Metformin is typically the first pharmacologic treatment recommended for
type 2 diabetes mellitus (T2DM), but many patients do not achieve
glycemic control with
metformin alone and eventually require combination
therapy with other agents.
Canagliflozin, a
sodium glucose co-transporter 2 (
SGLT2) inhibitor, was assessed in a comprehensive Phase 3 clinical development program consisting of ~10,000 participants, of which ~80% were on background
therapy that consisted of
metformin alone or in combination with other
antihyperglycemic agents (AHAs; e.g.,
pioglitazone, sulfonylurea, and
insulin). In addition, the efficacy and safety of
canagliflozin and
metformin as the initial combination
therapy and
canagliflozin monotherapy were assessed versus
metformin in treatment-naïve patients with T2DM. Across studies in patients with T2DM who were on
metformin alone or in combination with other AHAs,
canagliflozin 100 and 300 mg provided improvements in
glycated hemoglobin for up to 104 weeks.
Canagliflozin was also associated with reductions in
body weight and systolic blood pressure when added to background
therapy consisting of
metformin alone or with other AHAs.
Canagliflozin was generally well tolerated, with increased incidence of adverse events (AEs) related to the mechanism of SGLT2 inhibition (i.e., genital mycotic
infections, urinary tract infections, and osmotic diuresis-related AEs). Consistent with its
insulin-independent mechanism of action,
canagliflozin was associated with low rates of
hypoglycemia when background
therapy did not include sulfonylurea or
insulin. Due to its favorable efficacy and safety profile, these results suggest that adding
canagliflozin to a background regimen consisting of
metformin or implementing treatment with a fixed-dose regimen of
canagliflozin and
metformin would provide an effective and safe treatment regimen for T2DM management.
FUNDING: Janssen Global Services, LLC.