1. 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 Nov;18(7):A598.
Neal B, et al. Poster presented at IDF, 2013 (P-1093).

2. 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 Nov;18(7):A598.

3. 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 Nov;18(7):A598.

4. 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 Nov;18(7):A598.

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

6. Glycaemic efficacy end-points

7. 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 Nov;18(7):A598.
CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, PIO: Pioglitazone, LIXI: Lixisenatide, EXEN: Exenatide

8. Other efficacy end-points

9. 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 Nov;18(7):A598.
CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, PIO: Pioglitazone, LIXI: Lixisenatide, EXEN: Exenatide, VILDA: Vildagliptin, SITA: Sitagliptin, SAXA: Saxagliptin

10. 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 Nov;18(7):A598.
CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, SAXA: Saxagliptin, EXEN: Exenatide

11. 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 Nov;18(7):A598.
CANA: Canagliflozin, DAPA: Dapagliflozin, MET: Metformin, PIO: Pioglitazone, LIXI: Lixisenatide, EXEN: Exenatide, GLIM: Glimepiride