks of hypoglycemia and death were analyzed using Cox proportional hazards models, with end-stage renal disease and anti-diabetic drugs as time-dependent variables.

Fresh users and matched non-users of meglitinides (both n = 2,793) were analyzed. The use of meglitinides increased the risk of hypoglycemia (HR, 1.94, p<0.001), as did other anti-diabetic agents. Concomitant use of meglitinide and insuilin will incresase the hypoglycemic risk. (HR, 1.69, p=0.018) Moreover, it was not the use of meglitinides, but the presence of hypoglycemia that predicted mortality. The function curve showed an insignificant trend towards increased hypoglycemic risk in patients aged > 62 and ≤ 33 years from the generalized additive model.

This study suggests that the use of short-acting meglitinides could be associated with increased risk of hypoglycemia in diabetic patients with advanced CKD, especially in patients aged > 62 and ≤ 33 years. Meglitinide combined with insulin will increase hypoglycemia in patients with advanced CKD.


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