metformin and Renal Insufficiency, Chronic studies

Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.

Renal Insufficiency, Chronic: Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)

Research Excerpts

Excerpt	Relevance	Reference
" However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis."	9.22	Lactic Acidosis Associated with Metformin in Patients with Diabetic Kidney Disease. ( Rahman, F; Tuba, S, 2022)
"There is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis."	9.01	The Association between Metformin Therapy and Lactic Acidosis. ( Duffull, SB; Kuan, IHS; Savage, RL; Walker, RJ; Wright, DFB, 2019)
"To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment."	8.95	Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review. ( Cameron, CB; Crowley, MJ; Diamantidis, CJ; Kosinski, AS; McDuffie, JR; Mock, CK; Nagi, A; Stanifer, JW; Tang, S; Wang, X; Williams, JW, 2017)
"Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality."	8.93	Metformin associated lactic acidosis (MALA): clinical profiling and management. ( Coclite, D; Manzione, A; Maresca, B; Menè, P; Moioli, A; Napoletano, AM; Pirozzi, N; Punzo, G, 2016)
"There is an ongoing controversy regarding the safety and effectiveness of metformin in the setting of heart failure (HF)."	8.89	Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. ( Eurich, DT; Johnson, JA; Majumdar, SR; McAlister, FA; Tjosvold, L; Tsuyuki, RT; Vanderloo, SE; Weir, DL, 2013)
"This study demonstrates that HIF1α stimulates both TG2 expression and activity via ZEB2/TRPC6 axis, whereas abrogation of HIF1α by metformin prevented hypoxia-induced glomerular injury."	8.31	Metformin prevents hypoxia-induced podocyte injury by regulating the ZEB2/TG2 axis. ( Kavvuri, R; Kolligundla, LP; Mukhi, D; Pasupulati, AK; Singh, AK, 2023)
"Lactic acidosis is a disease in which lactic acid accumulates in the blood and causes acidosis in the patient."	8.31	Metformin-associated severe lactic acidosis combined with multi-organ insufficiency induced by infection with Aeromonas veronii: A case report. ( Wu, C; Xia, Y; Zhu, X, 2023)
" The potential protective outcome of the antidiabetic and pleiotropic drug metformin against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before."	8.31	Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension. ( Al-Ani, B; Albawardi, A; Alqahtani, SM; Alshahrani, MY; Bayoumy, NM; Ebrahim, HA; Haidara, MA; Kamar, SS; ShamsEldeen, AM, 2023)
"This retrospective cohort study determines whether metformin monotherapy or combination therapies can decrease anemia risk in the progress of advanced chronic kidney disease for patients with type 2 diabetes mellitus."	8.12	Metformin and the Risk of Anemia of Advanced Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus. ( Fu, SL; Hsiung, CA; Jung, HK; Lai, JN; Liu, HY; Tsai, YT; Wu, CT, 2022)
"Evidence of metformin-associated lactic acidosis (MALA) in advanced chronic kidney disease (CKD) has been limited due to high mortality rate but rare incidence rate."	8.12	Relationship between metformin use and lactic acidosis in advanced chronic kidney disease: The REMIND-TMU study. ( Chang, TH; Chen, C; Chen, CC; Chen, CH; Hung, YJ; Ke, SS; Ko, Y; Kuo, KN; Wei, TE, 2022)
"Compare rates of lactic acidosis (LA) among metformin-exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD)."	8.02	Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study. ( Alvarez, CA; Chansard, M; Halm, EA; Hennessy, S; Lingvay, I; McGuire, DK; Miller, RT; Mortensen, EM; Pugh, MJV; Vouri, SM; Yang, H; Zullo, AR, 2021)
"The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis."	7.91	Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease: study protocol for a multicenter population-based case-control study using health databases. ( Ávila, M; Gómez-Lumbreras, A; Manríquez, M; Morros, R; Pedrós, C, 2019)
"To study the incidence of lactic acidosis due to metformin in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) stage 3-5."	7.91	Lactic acidosis due to metformin in type 2 diabetes mellitus and chronic kidney disease stage 3-5: is it significant? ( Guddattu, V; Mareddy, AS; Nagaraju, SP; Prabhu, RA; Rangaswamy, D, 2019)
"To estimate the incidence of lactic acidosis (LA) and role of metformin in Japanese patients with type 2 diabetes mellitus (T2DM) treated with anti-diabetes drugs."	7.83	Epidemiology of lactic acidosis in type 2 diabetes patients with metformin in Japan. ( Chang, CH; Dolin, P; Sakaguchi, M, 2016)
"In conclusion, our findings support the low risk of MALA among patients with mild-to-moderate renal impairment and the likelihood of metformin to be an innocent bystander without a pathogenic role in the lactic acidosis in most cases."	7.83	Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease. ( Acikgoz, SB; Genc, AB; Nalbant, A; Sipahi, S; Solak, Y; Tamer, A; Yildirim, M; Yilmaz, U, 2016)
"Prediabetes was induced by exposing male Sprague Dawley rats (150-180 g) to high-fat high- carbohydrate (HFHC) diet for 20 weeks."	5.62	Preventing the onset of diabetes-induced chronic kidney disease during prediabetes: The effects of oleanolic acid on selected markers of chronic kidney disease in a diet-induced prediabetic rat model. ( Gamede, M; Khathi, A; Mabuza, L; Ngubane, P, 2021)
"Metformin is a first-line oral antidiabetic therapy for patients with type 2 diabetes mellitus."	5.46	Hemodialysis-refractory metformin-associated lactate acidosis with hypoglycemia, hypothermia, and bradycardia in a diabetic patient with belated diagnosis and chronic kidney disease . ( Zibar, K; Zibar, L, 2017)
"Metformin is a basic drug used for the treatment of type 2 diabetes mellitus."	5.43	[Chronic kidney diseases, metformin and lactic acidosis]. ( Borbély, Z, 2016)
"All-cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non-users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin-alfa) Therapy (TREAT) (NCT00093015)."	5.30	Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease. ( Burdmann, EA; Charytan, DM; Claggett, B; Cooper, ME; Eckardt, KU; Ivanovich, P; Levey, AS; Lewis, EF; Liu, J; McGill, JB; McMurray, JJV; Parfrey, P; Parving, HH; Pfeffer, MA; Remuzzi, G; Singh, AK; Solomon, SD; Weinrauch, LA, 2019)
" However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis."	5.22	Lactic Acidosis Associated with Metformin in Patients with Diabetic Kidney Disease. ( Rahman, F; Tuba, S, 2022)
"There is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis."	5.01	The Association between Metformin Therapy and Lactic Acidosis. ( Duffull, SB; Kuan, IHS; Savage, RL; Walker, RJ; Wright, DFB, 2019)
"To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment."	4.95	Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review. ( Cameron, CB; Crowley, MJ; Diamantidis, CJ; Kosinski, AS; McDuffie, JR; Mock, CK; Nagi, A; Stanifer, JW; Tang, S; Wang, X; Williams, JW, 2017)
"Metformin (MF) accumulation during acute kidney injury is associated with high anion gap lactic acidosis type B (MF-associated lactic acidosis, MALA), a serious medical condition leading to high mortality."	4.93	Metformin associated lactic acidosis (MALA): clinical profiling and management. ( Coclite, D; Manzione, A; Maresca, B; Menè, P; Moioli, A; Napoletano, AM; Pirozzi, N; Punzo, G, 2016)
"There is an ongoing controversy regarding the safety and effectiveness of metformin in the setting of heart failure (HF)."	4.89	Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. ( Eurich, DT; Johnson, JA; Majumdar, SR; McAlister, FA; Tjosvold, L; Tsuyuki, RT; Vanderloo, SE; Weir, DL, 2013)
" This is the case for metformin (risk of lactic acidosis) and for many sulfonylureas (risk of hypoglycemia)."	4.89	Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. ( Scheen, AJ, 2013)
"Lactic acidosis is a disease in which lactic acid accumulates in the blood and causes acidosis in the patient."	4.31	Metformin-associated severe lactic acidosis combined with multi-organ insufficiency induced by infection with Aeromonas veronii: A case report. ( Wu, C; Xia, Y; Zhu, X, 2023)
"This study demonstrates that HIF1α stimulates both TG2 expression and activity via ZEB2/TRPC6 axis, whereas abrogation of HIF1α by metformin prevented hypoxia-induced glomerular injury."	4.31	Metformin prevents hypoxia-induced podocyte injury by regulating the ZEB2/TG2 axis. ( Kavvuri, R; Kolligundla, LP; Mukhi, D; Pasupulati, AK; Singh, AK, 2023)
" The potential protective outcome of the antidiabetic and pleiotropic drug metformin against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before."	4.31	Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension. ( Al-Ani, B; Albawardi, A; Alqahtani, SM; Alshahrani, MY; Bayoumy, NM; Ebrahim, HA; Haidara, MA; Kamar, SS; ShamsEldeen, AM, 2023)
"This retrospective cohort study determines whether metformin monotherapy or combination therapies can decrease anemia risk in the progress of advanced chronic kidney disease for patients with type 2 diabetes mellitus."	4.12	Metformin and the Risk of Anemia of Advanced Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus. ( Fu, SL; Hsiung, CA; Jung, HK; Lai, JN; Liu, HY; Tsai, YT; Wu, CT, 2022)
"Evidence of metformin-associated lactic acidosis (MALA) in advanced chronic kidney disease (CKD) has been limited due to high mortality rate but rare incidence rate."	4.12	Relationship between metformin use and lactic acidosis in advanced chronic kidney disease: The REMIND-TMU study. ( Chang, TH; Chen, C; Chen, CC; Chen, CH; Hung, YJ; Ke, SS; Ko, Y; Kuo, KN; Wei, TE, 2022)
"This study aims to assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and their combined presence in type 2 diabetes (T2D) patients in primary care for whom the 2019 ADA/EASD consensus update "Management of Hyperglycemia in Type 2 Diabetes" recommends GLP-1 receptor agonists (GLP-1RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-I) as first-line medications after metformin."	4.12	Prevalence of Atherosclerotic Cardiovascular Disease, Heart Failure, and Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Primary Care Research Network-based Study. ( Goderis, G; Mamouris, P; Mathieu, C; Vaes, B; van Craeyveld, E, 2022)
"Compare rates of lactic acidosis (LA) among metformin-exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD)."	4.02	Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study. ( Alvarez, CA; Chansard, M; Halm, EA; Hennessy, S; Lingvay, I; McGuire, DK; Miller, RT; Mortensen, EM; Pugh, MJV; Vouri, SM; Yang, H; Zullo, AR, 2021)
" The secondary outcome was metformin-associated lactic acidosis."	3.96	The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease. ( An, JN; Kim, CT; Kim, DK; Kim, YC; Kim, YS; Kwon, S; Lee, J; Lee, JP; Lim, CS; Oh, S; Oh, YK; Park, JY; Park, S, 2020)
"Metformin, an AMP-activated protein kinase (AMPK) activator, has been shown in previous studies to reduce kidney fibrosis in different models of experimental chronic kidney disease (CKD)."	3.96	Metformin arrests the progression of established kidney disease in the subtotal nephrectomy model of chronic kidney disease. ( Borges, CM; de Ávila, VF; Formigari, GP; Fujihara, CK; Lopes de Faria, JB; Malheiros, DMAC, 2020)
"To study the incidence of lactic acidosis due to metformin in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) stage 3-5."	3.91	Lactic acidosis due to metformin in type 2 diabetes mellitus and chronic kidney disease stage 3-5: is it significant? ( Guddattu, V; Mareddy, AS; Nagaraju, SP; Prabhu, RA; Rangaswamy, D, 2019)
"The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis."	3.91	Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease: study protocol for a multicenter population-based case-control study using health databases. ( Ávila, M; Gómez-Lumbreras, A; Manríquez, M; Morros, R; Pedrós, C, 2019)
"To estimate the incidence of lactic acidosis (LA) and role of metformin in Japanese patients with type 2 diabetes mellitus (T2DM) treated with anti-diabetes drugs."	3.83	Epidemiology of lactic acidosis in type 2 diabetes patients with metformin in Japan. ( Chang, CH; Dolin, P; Sakaguchi, M, 2016)
"In conclusion, our findings support the low risk of MALA among patients with mild-to-moderate renal impairment and the likelihood of metformin to be an innocent bystander without a pathogenic role in the lactic acidosis in most cases."	3.83	Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease. ( Acikgoz, SB; Genc, AB; Nalbant, A; Sipahi, S; Solak, Y; Tamer, A; Yildirim, M; Yilmaz, U, 2016)
" Metformin - an oral hypoglycemic drug universally recommended as the first-line treatment for type 2 diabetes mellitus (T2DM) - undergoes significant accumulation in advanced CKD that may ultimately lead to lactic acidosis."	3.81	Prescription-medication sharing among family members: an unrecognized cause of a serious drug adverse event in a patient with impaired renal function. ( Makówka, A; Nowicki, M; Zawiasa, A, 2015)
"Metformin therapy is limited in patients with chronic kidney disease (CKD) due to the potential risk of lactic acidosis."	3.78	Metformin therapy in patients with chronic kidney disease. ( Day, RO; Duong, JK; Furlong, TJ; Graham, GG; Greenfield, JR; Kirkpatrick, CM; Kumar, SS; Roberts, DM; Williams, KM, 2012)
"The current aim of ADPKD therapy is the inhibition of cyst development and retardation of chronic kidney disease progression."	2.82	Autosomic dominant polycystic kidney disease and metformin: Old knowledge and new insights on retarding progression of chronic kidney disease. ( Andreucci, M; Bolignano, D; Casarella, A; Coppolino, G; De Sarro, G; Deodato, F; Nicotera, R; Presta, P; Russo, E; Urso, A; Zicarelli, MT, 2022)
"Glucose-lowering treatment options for type 2 diabetes mellitus patients with chronic kidney disease are limited."	2.80	Combination of the dipeptidyl peptidase-4 inhibitor linagliptin with insulin-based regimens in type 2 diabetes and chronic kidney disease. ( Crowe, S; McGill, JB; von Eynatten, M; Woerle, HJ; Yki-Järvinen, H, 2015)
"Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e."	2.72	Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide. ( Gallwitz, B; Giorgino, F, 2021)
"However, statin failed to reduce chronic kidney diseases (CKD) and heart failure (HF)."	2.66	Second revolution in cardiovascular prevention. ( Chao, TF; Cheng, HM; Chiang, CE; Sung, SH; Wang, KL, 2020)
" The available literature with regard to incidence of adverse events and toxicity of hypoglycemic therapies is reviewed."	2.66	Toxicity of Metformin and Hypoglycemic Therapies. ( Akhter, MS; Uppal, P, 2020)
"Metformin is a frontline hypoglycemic agent, which is mainly prescribed to manage type 2 diabetes mellitus with obesity."	2.66	Metformin: the updated protective property in kidney disease. ( Chen, X; Guo, F; Liao, S; Liu, HF; Lu, X; Pan, Q; Yang, C; Zhao, C, 2020)
" The purpose of this article was to review the pharmacology, clinical trials, safety profile, along with recommended dosing and costs, of oral semaglutide used for managing patients with T2DM."	2.66	Oral Semaglutide: The First-available Noninjectable Glucagon-like Peptide 1 Receptor Agonist. ( Piszczatoski, C; Powell, J; Taylor, JR, 2020)
"Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0."	2.66	Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease-A Systematic Review and Meta-Analysis. ( Fu, P; Hu, Y; Huang, X; Ke, G; Lei, M; Peng, X; Zhong, L, 2020)
"Mycophenolic acid was detected in all cats."	2.61	( Abrams, G; Adolfsson, E; Agarwal, PK; Akkan, AG; Al Alhareth, NS; Alves, VGL; Armentano, R; Bahroos, E; Baig, M; Baldridge, KK; Barman, S; Bartolucci, C; Basit, A; Bertoli, SV; Bian, L; Bigatti, G; Bobenko, AI; Boix, PP; Bokulic, T; Bolink, HJ; Borowiec, J; Bulski, W; Burciaga, J; Butt, NS; Cai, AL; Campos, AM; Cao, G; Cao, Y; Čapo, I; Caruso, ML; Chao, CT; Cheatum, CM; Chelminski, K; Chen, AJW; Chen, C; Chen, CH; Chen, D; Chen, G; Chen, H; Chen, LH; Chen, R; Chen, RX; Chen, X; Cherdtrakulkiat, R; Chirvony, VS; Cho, JG; Chu, K; Ciurlino, D; Coletta, S; Contaldo, G; Crispi, F; Cui, JF; D'Esposito, M; de Biase, S; Demir, B; Deng, W; Deng, Z; Di Pinto, F; Domenech-Ximenos, B; Dong, G; Drácz, L; Du, XJ; Duan, LJ; Duan, Y; Ekendahl, D; Fan, W; Fang, L; Feng, C; Followill, DS; Foreman, SC; Fortunato, G; Frew, R; Fu, M; Gaál, V; Ganzevoort, W; Gao, DM; Gao, X; Gao, ZW; Garcia-Alvarez, A; Garza, MS; Gauthier, L; Gazzaz, ZJ; Ge, RS; Geng, Y; Genovesi, S; Geoffroy, V; Georg, D; Gigli, GL; Gong, J; Gong, Q; Groeneveld, J; Guerra, V; Guo, Q; Guo, X; Güttinger, R; Guyo, U; Haldar, J; Han, DS; Han, S; Hao, W; Hayman, A; He, D; Heidari, A; Heller, S; Ho, CT; Ho, SL; Hong, SN; Hou, YJ; Hu, D; Hu, X; Hu, ZY; Huang, JW; Huang, KC; Huang, Q; Huang, T; Hwang, JK; Izewska, J; Jablonski, CL; Jameel, T; Jeong, HK; Ji, J; Jia, Z; Jiang, W; Jiang, Y; Kalumpha, M; Kang, JH; Kazantsev, P; Kazemier, BM; Kebede, B; Khan, SA; Kiss, J; Kohen, A; Kolbenheyer, E; Konai, MM; Koniarova, I; Kornblith, E; Krawetz, RJ; Kreouzis, T; Kry, SF; Laepple, T; Lalošević, D; Lan, Y; Lawung, R; Lechner, W; Lee, KH; Lee, YH; Leonard, C; Li, C; Li, CF; Li, CM; Li, F; Li, J; Li, L; Li, S; Li, X; Li, Y; Li, YB; Li, Z; Liang, C; Lin, J; Lin, XH; Ling, M; Link, TM; Liu, HH; Liu, J; Liu, M; Liu, W; Liu, YP; Lou, H; Lu, G; Lu, M; Lun, SM; Ma, Z; Mackensen, A; Majumdar, S; Martineau, C; Martínez-Pastor, JP; McQuaid, JR; Mehrabian, H; Meng, Y; Miao, T; Miljković, D; Mo, J; Mohamed, HSH; Mohtadi, M; Mol, BWJ; Moosavi, L; Mosdósi, B; Nabu, S; Nava, E; Ni, L; Novakovic-Agopian, T; Nyamunda, BC; Nyul, Z; Önal, B; Özen, D; Özyazgan, S; Pajkrt, E; Palazon, F; Park, HW; Patai, Á; Patai, ÁV; Patzke, GR; Payette, G; Pedoia, V; Peelen, MJCS; Pellitteri, G; Peng, J; Perea, RJ; Pérez-Del-Rey, D; Popović, DJ; Popović, JK; Popović, KJ; Posecion, L; Povall, J; Prachayasittikul, S; Prachayasittikul, V; Prat-González, S; Qi, B; Qu, B; Rakshit, S; Ravelli, ACJ; Ren, ZG; Rivera, SM; Salo, P; Samaddar, S; Samper, JLA; Samy El Gendy, NM; Schmitt, N; Sekerbayev, KS; Sepúlveda-Martínez, Á; Sessolo, M; Severi, S; Sha, Y; Shen, FF; Shen, X; Shen, Y; Singh, P; Sinthupoom, N; Siri, S; Sitges, M; Slovak, JE; Solymosi, N; Song, H; Song, J; Song, M; Spingler, B; Stewart, I; Su, BL; Su, JF; Suming, L; Sun, JX; Tantimavanich, S; Tashkandi, JM; Taurbayev, TI; Tedgren, AC; Tenhunen, M; Thwaites, DI; Tibrewala, R; Tomsejm, M; Triana, CA; Vakira, FM; Valdez, M; Valente, M; Valentini, AM; Van de Winckel, A; van der Lee, R; Varga, F; Varga, M; Villarino, NF; Villemur, R; Vinatha, SP; Vincenti, A; Voskamp, BJ; Wang, B; Wang, C; Wang, H; Wang, HT; Wang, J; Wang, M; Wang, N; Wang, NC; Wang, Q; Wang, S; Wang, X; Wang, Y; Wang, Z; Wen, N; Wesolowska, P; Willis, M; Wu, C; Wu, D; Wu, L; Wu, X; Wu, Z; Xia, JM; Xia, X; Xia, Y; Xiao, J; Xiao, Y; Xie, CL; Xie, LM; Xie, S; Xing, Z; Xu, C; Xu, J; Yan, D; Yan, K; Yang, S; Yang, X; Yang, XW; Ye, M; Yin, Z; Yoon, N; Yoon, Y; Yu, H; Yu, K; Yu, ZY; Zhang, B; Zhang, GY; Zhang, H; Zhang, J; Zhang, M; Zhang, Q; Zhang, S; Zhang, W; Zhang, X; Zhang, Y; Zhang, YW; Zhang, Z; Zhao, D; Zhao, F; Zhao, P; Zhao, W; Zhao, Z; Zheng, C; Zhi, D; Zhou, C; Zhou, FY; Zhu, D; Zhu, J; Zhu, Q; Zinyama, NP; Zou, M; Zou, Z, 2019)
" Based on this new evidence, together with past epidemiologic data and systematic reviews, metformin appears to be a safe option for patients with CKD, assuming that the dosage is adjusted individually."	2.61	Safe Use of Metformin in Adults With Type 2 Diabetes and Chronic Kidney Disease: Lower Dosages and Sick-Day Education Are Essential. ( MacCallum, L; Senior, PA, 2019)
"Metformin has been shown to exert beneficial effects on the kidney in various clinical trials and experimental studies performed in divergent rodent models representing different types of renal diseases going from AKI to CKD."	2.58	Metformin: A Candidate Drug for Renal Diseases. ( Corremans, R; D'Haese, PC; Neven, E; Verhulst, A; Vervaet, BA, 2018)
" Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications."	2.58	Glycemic control of type 2 diabetes mellitus across stages of renal impairment: information for primary care providers. ( Adler, S; Tong, L, 2018)
"Metformin is a first-line therapy in patients with Type 2 diabetes, as it appears to be effective in reducing diabetes related end points and mortality in overweight patients."	2.55	Could metformin be used in patients with diabetes and advanced chronic kidney disease? ( Abraham, G; Chowdhury, TA; Fan, SL; McCafferty, K; Oei, EL; Srirathan, D; Yaqoob, MM, 2017)
"Metformin has a dominant position in the treatment of type 2 diabetes that is deserved due to its favorable and robust effects on cardiovascular risk."	2.53	METFORMIN: NONGLYCEMIC EFFECTS AND POTENTIAL NOVEL INDICATIONS. ( Anabtawi, A; Miles, JM, 2016)
"Metformin has traditionally been regarded as contraindicated in chronic kidney disease (CKD), though guidelines in recent years have been relaxed to permit therapy if the glomerular filtration rate (GFR) is > 30 mL/min."	2.50	Metformin in chronic kidney disease: time for a rethink. ( Heaf, J, 2014)
"One of the commonest complications of type 2 diabetes is renal disease."	2.50	Novel hypoglycaemic agents: considerations in patients with chronic kidney disease. ( Game, F, 2014)
"However, lactic acidosis is always associated with acute events, such as hypovolemia, acute cardiorespiratory illness, severe sepsis and acute renal or hepatic failure."	2.48	[Proposal for the modification of metformin use in patients with chronic kidney disease]. ( Balogh, Z; Mátyus, J, 2012)
"Metformin was the most common choice for patients with T2D and CKD."	1.91	Prescriber Uncertainty as Opportunity to Improve Care of Type 2 Diabetes with Chronic Kidney Disease: Mixed Methods Study. ( Flory, JH; Goytia, C; Guelce, D; Li, J; Mayer, V; Min, JY; Mushlin, A; Orloff, J, 2023)
" Chronic adenine dosing resulted in severe CKD in vehicle-treated rats as indicated by a marked rise in serum creatinine levels, a marked decrease in creatinine clearance, and a disturbed mineral metabolism."	1.72	Progression of established non-diabetic chronic kidney disease is halted by metformin treatment in rats. ( Corremans, R; D'Haese, PC; De Broe, ME; Leysen, H; Maudsley, S; Neven, E; Verhulst, A; Vervaet, BA, 2022)
"Lactic acidosis was present in 2 patients at presentation and serum lactate was elevated in 7/15 patients tested."	1.72	The extrapyramidal syndromes of chronic kidney disease and dialysis (EPS-CKDD): diagnostic criteria, risk factors and prognosis. ( Agarwal, A; Chemmanam, T; Irish, AB; Manickavasagar, R; Prentice, DA; Youssef, A, 2022)
"This research explored the intact nephron hypothesis (INH) as a model for metformin dosing in patients with chronic kidney disease (CKD)."	1.62	Does the intact nephron hypothesis provide a reasonable model for metformin dosing in chronic kidney disease? ( Duffull, SB; Kuan, IHS; Pradhan, S; Putt, TL; Schollum, JBW; Walker, RJ; Wilson, LC; Wright, DFB, 2021)
"Prediabetes was induced by exposing male Sprague Dawley rats (150-180 g) to high-fat high- carbohydrate (HFHC) diet for 20 weeks."	1.62	Preventing the onset of diabetes-induced chronic kidney disease during prediabetes: The effects of oleanolic acid on selected markers of chronic kidney disease in a diet-induced prediabetic rat model. ( Gamede, M; Khathi, A; Mabuza, L; Ngubane, P, 2021)
"Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0."	1.56	A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study. ( Clemens, KK; Hougen, I; Komenda, P; Rigatto, C; Tangri, N; Whitlock, RH, 2020)
"Cimetidine is a potent organic cation transporter 2/multidrug and toxin extrusion protein inhibitor."	1.56	A Comprehensive Whole-Body Physiologically Based Pharmacokinetic Drug-Drug-Gene Interaction Model of Metformin and Cimetidine in Healthy Adults and Renally Impaired Individuals. ( Ebner, T; Hanke, N; Ishiguro, N; Lehr, T; Müller, F; Nock, V; Selzer, D; Stopfer, P; Türk, D; Wiebe, S, 2020)
" Study aims were to, in a cohort of Australians with T2D and renal impairment attending general practice, (1) investigate whether the prescribing of non-insulin diabetes medications is consistent with dosing adjustments recommended within current Australian Diabetes Society (ADS) guidelines; and (2) identify patient socio-demographic and clinical factors associated with at least one prescription of a non-insulin diabetes medication inconsistent with current ADS guidelines for medication doses."	1.51	Prescribing of diabetes medications to people with type 2 diabetes and chronic kidney disease: a national cross-sectional study. ( Furler, J; Jenkins, A; Kilov, G; Manski-Nankervis, JA; O'Neal, D; Sluggett, JK; Thuraisingam, S, 2019)
"For patients with type 2 diabetes and chronic kidney disease (CKD), high-quality evidence about the relative benefits and harms of oral glucose-lowering drugs is limited."	1.48	Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort Study of Veterans with Diabetes and Chronic Kidney Disease. ( Boyko, EJ; de Boer, IH; Floyd, JS; Forsberg, CW; Marcum, ZA; Moore, KP; Smith, NL, 2018)
"First, in the dose-finding study, the appropriate daily dosing schedules were 1,500 mg (0."	1.48	Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4. ( Belpaire, F; Bennis, Y; De Broe, ME; Hurtel-Lemaire, AS; Kajbaf, F; Lalau, JD, 2018)
" In the cross-sectional analysis, the distribution of CKD stages and the appropriate dosage of metformin and DPP-4i in 2013 was examined according to renal function among T2DM patients."	1.48	Dose adjustment of metformin and dipeptidyl-peptidase IV inhibitors in diabetic patients with renal dysfunction. ( Azuri, J; Chodick, G; Karasik, A; Leuschner, PJ; Melzer-Cohen, C; Shalev, V, 2018)
"Metformin-treated rats did not develop hyperphosphatemia or hypocalcemia and this prevented the development of vascular calcification and inhibited the progression toward high bone turnover disease."	1.48	Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder. ( Brand, K; D'Haese, PC; De Broe, ME; De Maré, A; Gottwald-Hostalek, U; Kamel, S; Lalau, JD; Neven, E; Opdebeeck, B; Verhulst, A; Vervaet, B, 2018)
"The metformin eligibility was assessed by the sCr level (1."	1.46	Effect of prescribing metformin according to eGFR instead of serum creatinine level: A study based on Korean National Health and Nutrition Examination Survey (KNHANES) 2009-2014. ( Ahn, CH; Cho, YM; Moon, SJ, 2017)
"A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent."	1.46	Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data. ( Kalantar-Zadeh, K; Kovesdy, CP; Rhee, CM, 2017)
"Metformin is a first-line oral antidiabetic therapy for patients with type 2 diabetes mellitus."	1.46	Hemodialysis-refractory metformin-associated lactate acidosis with hypoglycemia, hypothermia, and bradycardia in a diabetic patient with belated diagnosis and chronic kidney disease . ( Zibar, K; Zibar, L, 2017)
"Metformin is and has been considered as first-line therapy for type 2 diabetes for over a quarter of a century."	1.43	Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? No, We Should Never Again Compromise Safety! ( Kalantar-Zadeh, K; Kovesdy, CP, 2016)
"Metformin is and has been considered as first-line therapy for type 2 diabetes for over a quarter of a century."	1.43	Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? Yes, They Should Be Relaxed! What's the Fuss? ( Bakris, GL; Molitch, ME, 2016)
"Metformin is a basic drug used for the treatment of type 2 diabetes mellitus."	1.43	[Chronic kidney diseases, metformin and lactic acidosis]. ( Borbély, Z, 2016)
"813 metformin users were matched by propensity score to 2439 non-users."	1.42	Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study. ( Chang, YK; Chen, YH; Hsu, CC; Hung, SC; Kuo, KL; Liu, JS; Tarng, DC, 2015)
"Metformin eligibility was assessed among 3,902 adults with diabetes who participated in the 1999-2010 National Health and Nutrition Examination Surveys and reported routine access to health care, using conventional sCr thresholds (eligible if <1."	1.42	Potential Impact of Prescribing Metformin According to eGFR Rather Than Serum Creatinine. ( Grubbs, V; Hsu, CY; Lin, F; Powe, NR; Saran, R; Saydah, S; Shahinian, V; Shlipak, MG; Tuot, DS; Williams, DE; Yee, J, 2015)
"Metformin was the most common PIM at admission."	1.42	Retrospective evaluation of potentially inappropriate prescribing in hospitalized patients with renal impairment. ( Castelino, RL; Doody, HK; Peterson, GM; Watson, D, 2015)
"To determine how many ambulatory older adults with chronic kidney disease receive medications that are contraindicated or dosed excessively given their level of renal function."	1.42	Use of Renally Inappropriate Medications in Older Veterans: A National Study. ( Chang, F; Miao, Y; O'Hare, AM; Steinman, MA, 2015)
" The place of metformin is of particular interest since most scientific societies now recommend using half the dosage in moderate RI and abstaining from use in severe RI, while the classic contraindication with RI has not been removed from the label."	1.40	How are patients with type 2 diabetes and renal disease monitored and managed? Insights from the observational OREDIA study. ( Blicklé, JF; Dejager, S; Fiquet, B; Penfornis, A; Quéré, S, 2014)
"Metformin was immediately stopped, and regular hemodialysis was conducted."	1.39	Two additional cases of metformin-associated encephalopathy in patients with end-stage renal disease undergoing hemodialysis. ( Bae, EJ; Chang, SH; Cho, HS; Jeon, DH; Kang, YJ; Kim, HJ; Park, DJ; Seo, JW, 2013)

Research

Studies (134)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

Adiposity

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	1 (0.75)	29.6817
2010's	79 (58.96)	24.3611
2020's	54 (40.30)	2.80

Authors	Studies
Wu, CT	1
Tsai, YT	1
Jung, HK	1
Fu, SL	1
Hsiung, CA	1
Liu, HY	1
Lai, JN	1
Lalau, JD	6
Bennis, Y	3
Al-Salameh, A	1
Hurtel-Lemaire, AS	2
Fendri, S	1
Corremans, R	2
Neven, E	4
Maudsley, S	2
Leysen, H	1
De Broe, ME	4
D'Haese, PC	4
Vervaet, BA	2
Verhulst, A	4
Pruijm, M	1
Phan, O	1
Zanchi, A	1
Chen, CC	1
Ko, Y	1
Chen, CH	2
Hung, YJ	1
Wei, TE	1
Chang, TH	1
Ke, SS	1
Kuo, KN	1
Chen, C	2
Seetharaman, R	1
Liaw, J	1
Harhay, M	1
Setoguchi, S	1
Gerhard, T	1
Dave, CV	1
Ofori, E	1
Gyan, KF	1
Gyabaah, S	1
Nguah, SB	1
Sarfo, FS	1
de Boer, IH	2
Khunti, K	1
Sadusky, T	1
Tuttle, KR	1
Neumiller, JJ	1
Rhee, CM	5
Rosas, SE	1
Rossing, P	1
Bakris, G	1
Kolligundla, LP	1
Kavvuri, R	1
Singh, AK	2
Mukhi, D	1
Pasupulati, AK	1
Rahman, F	1
Tuba, S	1
Flory, JH	2
Guelce, D	1
Goytia, C	1
Li, J	6
Min, JY	2
Mushlin, A	1
Orloff, J	2
Mayer, V	1
Xia, Y	2
Zhu, X	1
Wu, C	2
Alshahrani, MY	1
Ebrahim, HA	1
Alqahtani, SM	1
Bayoumy, NM	1
Kamar, SS	1
ShamsEldeen, AM	1
Haidara, MA	1
Al-Ani, B	1
Albawardi, A	1
Bobenko, AI	1
Heller, S	1
Schmitt, N	1
Cherdtrakulkiat, R	1
Lawung, R	1
Nabu, S	1
Tantimavanich, S	1
Sinthupoom, N	1
Prachayasittikul, S	1
Prachayasittikul, V	1
Zhang, B	1
Zhang, Z	2
Yan, K	1
Li, C	2
Li, Y	4
Li, L	4
Zheng, C	1
Xiao, Y	1
He, D	1
Zhao, F	1
Su, JF	1
Lun, SM	1
Hou, YJ	1
Duan, LJ	1
Wang, NC	1
Shen, FF	1
Zhang, YW	1
Gao, ZW	1
Du, XJ	1
Zhou, FY	1
Yin, Z	1
Zhu, J	2
Yan, D	1
Lou, H	1
Yu, H	1
Feng, C	1
Wang, Z	1
Wang, Y	4
Hu, X	1
Li, Z	2
Shen, Y	1
Hu, D	1
Chen, H	1
Wu, X	2
Duan, Y	1
Zhi, D	1
Zou, M	2
Zhao, Z	1
Zhang, X	2
Yang, X	2
Zhang, J	2
Wang, H	1
Popović, KJ	1
Popović, DJ	1
Miljković, D	1
Lalošević, D	1
Čapo, I	1
Popović, JK	1
Liu, M	1
Song, H	2
Xing, Z	1
Lu, G	1
Chen, D	1
Valentini, AM	1
Di Pinto, F	1
Coletta, S	1
Guerra, V	1
Armentano, R	1
Caruso, ML	1
Gong, J	1
Wang, N	1
Bian, L	1
Wang, M	1
Ye, M	1
Wen, N	1
Fu, M	1
Fan, W	1
Meng, Y	1
Dong, G	1
Lin, XH	1
Liu, HH	1
Gao, DM	1
Cui, JF	1
Ren, ZG	1
Chen, RX	1
Önal, B	1
Özen, D	1
Demir, B	1
Akkan, AG	1
Özyazgan, S	1
Payette, G	1
Geoffroy, V	1
Martineau, C	1
Villemur, R	1
Jameel, T	1
Baig, M	1
Gazzaz, ZJ	1
Tashkandi, JM	1
Al Alhareth, NS	1
Khan, SA	1
Butt, NS	1
Wang, J	2
Geng, Y	1
Zhang, Y	3
Wang, X	3
Liu, J	3
Basit, A	1
Miao, T	1
Liu, W	1
Jiang, W	1
Yu, ZY	1
Wu, L	2
Qu, B	1
Sun, JX	1
Cai, AL	1
Xie, LM	1
Groeneveld, J	1
Ho, SL	1
Mackensen, A	1
Mohtadi, M	1
Laepple, T	1
Genovesi, S	1
Nava, E	1
Bartolucci, C	1
Severi, S	1
Vincenti, A	1
Contaldo, G	1
Bigatti, G	1
Ciurlino, D	1
Bertoli, SV	1
Slovak, JE	1
Hwang, JK	1
Rivera, SM	1
Villarino, NF	1
Li, S	1
Cao, G	1
Ling, M	1
Ji, J	1
Zhao, D	1
Sha, Y	1
Gao, X	1
Liang, C	2
Guo, Q	1
Zhou, C	1
Ma, Z	1
Xu, J	1
Wang, C	1
Zhao, W	1
Xia, X	1
Jiang, Y	1
Peng, J	1
Jia, Z	1
Li, F	1
Chen, X	3
Mo, J	1
Zhang, S	2
Li, X	1
Huang, T	1
Zhu, Q	1
Wang, S	1
Ge, RS	1
Fortunato, G	1
Lin, J	2
Agarwal, PK	1
Kohen, A	1
Singh, P	1
Cheatum, CM	1
Zhu, D	1
Hayman, A	1
Kebede, B	1
Stewart, I	1
Chen, G	1
Frew, R	1
Guo, X	1
Gong, Q	1
Borowiec, J	1
Han, S	1
Zhang, M	1
Willis, M	1
Kreouzis, T	1
Yu, K	1
Chirvony, VS	1
Sekerbayev, KS	1
Pérez-Del-Rey, D	1
Martínez-Pastor, JP	1
Palazon, F	1
Boix, PP	1
Taurbayev, TI	1
Sessolo, M	1
Bolink, HJ	1
Lu, M	1
Lan, Y	1
Xiao, J	1
Song, M	1
Huang, Q	1
Cao, Y	1
Ho, CT	1
Qi, B	1
Wang, Q	1
Zhang, W	1
Fang, L	1
Xie, CL	1
Chen, R	1
Yang, S	1
Xia, JM	1
Zhang, GY	1
Yang, XW	1
Domenech-Ximenos, B	1
Garza, MS	1
Prat-González, S	1
Sepúlveda-Martínez, Á	1
Crispi, F	1
Perea, RJ	1
Garcia-Alvarez, A	1
Sitges, M	1
Kalumpha, M	1
Guyo, U	1
Zinyama, NP	1
Vakira, FM	1
Nyamunda, BC	1
Varga, M	1
Drácz, L	1
Kolbenheyer, E	1
Varga, F	1
Patai, ÁV	1
Solymosi, N	1
Patai, Á	1
Kiss, J	1
Gaál, V	1
Nyul, Z	1
Mosdósi, B	1
Valdez, M	1
Moosavi, L	1
Heidari, A	1
Novakovic-Agopian, T	1
Kornblith, E	1
Abrams, G	1
McQuaid, JR	1
Posecion, L	1
Burciaga, J	1
D'Esposito, M	1
Chen, AJW	1
Samy El Gendy, NM	1
Wesolowska, P	1
Georg, D	1
Lechner, W	1
Kazantsev, P	1
Bokulic, T	1
Tedgren, AC	1
Adolfsson, E	1
Campos, AM	1
Alves, VGL	1
Suming, L	1
Hao, W	1
Ekendahl, D	1
Koniarova, I	1
Bulski, W	1
Chelminski, K	1
Samper, JLA	1
Vinatha, SP	1
Rakshit, S	1
Siri, S	1
Tomsejm, M	1
Tenhunen, M	1
Povall, J	1
Kry, SF	1
Followill, DS	1
Thwaites, DI	1
Izewska, J	1
Kang, JH	1
Yoon, Y	1
Song, J	1
Van de Winckel, A	1
Gauthier, L	1
Chao, CT	1
Lee, YH	1
Li, CM	1
Han, DS	1
Huang, JW	1
Huang, KC	1
Ni, L	1
Güttinger, R	1
Triana, CA	1
Spingler, B	1
Baldridge, KK	1
Patzke, GR	1
Shen, X	1
Wang, B	1
Xie, S	1
Deng, W	1
Wu, D	1
Zhang, Q	1
Voskamp, BJ	1
Peelen, MJCS	1
Ravelli, ACJ	1
van der Lee, R	1
Mol, BWJ	1
Pajkrt, E	1
Ganzevoort, W	1
Kazemier, BM	1
Tibrewala, R	1
Bahroos, E	1
Mehrabian, H	1
Foreman, SC	1
Link, TM	1
Pedoia, V	1
Majumdar, S	1
Jablonski, CL	1
Leonard, C	1
Salo, P	1
Krawetz, RJ	1
Yoon, N	1
Hong, SN	1
Cho, JG	1
Jeong, HK	1
Lee, KH	1
Park, HW	1
Barman, S	1
Konai, MM	1
Samaddar, S	1
Haldar, J	1
Mohamed, HSH	1
Li, CF	1
Hu, ZY	1
Deng, Z	1
Chen, LH	1
Su, BL	1
Chu, K	1
Liu, YP	1
Li, YB	1
Zhang, H	1
Xu, C	1
Zou, Z	1
Wu, Z	1
Zhao, P	2
Wang, HT	1
de Biase, S	1
Pellitteri, G	1
Gigli, GL	1
Valente, M	1
Hennessy, S	2
Bailey, CJ	1
Inzucchi, SE	2
Gosmanova, EO	1
Shahzad, SR	1
Sumida, K	1
Kovesdy, CP	3
Gosmanov, AR	1
Whitlock, RH	1
Hougen, I	1
Komenda, P	1
Rigatto, C	1
Clemens, KK	1
Tangri, N	2
Mohamad, HE	1
Asker, ME	1
Keshawy, MM	1
Abdel Aal, SM	1
Mahmoud, YK	1
Hur, KY	1
Kim, MK	1
Ko, SH	1
Han, M	1
Lee, DW	1
Kwon, HS	1
Chiang, CE	1
Wang, KL	1
Cheng, HM	1
Sung, SH	1
Chao, TF	1
Kwon, S	1
Kim, YC	1
Park, JY	1
Lee, J	1
An, JN	1
Kim, CT	1
Oh, S	1
Park, S	1
Kim, DK	1
Oh, YK	1
Kim, YS	1
Lim, CS	1
Lee, JP	1
Akhter, MS	1
Uppal, P	1
Borges, CM	1
Fujihara, CK	1
Malheiros, DMAC	1
de Ávila, VF	1
Formigari, GP	1
Lopes de Faria, JB	1
Pan, Q	1
Lu, X	1
Zhao, C	1
Liao, S	1
Guo, F	1
Yang, C	1
Liu, HF	1
Hirsch, IB	1
Gaudiani, LM	1
Hanke, N	1
Türk, D	1
Selzer, D	1
Ishiguro, N	1
Ebner, T	1
Wiebe, S	1
Müller, F	1
Stopfer, P	1
Nock, V	1
Lehr, T	1
Awal, HB	1
Nandula, SR	1
Domingues, CC	1
Dore, FJ	1
Kundu, N	1
Brichacek, B	1
Fakhri, M	1
Elzarki, A	1
Ahmadi, N	1
Safai, S	1
Fosso, M	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Role of Linagliptin in Improving Renal Failure by Improving CD34+ Stem Cell Number, Function and Gene Expression in Renal Function Impaired Type 2 Diabetes Patients.[NCT02467478]	Phase 4	31 participants (Actual)	Interventional	2015-04-30	Completed
A Prospective, Randomized Open-Label Phase II Study of the Safety and Tolerability of Metformin in Combination With Standard Antimicrobial Treatment of Pulmonary Tuberculosis in People With TB and Co-infected With HIV[NCT04930744]	Phase 2	112 participants (Anticipated)	Interventional	2021-08-03	Recruiting
Metformin Use in Chronic Kidney Disease: The CKD-Met Study[NCT02844153]		1,000 participants (Anticipated)	Observational	2014-03-31	Recruiting
A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes[NCT02692716]	Phase 3	3,183 participants (Actual)	Interventional	2017-01-17	Completed
Feasibility Study of Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease.[NCT02903511]	Phase 2	56 participants (Actual)	Interventional	2016-11-30	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Measured using the Tanita Body Composition Analyzer scale, measured as percentage body fat. (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Estimation of Creatinine Clearance

Intervention	percentage of body fat (Mean)
Placebo	30.6
Linagliptin	31.2

Measured via blood biochemistry eGFR, an alternative measurement to spot urine urine microalbumin/creatinine ratio presented above (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Glycemic Control

Intervention	mL/min/1.73m^2 (Mean)
Placebo	84.12
Linagliptin	79.46

Glycemic control is evaluated by measuring HbA1c levels to gauge changes in blood sugar control over last ~90 days (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Glycemic Control: Fasting Glucose

Intervention	percentage of hemoglobin (Mean)
Placebo	7.27
Linagliptin	6.66

Glycemic control is evaluated by measuring fasting blood glucose at time of measurement (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Glycemic Control: Insulin

Intervention	mg/dL (Mean)
Placebo	129.68
Linagliptin	109.93

Glycemic control is evaluated by measuring insulin levels at the time of the visit (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Pulse Wave Velocity

Intervention	mIU/L (Mean)
Placebo	20.82
Linagliptin	20.52

Vessel health is assessed by looking at Arterial stiffness. Pulse wave velocity (PWV) measures the delay between the pulse registered at the femoral artery from the pulse at the carotid. The difference in distance between these two measurement points from the aortic notch is divided by this delay to give a speed. In stiffer, less healthy vessels, the PWV is increased. We used Vascular Flow and wave measurement equipment, SphygmoCor Central Pressure system from AtCor to perform this calculation. (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Resting Metabolic Rate (RMR)

Intervention	m/s (Mean)
Placebo	10.23
Linagliptin	10.53

(RMR, similar to Resting Energy expenditure measurement): Evaluation of changes in Basal Metabolic Rate (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Serum Endothelial Inflammatory Markers

Intervention	Calories/day (Mean)
Placebo	1650.07
Linagliptin	1657.6

Serum endothelial inflammatory markers included here: high sensitivity C-reactive protein (hs-CRP) (NCT02467478)
Timeframe: 12 weeks post Linagliptin or Placebo treatment

Serum Endothelial Inflammatory Markers

Intervention	mg/L (Mean)
Placebo	3.08
Linagliptin	5.17

Serum endothelial inflammatory markers included here: Interleukin 6 (IL-6) (NCT02467478)
Timeframe: 12 weeks post Linagliptin or Placebo treatment

Urinary Function Marker in CKD

Intervention	pg/mL (Mean)
Placebo	2.18
Linagliptin	5.09

We measure using microalbumin/creatinine ratio provided from a random spot urine sample. (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Cellular Markers

Intervention	ratio (Mean)
Placebo	51.12
Linagliptin	39.70

The investigators will use participants' peripheral blood derived CD34+ cells looking at number, function, and gene expression. Post Linagliptin will be compared to pre Linagliptin measurements. Here we report fold changes in protein populations as determined by ELISA. (NCT02467478)
Timeframe: Week 12 expression as a fold difference to Week 0

Fasting Lipid Profile

Intervention	Fold Change (Mean)
	PECAM	VEGFA	SOD3	SOD2	GPX3
Linagliptin	2.48	2.4	1.15	2.47	1.36
Placebo	1.48	1.43	1.13	1.40	1.59

Measured through serum biochemistry Lipid Panel (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Pulse Wave Analysis

Intervention	mg/dl (Mean)
	Cholesterol	Triglycerides
Linagliptin	159.69	124.31
Placebo	171.45	127.76

Vessel health is assessed by looking at Arterial stiffness. Augmentation index (AI) is defined as the ratio of the augmentation pressure to the pulse pressure, times 100, to give a percentage. Augmentation index 75 normalizes this value to an estimate of the AI at a heart rate of 75bpm. We used Vascular Flow and wave measurement equipment, SphygmoCor Central Pressure system from AtCor. (NCT02467478)
Timeframe: 12 weeks post beginning Linagliptin or placebo treatment

Change in Body Weight

Intervention	Percentage (of pulse pressure) (Mean)
	Augmentation Index 75	Augmentation Index
Linagliptin	22.33	24.93
Placebo	21.37	24.17

Change from baseline (week 0) in body weight measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Glycosylated Haemoglobin (HbA1c)

Intervention	Kg (Mean)
Oral Semaglutide	-4.2
Placebo	-0.8

Change from baseline (week 0) in HbA1c measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in HDL-cholesterol - Ratio to Baseline

Intervention	Percentage of HbA1c (Mean)
Oral Semaglutide	-1.0
Placebo	-0.3

Change from baseline (week 0) in HDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in LDL-cholesterol - Ratio to Baseline

Intervention	Ratio of HDL-cholesterol (Geometric Mean)
Oral Semaglutide	1.05
Placebo	1.02

Change from baseline (week 0) in LDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Pulse Rate

Intervention	Ratio of LDL-cholesterol (Geometric Mean)
Oral Semaglutide	0.96
Placebo	0.97

Change from baseline (week 0) in pulse rate measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Total Cholesterol - Ratio to Baseline

Intervention	Beats/minute (Mean)
Oral Semaglutide	4
Placebo	-0

Change from baseline (week 0) in total cholesterol (mmol/L) at the end of treatment (week 83) visit is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Change in Triglycerides - Ratio to Baseline

Intervention	Ratio of total cholesterol (Geometric Mean)
Oral Semaglutide	0.97
Placebo	0.98

Change from baseline (week 0) in triglycerides (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week 0, End of treatment

Number of Serious Adverse Events

Intervention	Ratio of triglycerides (Geometric Mean)
Oral Semaglutide	0.92
Placebo	0.97

Number of serious adverse events were recorded from week 0 to week 87 in the study. Results are based on the on-treatment observation period which started at the date of first dose on trial product and ended on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window.

Time From Randomisation to All-cause Death

Intervention	Events (Number)
Oral Semaglutide	545
Placebo	618

Number of all-cause deaths in the study are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, Non-fatal Myocardial Infarction or Nonfatal Stroke

Intervention	Participants (Count of Participants)
Oral Semaglutide	23
Placebo	45

Participants experiencing first occurrence of a composite CV endpoint (defined as all-cause death, non-fatal myocardial infarction or nonfatal stroke) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE) Composite Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke

Intervention	Participants (Count of Participants)
Oral Semaglutide	69
Placebo	89

Number of participants experiencing a first event of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, UAP Requiring Hospitalisation or Hospitalisation for Heart Failure

Intervention	Participants (Count of Participants)
Oral Semaglutide	61
Placebo	76

Participants experiencing first occurrence of an expanded composite CV endpoint [defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, UAP (unstable angina pectoris) requiring hospitalisation or heart failure requiring hospitalisation] are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of Fatal or Non-fatal Myocardial Infarction

Intervention	Participants (Count of Participants)
Oral Semaglutide	83
Placebo	100

Number of participants experiencing a first event of a fatal or non-fatal myocardial infarction are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time From Randomisation to First Occurrence of Fatal or Non-fatal Stroke

Intervention	Participants (Count of Participants)
Oral Semaglutide	37
Placebo	35

Number of participants experiencing a first event of a fatal or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Time to First AE Leading to Permanent Trial Product Discontinuation

Intervention	Participants (Count of Participants)
Oral Semaglutide	13
Placebo	17

Number of participants who permanently discontinued trial product in ths study are presented. Results are based on the on-treatment observation period which starts at the date of first dose on trial product; ends on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window.

Change in Eye Examination Category

Intervention	Participants (Count of Participants)
Oral Semaglutide	184
Placebo	104

Participants with eye examination findings, normal, abnormal non clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -3) and end of treatment visit (week 83) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Week -3, End of treatment

Change in Systolic and Diastolic Blood Pressure

Intervention	Participants (Count of Participants)
	Left eye fundoscopy (week -3): Normal	Left eye fundoscopy (week -3): Abnormal NCS	Left eye fundoscopy (week -3): Abnormal CS	Right eye fundoscopy (week -3): Normal	Right eye fundoscopy (week -3): Abnormal NCS	Right eye fundoscopy (week -3): Abnormal CS	Left eye fundoscopy (EOT): Normal	Left eye fundoscopy (EOT): Abnormal NCS	Left eye fundoscopy (EOT): Abnormal CS	Right eye fundoscopy (EOT): Normal	Right eye fundoscopy (EOT): Abnormal NCS	Right eye fundoscopy (EOT): Abnormal CS
Oral Semaglutide	848	657	86	845	659	86	783	599	83	780	601	81
Placebo	843	673	74	858	661	72	790	597	62	787	599	64

Change from baseline (week 0) in systolic and diastolic blood pressure measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window). (NCT02692716)
Timeframe: Week 0, End of treatment

Time From Randomisation to First Occurrence of Each of the Individual Components in the Expanded Composite Cardiovascular Endpoint

Intervention	mmHg (Mean)
	Systolic blood pressure	Diastolic blood pressure
Oral Semaglutide	-5	-1
Placebo	-2	-2

Participants experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or heart failure requiring hospitalisation) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment. (NCT02692716)
Timeframe: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period.

Change in Kidney Function

Intervention	Participants (Count of Participants)
	Cardiovascular death	Non-fatal myocardial infarction	Non-fatal stroke	Unstable angina requiring hospitalisation	Heart failure requiring hospitalisation
Oral Semaglutide	15	37	12	11	21
Placebo	30	31	16	7	24

Estimated glomerular filtration rate (eGFR) will be calculated from serum creatinine measurements at baseline and after 3, 6, 9 and 12 months. Change from baseline at 12 months is reported. (NCT02903511)
Timeframe: 12 months

Change in Total Kidney Volume

Intervention	mL/min/1.73 m^2 (Mean)
Metformin	-0.41
Placebo	-3.35

Total kidney volume will be measured by MRI (magnetic resonance imaging) at baseline and at 12 months. Percentage change from baseline in height-adjusted total kidney volume is reported. (NCT02903511)
Timeframe: 12 months

Rate of Serious Adverse Events (SAE)

Intervention	percent change (Mean)
Metformin	3.45
Placebo	3.15

Serious adverse events occurring from the time of signing informed consent until the end of the study will be monitored in both treatment arms (NCT02903511)
Timeframe: 12 months

Safety and Tolerability of Metformin

Intervention	Participants (Count of Participants)
Metformin	2
Placebo	0

Percentage of participants who at the end of 12 months are still prescribed the full randomized dose of metformin or placebo, and the percentage of participants who are prescribed at least 50% of the randomized dose (NCT02903511)
Timeframe: 12 months

Article	Year
Lactic Acidosis Associated with Metformin in Patients with Diabetic Kidney Disease. Medical archives (Sarajevo, Bosnia and Herzegovina), 2022, Volume: 76, Issue:4 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hypoglycemic Agents; La	2022
Proceedings. Mathematical, physical, and engineering sciences, 2019, Volume: 475, Issue:2227 Topics: Acetylcholine; Acinetobacter baumannii; Actinobacteria; Action Potentials; Adalimumab; Adaptation, P	2019
Metformin Treatment for Patients with Diabetes and Chronic Kidney Disease: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement. Diabetes & metabolism journal, 2020, Volume: 44, Issue:1 Topics: Contrast Media; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Humans; Hypoglycemic Agents;	2020
Second revolution in cardiovascular prevention. Journal of the Chinese Medical Association : JCMA, 2020, Volume: 83, Issue:4 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Lik	2020
Toxicity of Metformin and Hypoglycemic Therapies. Advances in chronic kidney disease, 2020, Volume: 27, Issue:1 Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Monitoring; Humans; Hypoglycemic A	2020
Metformin: the updated protective property in kidney disease. Aging, 2020, 05-01, Volume: 12, Issue:9 Topics: Acidosis, Lactic; Acute Kidney Injury; AMP-Activated Protein Kinases; Animals; Disease Models, Anima	2020
Type 2 diabetes mellitus management in patients with chronic kidney disease: an update. Hormones (Athens, Greece), 2020, Volume: 19, Issue:4 Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glucagon-Like Peptide-1 Receptor; Humans; Hypogly	2020
Oral Semaglutide: The First-available Noninjectable Glucagon-like Peptide 1 Receptor Agonist. Clinical therapeutics, 2020, Volume: 42, Issue:10 Topics: Administration, Oral; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Pep	2020
Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease-A Systematic Review and Meta-Analysis. Frontiers in endocrinology, 2020, Volume: 11 Topics: Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Met	2020
Metformin use in patients with type 2 diabetes mellitus and chronic kidney disease: An evidence-based review. Annals of the Academy of Medicine, Singapore, 2021, Volume: 50, Issue:2 Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuf	2021
Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide. Frontiers in endocrinology, 2021, Volume: 12 Topics: Administration, Oral; Body Weight; Cardiovascular Diseases; Comorbidity; Decision Making; Diabetes M	2021
Autosomic dominant polycystic kidney disease and metformin: Old knowledge and new insights on retarding progression of chronic kidney disease. Medicinal research reviews, 2022, Volume: 42, Issue:1 Topics: Diabetes Mellitus, Type 2; Humans; Kidney; Metformin; Mutation; Polycystic Kidney, Autosomal Dominan	2022
Glycemic control of type 2 diabetes mellitus across stages of renal impairment: information for primary care providers. Postgraduate medicine, 2018, Volume: 130, Issue:4 Topics: Benzamides; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl-Peptidase I	2018
Safe Use of Metformin in Adults With Type 2 Diabetes and Chronic Kidney Disease: Lower Dosages and Sick-Day Education Are Essential. Canadian journal of diabetes, 2019, Volume: 43, Issue:1 Topics: Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Glomerular Filtration Rate; Humans; Hyp	2019
Metformin: A Candidate Drug for Renal Diseases. International journal of molecular sciences, 2018, Dec-21, Volume: 20, Issue:1 Topics: Acidosis, Lactic; Acute Kidney Injury; AMP-Activated Protein Kinases; Animals; Clinical Trials as To	2018
The Association between Metformin Therapy and Lactic Acidosis. Drug safety, 2019, Volume: 42, Issue:12 Topics: Acidosis, Lactic; Causality; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Rena	2019
Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. Expert opinion on drug metabolism & toxicology, 2013, Volume: 9, Issue:5 Topics: Creatinine; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glomerular Filtration Rat	2013
Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circulation. Heart failure, 2013, Volume: 6, Issue:3 Topics: Comorbidity; Comparative Effectiveness Research; Contraindications; Diabetic Angiopathies; Heart Fai	2013
Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world. Pharmacoepidemiology and drug safety, 2013, Volume: 22, Issue:10 Topics: Contraindications; Diabetes Complications; Diabetes Mellitus; Global Health; Guidelines as Topic; Hu	2013
Novel hypoglycaemic agents: considerations in patients with chronic kidney disease. Nephron. Clinical practice, 2014, Volume: 126, Issue:1 Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors	2014
Metformin in chronic kidney disease: time for a rethink. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis, 2014, Volume: 34, Issue:4 Topics: Acidosis, Lactic; Contraindications; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metform	2014
Use of metformin in diseases of aging. Current diabetes reports, 2014, Volume: 14, Issue:6 Topics: Aging; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administratio	2014
Chronic kidney disease in type 2 diabetes: lessons from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Nutrition, metabolism, and cardiovascular diseases : NMCD, 2014, Volume: 24, Issue:8 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Glycated Hem	2014
Metformin associated lactic acidosis (MALA): clinical profiling and management. Journal of nephrology, 2016, Volume: 29, Issue:6 Topics: Acid-Base Equilibrium; Acidosis, Lactic; Aged; Aged, 80 and over; Diabetes Mellitus; Diabetic Nephro	2016
METFORMIN: NONGLYCEMIC EFFECTS AND POTENTIAL NOVEL INDICATIONS. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2016, Volume: 22, Issue:8 Topics: Animals; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Rep	2016
Could metformin be used in patients with diabetes and advanced chronic kidney disease? Diabetes, obesity & metabolism, 2017, Volume: 19, Issue:2 Topics: Acidosis, Lactic; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hypoglycem	2017
Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review. Annals of internal medicine, 2017, Feb-07, Volume: 166, Issue:3 Topics: Cause of Death; Chronic Disease; Contraindications; Diabetes Mellitus, Type 2; Heart Failure; Humans	2017
[Proposal for the modification of metformin use in patients with chronic kidney disease]. Orvosi hetilap, 2012, Sep-30, Volume: 153, Issue:39 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination	2012
Noninsulin glucose-lowering agents for the treatment of patients on dialysis. Nature reviews. Nephrology, 2013, Volume: 9, Issue:3 Topics: Adamantane; Biguanides; Diabetic Nephropathies; Dipeptides; Dipeptidyl-Peptidase IV Inhibitors; Dise	2013

Article	Year
Linagliptin, when compared to placebo, improves CD34+ve endothelial progenitor cells in type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin: a randomized controlled trial. Cardiovascular diabetology, 2020, 06-03, Volume: 19, Issue:1 Topics: Adult; Aged; Antigens, CD34; Biomarkers; Cells, Cultured; Diabetes Mellitus, Type 2; Diabetic Nephro	2020
Pharmacokinetics of metformin in patients with chronic kidney disease stage 4 and metformin-naïve type 2 diabetes. Pharmacology research & perspectives, 2018, Volume: 6, Issue:5 Topics: Administration, Oral; Adult; Aged; Creatinine; Diabetes Mellitus, Type 2; Female; Glomerular Filtrat	2018
Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial. Diabetes, obesity & metabolism, 2019, Volume: 21, Issue:3 Topics: Administration, Oral; Aged; Aged, 80 and over; Cardiovascular Diseases; Cardiovascular System; Diabe	2019
Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease. Diabetes, obesity & metabolism, 2019, Volume: 21, Issue:5 Topics: Aged; Cardiovascular Diseases; Cause of Death; Darbepoetin alfa; Diabetes Mellitus, Type 2; Diabetic	2019
Combination of the dipeptidyl peptidase-4 inhibitor linagliptin with insulin-based regimens in type 2 diabetes and chronic kidney disease. Diabetes & vascular disease research, 2015, Volume: 12, Issue:4 Topics: Aged; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl-P	2015

Article	Year
Metformin and the Risk of Anemia of Advanced Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus. Journal of clinical pharmacology, 2022, Volume: 62, Issue:2 Topics: Adult; Age Factors; Aged; Anemia; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Hemo	2022
Pharmacodynamics and pharmacokinetics of extended-release metformin in patients with type 2 diabetes and chronic kidney disease stage 3B. Diabetes, obesity & metabolism, 2022, Volume: 24, Issue:1 Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Rena	2022
Progression of established non-diabetic chronic kidney disease is halted by metformin treatment in rats. Kidney international, 2022, Volume: 101, Issue:5 Topics: Adenine; Animals; Canagliflozin; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans;	2022
Metformin versus SGLT-2 inhibitors: how low can we go? Kidney international, 2022, Volume: 101, Issue:5 Topics: Animals; Canagliflozin; Female; Humans; Hypoglycemic Agents; Male; Metformin; Rats; Renal Insufficie	2022
Relationship between metformin use and lactic acidosis in advanced chronic kidney disease: The REMIND-TMU study. The American journal of the medical sciences, 2022, Volume: 364, Issue:5 Topics: Acidosis, Lactic; Adult; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal In	2022
The case for reduced-dose metformin in the management of type 2 diabetes mellitus with stage 4 chronic kidney disease. Diabetic medicine : a journal of the British Diabetic Association, 2022, Volume: 39, Issue:10 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2022
Trends in Prescribing Preferences for Antidiabetic Medications Among Patients With Type 2 Diabetes in the U.K. With and Without Chronic Kidney Disease, 2006-2020. Diabetes care, 2022, 10-01, Volume: 45, Issue:10 Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl	2022
Predictors of rapid progression of estimated glomerular filtration rate among persons living with diabetes and/or hypertension in Ghana: Findings from a multicentre study. Journal of clinical hypertension (Greenwich, Conn.), 2022, Volume: 24, Issue:10 Topics: Adult; Angiotensins; Creatinine; Diabetes Mellitus; Disease Progression; Ghana; Glomerular Filtratio	2022
Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Kidney international, 2022, Volume: 102, Issue:5 Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucose; Humans; Kidney; Metformin; Mineralocort	2022
Metformin prevents hypoxia-induced podocyte injury by regulating the ZEB2/TG2 axis. Nephrology (Carlton, Vic.), 2023, Volume: 28, Issue:1 Topics: Animals; Hypoxia; Metformin; Mice; Podocytes; Protein Glutamine gamma Glutamyltransferase 2; Renal I	2023
Prescriber Uncertainty as Opportunity to Improve Care of Type 2 Diabetes with Chronic Kidney Disease: Mixed Methods Study. Journal of general internal medicine, 2023, Volume: 38, Issue:6 Topics: Adult; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chron	2023
Metformin-associated severe lactic acidosis combined with multi-organ insufficiency induced by infection with Aeromonas veronii: A case report. Medicine, 2023, Jan-13, Volume: 102, Issue:2 Topics: Acidosis, Lactic; Aeromonas veronii; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic A	2023
Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension. Molecules (Basel, Switzerland), 2023, Mar-18, Volume: 28, Issue:6 Topics: AMP-Activated Protein Kinases; Animals; Down-Regulation; Dyslipidemias; Fibrosis; Hypertension; Infl	2023
Reports of Lactic Acidosis Attributed to Metformin, 2015-2018. Diabetes care, 2020, Volume: 43, Issue:1 Topics: Acidosis, Lactic; Adult; Adverse Drug Reaction Reporting Systems; Aged; Diabetic Nephropathies; Fema	2020
Metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and CKD stage 3: A case-control study. Journal of diabetes and its complications, 2020, Volume: 34, Issue:1 Topics: Age Factors; Aged; Aged, 80 and over; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Neph	2020
A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study. Mayo Clinic proceedings, 2020, Volume: 95, Issue:1 Topics: Canada; Cardiovascular Diseases; Creatinine; Diabetes Mellitus, Type 2; Drug Monitoring; Effect Modi	2020
Infliximab ameliorates tumor necrosis factor-alpha exacerbated renal insulin resistance induced in rats by regulating insulin signaling pathway. European journal of pharmacology, 2020, Apr-05, Volume: 872 Topics: Animals; Blood Glucose; Disease Models, Animal; Glucose Tolerance Test; Humans; Hyperglycemia; Infli	2020
The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease. Diabetes care, 2020, Volume: 43, Issue:5 Topics: Acidosis, Lactic; Aged; Aged, 80 and over; Cause of Death; Cohort Studies; Diabetes Mellitus, Type 2	2020
Metformin arrests the progression of established kidney disease in the subtotal nephrectomy model of chronic kidney disease. American journal of physiology. Renal physiology, 2020, 05-01, Volume: 318, Issue:5 Topics: Albuminuria; AMP-Activated Protein Kinases; Animals; Disease Models, Animal; Disease Progression; En	2020
Using Insulin to Treat Poorly Controlled Type 2 Diabetes in 2020. JAMA, 2020, Jun-16, Volume: 323, Issue:23 Topics: Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drug Costs; Glucagon-Like Peptide	2020
A Comprehensive Whole-Body Physiologically Based Pharmacokinetic Drug-Drug-Gene Interaction Model of Metformin and Cimetidine in Healthy Adults and Renally Impaired Individuals. Clinical pharmacokinetics, 2020, Volume: 59, Issue:11 Topics: Adult; Cimetidine; Drug Interactions; Humans; Hypoglycemic Agents; Metformin; Pharmacogenetics; Rena	2020
Comparison of Outcomes With Metformin and Sulfonylureas in Chronic Kidney Disease. Mayo Clinic proceedings, 2020, Volume: 95, Issue:7 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic; Ret	2020
In Reply - Comparison of Outcomes With Metformin and Sulfonylureas in Chronic Kidney Disease. Mayo Clinic proceedings, 2020, Volume: 95, Issue:7 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic; Ret	2020
Improving Equity in Medication Use through Better Kidney Function Measurement. Journal of the American Society of Nephrology : JASN, 2020, Volume: 31, Issue:8 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Kidney; Metformin; Prescriptions; Renal Insu	2020
Authors' Reply. Journal of the American Society of Nephrology : JASN, 2020, Volume: 31, Issue:11 Topics: Glomerular Filtration Rate; Humans; Metformin; Prescriptions; Racial Groups; Renal Insufficiency, Ch	2020
The FDA Metformin Label Change and Racial and Sex Disparities in Metformin Prescription among Patients with CKD Injury. Journal of the American Society of Nephrology : JASN, 2020, Volume: 31, Issue:11 Topics: Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Metformin; Prescriptions; Renal Insufficien	2020
Does metformin do more benefit or harm in chronic kidney disease patients? Kidney international, 2020, Volume: 98, Issue:5 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2020
Metformin in chronic kidney disease: a strong dose of caution. Kidney international, 2020, Volume: 98, Issue:5 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuffici	2020
Metformin-to use or not to use . . . is that the question? Kidney international, 2020, Volume: 98, Issue:5 Topics: Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2020
Cardiovascular and renal safety of metformin in patients with diabetes and moderate or severe chronic kidney disease: Observations from the EXSCEL and SAVOR-TIMI 53 cardiovascular outcomes trials. Diabetes, obesity & metabolism, 2021, Volume: 23, Issue:5 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Humans; Kidney; Metf	2021
Rates of Metformin Use in Stage 3b Chronic Kidney Disease Rose After FDA Label Change. Journal of general internal medicine, 2021, Volume: 36, Issue:10 Topics: Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2021
Metformin inhibits chronic kidney disease-induced DNA damage and senescence of mesenchymal stem cells. Aging cell, 2021, Volume: 20, Issue:2 Topics: Animals; Cells, Cultured; Cellular Senescence; Coculture Techniques; DNA Damage; Female; Humans; Hyp	2021
Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study. Endocrinology, diabetes & metabolism, 2021, Volume: 4, Issue:1 Topics: Acidosis, Lactic; Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies;	2021
Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease. Scientific reports, 2021, 04-02, Volume: 11, Issue:1 Topics: Adenylate Kinase; Animals; Apoptosis; Body Weight; Brain Infarction; Enzyme Activation; Female; Gene	2021
Black Race Coefficient in GFR Estimation and Diabetes Medications in CKD: National Estimates. Journal of the American Society of Nephrology : JASN, 2021, 06-01, Volume: 32, Issue:6 Topics: Aged; Black or African American; Creatinine; Diabetes Mellitus, Type 2; Female; Glomerular Filtratio	2021
Preventing the onset of diabetes-induced chronic kidney disease during prediabetes: The effects of oleanolic acid on selected markers of chronic kidney disease in a diet-induced prediabetic rat model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2021, Volume: 139 Topics: Animals; Biomarkers; Diabetic Nephropathies; Diet; Diet, High-Fat; Dietary Carbohydrates; Glomerular	2021
National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race. Journal of the American Society of Nephrology : JASN, 2021, 06-01, Volume: 32, Issue:6 Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Anti-Bac	2021
Does the intact nephron hypothesis provide a reasonable model for metformin dosing in chronic kidney disease? British journal of clinical pharmacology, 2021, Volume: 87, Issue:12 Topics: Creatinine; Glomerular Filtration Rate; Humans; Kidney; Kidney Function Tests; Metformin; Nephrons;	2021
The extrapyramidal syndromes of chronic kidney disease and dialysis (EPS-CKDD): diagnostic criteria, risk factors and prognosis. QJM : monthly journal of the Association of Physicians, 2022, Jun-07, Volume: 115, Issue:6 Topics: Acidosis, Lactic; Basal Ganglia Diseases; Child, Preschool; Diabetes Mellitus, Type 2; Female; Human	2022
The Effect of Metformin in Diabetic and Non-Diabetic Rats with Experimentally-Induced Chronic Kidney Disease. Biomolecules, 2021, 05-30, Volume: 11, Issue:6 Topics: Adenine; Animals; Diabetes Mellitus, Experimental; Kidney; MAP Kinase Signaling System; Metformin; R	2021
Prevalence of Atherosclerotic Cardiovascular Disease, Heart Failure, and Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Primary Care Research Network-based Study. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2022, Volume: 130, Issue:7 Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypoglycemic Agents; Metf	2022
Refining metformin prescribing in New Zealand. The New Zealand medical journal, 2017, Mar-24, Volume: 130, Issue:1452 Topics: Acidosis, Lactic; Comorbidity; Diabetes Mellitus, Type 2; Drug Dosage Calculations; Glomerular Filtr	2017
Effect of prescribing metformin according to eGFR instead of serum creatinine level: A study based on Korean National Health and Nutrition Examination Survey (KNHANES) 2009-2014. PloS one, 2017, Volume: 12, Issue:4 Topics: Aged; Creatinine; Female; Glomerular Filtration Rate; Humans; Male; Metformin; Middle Aged; Renal In	2017
Review: Metformin is linked to reduced mortality in type 2 diabetes with comorbid CKD and CHF. Annals of internal medicine, 2017, 04-18, Volume: 166, Issue:8 Topics: Comorbidity; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency,	2017
The Effect of Uremic Solutes on the Organic Cation Transporter 2. Journal of pharmaceutical sciences, 2017, Volume: 106, Issue:9 Topics: Biological Transport; Dimethylamines; Glomerular Filtration Rate; Glucuronates; Glutathione Disulfid	2017
Targeting Oxygen-Sensing Prolyl Hydroxylase for Metformin-Associated Lactic Acidosis Treatment. Molecular and cellular biology, 2017, Aug-15, Volume: 37, Issue:16 Topics: Acidosis, Lactic; Adenine; Animals; Disease Models, Animal; Enzyme Inhibitors; Gluconeogenesis; Kidn	2017
Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort Study of Veterans with Diabetes and Chronic Kidney Disease. Journal of general internal medicine, 2018, Volume: 33, Issue:2 Topics: Aged; Cohort Studies; Contraindications, Drug; Diabetes Mellitus, Type 2; Female; Glomerular Filtrat	2018
Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4. Diabetes care, 2018, Volume: 41, Issue:3 Topics: Creatinine; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin	2018
Dose adjustment of metformin and dipeptidyl-peptidase IV inhibitors in diabetic patients with renal dysfunction. Current medical research and opinion, 2018, Volume: 34, Issue:10 Topics: Aged; Comorbidity; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Dosage Calcul	2018
Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder. Kidney international, 2018, Volume: 94, Issue:1 Topics: Adenine; Animals; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Models, Animal; Humans;	2018
Should Metformin Be First-line Therapy for Patients With Type 2 Diabetes and Chronic Kidney Disease?: Informed Patients Should Decide. JAMA internal medicine, 2018, 07-01, Volume: 178, Issue:7 Topics: Acidosis, Lactic; Cohort Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin;	2018
Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study. JAMA internal medicine, 2018, 07-01, Volume: 178, Issue:7 Topics: Acidosis, Lactic; Aged; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Humans; Hypog	2018
Metformin misuse in chronic kidney disease. Diabetes & metabolism, 2020, Volume: 46, Issue:4 Topics: Acidosis, Lactic; Aged; Contraindications, Drug; Diabetes Mellitus, Type 2; Female; Humans; Hypoglyc	2020
Prescribing of diabetes medications to people with type 2 diabetes and chronic kidney disease: a national cross-sectional study. BMC family practice, 2019, 02-18, Volume: 20, Issue:1 Topics: Aged; Aged, 80 and over; Australia; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Dipeptidyl-P	2019
Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance. Journal of the American Society of Nephrology : JASN, 2019, Volume: 30, Issue:5 Topics: Animals; Biological Products; Biopsy, Needle; Carbamates; Disease Models, Animal; Glucose Intoleranc	2019
Lactic acidosis due to metformin in type 2 diabetes mellitus and chronic kidney disease stage 3-5: is it significant? International urology and nephrology, 2019, Volume: 51, Issue:7 Topics: Acidosis, Lactic; Creatinine; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Moni	2019
Dethroning the king?: The future of metformin as first line therapy in type 2 diabetes. Journal of diabetes and its complications, 2019, Volume: 33, Issue:6 Topics: Contraindications, Drug; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug Administration Sche	2019
Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease: study protocol for a multicenter population-based case-control study using health databases. BMC nephrology, 2019, 05-30, Volume: 20, Issue:1 Topics: Acidosis, Lactic; Case-Control Studies; Databases, Factual; Diabetes Mellitus, Type 2; Female; Follo	2019
Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease. American journal of physiology. Renal physiology, 2013, Sep-01, Volume: 305, Issue:5 Topics: Adenylate Kinase; Animals; Disease Models, Animal; Enzyme Induction; Male; Metformin; Nephrectomy; R	2013
Case records of the Massachusetts General Hospital. Case 23-2013. A 54-year-old woman with abdominal pain, vomiting, and confusion. The New England journal of medicine, 2013, Jul-25, Volume: 369, Issue:4 Topics: Abdominal Pain; Acidosis, Lactic; Confusion; Diabetes Mellitus, Type 2; Diagnosis, Differential; Fem	2013
Metformin use in chronic kidney disease: new evidence to guide dosing. QJM : monthly journal of the Association of Physicians, 2013, Volume: 106, Issue:11 Topics: Acidosis, Lactic; Biomarkers, Pharmacological; Blood Glucose; Humans; Metformin; Renal Insufficiency	2013
Assessment of serum creatinine and kidney function among incident metformin users. Canadian journal of diabetes, 2013, Volume: 37, Issue:4 Topics: Aged; Aged, 80 and over; Cohort Studies; Contraindications; Creatinine; Diabetes Mellitus, Type 2; F	2013
Prescription-medication sharing among family members: an unrecognized cause of a serious drug adverse event in a patient with impaired renal function. Clinical nephrology, 2015, Volume: 83, Issue:3 Topics: Acidosis, Lactic; Aged; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug-Related Side Effects	2015
Metformin OK in CKD? Drug and therapeutics bulletin, 2014, Volume: 52, Issue:4 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuffici	2014
Medication safety and chronic kidney disease in older adults prescribed metformin: a cross-sectional analysis. BMC nephrology, 2014, Jun-07, Volume: 15 Topics: Aged; Contraindications; Cross-Sectional Studies; Diabetes Mellitus; Female; Glomerular Filtration R	2014
How are patients with type 2 diabetes and renal disease monitored and managed? Insights from the observational OREDIA study. Vascular health and risk management, 2014, Volume: 10 Topics: Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Ne	2014
Retrospective evaluation of potentially inappropriate prescribing in hospitalized patients with renal impairment. Current medical research and opinion, 2015, Volume: 31, Issue:3 Topics: Aged; Aged, 80 and over; Australia; Drug-Related Side Effects and Adverse Reactions; Female; Hospita	2015
Estimating kidney function and use of oral antidiabetic drugs in elderly. Fundamental & clinical pharmacology, 2015, Volume: 29, Issue:3 Topics: Administration, Oral; Age Factors; Aged; Aged, 80 and over; Biomarkers; Creatinine; Cross-Sectional	2015
Metformin should not be contraindicated in patients with type 2 diabetes and mild to moderate renal impairment. Evidence-based medicine, 2015, Volume: 20, Issue:3 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuffici	2015
Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations? American journal of kidney diseases : the official journal of the National Kidney Foundation, 2015, Volume: 66, Issue:2 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuffici	2015
Metformin in chronic kidney disease: more harm than help? The lancet. Diabetes & endocrinology, 2015, Volume: 3, Issue:8 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2015
Metformin use and mortality in patients with advanced chronic kidney disease: national, retrospective, observational, cohort study. The lancet. Diabetes & endocrinology, 2015, Volume: 3, Issue:8 Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Creatinine; Diabetes Mellitus, Type 2; Follow-Up Stu	2015
Chronic kidney disease: Metformin increases risk of mortality in patients with advanced chronic kidney disease. Nature reviews. Nephrology, 2015, Volume: 11, Issue:8 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2015
Therapy: Risk of metformin use in patients with T2DM and advanced CKD. Nature reviews. Endocrinology, 2015, Volume: 11, Issue:12 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2015
Mortality and metformin use in patients with advanced chronic kidney disease. The lancet. Diabetes & endocrinology, 2015, Volume: 3, Issue:9 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2015
Mortality and metformin use in patients with advanced chronic kidney disease--Authors' reply. The lancet. Diabetes & endocrinology, 2015, Volume: 3, Issue:9 Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2015
Potential Impact of Prescribing Metformin According to eGFR Rather Than Serum Creatinine. Diabetes care, 2015, Volume: 38, Issue:11 Topics: Adult; Aged; Aged, 80 and over; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Drug	2015
Metformin initiation and renal impairment: a cohort study in Denmark and the UK. BMJ open, 2015, Sep-02, Volume: 5, Issue:9 Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Denmark; Diabetes Mellitus, Type 2; Diabetic Nephrop	2015
Effect of metformin monotherapy on cardiovascular diseases and mortality: a retrospective cohort study on Chinese type 2 diabetes mellitus patients. Cardiovascular diabetology, 2015, Oct-09, Volume: 14 Topics: Aged; Asian People; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Diabetes Mellitus, Ty	2015
Use of Renally Inappropriate Medications in Older Veterans: A National Study. Journal of the American Geriatrics Society, 2015, Volume: 63, Issue:11 Topics: Aged; Aged, 80 and over; Allopurinol; Aminohydrolases; Body Weight; Comorbidity; Cross-Sectional Stu	2015
[Metformin is commonly used in patients with renal impairment]. Deutsche medizinische Wochenschrift (1946), 2015, Volume: 140, Issue:22 Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Hypoglycemic Agents; Male; Metfor	2015
In Reply to 'Restricting Metformin in CKD: Continued Caution Warranted'. American journal of kidney diseases : the official journal of the National Kidney Foundation, 2015, Volume: 66, Issue:6 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuffici	2015
Restricting Metformin in CKD: Continued Caution Warranted. American journal of kidney diseases : the official journal of the National Kidney Foundation, 2015, Volume: 66, Issue:6 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuffici	2015
Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD: A National Cross-Sectional Study. Medicine, 2015, Volume: 94, Issue:51 Topics: Acidosis; Adult; Aged; Bicarbonates; Chlorides; Cross-Sectional Studies; Diabetes Mellitus; Diet; Fe	2015
Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease. International urology and nephrology, 2016, Volume: 48, Issue:8 Topics: Acidosis, Lactic; Adult; Aged; Cohort Studies; Comorbidity; Creatinine; Diabetes Mellitus, Type 2; F	2016
Epidemiology of lactic acidosis in type 2 diabetes patients with metformin in Japan. Pharmacoepidemiology and drug safety, 2016, Volume: 25, Issue:10 Topics: Acidosis, Lactic; Adolescent; Adult; Aged; Cohort Studies; Databases, Factual; Diabetes Mellitus, Ty	2016
[Chronic kidney diseases, metformin and lactic acidosis]. Vnitrni lekarstvi, 2016, Volume: 62, Issue:4 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Renal Insuffici	2016
Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? No, We Should Never Again Compromise Safety! Diabetes care, 2016, Volume: 39, Issue:7 Topics: Acidosis, Lactic; Acute Kidney Injury; Creatinine; Diabetes Mellitus, Type 2; Glomerular Filtration	2016
Should Restrictions Be Relaxed for Metformin Use in Chronic Kidney Disease? Yes, They Should Be Relaxed! What's the Fuss? Diabetes care, 2016, Volume: 39, Issue:7 Topics: Acidosis, Lactic; Acute Kidney Injury; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metfo	2016
USE OF METFORMIN IN CLINICAL ENDOCRINOLOGY. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2016, Volume: 22, Issue:8 Topics: Diabetes Mellitus; Endocrinology; Glomerular Filtration Rate; Humans; Metformin; Renal Insufficiency	2016
Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study. BMJ (Clinical research ed.), 2016, Jul-13, Volume: 354 Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Neph	2016
Metformin in Chronic Kidney Disease - Should We Worry? The American journal of medicine, 2016, Volume: 129, Issue:9 Topics: Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2016
Could metformin be used in patients with advanced chronic kidney disease? Diabetes, obesity & metabolism, 2017, Volume: 19, Issue:2 Topics: Humans; Hypoglycemic Agents; Metformin; Renal Insufficiency, Chronic	2017
Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data. Nephron, 2017, Volume: 135, Issue:2 Topics: Acidosis, Lactic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hypoglycemic Agents; Me	2017
Hemodialysis-refractory metformin-associated lactate acidosis with hypoglycemia, hypothermia, and bradycardia in a diabetic patient with belated diagnosis and chronic kidney disease . International journal of clinical pharmacology and therapeutics, 2017, Volume: 55, Issue:4 Topics: Acidosis, Lactic; Aged; Biomarkers; Bradycardia; Delayed Diagnosis; Diabetes Mellitus, Type 2; Drug	2017
Comparative effectiveness of incident oral antidiabetic drugs on kidney function. Kidney international, 2012, Volume: 81, Issue:7 Topics: Administration, Oral; Aged; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Femal	2012
Two additional cases of metformin-associated encephalopathy in patients with end-stage renal disease undergoing hemodialysis. Hemodialysis international. International Symposium on Home Hemodialysis, 2013, Volume: 17, Issue:1 Topics: Brain Diseases; Contraindications; Female; Humans; Hypoglycemic Agents; Kidney Failure, Chronic; Mag	2013
Metformin therapy in patients with chronic kidney disease. Diabetes, obesity & metabolism, 2012, Volume: 14, Issue:10 Topics: Acidosis, Lactic; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Dose-Response Relationship, Dr	2012
Soluble serum Klotho in diabetic nephropathy: relationship to VEGF-A. Clinical biochemistry, 2012, Volume: 45, Issue:16-17 Topics: Aged; Albuminuria; Biomarkers; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic	2012
Use of an electronic medical record to detect patients at high risk of metformin-induced lactic acidosis. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2006, Apr-01, Volume: 63, Issue:7 Topics: Acidosis, Lactic; Aged; Creatinine; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Male; Me	2006

metformin and Renal Insufficiency, Chronic

Research Excerpts

Research

Studies (134)

Authors

Clinical Trials (5)

Trial Overview

Trial Outcomes

Adiposity

Estimation of Creatinine Clearance

Glycemic Control

Glycemic Control: Fasting Glucose

Glycemic Control: Insulin

Pulse Wave Velocity

Resting Metabolic Rate (RMR)

Serum Endothelial Inflammatory Markers

Serum Endothelial Inflammatory Markers

Urinary Function Marker in CKD

Cellular Markers

Fasting Lipid Profile

Pulse Wave Analysis

Change in Body Weight

Change in Glycosylated Haemoglobin (HbA1c)

Change in HDL-cholesterol - Ratio to Baseline

Change in LDL-cholesterol - Ratio to Baseline

Change in Pulse Rate

Change in Total Cholesterol - Ratio to Baseline

Change in Triglycerides - Ratio to Baseline

Number of Serious Adverse Events

Time From Randomisation to All-cause Death

Time From Randomisation to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, Non-fatal Myocardial Infarction or Nonfatal Stroke

Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE) Composite Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke

Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, UAP Requiring Hospitalisation or Hospitalisation for Heart Failure

Time From Randomisation to First Occurrence of Fatal or Non-fatal Myocardial Infarction

Time From Randomisation to First Occurrence of Fatal or Non-fatal Stroke

Time to First AE Leading to Permanent Trial Product Discontinuation

Change in Eye Examination Category

Change in Systolic and Diastolic Blood Pressure

Time From Randomisation to First Occurrence of Each of the Individual Components in the Expanded Composite Cardiovascular Endpoint

Change in Kidney Function

Change in Total Kidney Volume

Rate of Serious Adverse Events (SAE)

Safety and Tolerability of Metformin

Reviews

Trials

Other Studies