Taieb V, et al. Value Health. 2015 Nov;18(7):A598. Bayesian Network Meta-Analysis to Assess the Relative Efficacy of Canagliflozin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Insulin Taieb V, et al. Value Health. 2015 Nov;18(7):A598. Neal B, et al. Poster presented at IDF, 2013 (P-1093).

Research Design and Methods Bayesian Network Meta-analysis (NMAs) were conducted based on a systematic literature review Outcomes of interest included change in HbA1c, weight, and systolic BP (SBP) from baseline to 26 (±4) weeks Networks of evidence were based on treatment- and dose- specific nodes for DPP-4 inhibitors, GLP-1 receptor agonists, pioglitazone (PIO), and SGLT2 inhibitors Value Health. 2015 Nov;18(7):A598.

Research Design and Methods Differences between treatments (∆) and Bayesian pairwise probabilities (P; i.e., probability of CANA to perform better versus comparators) were estimated As there is no clear threshold for interpreting results in the Bayesian framework, for ease of interpretation, P ≤30% and P ≥70% were chosen to indicate a smaller and larger effect, respectively Value Health. 2015 Nov;18(7):A598.

Results The literature review identified 18 trials that reported mean change in HbA1c, weight, or SBP at 26 (±4) weeks 26-week efficacy data on file from the CANagliflozin cardioVascular Assessment Study (CANVAS) insulin substudy were used in the NMA Background therapy consisted of insulin +/– other anti-hyperglycemic agents (AHAs) in 12 of the trials (including the CANVAS insulin substudy) In 6 of the trials, background therapy consisted of insulin exclusively Value Health. 2015 Nov;18(7):A598.

Network of Evidence Value Health. 2015 Nov;18(7):A598. CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, PIO: Pioglitazone

Glycaemic efficacy end-points

HbA1c Change From Baseline with CANA 100 mg Had a similar or greater HbA1c reduction compared to DPP-4 inhibitors, with HbA1c differences ranging from –0.04% to –0.23% (P ≥68%) Greater HbA1c reduction compared to DAPA 5 mg (Δ = –0.05%; P = 73%) and similar to DAPA 10 mg (Δ = –0.04%; P = 68%) Had a similar HbA1c reduction compared to MET (Δ = –0.05%; P = 61%) Greater HbA1c reduction compared to LIXI 20 μg (Δ = –0.34%; P = 100%), similar HbA1c reduction compared to EXEN 20 μg (Δ = 0.06%; P = 32%) Similar HbA1c reduction compared to GLIM (Δ = –0.10%; P = 61%) HbA1c reduction was similar for CANA 100 mg compared to PIO 30 mg (Δ = 0.01%; P = 48%) CrI, credible interval. *Data are median (95% CrI). †Bayesian probability for CANA to be more effective versus comparator. Value Health. 2015 Nov;18(7):A598. CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, PIO: Pioglitazone, LIXI: Lixisenatide, EXEN: Exenatide

Other efficacy end-points

Weight Change From Baseline with CANA As add-on to insulin, CANA 300 and 100 had greater weight reductions compared to DPP-4 inhibitors (Δ = –2.13 kg to –3.45 kg; P = 100%) LIXI 20 μg (Δ = –1.62 kg and –1.00 kg, respectively; P = 100%) DAPA 10 and 5 mg (Δ = –0.44 kg to –1.73 kg; P ≥92%) CANA 300 and 100 had greater weight reductions compared to GLIB (Δ = –8.25 kg and –7.61 kg; P = 81% and 79%, respectively) PIO 30 mg (Δ = –3.95 kg and –3.34 kg; P = 82% and 78%, respectively) The reduction in weight was similar for CANA 300 and 100 mg compared to MET (Δ = –0.30 kg and 0.32 kg; P = 58% and 42%, respectively) *Data are median (95% CrI). †Bayesian probability for CANA to be more effective versus comparator. Value Health. 2015 Nov;18(7):A598. CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, PIO: Pioglitazone, LIXI: Lixisenatide, EXEN: Exenatide, VILDA: Vildagliptin, SITA: Sitagliptin, SAXA: Saxagliptin

SBP Change From Baseline with CANA CANA 100 mg had a Greater SBP reduction compared to DAPA 10 and 5 mg (Δ = –1.25 mmHg and –1.97 mmHg, respectively; P ≥78%), SAXA 5 mg (Δ = –4.31 mmHg; P = 100%) Similar reduction in SBP compared to EXEN 20 μg (Δ = 0.04 mmHg; P = 49%) Value Health. 2015 Nov;18(7):A598. CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, SAXA: Saxagliptin, EXEN: Exenatide

Discussion and Conclusion In patients with T2DM inadequately controlled with insulin, Canagliflozin provide At least similar or greater reductions in HbA1c versus DPP-4 inhibitors, DAPA, MET, LIXI, EXEN, GLIM, and PIO 30 mg Afford additional benefits in terms of weight reduction and SBP lowering These results suggest that CANA is a valuable treatment option as add- on to insulin therapy, as it provides not only similar or better glucose lowering than many other options, but also weight loss and improvements in BP Value Health. 2015 Nov;18(7):A598. CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, PIO: Pioglitazone, LIXI: Lixisenatide, EXEN: Exenatide, GLIM: Glimepiride