Table 2 Mean difference from baseline ( 95% CrIs) for HbA1c (%) at 52 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

0.12 (-0.26, 0.55)

-0.18 (-1.12, 0.76)

0.06 (-0.23, 0.37)

0.03 (-0.27, 0.33)

0.01 (-0.72, 0.68)

-0.02 (-0.39, 0.34)

0.10 (-0.18, 0.40)

0.06 (-0.22, 0.34)

 Empagliflozin^a

-0.14 (-0.62, 0.40)

-0.24 (-1.21, 0.50)

-0.15 (-0.51, 0.20)

-0.12 (-0.47, 0.21)

-0.17 (-0.90, 0.53)

-0.14 (-0.53, 0.24)

-0.15 (-0.48, 0.20)

-0.15 (-0.45, 0.17)

 Exenatide BID

-

0.20 (-0.86, 0.53)

0.32 (-0.28, 0.90)

0.14 (-0.32, 0.62)

0.27 (-0.84, 1.30)

0.08 (-0.4, 0.6)

0.49 (-0.46, 1.30)

0.14 (-0.80, 1.07)

 Lixisenatide

-

0.17 (-0.66, 0.48)

0.18 (-0.24, 0.67)

0.1 (-0.28, 0.62)

0.14 (-0.89, 1.14)

0.04 (-0.4, 0.5)

0.24 (-0.40, 0.88)

-0.11 (-0.82, 0.66)

 Dulaglutide

-

-0.07 (-0.94, 0.46)

-0.07 (-0.47, 0.36)

-0.05 (-0.42, 0.34)

-0.07 (-1.07, 0.93)

-0.06 (-0.49, 0.37)

0.05 (-0.66, 0.66)

-0.20 (-0.91, 0.48)

 Exenatide QW

-0.03 (-0.61, 0.60)

0.18 (-0.70, 0.46)

0.14 (-0.23, 0.52)

0.14 (-0.42, 0.34)

0.10 (-0.64, 0.81)

0.08 (-0.32, 0.47)

0.10 (-0.30, 0.51)

-0.09 (-0.54, 0.37)

 Liraglutide

-

0.17 (-0.62, 0.43)

0.19 (-0.16, 0.57)

0.14 (-0.21, 0.49)

0.18 (-0.83, 1.15)

0.07 (-0.36, 0.5)

0.08 (-0.49, 0.72)

-0.25 (-0.89, 0.47)

 Placebo

0.71 (0.44, 1.04)

-

0.69 (0.45, 0.94)

0.71 (0.47, 0.96)

0.70 (-0.23, 1.66)

0.72 (0.28, 1.17)

0.70 (0.49, 0.94)

0.69 (0.49, 0.90)

 Ertugliflozin^a

-0.09 (-0.61, 0.48)

-

-0.11 (-0.60, 0.40)

-0.07 (-0.5, 0.35)

-0.10 (-1.10, 0.92)

-0.08 (-0.55, 0.39)

-0.10 (-0.53, 0.36)

-0.11 (-0.52, 0.31)

 Albiglutide

-0.10 (-0.53, 0.34)

-

-0.12 (-0.52, 0.25)

-0.07 (-0.4, 0.31)

-0.11 (-1.07, 0.87)

-0.06 (-0.44, 0.35)

-0.11 (-0.45, 0.23)

-0.12 (-0.44, 0.19)

 Semaglutide

-0.66 (-1.36, 0.09)

-

-0.49 (-1.01, 0.05)

-0.29 (-0.76, 0.26)

-0.59 (-1.69, 0.42)

-0.25 (-0.8, 0.28)

-0.54 (-1.03, 0.00)

-0.72 (-1.26, 0.18)

Class-level effects and bias

 d. SGLT-2i

-0.05 (-0.99, 0.85)

-0.08 (-1.05, 0.87)

 d. GLP-1RA

0.02 (-0.36, 0.41)

-0.01 (-0.4, 0.39)

 Bias

0.21 (-0.5, 0.8)

 Bias. SGLT-2i

-0.21 (-1.06, 0.61)

 Bias. GLP-1RA

0.26 (-0.34, 0.78)

Heterogeneity

 SD

0.10 (0.01, 0.5)

0.27 (0.02, 1.04)

0.13 (0.01, 0.33)

0.14 (0.01, 0.33)

0.11 (0.01, 0.32)

0.11 (0.01, 0.3)

0.09 (0.00, 0.3)

0.08 (0.00, 0.28)

 SD. SGLT-2i

0.23 (0.01, 2.7)

0.23 (0.01, 2.81)

 SD. GLP-1RA

0.23 (0.03, 0.64)

0.2 (0.01, 0.64)

 SD.design

0.21 (0.01, 1.38)

0.14 (0.01, 0.39)a

 SD.bias

0.19 (0.01, 0.62)

0.14 (0.01, 0.57)