SITA 100 mg (n = 378)

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Supplementary Table 1. Summary of Sulfonylurea Background Therapy at Baseline and During the Treatment Period. Sulfonylurea at baseline, n (%) SITA 100 mg (n = 378) CANA 300 mg (n = 377) Total (N = 755) Glipizide 40 (11) 47 (12) 87 (12) Glipizide extended release 18 (5) 16 (4) 34 (5) Glyburide/glibenclamide 133 (35) 128 (34) 261 (35) Glimepiride 106 (28) 121 (32) 227 (30) Gliclazide 30 (8) 26 (7) 56 (7) Gliclazide modified release 50 (13) 37 (10) 87 (12) Glyburide micronized 0 2 (1) 2 (<1) Tolazamide 1 (<1) 0 1 (<1) Sulfonylurea daily dose at baseline, n (%) < Minimum daily dose required * 5 (1) 7 (2) 12 (2) Minimum daily dose required * 373 (99) 370 (98) 743 (98) Changed sulfonylurea dose, n (%) Unchanged 338 (89) 345 (92) 683 (90) Changed 40 (11) 32 (8) 72 (10) Decreased 33 (9) 31 (8) 64 (8) Increased 5 (1) 3 (1) 8 (1) Interrupted 4 (1) 0 4 (1) SITA, sitagliptin; CANA, canagliflozin. * Sulfonylurea minimum daily dose required at randomization is defined as: glipizide, 20 mg; glipizide extended release, 10 mg; glyburide/glibenclamide, 10 mg; glimepiride, 4 mg; gliclazide, 160 mg; gliclazide modified release, 60 mg; glyburide micronized, 6 mg. Only for subjects who had sulfonylurea dose change on at least 7 consecutive days.

Supplementary Table 2. Summary of Blood Pressure and Fasting Plasma Lipid Findings at Week 52 (LOCF). Parameter SITA 100 mg CANA 300 mg Systolic BP, n 367 375 Mean ± SD baseline, mm Hg 130.1 ± 14.0 131.2 ± 13.2 LS mean ± SE change 0.9 ± 0.7 5.1 ± 0.7 Difference vs SITA (95% CI) 5.9 ( 7.6, 4.2) * Diastolic BP, n 367 375 Mean ± SD baseline, mm Hg 78.6 ± 8.9 79.2 ± 7.8 LS mean ± SE change 0.3 ± 0.4 3.0 ± 0.4 Difference vs SITA (95% CI) 2.7 ( 3.8, 1.7) Triglycerides, n 353 365 Mean ± SD baseline, mmol/l (mg/dl) 1.9 ± 1.3 (168.2 ± 117.5) 2.1 ± 1.4 (182.7 ± 123.0) LS mean ± SE change, mmol/l (mg/dl) 0.06 ± 0.06 (5.7 ± 5.2) 0.03 ± 0.06 (2.4 ± 5.1) Median (IQR) percent change 4.8 ( 17.1, 33.0) 4.0 ( 26.8, 26.2) LS mean ± SE percent change 11.9 ± 2.9 9.6 ± 2.8 Difference vs SITA (95% CI) 2.3 ( 9.8, 5.3) LDL-C, n 352 363 Mean ± SD baseline, mmol/l (mg/dl) 2.5 ± 0.9 (96.3 ± 35.8) 2.6 ± 1.0 (101.1 ± 36.7) LS mean ± SE change, mmol/l (mg/dl) 0.01 ± 0.04 (0.4 ± 1.5) 0.16 ± 0.04 (6.3 ± 1.5) Median (IQR) percent change 1.3 ( 12.7, 16.7) 4.4 ( 9.9, 22.4) LS mean ± SE percent change 5.2 ± 1.8 11.7 ± 1.8 Difference vs SITA (95% CI) 6.4 (1.7, 11.2) HDL-C, n 353 364 Mean ± SD baseline, mmol/l (mg/dl) 1.2 ± 0.3 (45.7 ± 11.9) 1.2 ± 0.3 (45.6 ± 11.9) LS mean ± SE change, mmol/l (mg/dl) 0.01 ± 0.01 ( 0.5 ± 0.4) 0.07 ± 0.01 (2.9 ± 0.4) Median (IQR) percent change 1.7 ( 9.1, 9.2) 7.0 ( 2.7, 17.1) LS mean ± SE percent change 0.6 ± 0.9 7.6 ± 0.9 Difference vs SITA (95% CI) 7.0 (4.6, 9.3) LDL-C/HDL-C, n 352 363 Mean ± SD baseline 2.2 ± 0.9 2.3 ± 0.9 LS mean ± SE change 0.03 ± 0.04 0.01 ± 0.04 Median (IQR) percent change 0.6 ( 14.8, 20.1) 2.4 ( 17.6, 16.6) LS mean ± SE percent change 7.2 ± 2.0 6.1 ± 2.0 Difference vs SITA (95% CI) 1.1 ( 6.3, 4.2) Non HDL-C, n 353 364

Mean ± SD baseline, mmol/l (mg/dl) 3.3 ± 1.0 (129.3 ± 40.2) 3.5 ± 1.1 (136.6 ± 41.2) LS mean ± SE change, mmol/l (mg/dl) 0.04 ± 0.05 (1.6 ± 1.8) 0.18 ± 0.04 (6.7 ± 1.7) Median (IQR) percent change 0.7 ( 10.1, 13.7) 2.7 ( 9.0, 16.1) LS mean ± SE percent change 4.0 ± 1.5 7.9 ± 1.5 Difference vs SITA (95% CI) 3.9 (0.0, 7.7) LOCF, last observation carried forward; SITA, sitagliptin; CANA, canagliflozin; BP, blood pressure; SD, standard deviation; LS, least squares; SE, standard error; CI, confidence interval; IQR, interquartile range; LDL-C, low-density lipoprotein cholesterol; HDL-C, highdensity lipoprotein cholesterol; NS, not significant. * p<0.001 versus SITA. Statistical comparison versus SITA not pre-specified. p = NS versus SITA. Statistical comparison versus SITA not performed due to multiplicity control.

Supplementary Table 3. Summary of Changes in Indices of β-cell function at Week 52 (LOCF). Parameter SITA 100 mg (n = 378) CANA 300 mg (n = 377) HOMA2-%B, n 330 347 Mean (SD) baseline 56.8 (35.1) 52.5 (30.1) LS mean change (SE) 9.0 (2.6) 21.6 (2.5) Difference vs SITA (95% CI) 12.6 (5.8, 19.3) Proinsulin/insulin ratio, n 274 275 Mean (SD) baseline, pmol/miu 4.4 (2.5) 4.2 (2.6) LS mean change (SE) 0.2 (0.2) 0.6 (0.2) Difference vs SITA (95% CI) 0.4 ( 0.1, 0.9) Proinsulin/C-peptide ratio, n 193 221 Mean (SD) baseline, pmol/nmol 46.0 (21.5) 46.9 (24.3) LS mean change (SE) 1.0 (1.4) 3.3 (1.2) Difference vs SITA (95% CI) 4.3 ( 7.7, 1.0) AUC C /AUC G ratio (0-3 h), n 77 84 Mean (SD) baseline, pmol/mmol 122.7 (54.1) 113.4 (46.4) LS mean change (SE) 19.3 (4.2) 18.1 (3.9) Difference vs SITA (95% CI) 1.2 ( 12.2, 9.8) LOCF, last observation carried forward; SITA, sitagliptin; CANA, canagliflozin; HOMA, Homeostasis Model Assessment; SD, standard deviation; LS, least squares; SE, standard error; CI, confidence interval; AUC C, C-peptide area under the curve; AUC G, glucose area under the curve.

Supplementary Table 4. Summary of Laboratory Parameters at Baseline and Week 52. Parameter SITA 100 mg CANA 300 mg ALT, n Mean baseline, U/L 209 26.3 7.9 (50.0) 28.0 3.5 (38.1) Bilirubin, n Mean baseline, μmol/l BUN, n Mean baseline, mmol/l egfr, n Mean baseline, ml/min/1.73 m 2 Urate, n Mean baseline, μmol/l Hemoglobin, n Mean baseline, g/l 8.0 2.7 (35.5) 5.6 5.0 (25.2) 89.5 4.5 (14.6) 320.9 6.2 (18.3) 201 139.5 1.8 (6.5) 8.1 12.2 (40.1) 5.4 18.1 (30.5) 88.3 4.7 (11.6) 332.0 6.5 (18.2) 246 140.4 3.7 (6.2) SITA, sitagliptin; CANA, canagliflozin; ALT, alanine aminotransferase; SD, standard deviation; BUN, blood urea nitrogen; egfr, estimated glomerular filtration rate. Supplementary Figure 1. Change in A1C over time (Per-protocol). SITA, sitagliptin; CANA, canagliflozin; LS, least squares; SE, standard error; CI, confidence interval.

Supplementary Figure 2. Change in A1C from baseline to Week 52 by baseline A1C subgroup. * LS, least squares; SE, standard error; SITA, sitagliptin; CANA, canagliflozin. * A1C <8.0%: SITA 100 mg (n = 174), CANA 300 mg (n = 185); A1C 8.0 to <9.0%: SITA 100 mg (n = 122), CANA 300 mg (n = 125); A1C 9.0%: SITA 100 mg (n = 82), CANA 300 mg (n = 67).