AIMS: To identify and synthesize phase 3 and phase 4 randomized controlled 
trials (RCTs) of sodium-glucose co-transporter (SGLT) inhibitors and metformin 
as adjuncts to insulin in type 1 diabetes (T1DM) using network meta-analysis 
(NMA).
MATERIALS AND METHODS: A systematic literature review (SLR) identified relevant 
RCTs of ≥12 Weeks duration. MEDLINE, Embase, the Cochrane Library and grey 
literature were searched through October 2018. NMAs indirectly compared SGLT 
inhibitors and metformin for change from baseline in HbA1c, weight, total daily 
insulin dose and systolic blood pressure at Week 24 to 26 and Week 52. Safety 
outcomes were also explored.
RESULTS: Nine trials (N = 6780) were included in the SLR. NMAs indicated that 
all therapies performed better than placebo for the efficacy outcomes at both 
time points. Compared with metformin at Week 24 to 26, the SGLT inhibitors 
dapagliflozin (5 mg), sotagliflozin (200 mg) and empagliflozin (10 mg) had 
larger reductions in HbA1c (mean difference [MD] = -0.24, 95% credible interval 
[CrI], -0.41 to -0.07, MD = -0.23, 95% CrI, -0.39 to -0.08 and MD = -0.35, 95% 
CrI, -0.51 to -0.19, respectively) and in weight, which were sustained in 
sensitivity analyses. There were few differences observed in the results of 
safety outcomes, such as risk of diabetic ketoacidosis (DKA), which should be 
interpreted cautiously because of wide CrIs.
CONCLUSIONS: Adjunctive use of SGLT inhibitors in T1DM can improve glycaemic 
control compared with metformin while enabling weight loss, with consistent 
efficacy across the class. However, these results are based on indirect evidence 
so confirmation in a head-to-head study would be valuable.