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. 2024 Oct 14;17(10):1369.
doi: 10.3390/ph17101369.

Trends in Antidiabetic Drug Use and Safety of Metformin in Diabetic Patients with Varying Degrees of Chronic Kidney Disease from 2010 to 2021 in Korea: Retrospective Cohort Study Using the Common Data Model

Sung Hwan Joo  1   2 , Seungwon Yang  1   2   3 , Suhyun Lee  3 , Seok Jun Park  1   2 , Taemin Park  1   2   3 , Sang Youl Rhee  4   5 , Jae Myung Cha  6 , Sandy Jeong Rhie  7   8 , Hyeon Seok Hwang  9 , Yang Gyun Kim  10 , Eun Kyoung Chung  1   2   3   11
Affiliations

Trends in Antidiabetic Drug Use and Safety of Metformin in Diabetic Patients with Varying Degrees of Chronic Kidney Disease from 2010 to 2021 in Korea: Retrospective Cohort Study Using the Common Data Model

Sung Hwan Joo et al. Pharmaceuticals (Basel). .

Abstract

Background/objectives: This study aimed to investigate trends in antidiabetic drug use and assess the risk of metformin-associated lactic acidosis (MALA) in patients with chronic kidney disease (CKD).

Methods: A retrospective observational analysis based on the common data model was conducted using electronic medical records from 2010 to 2021. The patients included were aged ≥18, diagnosed with CKD and type 2 diabetes, and had received antidiabetic medications for ≥30 days. MALA was defined as pH ≤ 7.35 and arterial lactate ≥4 mmol/L.

Results: A total of 8318 patients were included, with 6185 in CKD stages 1-2 and 2133 in stages 3a-5. Metformin monotherapy was the most prescribed regimen, except in stage 5 CKD. As CKD progressed, metformin use significantly declined; insulin and meglitinides were most frequently prescribed in end-stage renal disease. Over the study period, the use of SGLT2 inhibitors (13.3%) and DPP-4 inhibitors (24.5%) increased significantly, while sulfonylurea use decreased (p < 0.05). Metformin use remained stable in earlier CKD stages but significantly decreased in stage 3b or worse. The incidence rate (IR) of MALA was 1.22 per 1000 patient-years, with a significantly increased IR in stage 4 or worse CKD (p < 0.001).

Conclusions: Metformin was the most prescribed antidiabetic drug in CKD patients in Korea with a low risk of MALA. Antidiabetic drug use patterns varied across CKD stages, with a notable decline in metformin use in advanced CKD and a rise in SGLT2 inhibitor prescriptions, underscoring the need for further optimized therapy.

Keywords: chronic kid-ney disease; common data model (CDM); metformin-associated lactic acidosis; observational medical outcomes partnership (OMOP); pharmacoepidemiology; pharmacovigilance; real-world data (RWD); type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of study patient selection. OMOP CDM, the observational medical outcomes partnership common data model; CKD, chronic kidney disease.
Figure 2
Figure 2
Patterns of prescribing antidiabetic drug regimen in patients with chronic kidney disease (CKD) by stages: (a) mild CKD (i.e., stage 1 to 2); (b) CKD stage 3a; (c) CKD stage 3b; (d) CKD stage 4; (e) CKD stage 5 receiving dialysis; and (f) CKD stage 5 not receiving dialysis. Abbreviations: AGI, alpha-glucosidase inhibitor; DPP4i, dipeptidyl peptidase-4 inhibitor; Glinide, meglitinide; MET, metformin; SU, sulfonylurea; TZD, thiazolidinedione.
Figure 3
Figure 3
Temporal trends of prescribing antidiabetic drugs in patients with chronic kidney disease (CKD) by stages: (a) mild CKD (i.e., stage 1 to 2); (b) CKD stage 3a; (c) CKD stage 3b to 5. Alpha-glucosidase inhibitor is not shown on the plot due to minimal use throughout the study period. Abbreviations: DPP4i, dipeptidyl peptidase-4 inhibitor; glinide, meglitinide; MET, metformin; SGLT2i, sodium-glucose cotransporter-2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione.
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