Supplemental Table 1. ICD-9-CM codes and ATC codes used in this study

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1 Supplemental Table 1. ICD-9-CM codes and ATC codes used in this study Comorbidities ICD-9-CM codes Medication ATC codes Diabetes 250 Angiotensin-converting enzyme inhibitors C09AA Ischemic heart disease Angiotensin receptor blockers C09CA 410, 412 Alpha-blockers C02CA Congestive heart failure Cerebrovascular disease 428 Beta-blockers C07A Calcium channel blockers C08 433, 434, 436 (exclude 800, 801, 802, 803, 804, 850, 851, 852, 853, 854,V57) Diuretics C03 Peripheral arterial disease 440.2, 440.4, , Other anti-hypertensive agents C02A, C02B, C02CC, C02D Retinopathy 250.5, 362, 364.0, 364.4, , , 377 Nitrate C01DA Nephropathy 250.4, , 590, 593, 595, 596, 599, Insulin A10A Neuropathy 250.6, 337.1, 354, 355, 356.8, 357.2, 358.1, 713.5, Chronic renal disease , , , , , , , , , 585, V45.1, V56.0, V56.8 Chronic liver disease 070.2x, 070.3x, V02.61, , , , , V02.62, 571.0, 571.1, 571.2, 571.3, 571.4, 571.5, Sulfonylurea Metformin Thiazolidinediones A10BB A10BA02 A10BG02, A10BG03 Chronic lung disease , Glinides A10BX02, A10BX03 Depression 296.2,296.3,298.0,300.4,309.0,309.1, ,296.90,309.28,296.82, 311 Acarbose A10BF01 Hypertension DPP4 inhibitors A10BH Dyslipidemia 272 Statins C10AA Fibrates Warfarin Aspirin Clopidogrel COX-2 nonselective NSAIDs C10AB B01AA03 B01AC06, N02BA01 B01AC04 M01A (exclude M01AH,

2 M01AX05) COX-2 selective NSAIDs Digitalis Anti-arrhythmics Class I and III M01AH C01AA C01B

3 Supplemental Table 2. Logistic regression model for the probability of initiating acarbose versus metformin as the first-line therapy among newly diagnosed type 2 diabetic patients β-coefficients Standard deviation Patient characteristics Female Age Diabetes duration in days Comorbidities Ischemic heart disease Cerebrovascular disease Peripheral arterial disease Retinopathy Neuropathy Nephropathy Chronic liver disease Chronic lung disease Depression Hypertension Dyslipidemia Diabetes complication severity index Charlson's index Monthly income level 75 th th - 50 th th - 25 th

4 25 th - low income Medication use Aspirin Clopidogrel Warfarin Angiotensin-converting enzyme inhibitors Angiotensin receptor blockers Alpha-blockers Beta-blockers Calcium channel blockers Diuretics Other anti-hypertensive agents Nitrates Statins Fibrates Digitalis glycoside Antiarrhythmics class I and III COX-2 non-selective NSAIDs COX-2 selective NSAIDs Number of different prescription drugs Number of cardiovascular-related medications Resource utilization Number of A 1 C measurement Number of lipid-related lab test Number of outpatient visits Number of emergency department visit Number of cardiology outpatient visits Number of cardiovascular-related physician visits Coronary revascularization Number of hospitalizations Number of hospitalizations due to cardiovascular-related diseases Number of hospital days Number of cardiovascular-related hospital days *c-statistics for propensity score model = 0.623

5 Supplemental Table 3. Hazard ratios of cardiovascular event comparing acarbose (n= 17,366) with metformin (n = 230,203) as the first-line therapy in type 2 diabetic patients stratified on baseline propensity score quintile Crude HR Adjusted HR Intention-to-treat 1.43 (1.39, 1.48)* 1.10 (1.06, 1.14)* 1.44 (1.28, 1.62)* 1.04 (0.93, 1.17) 1.70 (1.60, 1.81)* 1.20 (1.13, 1.27)* 1.36 (1.30, 1.41)* 1.07 (1.03, 1.12)* As-treated 1.41 (1.35, 1.47)* 1.09 (1.04, 1.14)* 1.41 (1.21, 1.66)* 1.00 (0.85, 1.17) 1.77 (1.63, 1.92)* 1.22 (1.12, 1.33)* 1.33 (1.26, 1.40)* 1.07 (1.02, 1.13)* * P-value less than 0.05

6 Supplemental Table 4. Hazard ratios of cardiovascular event comparing acarbose with metformin as the 1st-line therapy among different subgroups by intention-to-treat (ITT) approach stratified on baseline propensity score quintile Men (n=118,920) Women (n=128,469) 1.39* 1.07* 1.48* 1.13* (1.33, 1.46) (1.02, 1.12) (1.41, 1.55) (1.07, 1.18) 1.44* * 1.01 (1.26, 1.66) (0.91, 1.19) (1.12, 1.74) (0.81, 1.26) 1.76* 1.22* 1.66* 1.18* (1.61, 1.92) (1.12, 1.34) (1.52, 1.81) (1.08, 1.29) 1.31* * 1.10* (1.24, 1.38) (0.99, 1.11) (1.32, 1.48) (1.04, 1.16) Age<65 (n = 154,727) Age 65 (n = 92,662) 1.29* * 1.128* (1.21, 1.38) (0.97, 1.11) (1.21, 1.31) (1.08, 1.17) 1.41* * 1.07 (1.16, 1.72) (0.83, 1.23) (1.12, 1.49) (0.93, 1.24) 1.50* * 1.23* (1.31, 1.71) (0.95, 1.24) (1.38, 1.59) (1.15, 1.32) 1.24* * 1.08* (1.14, 1.34) (0.96, 1.12) (1.12, 1.23) (1.04, 1.14) Patients with hypertension (n=136,824) Patients without hypertension (n=110,565) 1.31* 1.10* 1.60* 1.08* (1.26, 1.37) (1.06, 1.15) (1.50, 1.70) (1.01, 1.15) 1.28* * 1.08 (1.11, 1.49) (0.88, 1.18) (1.42, 2.08) (0.89, 1.31) 1.60* 1.24* 1.81* 1.10 (1.49, 1.72) (1.15, 1.33) (1.60, 2.03) (0.97, 1.24) 1.24* 1.08* 1.50* 1.06 (1.19, 1.30) (1.03, 1.13) (1.38, 1.62) (0.98, 1.15) Patients with ischemic heart disease (n=38,892) Patients without ischemic heart disease (n=208,497)

7 * P-value less than * (1.19, 1.35) (1.06, 1.19) 1.42* (1.36, 1.48) 1.09* (1.04, 1.13) * 1.17 (0.96, 1.27) (0.85, 1.13) (1.14, 1.74) (0.95, 1.45) 1.39* 1.19* 1.71* 1.20* (1.26, 1.53) (1.08, 1.31) (1.58, 1.85) (1.11, 1.30) 1.25* 1.12* 1.36* 1.06* (1.15, 1.35) (1.03, 1.21) (1.29, 1.42) (1.01, 1.11) Patients with cerebrovascular Patients without disease cerebrovascular disease (n=24,570) (n=222,819) * 1.14* (0.97, 1.08) (0.97, 1.07) (1.43, 1.57) (1.09, 1.20) * 1.03 (0.97, 1.74) (0.85, 1.52) (1.28, 1.65) (0.90, 1.17) 1.45* 1.20* 1.72* 1.19* (1.26, 1.66) (1.05, 1.38)* (1.60, 1.84) (1.11, 1.28) * 1.13* (0.94, 1.04) (0.95, 1.05) (1.28, 1.46) (1.06, 1.21)

8 Supplemental Table 5. Hazard ratios of cardiovascular event comparing acarbose with metformin as the first-line therapy among different subgroups by as-treated (AT) approach stratified on baseline propensity score quintile Men (n=118,920) Women (n=128,469) 1.37* 1.06* 1.44* 1.11* (1.30, 1.46) (1.00, 1.13) (1.35, 1.53) (1.04, 1.18) 1.47* (1.23, 1.76) (0.85, 1.22) (0.81, 1.64) (0.59, 1.18) 1.87* 1.26* 1.68* 1.18* (1.66, 2.11) (1.12, 1.43) (1.49, 1.89) (1.05, 1.33) 1.29* * 1.09* (1.21, 1.39) (0.98, 1.13) (1.26, 1.46) (1.01, 1.17) Age<65 (n = 154,727) Age 65 (n = 92,662) 1.20* * 1.13* (1.10, 1.31) (0.88, 1.05) (1.21, 1.33) (1.08, 1.19) 1.35* * 1.07 (1.04, 1.76) (0.70, 1.19) (1.09, 1.63) (0.87, 1.30) 1.47* * 1.28* (1.22, 1.77) (0.85, 1.23) (1.44, 1.75) (1.16, 1.40) 1.14* * 1.10* (1.03, 1.27) (0.87, 1.08) (1.12, 1.25) (1.04, 1.17) Patients with hypertension (n=136,824) Patients without hypertension(n=110,565) 1.30* 1.09* 1.62* 1.08* (1.23, 1.36)* (1.03, 1.14) (1.49, 1.76) (1.00, 1.18) * 1.12 (0.95, 1.46) (0.72, 1.11) (1.46, 2.33) (0.89, 1.42) 1.68* 1.25* 1.91* 1.15 (1.52, 1.86)* (1.13, 1.38) (1.63, 2.24) (0.98, 1.34) 1.23* 1.07* 1.49* 1.06 (1.16, 1.31)* (1.01, 1.14) (1.35, 1.66) (0.96, 1.18) Patients with ischemic heart disease (n=38,892) Patients without ischemic heart disease(n=208,497)

9 * P-value less than * (1.14, 1.34) 1.09* (1.01, 1.18) 1.41* (1.34, 1.48) 1.09* (1.03, 1.15) * 1.28 (0.89, 1.26) (0.79, 1.12) (1.04, 2.27) (0.87, 1.90) 1.41* 1.21* 1.81* 1.22* (1.24, 1.60) (1.07, 1.38) (1.62, 2.03) (1.09, 1.37) 1.27* 1.13* 1.33* 1.06* (1.14, 1.40) (1.02, 1.25) (1.26, 1.41) (1.00, 1.12) Patients with cerebrovascular Patients without disease cerebrovascular disease (n=24,570) (n=222,819) * 1.14* (0.96, 1.08) (0.96, 1.08) (1.43, 1.65) (1.06, 1.22) 1.56* * 0.95 (1.07, 2.28) (0.90, 1.93) (1.16, 1.64) (0.79, 1.13) 1.59* 1.29* 1.77* 1.20* (1.32, 1.91) (1.07, 1.56) (1.61, 1.94) (1.09, 1.32) * 1.16* (0.94, 1.05) (0.95, 1.06) (1.22, 1.53) (1.03, 1.30)

10 Supplemental Table 6. Hazard ratios of cardiovascular event comparing acarbose (n= 14,724) with metformin (n = 209,917) as the first-line therapy in type 2 diabetic patients aged years weighted by propensity score. Crude HR Adjusted HR 1.37 (1.31, 1.42)* 1.07 (1.03, 1.12)* 1.38 (1.20, 1.58)* 0.90 (0.77, 1.07) 1.63 (1.51, 1.76)* 1.12 (1.02, 1.23)* 1.30 (1.24, 1.37)* 1.08 (1.03, 1.14)* * P-value less than 0.05

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Supplemental tables and figures

Supplemental tables and figures Supplemental Table S1. Demographic and clinical parameters by quartiles of white Variables blood cell count. WBC quartiles( 1 9 cells/l) Q1(.6-5.3, n=2587) Q2(5.4-6.3, n=263)