Table 2

Summary of efficacy findings at week 26*

ParameterCANA100/METCANA300/METCANA100CANA300MET
HbA1c, n235236230234230
 Mean ± SD baseline, % (mmol/mol)8.8 ± 1.1 (73 ± 12)8.9 ± 1.2 (74 ± 13)8.8 ± 1.2 (73 ± 13)8.8 ± 1.2 (73 ± 13)8.8 ± 1.2 (73 ± 13)
 LS mean ± SE change, % (mmol/mol)−1.77 ± 0.07 (–19.3 ± 0.8)−1.78 ± 0.07 (–19.5 ± 0.8)−1.37 ± 0.07 (–15.0 ± 0.8)−1.42 ± 0.07 (–15.5 ± 0.8)−1.30 ± 0.07 (–14.2 ± 0.8)
 Difference vs. MET (95% CI), % [mmol/mol]−0.46 (–0.66, –0.27) [–5.0 (–7.2, –3.0)]−0.48 (–0.67, –0.28) [–5.2 (–7.3, –3.1)]−0.06 (–0.26, 0.13) [–0.7 (–2.8, 1.4)]−0.11 (–0.31, 0.08) [–1.2 (–3.4, 0.9)]
 Difference vs. CANA100 (95% CI), % [mmol/mol]−0.40 (–0.59, –0.21)§ [–4.4 (–6.4, –2.3)]
 Difference vs. CANA300 (95% CI), % [mmol/mol]−0.36 (–0.56, –0.17) [–3.9 (–6.1, –1.9)]
FPG, n235236230234230
 Mean ± SD baseline, mg/dL (mmol/L)191 ± 51 (10.6 ± 2.8)201 ± 56 (11.2 ± 3.1)196 ± 54 (10.9 ± 3.0)193 ± 52 (10.7 ± 2.9)191 ± 49 (10.6 ± 2.7)
 LS mean ± SE change, mg/dL (mmol/L)−53 ± 3 (–2.9 ± 0.1)−56 ± 3 (–3.1 ± 0.1)−38 ± 3 (–2.1 ± 0.1)−44 ± 3 (–2.5 ± 0.1)−35 ± 3 (–1.9 ± 0.1)
 Difference vs. MET (95% CI), mg/dL [mmol/L]−18 (–25, –11) [–1.0 (–1.4, –0.6)]−22 (–29, –15) [–1.2 (–1.6, –0.8)]−3 (–10, 4) [–0.2 (–0.6, 0.2)]−10 (–17, –3) [–0.5 (–0.9, –0.1)]
 Difference vs. CANA100 (95% CI), mg/dL [mmol/L]−15 (–22, –8) [–0.8 (–1.2, –0.4)]
 Difference vs. CANA300 (95% CI), mg/dL [mmol/L]−12 (–19, –5) [–0.7 (–1.1, –0.3)]
Body weight, n237236236236237
 Mean ± SD baseline, kg88.3 ± 17.691.5 ± 21.490.3 ± 18.693.0 ± 20.092.1 ± 20.1
 LS mean change ± SE, % (kg)−3.5 ± 0.3 (–3.2 ± 0.2)−4.2 ± 0.3 (–3.9 ± 0.2)−3.0 ± 0.3 (–2.8 ± 0.2)−3.9 ± 0.3 (–3.7 ± 0.2)−2.1 ± 0.3 (–1.9 ± 0.2)
 Difference vs. MET (95% CI), % [kg]−1.4 (–2.1, –0.6) [–1.2 (–1.9, –0.6)]−2.1 (–2.9, –1.4) [–2.0 (–2.6, –1.3)]−0.9 (–1.6, –0.2) [–0.9 (–1.6, –0.2)]−1.8 (–2.6, –1.1)# [–1.8 (–2.4, –1.1)]
SBP, n237236236236237
 Mean ± SD baseline, mmHg127.6 ± 11.5128.1 ± 12.2128.9 ± 11.7130.1 ± 11.5129.4 ± 12.0
 LS mean ± SE change, mmHg−2.2 ± 0.6−1.7 ± 0.6−2.2 ± 0.6−2.4 ± 0.6−0.3 ± 0.6
 Difference vs. MET (95% CI)−1.9 (–3.6, –0.2)**−1.3 (–3.1, 0.4)**
DBP, n237236236236237
 Mean ± SD baseline, mmHg78.4 ± 7.778.1 ± 8.379.0 ± 7.878.5 ± 7.878.3 ± 7.8
 LS mean ± SE change, mmHg−1.5 ± 0.4−1.02 ± 0.4−1.1 ± 0.4−1.7 ± 0.4−0.5 ± 0.4
 Difference vs. MET (95% CI)−1.1 (–2.3, 0.1)††−0.6 (–1.8, 0.6)††−0.7 (–1.9, 0.6)††−1.3 (–2.5, –0.1)††
HDL-C, n227225225228222
 Mean ± SD baseline, mg/dL (mmol/L)44.4 ± 10.9 (1.2 ± 0.3)43.5 ± 10.3 (1.1 ± 0.3)43.1 ± 9.1 (1.1 ± 0.2)44.0 ± 11.9 (1.1 ± 0.3)43.7 ± 10.6 (1.1 ± 0.3)
 LS mean ± SE change, mg/dL (mmol/L)6.4 ± 0.6 (0.16 ± 0.02)5.5 ± 0.7 (0.14 ± 0.02)6.9 ± 0.7 (0.18 ± 0.02)6.8 ± 0.6 (0.17 ± 0.02)3.9 ± 0.7 (0.10 ± 0.02)
 LS mean ± SE percent change15.5 ± 1.514.5 ± 1.517.6 ± 1.516.6 ± 1.510.2 ± 1.5
 Difference vs. MET (95% CI)5.3 (1.2, 9.5)‡‡4.3 (0.2, 8.5)‡‡7.4 (3.2, 11.6)††6.5 (2.3, 10.6)††
Triglycerides, n229225225229223
 Mean ± SD baseline, mg/dL (mmol/L)166.6 ± 84.1 (1.9 ± 0.9)179.0 ± 105.1 (2.0 ± 1.2)187.1 ± 118.8 (2.1 ± 1.3)173.4 ± 108.7 (2.0 ± 1.2)188.6 ± 126.6 (2.1 ± 1.4)
 LS mean ± SE change, mg/dL (mmol/L)−1.4 ± 6.7 (–0.02 ± 0.08)15.5 ± 6.8 (0.17 ± 0.08)−15.9 ± 6.8 (–0.18 ± 0.08)−17.4 ± 6.7 (–0.20 ± 0.08)15.2 ± 6.8 (0.17 ± 0.08)
 Median percent change (range)2.9 (–82.2, 1,022.6)7.8 (–81.4, 415.1)−8.7 (–81.2, 268.2)−7.3 (–76.9, 620.8)4.2 (–83.1, 278.6)
 Hodges-Lehmann estimate (95% CI)−3.7 (–11.1, 3.4)‡‡1.3 (–7.3, 10.0)‡‡
LDL-C, n225223222228222
 Mean ± SD baseline, mg/dL (mmol/L)118.6 ± 37.6 (3.1 ± 1.0)118.8 ± 41.2 (3.1 ± 1.1)116.0 ± 38.1 (3.0 ± 1.0)122.5 ± 38.0 (3.2 ± 1.0)115.5 ± 36.3 (3.0 ± 0.9)
 LS mean ± SE change, mg/dL (mmol/L)−1.1 ± 2.1 (–0.03 ± 0.05)−0.4 ± 2.1 (–0.01 ± 0.05)9.8 ± 2.1 (0.25 ± 0.05)9.0 ± 2.1 (0.23 ± 0.05)−0.6 ± 2.1 (–0.02 ± 0.05)
 LS mean ± SE percent change3.8 ± 2.25.2 ± 2.214.3 ± 2.211.4 ± 2.24.0 ± 2.2
 Difference vs. MET (95% CI)−0.2 (–6.2, 5.9)††1.2 (–4.8, 7.3)††10.3 (4.2, 16.4)††7.4 (1.4, 13.4)††
  • *Changes in HbA1c, FPG, body weight, and BP were analyzed with an MMRM using a restricted maximum likelihood approach using observed data. Changes in lipids were analyzed using an ANCOVA, with missing data imputed using the last observation carried forward; given the skewed nature of the distribution of the percent change in triglycerides, this secondary end point was analyzed using nonparametric methods.

  • P = 0.001 vs. MET.

  • ‡Noninferiority P = 0.001 vs. MET.

  • §P = 0.001 vs. CANA100.

  • P = 0.001 vs. CANA300.

  • P = 0.016 vs. MET.

  • #P = 0.002 vs. MET.

  • **P = NS vs. MET.

  • ††Statistical testing not performed (not prespecified).

  • ‡‡Statistical testing not performed due to the hierarchical testing sequence.