SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis

Abstract

Objective: Because of the lack of head-to-head trials, the aim was to indirectly compare sodium glucose transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes.

Design: Systematic review and network meta-analysis.

Data sources: MEDLINE and EMBASE were searched from January 2005 to January 2015.

Eligibility criteria: Randomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy. Minimum duration 24 weeks. Indirect comparison was undertaken using Bayesian methods.

Results: In monotherapy, a greater proportion of patients achieved a glycated haemoglobin (HbA1c) level of <7% on canagliflozin 300 mg than on canagliflozin 100 mg (risk ratio (RR) 0.72%, 95% credible intervals (CrI) 0.59% to 0.87%) and dapagliflozin 10 mg (RR 0.63, 95% CrI 0.48 to 0.85) but there were no significant differences compared with either dose of empagliflozin. In monotherapy, canagliflozin 300 mg reduced HbA1c more than other SGLT-2 inhibitors (mean difference ranged from 0.20% to 0.64%). There were no significant differences in weight reduction. All the flozins reduced systolic blood pressure (SBP) more than placebo, ranging from a reduction of 6 mm Hg with canagliflozin 300-2.6 mm Hg with empagliflozin 10 mg. In dual therapy with metformin, all flozins were more effective than placebo for achieving HbA1c <7%, and reducing HbA1c, weight and SBP. The proportions achieving HbA1c level of <7% were mostly similar. Canagliflozin 300 mg reduced HbA1c more than the other drugs but this just reached statistical significance only against canagliflozin 100 mg (MD 0.15, CrI 0.04 to 0.26).

Conclusions: There were few differences among the SGLT-2 inhibitors, but in monotherapy, the glucose-lowering effect of canagliflozin 300 mg is slightly greater than most other SGLT-2 inhibitors.

Keywords: SGLT2 inhibitors; type 2 diabetes.

Figure 1

Study selection flow diagram.

Figure 2

Network plot—monotherapy (mean change in glygated haemoglobin).

Figure 3

Network plot—dual therapy (% of patients achieving glycated haemoglobin <7%).

Figure 4

Risk of bias.

Figure 5

Proportion of patients achieving HbA1c level of <7%—monotherapy. HbA1c, glycated haemoglobin; NA, not available; NMA, network meta-analysis.

Figure 6

Mean change in HbA1c (%)—monotherapy. HbA1c, glycated haemoglobin; NA, not available; NMA, network meta-analysis.

Figure 7

Mean change in weight (kg)—monotherapy. NA, not available; NMA, network meta-analysis.

Figure 8

Mean change in SBP (mm Hg)—monotherapy. NA, not available; NMA, network meta-analysis; SBP, systolic blood pressure.

Figure 9

Proportion of patients achieving HbA1c level of <7.0%—dual therapy. HbA1c, glycated haemoglobin; NA, not available; NMA, network meta-analysis.

Figure 10

Mean change in HbA1c (%)—dual therapy. HbA1c, glycated haemoglobin; NA, not available; NMA, network meta-analysis.

Figure 11

Mean change in weight (kg)—dual therapy. NA, not available; NMA, network meta-analysis.

Figure 12

Mean change in SBP (mm Hg)—dual therapy. NA, not available; NMA, network meta-analysis; SBP, systolic blood pressure.

Figure 13

Proportion of patients achieving HbA1c level of <7.0% (dual therapy), sensitivity analysis including Henry et al and Kashiwagi et al. HbA1c, glycated haemoglobin; NA, not available; NMA, network meta-analysis.

Figure 14

Mean change in weight (kg; dual therapy), sensitivity analysis including Bolinder et al, Henry et al 2012 and Kashiwagi et al. NA, not available; NMA, network meta-analysis.

Figure 15

Mean change in SBP (mm Hg; dual therapy), sensitivity analysis including Kashiwagi et al. NA, not available; NMA, network meta-analysis; SBP, systolic blood pressure.

Figure 16

Mean change in HbA1c (%; dual therapy), sensitivity analysis including Bolinder et al, Henry et al and Kashiwagi et al. HbA1c, glycated haemoglobin; NA, not available; NMA, network meta-analysis.