Canagliflozin + metformin ER for the treatment of type 2 diabetes: the evidence to date

ABSTRACT

Introduction

Patients with type 2 diabetes (T2D) usually show progressive deterioration in glycemic control and sequential additions of therapy are generally needed. Many new options for glucose lowering therapy have been introduced recently and it is becoming common practice to use fixed-dose combinations (FDCs) of glucose lowering agents from different classes. This article reviews the FDC of canagliflozin with metformin extended release.

Areas covered

A literature search was performed to identify publications describing the efficacy and safety of canagliflozin and metformin when used separately and in combinations.

Expert opinion

Canagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor which has shown benefits in reducing progression of renal disease and heart failure in patients with T2D. There was an increased incidence of amputation with canagliflozin in one study, but canagliflozin results in weight loss and reduction of blood pressure which contribute to the overall benefit. Metformin has been the first line oral hypoglycemic agent for many years and is thought to have many advantages, but it should be avoided in patients with severely decreased renal function because of the risk of lactic acidosis. The combination in a single tablet given once daily should help to simplify therapy and improve medication adherence in T2D.

KEYWORDS:

• Canagliflozin
• fixed-dose combination
• metformin
• SGLT2 inhibitor
• type 2 diabetes

Article highlights

• Canagliflozin and metformin have complementary mechanisms of action and the combination provides additional reductions in HbA1c compared to each drug used alone

• The addition of canagliflozin to metformin provides greater and more durable reductions in HbA1c compared to adding some other classes of oral glucose lowering agents

• The combination has the combined contraindications of each drug separately but there is little increase in the risk for hypoglycemia compared to the individual components

• Canagliflozin has been shown to have cardiovascular and renal protective effects and is indicated for patients at increased risk for these events

• The FDC with once daily dosing should improve adherence to long-term therapy

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Pharmaserve Lilly, and Novo Nordisk; for advisory boards from Novo Nordisk and Boehringer Ingelheim and have participated in sponsored studies by Eli-Lilly and Novo Nordisk. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was funded by a grant for the “Overseas Famous Teachers” Project of Guangdong Provincial Department of Science and Technology and Research Funding from the Faculty of Medicine, Macau University of Science and Technology.