A Network Meta-Analysis (NMA) to Assess the Longer-Term Relative Efficacy of Canagliflozin in Patients with Type 2 Diabetes Inadequately Controlled on Metformin

Abstract

Objectives: To assess the relative efficacy of canagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2) as add-on to insulin +/-oral antihyperglycaemic drugs for the treatment of T2DM compared to dipeptidyl peptidase-4 inhibitors (DPP-4s), glucagon-like peptide-1 receptor agonists (GLP-1s), sulphonylureas, pioglitazone, and other SGLT2 inhibitors, using Bayesian NMA methods. MethOds: A systematic literature review was conducted according to NICE guidelines and available data on HbA1c, weight and systolic blood pressure (SBP) were extracted. Networks were based on treatment-and dose-specific nodes, except for sulphonylureas where doses were combined. Selection of fixed versus random effects was based on the deviance information criterion. Results were interpreted based on absolute differences and Bayesian probabilities for treatments to perform better than others (P), where P≤ 30% indicated a smaller effect and P≥ 70% a larger effect. Results: Eighteen trials reported results at 26 +/-4 weeks. HbA1c reductions were highest for liraglutide 1.8mg, pioglitazone 45mg and glibenclamide. Canagliflozin 300mg had greater HbA1c reductions than all remaining comparators, except for exenatide where the reduction was similar. Canagliflozin 100mg had a greater reduction than dapagliflozin 5mg, vildagliptin, saxagliptin and lixisenatide and a similar reduction versus DPP-4s, glimepiride, lixisenatide, pioglitazone 30mg, metformin and dapagliflozin 10mg. Both dosages of canagliflozin were associated with greater weight loss than DPP-4s, glibenclamide, pioglitazone 30mg and dapagliflozin (Δ = -2.13 to -3.45kg; Δ = -7.61 to -8.25kg; Δ = -3.34 to -3.95kg; Δ = -0.44 to -1.73kg, respectively). Weight reductions were highest for liraglutide 1.8mg and exenatide 10μ g. Both dosages of canagliflozin had higher SBP reductions than dapagliflozin and saxagliptin; at least similar reductions were estimated versus exenatide 10μ g. cOnclusiOns:These results suggest that canagliflozin is a valuable treatment option as add-on to insulin therapy, as it provides not only similar or better glucose lowering than many other options, but also weight loss.

Safe and pragmatic use of sodium–glucose co-transporter 2 inhibitors in type 2 diabetes mellitus: South Asian Federation of Endocrine Societies consensus statement

“…[68] Canagliflozin has superiority over sitagliptin as greater proportion of patients receiving canagliflozin achieved composite target of A1c <7.5% and body weight reduction >3% (37.5%, 45%, and 19.2% proportion of patients achieving composite end point with canagliflozin 100 mg, canagliflozin 300 mg, and sitagliptin 100 mg, respectively). [8586878889] Similar results were observed with canagliflozin as compared with glimepiride as add-on to metformin at 52 weeks (72.4% with canagliflozin 100 mg, 78.5% with canagliflozin 300 mg, and 26.8% with glimepiride). [90] Furthermore, in an NMA of dual therapy studies, A1c reductions were greater for canagliflozin 300 mg and similar for 100 mg in comparison with glucagon-like peptide 1 receptor agent (GLP-1 RA).…”

“…[91] In an NMA of long-term studies (over 2 years) in patients (RCTs = 11) treated with canagliflozin as add-on to metformin, A1c reduction was greater for canagliflozin 300 mg compared with liraglutide 1.8 and 1.2 mg; weight reductions were similar between both the groups. In addition, glycemic efficacy was greater for canagliflozin 300 mg compared to dapagliflozin 10 and 5 mg and empagliflozin 25 mg.[89] In a study, dapagliflozin plus metformin therapy was noninferior and associated with reduction in body weight and fewer hypoglycemia versus glipizide plus metformin over 4 years. [7792] In combination with metformin, empagliflozin (25 mg once daily) was compared to glimepiride as the second-line agent.…”

A review of clinical efficacy and safety of canagliflozin 300 mg in the management of patients with type 2 diabetes mellitus

“…Across studies, patients received canagliflozin (100 and 300 mg), dapagliflozin (10 mg), empagliflozin (10 and 25 mg), exenatide (5, 10, and 20 µg), liraglutide (1.2 and 1.8 mg), and pioglitazone 30 mg. Canagliflozin 300 mg as add-on therapy achieved more effective glycemic control versus DPP-4is,[798081] exenatide (5 and 10 µg),[80] and liraglutide (1.2 mg)[82] and was similar to liraglutide (1.8 mg) and exenatide (20 µg). [808183]…”

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

“…Nesta revisão, foram encontrados poucos estudos com segmento maior que dois anos, sendo que outros artigos já descreveram os efeitos terapêuticos das gliptinas e gliflozinas em um período menor ou igual a dois anos (77,127,128).…”

“…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.…”