Soie Kwon1,2, Yong Chul Kim1, Jae Yoon Park3, Jeonghwan Lee4, Jung Nam An5, Clara Tammy Kim6, Sohee Oh7, Seokwoo Park8,9, Dong Ki Kim1,9, Yun Kyu Oh2,9, Yon Su Kim1, Chun Soo Lim2,9, Jung Pyo Lee4,9. 1. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. 2. Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea. 3. Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Korea. 4. Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea nephrolee@gmail.com. 5. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Korea. 6. Institute of Life and Death Studies, Hallym University, Chuncheon, Korea. 7. Department of Biostatistics, Seoul Metropolitan Government, Seoul National University Boramae Medical Center, Seoul, Korea. 8. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. 9. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Abstract
OBJECTIVE: Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted. RESULTS: All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73; P < 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77; P < 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276; P = 0.629). CONCLUSIONS: In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.
OBJECTIVE:Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted. RESULTS: All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73; P < 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77; P < 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276; P = 0.629). CONCLUSIONS: In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.
Authors: Godela M Brosnahan; Wei Wang; Berenice Gitomer; Taylor Struemph; Diana George; Zhiying You; Kristen L Nowak; Jelena Klawitter; Michel B Chonchol Journal: Am J Kidney Dis Date: 2021-08-12 Impact factor: 8.860
Authors: Yao Hu; Min Lei; Guibao Ke; Xin Huang; Xuan Peng; Lihui Zhong; Ping Fu Journal: Front Endocrinol (Lausanne) Date: 2020-10-07 Impact factor: 5.555