Canagliflozin in the treatment of type 2 diabetes: an evidence-based review of its place in therapy

Abstract

IntroductionDeciding on an optimal medication choice for type 2 diabetes is often challenging, due to the increasing number of treatment options. Canagliflozin is a novel glucose-lowering agent belonging to sodium–glucose co-transporter 2 (SGLT2) inhibitors.AimThe aim of this study was to examine and summarize the evidence based on the efficacy, safety, and cost-effectiveness of canagliflozin for type 2 diabetes.Evidence reviewCompared to placebo, canagliflozin 100 and 300 mg lower glycated hemoglobin (HbA1c) by ~0.6%–0.8%, respectively. Canagliflozin appears to be slightly more effective than dipeptidyl peptidase-4 (DPP-4) inhibitors in reducing HbA1c. It also has a favorable effect on body weight and blood pressure, both versus placebo and most active comparators. However, treatment with canagliflozin is associated with increased incidence of genital tract infections and osmotic diuresis-related adverse events. Based on short-term data, canagliflozin is not associated with increased risk for all-cause mortality and cardiovascular outcomes. Economic evaluation studies from various countries indicate that canagliflozin is a cost-effective option in dual- or triple-agent regimens.Place in therapyAs monotherapy, canagliflozin could be used in patients for whom metformin is contraindicated or not tolerated. For patients on background treatment with metformin, canagliflozin appears to be superior to sulfonylureas with respect to body weight, blood pressure and risk for hypoglycemia, and to DPP-4 inhibitors in terms of lowering HbA1c, body weight, and blood pressure. Canagliflozin also seems to be cost-effective compared with sulfonylureas and DPP-4 inhibitors as add-on to metformin monotherapy, and compared with DPP-4 inhibitors as add-on to metformin and sulfonylurea.ConclusionCurrent evidence on intermediate efficacy outcomes, short-term safety and cost-effectiveness support the use of canagliflozin in patients on background treatment with metformin. Robust long-term data regarding the effect of canagliflozin on cardiovascular endpoints will be available upon completion of the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial.

Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM)

“…Furthermore, in this study, the number of insulin units could be markedly reduced, suggesting the blood glucose-lowering effects of canagliflozin cover a decrease in the dose of insulin. In addition, it was considered to be cost-effective [ 12 ].…”

Evidence-Based Clinical Review on Cardiovascular Benefits of SGLT2 (Sodium-Glucose Co-Transporter Type 2) Inhibitors in Type 2 Diabetes Mellitus

“…The reduction in 3P-MACE for a composite score came out lower than the EMPA-REG trial, though the participants in both the trials received statins or lipid-lowering medication, antiplatelet, and renin-angiotensin-aldosterone inhibitors (RAASi) [ 7 ]. A meta-analysis of six RCTs assessed the efficacy of canagliflozin along with metformin monotherapy and was found that administration of canagliflozin reduces HbA1c [ 19 ], but it was found to be associated with an increased risk of below-knee amputation as compared to the placebo. Thus, it is imperative to assess the patients thoroughly before giving the drug [ 25 ].…”

“…Similar to the EMPA-REG-OUTCOME trial, various other clinical trials have been carried out among different populations and by administering different types of SGLT2i and have reported cardioprotective effects of these anti-diabetic drugs [ 15 - 17 ]. Moreover, the first renal outcome trial on SGLT2i has reported positive renal and CV benefits as well [ 18 , 19 ].…”

Pharmacological evaluation of HM41322, a novel SGLT1/2 dual inhibitor, in vitro and in vivo

“…Several SGLT2 inhibitors, such as empagliflozin [20], canagliflozin [21], and dapagliflozin [22], have been clinically used as antidiabetic drugs. Numerous reports have provided evidence to support their usefulness in reducing hyperglycemia by increasing urinary glucose excretion, both in nonclinical animal models [1823] and in patients with type 2 diabetes [1124].…”