BACKGROUND: Despite the number of medications for type 2 diabetes, many people 
with the condition do not achieve good glycaemic control. Some existing 
glucose-lowering agents have adverse effects such as weight gain or 
hypoglycaemia. Type 2 diabetes tends to be a progressive disease, and most 
patients require treatment with combinations of glucose-lowering agents. The 
sodium glucose co-transporter 2 (SGLT2) receptor inhibitors are a new class of 
glucose-lowering agents.
OBJECTIVE: To assess the clinical effectiveness and safety of the SGLT2 receptor 
inhibitors in dual or triple therapy in type 2 diabetes.
DATA SOURCES: MEDLINE, Embase, Cochrane Library (all sections); Science Citation 
Index; trial registries; conference abstracts; drug regulatory authorities; 
bibliographies of retrieved papers.
INCLUSION CRITERIA: Randomised controlled trials of SGLT2 receptor inhibitors 
compared with placebo or active comparator in type 2 diabetes in dual or 
combination therapy.
METHODS: Systematic review. Quality assessment used the Cochrane risk of bias 
score.
RESULTS: Seven trials, published in full, assessed dapagliflozin and one 
assessed canagliflozin. Trial quality appeared good. Dapagliflozin 10 mg reduced 
HbA1c by -0.54% (weighted mean differences (WMD), 95% CI -0.67 to -0.40) 
compared to placebo, but there was no difference compared to glipizide. 
Canagliflozin reduced HbA1c slightly more than sitagliptin (up to -0.21% vs 
sitagliptin). Both dapagliflozin and canagliflozin led to weight loss 
(dapagliflozin WMD -1.81 kg (95% CI -2.04 to -1.57), canagliflozin up to -2.3 kg 
compared to placebo).
LIMITATIONS: Long-term trial extensions suggested that effects were maintained 
over time. Data on canagliflozin are currently available from only one paper. 
Costs of the drugs are not known so cost-effectiveness cannot be assessed. More 
data on safety are needed, with the Food and Drug Administration having concerns 
about breast and bladder cancers.
CONCLUSIONS: Dapagliflozin appears effective in reducing HbA1c and weight in 
type 2 diabetes, although more safety data are needed.