network meta-analysis of safety with SGLT2 inhibitors1

SGLT2i network meta-analysis study design1
Objective Indirectly assess comparative efficacy and safety of SGLT2 inhibitors in patients with type 2 diabetes
Treatments INVOKANA® (canagliflozin), Jardiance® (empagliflozin), Farxiga® (dapagliflozin)
Studies analyzed 38 randomized, placebo-controlled trials published up to November 3, 2015
Duration of studies ≥24 weeks
Number of patients (overall) 23,997
Outcomes ≥1 cardiometabolic or safety outcomes

The number of available studies analyzed may vary by outcome endpoint.

Limitations of the network meta-analysis1:

  • Data were sourced only from journal articles or from, which could risk publication bias
  • In some studies, outcomes may not be reported or it may not be possible to extract them in a suitable way; however, information was retrieved from all 38 trials for A1C and from 37 trials for body weight
  • Diabetic ketoacidosis and bone fractures were reported in 3 and 9 studies, respectively; therefore, a formal analysis was not performed
  • Across randomized controlled trials, ethnicities of participants, follow-up durations, outcomes selection, definition, and ascertainment could differ; however, the authors deemed the network used in this analysis as consistent for A1C outcomes

There have been no head-to-head clinical trials comparing the efficacy or safety of SGLT2 inhibitors. No direct evaluation of comparative clinical profiles can be made.

safety analysis1

Risk vs placebo

  Hypoglycemia Urinary tract infection Genital infection
Farxiga® (dapagliflozin) 10 mg
Jardiance® (empagliflozin) 25 mg
INVOKANA® (canagliflozin) 300 mg

Increased risk vs placebo

Similar risk vs placebo

SGLT2=sodium-glucose co-transporter 2.

  • In an analysis excluding studies with a background sulfonylurea (SU) or insulin, the risk of hypoglycemia was similar to placebo for all SGLT2 inhibitors, suggesting an imbalance of an SU or insulin use across studies where SGLT2 inhibitors were compared with placebo

Reference: 1. Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016;18(8):783-794.