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

Abstract

ObjectiveBecause 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.DesignSystematic review and network meta-analysis.Data sourcesMEDLINE and EMBASE were searched from January 2005 to January 2015.Eligibility criteriaRandomised 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.ResultsIn 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).ConclusionsThere 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.

Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

“…SGLT2-i are widely studied and several reviews and meta-analyses have recently been published [34–36]. Compared to these studies our systematic review with meta-analysis has distinct differences in the dosages and outcomes that we address.…”

“…In contrast to previous meta-analyses evaluating the effects of SGLT2-i in type 2 diabetes, we only included trials, which used the recommended maximum daily doses of the SGLT2-i [24–36] as we expect these dosages to be the most widely used in the clinic [4–10]. Lower or higher doses of SGLT2-i might overestimate or underestimate the efficacy or the risk of adverse events.…”

Comparative effectiveness and safety of empagliflozin on cardiovascular mortality and morbidity in adults with type 2 diabetes

“…Older meta-analyses focused on intermediate outcomes of empagliflozin when compared with placebo; e.g., HbA1c, blood pressure, and body weight (7)(8)(9)(10)(11)(12)(13)(14)(15). The most recent high-quality meta-analyses included 13 (6) and 16 (5) randomized controlled trials (RCTs) that reported mortality and morbidity in adults with type 2 diabetes treated with empagliflozin but did not examine the comparative effectiveness of empagliflozin and other specific antidiabetic drugs (5,6).…”

Eficácia em longo prazo das gliflozinas versus gliptinas no tratamento do diabetes mellitus tipo 2 após falência da metformina como monoterapia: revisão sistemática e metanálise em rede

“…A literatura indica um risco maior de infecção urinária e genital na classe das gliflozinas (78), estudos recentes tem indicado também um perfil cardiovascular benéfico para as mesmas (142,144). O custo efetividade das classes ainda precisa ser estudado na população brasileira.…”

“…Até o momento, algumas revisões sistemáticas e metanálises publicadas comparam a eficácia de diferentes fármacos entre as classes das gliptinas e gliflozinas após a falência do tratamento com metformina (71)(72)(73)(74)(75)(76)(77), porém o tempo máximo de análise foi de dois anos (78). Essas duas novas classes terapêuticas recém introduzidas no tratamento para o DM2 precisam de mais estudos, principalmente no que diz respeito ao perfil de segurança e eficácia em longo prazo.…”