Table 1.
Detailed demographic characteristics and outcomes of studies included in the meta-analysis.
| Study | Sites | Studydesign | Sample size | Baseline years | Comparison group | Female(%Total) | Follow-up Duration (Years): Metformin users/ Comparison group | Mean Age (Years old) | HbA1c(%) | Duration of Diabetes (years) | BMI (kg/m2) | Smoker(%Total) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Masoudi et al. (26) | The United States |
Cohort study | 5859 | 1998-1999 or 2000-2001 |
Thiazolidinedione | NR | 1/1 | NR | NR | NR | NR | NR |
| Roussel et al. (16) | Multinational | Post hoc analysis of RCT |
16,535 | 2003-2004 | Metformin Non-users |
NR | 1.7/1.7 | NR | NR | NR | NR | NR |
| Aguilar et al. (27) | The United States |
Cohort study | 1246 | 2000-2002 | Metformin Non-users |
NR | 2/2 | NR | NR | NR | NR | NR |
| Weir et al. (17) | Canada | Nested case-control | 1644 | 1997-2008 | Glyburid Insulin |
51.3 | NR | NR | NR | NR | NR | NR |
| Ekström et al. (28) | Sweden | Cohort study | 51,675 | 2004-2010 | Metformin Non-users |
41.9 | 3.9/3.9 | 65.3 | 7.3 | 9.4 | 29.5 | 14.0 |
| Morgan et al. (29) | The United Kingdom | Cohort study | 11,481 | 2000-2012 | Sulphonylurea | NR | 2.9/3.1 | NR | NR | NR | NR | NR |
| Fung et al. (30) | Hong Kong | Cohort study | 6800 | 2008 | Lifestyle modifications. | 59.31 | 5.2/3.6-3.7 | 62.57 | 6.57 | NR | 25.59 | 5.96 |
| Hung et al. (15) | Taiwan | Cohort study | 3252 | 2000-2009 | Metformin Non-users |
51.0 | 2.1/2.1 | 67.2 | NR | 5.9 | NR | NR |
| Marcum et al. (31) | The United States |
Cohort study | 175,296 | 2004-2009 | Sulfonylurea | 1.57 | 1.7/1.7 | 65.44 | NR | NR | NR | NR |
| Bergmark et al. (24) | Multinational | Post hoc analysis of RCTs |
1332 | NR | Metformin Non-users |
43.17 | 2.1/2.1 | 69.6 | 7.62 | 14.6 | 31.33 | 8.93 |
| Charytan et al. (25) | Multinational | Post hoc analysis of RCT |
1016 | 2004-2009 | Metformin Non-users |
35.83 | 2.4/2.4 | 67.5 | 6.85 | 14.1 | 31.4 | 3.4 |
| Kwon et al. (18) | Korea | Cohort study | 5408 | 2001-2016 | Metformin Non-users |
42.45 | 7.3/7.3 | 67.4 | 7.4 | NR | 18.95 | NR |
| Whitlock et al. (32) | Canada | Cohort study | 21,996 | 2006-2017 | Sulfonylurea | 48.8 | 1.4/1.1 | 55.5 | NR | NR | NR |
| Study | Hypertension(%Total) | Dyslipidaemia(%Total) | Previous CVD(%Total) | Previous Stroke(%Total) | Previous Heart failure(%Total) | Stage of CKD[Criteria]/ eGFR[Criteria] (ml/min/1.73 m2) | Outcomes (HR/RR/OR[95%CI]) | Adjusting factors for all-cause mortality | |
|---|---|---|---|---|---|---|---|---|---|
| All-cause mortality | Cardiovascular events | ||||||||
| Masoudi et al. (26) | NR | NR | NR | NR | NR | CKD stage G1-5[a serum creatinine concentration ≥133 mol/L] | HR,0.86[0.75-0.98] | NR | markers of heart failure severity and comorbidities, differences in the treating physicians and hospitals, and the clustering of patients within hospitals |
| Roussel et al. (16) | NR | NR | NR | NR | NR | eGFR[MDRD] <30 30~44 45~59 30~59 <60 |
<30: HR,1.06[0.47-2.38] 30~44:HR,0.57[0.35-0.92] 45~59: HR,0.75[0.52-1.10] 30~59: HR,0.64[0.48-0.86] <60: HR,0.89[0.71-1.10] |
NR | Multivariable adjustment and propensity score |
| Aguilar et al. (27) | NR | NR | NR | NR | NR | eGFR[MDRD] <60 |
HR,0.60[0.40-0.90] | NR | Propensity score adjusted model |
| Weir et al. (17) | NR | NR | NR | NR | 40.4 | eGFR[MDRD] <30 <45 <60 |
<30(Insulin): HR,0.31[0.10-0.91] <30(Glyburide): HR,0.21[0.07-0.67] <45(Insulin): HR,0.11[0.06-0.23] <45(Glyburide): HR,0.13[0.06-0.27] <60(Insulin): HR,0.13[0.08-0.20] <60(Glyburide) : HR,0.17[0.10-0.26] |
NR | previous hypoglycaemic events, Charlson comorbidity index (1, 2 or ≥3), recent hospitalization, chronic liver disease, alcoholism,coronary artery disease, congestive heart failure, number of distinct medications used in the previous year (≤5, 6–10, 11–15, 16–20, 21–26 or ≥26), number of internist visits in the previous 5 years (≤5, 6–14 or≥15), concurrent use of corticosteroids, thiazide diuretics or atypical antipsychotics. |
| Ekström et al (28) | NR | 51.1 | 21.4 | NR | 5.9 | eGFR[MDRD] 30~44 45~59 ≥60 |
30~44:HR,1.02[0.84-1.24] 45~59: HR,0.87[0.77-0.99] ≥60: HR,0.87[0.81-0.94] |
30~44:HR,1.0[0.83-1.19] 45~59: HR,0.94[0.84-1.05] ≥60: HR,0.98[0.92-1.05] |
age, sex, diabetes duration, HbA1c, non-HDL-C, BMI, smoking, eGFR, multidose dispensation, previous hospitalisation, history of CVD and CHF, microalbuminuria, and treatment with antihypertensive agents, lipid-lowering agents and cardiac glycosides |
| Morgan et al. (29) | NR | NR | NR | NR | NR | CKD stage G1-5[a serum creatinine concentration >132 mol/L for males and >123 mol/L for females] | HR,0.61[0.53-0.69] | NR | Propensity score adjusted model |
| Fung et al. (30) | 23.81 | 3.68 | NR | NR | NR | CKD stage G1-3[eGFR] ≥90 60~89 30~59 |
HR,0.705[0.547-0.908] | HR,0.684[0.556-0.842] | Propensity score adjusted model |
| Hung et al. (15) | 79.7 | 49.85 | NR | 25.95 | 24.85 | CKD stage G 5[a serum creatinine concentration ≥530 mol/L] | HR,1.35[1.20-1.51] | NR | Age,sex, Diabetes duration, Comorbid disorders, Charlson comorbidity index score, Nephrologist visits, Antihypertensive drugs, Antidiabetic drugs, Geographic location, Propensity score |
| Marcum et al. (31) | 77.1 | 47.91 | NR | NR | 6.29 | CKD stage G 1-3[eGFR] ≥90 60~89 45~59 30~44 |
≥90:HR,0.59[0.50-0.70] 60~89:HR,0.65[0.60-0.71] 45~59:HR,0.80[0.71-0.91] 30~44:HR,0.72[0.51-1.01] |
NR | Demographics,Health behavior,eGFR,Comorbid conditions,Laboratory results,Cardiovascular medications |
| Bergmark et al. (24) | 85.66 | 76.7 | NR | 14.5 | NR | Moderate/Severe CKD [eGFR] ≤45 | HR,0.89[0.62-1.28] | NR | Propensity score adjusted model |
| Charytan et al. (25) | NR | NR | 57.5 | 9.7 | 23.4 | CKD stage G 1-5[eGFR] eGFR[CKD-EPI] ≥30 <30 |
CKD stage G1-3:HR,0.61[0.44-0.85] CKD stage G4-5:HR,0.83[0.54-1.24] |
CKD stage G1-3:HR,0.70[0.53-0.90] CKD stage G4-5:HR,0.99[0.71-1.39] |
Propensity score adjusted model |
| Kwon et al. (18) | 49.0 | NR | NR | NR | NR | eGFR[CKD-EPI] ≥45 30~44 <30 |
≥45:HR, 0.70[0.60-0.82] 30~44: HR, 0.64[0.47-0.86] <30: HR, 0.55[037-0.81] |
NR | Propensity score adjusted model |
| Whitlock et al. (32) | 61.9 | 34.9 | 33.2 | NR | NR | CKD stage G 1-5[eGFR] eGFR[CKD-EPI] ≥90 60~89 45~59 30~44 <30 |
≥90: HR, 0.38[0.27-0.53] 60~89: HR, 0.42[0.31-0.56] 45~59: HR, 0.92[0.53-1.61] 30~44: HR, 0.85[0.46-1.57] <30: HR, 1.51[0.58-3.95] |
≥90: HR, 0.64[0.52-0.86] 60~89: HR, 0.79[0.52-1.20] 45~59: HR, 0.86[0.45-1.64] 30~44: HR, 0.62[0.30-1.29] <30: HR, 0.56[0.18-1.69] |
IPTW adjusted |
RCT, randomized controlled trial; HbA1c, hemoglobin A1c; BMI, Body Mass Index; CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; OR, odds ratio; RR,risk ratio; HR, :Hazard Ratio; CI, confidence interval; IPTW, inverse probability of treatment weight; NR, not reported.