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

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 410-414 Angiotensin receptor blockers C09CA 410, 412 Alpha-blockers C02CA Congestive heart failure Cerebrovascular disease 428 Beta-blockers C07A 430-438 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, 443.81, 443.9 Other anti-hypertensive agents C02A, C02B, C02CC, C02D Retinopathy 250.5, 362, 364.0, 364.4, 365-366, 368-369, 377 Nitrate C01DA Nephropathy 250.4, 580-588, 590, 593, 595, 596, 599, 791.0 Insulin A10A Neuropathy 250.6, 337.1, 354, 355, 356.8, 357.2, 358.1, 713.5, 729.2 Chronic renal disease 403.01, 403.11, 403.91, 404.02, 404.03, 404.12, 404.13, 404.92, 404.93, 585, V45.1, V56.0, V56.8 Chronic liver disease 070.2x, 070.3x, V02.61, 070.41, 070.44, 070.51, 070.54, V02.62, 571.0, 571.1, 571.2, 571.3, 571.4, 571.5, 571.6 Sulfonylurea Metformin Thiazolidinediones A10BB A10BA02 A10BG02, A10BG03 Chronic lung disease 490-496, 500-508 Glinides A10BX02, A10BX03 Depression 296.2,296.3,298.0,300.4,309.0,309.1, 293.83,296.90,309.28,296.82, 311 Acarbose A10BF01 Hypertension 401-404 DPP4 inhibitors A10BH Dyslipidemia 272 Statins C10AA Fibrates Warfarin Aspirin Clopidogrel COX-2 nonselective NSAIDs C10AB B01AA03 B01AC06, N02BA01 B01AC04 M01A (exclude M01AH,

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

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 -0.0285 0.00836 Age 0.0163 0.000687 Diabetes duration in days -0.00032 0.000064 Comorbidities Ischemic heart disease -0.00539 0.0133 Cerebrovascular disease -0.05 0.0158 Peripheral arterial disease -0.0247 0.0325 Retinopathy -0.00568 0.0293 Neuropathy 0.0332 0.0206 Nephropathy 0.2346 0.0198 Chronic liver disease 0.0183 0.0122 Chronic lung disease 0.0144 0.0127 Depression 0.0382 0.0214 Hypertension 0.0408 0.0111 Dyslipidemia 0.00253 0.00974 Diabetes complication severity index 0.0964 0.0117 Charlson's index 0.049 0.00848 Monthly income level 75 th -0.0169 0.0156 75th - 50 th -0.00346 0.0177 50th - 25 th 0.0475 0.0138

25 th - low income 0.0169 0.0172 Medication use Aspirin -0.0737 0.0102 Clopidogrel 0.0833 0.0238 Warfarin -0.0376 0.0345 Angiotensin-converting enzyme inhibitors -0.0432 0.0124 Angiotensin receptor blockers 0.045 0.011 Alpha-blockers 0.0628 0.0175 Beta-blockers 0.0344 0.0103 Calcium channel blockers -0.0377 0.011 Diuretics -0.00197 0.0113 Other anti-hypertensive agents 0.0495 0.0383 Nitrates -0.0126 0.0154 Statins 0.0383 0.0112 Fibrates -0.00523 0.0143 Digitalis glycoside 0.0171 0.0254 Antiarrhythmics class I and III 0.0179 0.0235 COX-2 non-selective NSAIDs -0.0497 0.00995 COX-2 selective NSAIDs 0.0479 0.0153 Number of different prescription drugs 0.00224 0.000865 Number of cardiovascular-related medications 0.0277 0.00714 Resource utilization Number of A 1 C measurement 0.077 0.00658 Number of lipid-related lab test 0.00661 0.00238 Number of outpatient visits 0.000144 0.000092 Number of emergency department visit 0.000933 0.000291 Number of cardiology outpatient visits 0.00212 0.000304 Number of cardiovascular-related physician visits -0.00019 0.000133 Coronary revascularization -0.0498 0.049 Number of hospitalizations -0.0184 0.0174 Number of hospitalizations due to cardiovascular-related diseases 0.0322 0.0295 Number of hospital days -0.0002 0.000798 Number of cardiovascular-related hospital days -0.00541 0.00179 *c-statistics for propensity score model = 0.623

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

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* 1.04 1.39* 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* 1.05 1.40* 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* 1.03 1.25* 1.128* (1.21, 1.38) (0.97, 1.11) (1.21, 1.31) (1.08, 1.17) 1.41* 1.01 1.29* 1.07 (1.16, 1.72) (0.83, 1.23) (1.12, 1.49) (0.93, 1.24) 1.50* 1.09 1.48* 1.23* (1.31, 1.71) (0.95, 1.24) (1.38, 1.59) (1.15, 1.32) 1.24* 1.04 1.17* 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* 1.02 1.72* 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)

* P-value less than 0.05 1.27* (1.19, 1.35) 1.128 (1.06, 1.19) 1.42* (1.36, 1.48) 1.09* (1.04, 1.13) 1.10 0.98 1.41* 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) 1.02 1.01 1.50* 1.14* (0.97, 1.08) (0.97, 1.07) (1.43, 1.57) (1.09, 1.20) 1.30 1.14 1.45* 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) 0.99 0.99 1.37* 1.13* (0.94, 1.04) (0.95, 1.05) (1.28, 1.46) (1.06, 1.21)

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* 1.02 1.15 0.83 (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* 1.05 1.36* 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* 0.96 1.27* 1.13* (1.10, 1.31) (0.88, 1.05) (1.21, 1.33) (1.08, 1.19) 1.35* 0.91 1.33* 1.07 (1.04, 1.76) (0.70, 1.19) (1.09, 1.63) (0.87, 1.30) 1.47* 1.02 1.59* 1.28* (1.22, 1.77) (0.85, 1.23) (1.44, 1.75) (1.16, 1.40) 1.14* 0.97 1.18* 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) 1.18 0.90 1.85* 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)

* P-value less than 0.05 1.24* (1.14, 1.34) 1.09* (1.01, 1.18) 1.41* (1.34, 1.48) 1.09* (1.03, 1.15) 1.06 0.94 1.54* 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) 1.02 1.02 1.54* 1.14* (0.96, 1.08) (0.96, 1.08) (1.43, 1.65) (1.06, 1.22) 1.56* 1.32 1.38* 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) 0.99 1.00 1.37* 1.16* (0.94, 1.05) (0.95, 1.06) (1.22, 1.53) (1.03, 1.30)

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 20-79 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