Table 1 Mean difference from baseline ( 95% CrIs) for HbA1c (%) at 24 weeks for all models fitted vs reference treatment (canagliflozin) and median (95% CrIs) for the between-study standard deviation SD. Model A: naïve pooling, Model B1: two-level hierarchical model (treatment vs class), Model B2: two-level hierarchical model (treatment vs design), Model B3: three-level hierarchical model, Model C1: bias adjustment assuming the same bias by class, Model C2: bias adjustment allowing for bias to vary by class. ^aSGLT-2i therapies (the remaining treatments, apart from the placebo, are from the GLP-1RA class)

Effectiveness

 Dapagliflozin^a

0.17 (-0.01, 0.35)

-0.22 (-0.41, -0.03)

0.01 (-0.13, 0.16)

-0.00 (-0.14, 0.14)

0.00 (-0.24, 0.23)

-0.02 (-0.22, 0.19)

0.04 (-0.12, 0.22)

0.10 (-0.05, 0.25)

 Empagliflozin^a

0.10 (-0.09, 0.30)

-0.37 (-0.70, -0.04)

-0.03 (-0.21, 0.15)

-0.03 (-0.19, 0.13)

-0.05 (-0.34, 0.20)

-0.05 (-0.28, 0.16)

0.00 (-0.19, 0.19)

0.03 (-0.13, 0.19)

 Exenatide BID

0.18 (0.01, 0.35)

0.01 (-0.34, 0.38)

0.12 (-0.04, 0.28)

0.11 (-0.04, 0.27)

0.13 (-0.13, 0.39)

0.09 (-0.16, 0.32)

0.13 (-0.02, 0.29)

0.12 (-0.02, 0.26)

 Lixisenatide

0.30 (0.13, 0.47)

0.34 (-0.04, 0.74)

0.27 (0.11, 0.43)

0.26 (0.1, 0.42)

0.31 (0.06, 0.59)

0.24 (-0.06, 0.48)

0.27 (0.11, 0.43)

0.25 (0.11, 0.39)

 Albiglutide

-0.04 (-0.34, 0.25)

-0.36 (-0.70, -0.01)

-0.17 (-0.40, 0.06)

-0.17 (-0.39, 0.05)

-0.16 (-0.45, 0.13)

-0.15 (-0.41, 0.10)

-0.14 (-0.38, 0.10)

-0.13 (-0.34, 0.07)

 Dulaglutide

-0.26 (-0.44, -0.07)

-0.48 (-0.77, -0.18)

-0.33 (-0.50, -0.17)

-0.33 (-0.49, -0.17)

-0.32 (-0.58, -0.07)

-0.3 (-0.52, -0.06)

-0.31 (-0.48, -0.15)

-0.33 (-0.47, -0.18)

 Exenatide QW

-0.11 (-0.30, 0.08)

-0.30 (-0.57, 0.00)

-0.19 (-0.34, -0.02)

-0.19 (-0.34, -0.03)

-0.16 (-0.41, 0.09)

-0.16 (-0.37, 0.06)

-0.17 (-0.33, 0.00)

-0.18 (-0.32, -0.03)

 Liraglutide

-0.25 (-0.42, -0.08)

-0.30 (-0.56, -0.03)

-0.27 (-0.41, -0.12)

-0.26 (-0.41, -0.12)

-0.24 (-0.48, 0.00)

-0.23 (-0.44, 0.01)

-0.28 (-0.43, -0.12)

-0.31 (-0.45, -0.18)

 Placebo

0.78 (0.66, 0.91)

-

0.72 (0.60, 0.84)

0.72 (0.61, 0.84)

0.74 (0.44, 1.06)

0.74 (0.47, 1.08)

0.73 (0.61, 0.85)

0.73 (0.63, 0.83)

 Ertugliflozin^a

-0.06 (-0.28, 0.16)

-

-0.13 (-0.35, 0.09)

-0.08 (-0.3, 0.1)

-0.10 (-0.44, 0.25)

-0.07 (-0.34, 0.18)

-0.11 (-0.33, 0.10)

-0.11 (-0.30, 0.08)

 Semaglutide

-0.71 (-1.01, -0.41)

-

-0.77 (-1.08, -0.47)

-0.67 (-0.97, -0.37)

-0.75 (-1.14, -0.35)

-0.58 (-0.95, -0.14)

-0.76 (-1.06, -0.46)

-0.76 (-1.04, -0.48)

 Taspoglutide

-0.09 (-0.29, 0.11)

-

-0.15 (-0.36, 0.05)

-0.15 (-0.35, 0.04)

-0.13 (-0.46, 0.22)

-0.13 (-0.4, 0.14)

-0.14 (-0.34, 0.06)

-0.14 (-0.32, 0.04)

Class-level effects and bias

 D. SGLT-2i

-0.04 (-0.55, 0.46)

-0.05 (-0.66, 0.55)

 D. GLP-1RA

-0.17 (-0.48, 0.12)

-0.15 (-0.45, 0.14)

 Bias

0.06 (-0.09, 0.2)

 Bias. SGLT-2i

-0.24 (-0.43, -0.03)

 Bias. GLP-1RA

0.13 (0.00, 0.25)

Heterogeneity

 SD

0.1 (0.04, 0.16)

0.04 (0.00, 0.17)

0.11 (0.07, 0.16)

0.11 (0.07, 0.16)

0.09 (0.03, 0.14)

0.09 (0.02, 0.14)

0.1 (0.05, 0.16)

0.08 (0.01, 0.13)

 SD. SGLT-2i

0.1 (0.0, 1.78)

0.12 (0.0, 2.03)

 SD. GLP-1RA

0.33 (0.18, 0.7)

0.31 (0.12, 0.69)

 SD.design

0.11 (0.02, 0.28)

0.1 (0.02, 0.26)

 SD.bias

0.09 (0.0, 0.26)

0.04 (0.0, 0.15)