TABLE 1.

Summary of the Efficacy and Safety of Canagliflozin as Add-On to Metformin, Metformin Plus Sulfonylurea, and Insulin in Patients With Type 2 Diabetes Over 52 Weeks (3,3033,50,53)

Canagliflozin as:
Add-on to METAdd-on to MET + SUAdd-on to insulin
Changes in key efficacy parameters
A1C (%)GLIMPBOPBO
 Baseline: 7.8 Baseline: 8.1 Baseline: 8.2
 Change: –0.81 Change: +0.01 Change: +0.13
CANA 100 mgCANA 100 mgCANA 100 mg
 Baseline: 7.8 Baseline: 8.1 Baseline: 8.3
 Change: –0.82 Change: –0.74 Change: –0.58
CANA 300 mgCANA 300 mgCANA 300 mg
 Baseline: 7.8 Baseline: 8.1 Baseline: 8.3
 Change: –0.93 Change: –0.96 Change: –0.68
SITASITA
 Baseline: 7.9 Baseline: 8.1
 Change: –0.73 Change: –0.66
CANA 100 mgCANA 300 mg
 Baseline: 7.9 Baseline: 8.1
 Change: –0.73 Change: –1.03
CANA 300 mg
 Baseline: 8.0Patients with baseline A1C ≥9.0%
 Change: –0.88
SITA
 Baseline: 9.5
 Change: –1.44
CANA 300 mg
 Baseline: 9.6
 Change: –1.99
Body weight (kg)GLIMPBO:PBO
 Baseline: 86.6 Baseline: 90.8 Baseline: 97.7
 Change: +1.0% (+0.7) Change: –0.9% (–1.0) Change: +0.1% (+0.1)
CANA 100 mgCANA 100 mgCANA 100 mg
 Baseline: 86.8 Baseline: 93.5 Baseline: 96.9
 Change: –4.2% (–3.7) Change: –2.2% (–2.0) Change: –2.4% (–2.3)
CANA 300 mgCANA 300 mgCANA 300 mg
 Baseline: 86.6 Baseline: 93.5 Baseline: 96.7
 Change: –4.7% (–4.0) Change: –3.2% (–3.1) Change: –3.1% (–3.0)
SITASITA
 Baseline: 87.6 Baseline: 89.6
 Change: –1.3% (–1.2) Change: +0.3% (+0.1)
CANA 100 mgCANA 300 mg
 Baseline: 88.7 Baseline: 87.6
 Change: –3.8% (–3.3) Change: –2.5% (–2.3)
CANA 300 mg
 Baseline: 85.4
 Change: –4.2% (–3.7)
Systolic BP (mmHg)GLIMPBOPBO
 Baseline: 129.5 Baseline: 130.1 Baseline: 138.2
 Change: +0.2 Change: +0.1 Change: –1.4
CANA 100 mgCANA 100 mgCANA 100 mg
 Baseline: 130.0 Baseline: 130.4 Baseline: 137.0
 Change: –3.3 Change: –3.7 Change: –4.7
CANA 300 mgCANA 300 mgCANA 300 mg
 Baseline: 130.0 Baseline: 130.8 Baseline: 138.2
 Change: –4.6 Change: –2.9 Change: –7.6
SITASITA
 Baseline: 128.0 Baseline: 130.1
 Change: –0.7 Change: +0.9
CANA 100 mgCANA 300 mg
 Baseline: 128.0 Baseline: 131.2
 Change: –3.5 Change: –5.1
CANA 300 mg
 Baseline: 128.7
 Change: –4.7
Selected safety parameters
HypoglycemiaLow incidence, similar to SITA, significantly lower than GLIMIncidence similar to SITAHigher incidence compared to PBO
Genital mycotic infections
  • Higher incidence than PBO, GLIM, and SITA

  • Mild or moderate, respond to standard treatments

Urinary tract infections
  • Higher incidence than PBO and GLIM

  • Similar incidence than SITA

  • Upper urinary tract infections rare

Osmotic diuresis–related AEs
  • Higher incidence than PBO and SITA

  • Incidence low with few study discontinuations

Volume depletion–related AEs
  • Incidence low with few study discontinuations

Lipids
  • Increases in HDL cholesterol (PBO-subtracted changes of 5.4 and 6.3% with CANA 100 and 300 mg, respectively, in the pooled PBO-controlled studies)

  • Increases in LDL cholesterol (PBO-subtracted changes of 4.5 and 8.0% with CANA 100 and 300 mg, respectively, in the pooled PBO-controlled studies)

  • Increases in non-HDL cholesterol smaller than those in LDL cholesterol (PBO-subtracted changes of 1.5 and 3.6% with CANA 100 and 300 mg, respectively, in the pooled PBO-controlled studies)

  • No notable trends in change from baseline in LDL/HDL cholesterol ratio

Laboratory parameters
  • Modest improvements in liver function parameters

  • Increases in bilirubin and BUN

  • Reductions in serum urate

  • Transient decreases in eGFR with reciprocal increases in serum creatinine

  • Small increases in hemoglobin

  • BUN, blood urea nitrogen; CANA, canagliflozin; GLIM, glimepiride; MET, metformin; PBO, placebo; SITA, sitagliptin; SU, sulfonylurea.