Canagliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, for the Management of Type 2 Diabetes

Brunton, Stephen; Reid, Timothy

doi:10.3810/hp.2014.08.1122

Cited by 6 publications

(7 citation statements)

References 54 publications

(125 reference statements)

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“…Across phase III trials, canagliflozin was generally well tolerated (Table 1). [32][33][34][35][36][37][38][39][40][41][42][43][44]50,51 The incidence of discontinuations due to adverse events (AEs) was low overall, but slightly higher with canagliflozin compared with control due to an increased incidence of specific AEs likely related to canagliflozin's mechanism of action. The incidence of serious AEs was similar across treatment groups in all studies.…”

Section: Overall Safety and Tolerabilitymentioning

confidence: 99%

Canagliflozin: a sodium glucose co‐transporter 2 inhibitor for the treatment of type 2 diabetes mellitus

Rosenthal

Meininger

Ways

et al. 2015

Annals of the New York Academy of Sciences

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The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin is a novel treatment option for adults with type 2 diabetes mellitus (T2DM). In patients with hyperglycemia, SGLT2 inhibition lowers plasma glucose levels by reducing the renal threshold for glucose (RT G ) and increasing urinary glucose excretion (UGE). Increased UGE is also associated with a mild osmotic diuresis and net caloric loss, which can lead to reductions in body weight and blood pressure (BP). After promising results from preclinical and phase I/II studies, the efficacy and safety of canagliflozin was evaluated in a comprehensive phase III development program in over 10,000 patients with T2DM on various background therapies. Canagliflozin improved glycemic control and provided reductions in body weight and BP versus placebo and active comparators in studies of up to 2 years' duration. Canagliflozin was generally well tolerated, with higher incidences of adverse events (AEs) related to the mechanism of action, including genital mycotic infections and AEs related to osmotic diuresis. Results from the preclinical and clinical studies led canagliflozin to be the first-in-class SGLT2 inhibitor approved in the United States, and support canagliflozin as a safe and effective therapeutic option across a broad range of patients with T2DM.

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Section: Overall Safety and Tolerabilitymentioning

confidence: 99%

Canagliflozin: a sodium glucose co‐transporter 2 inhibitor for the treatment of type 2 diabetes mellitus

Rosenthal

Meininger

Ways

et al. 2015

Annals of the New York Academy of Sciences

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“…The newer agent was SGLT-2 inhibitor that inhibited the reabsorption of glucose in the kidney independent of insulin. 18 , 38 The first SGLT-2 inhibitor, dapagliflozin was approved by the European Medicines Agency (EMA) at the end of 2012. However, the US Food and Drug Administration (FDA) granted marketing to canagliflozin first and later dapagliflozin owing to safety concerned on the increased risk of bladder and breast cancer.…”

Section: Second Line Agent After Metforminmentioning

confidence: 99%

What's next after metformin? focus on sulphonylurea: add-on or combination therapy

Lim¹,

Chong²

2015

Pharm Pract (Granada)

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Introduction:The pathophysiology of type 2 diabetes (T2DM) mainly focused on insulin resistance and insulin deficiency over the past decades. Currently, the pathophysiologies expanded to ominous octet and guidelines were updated with newer generation of antidiabetic drug classes. However, many patients had yet to achieve their target glycaemic control. Although all the guidelines suggested metformin as first line, there was no definite consensus on the second line drug agents as variety of drug classes were recommended.Objectives:The aim of this review was to evaluate the drug class after metformin especially sulphonylurea and issues around add-on or fixed dose combination therapy.Methods:Extensive literature search for English language articles, clinical practice guidelines and references was performed using electronic databases.Results:Adding sulphonylurea to metformin targeted both insulin resistance and insulin deficiency. Sulphonylurea was efficacious and cheaper than thiazolidinedione, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide 1 analogue and insulin. The main side effect of sulphonylurea was hypoglycaemia but there was no effect on the body weight when combining with metformin. Fixed dose sulphonylurea/metformin was more efficacious at lower dose and reported to have fewer side effects with better adherence. Furthermore, fixed dose combination was cheaper than add-on therapy.In conclusion, sulphonylurea was feasible as the second line agent after metformin as the combination targeted on two pathways, efficacious, cost-effective and had long safety history. Fixed dose combination tablet could improve patient’s adherence and offered an inexpensive and more efficacious option regardless of original or generic product as compared to add-on therapy.

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“…Similar glycemic and nonglycemic efficacies were reported in comparison to other SGLT-2 inhibitors. [ 4 5 6 ] With the simple mechanism of discarding glucose into the urine (correcting glucotoxicity),[ 7 ] canagliflozin was shown to ameliorate impaired beta-cell function and insulin resistance. [ 4 5 6 ] Canagliflozin has been shown to possess some nonglycemic benefits such as weight reduction, blood pressure control, diuretic action, renal protection, and uric acid (UA) reduction.…”

Section: Introductionmentioning

confidence: 99%

“…[ 4 5 6 ] With the simple mechanism of discarding glucose into the urine (correcting glucotoxicity),[ 7 ] canagliflozin was shown to ameliorate impaired beta-cell function and insulin resistance. [ 4 5 6 ] Canagliflozin has been shown to possess some nonglycemic benefits such as weight reduction, blood pressure control, diuretic action, renal protection, and uric acid (UA) reduction. [ 4 5 6 ] However, as expected from its mechanism of action, this drug is associated with higher incidence of certain adverse events including genital mycotic infections, urinary tract infections, osmotic diuretic-related adverse events, and volume depletion-related adverse events.…”

Section: Introductionmentioning

confidence: 99%

“…[ 4 5 6 ] Canagliflozin has been shown to possess some nonglycemic benefits such as weight reduction, blood pressure control, diuretic action, renal protection, and uric acid (UA) reduction. [ 4 5 6 ] However, as expected from its mechanism of action, this drug is associated with higher incidence of certain adverse events including genital mycotic infections, urinary tract infections, osmotic diuretic-related adverse events, and volume depletion-related adverse events. [ 8 ] Canagliflozin and other SGLT-2 inhibitors are currently used as add-on therapy to metformin or other drugs as part of dual or triple therapy.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of metabolic parameters in responders and nonresponders treated with canagliflozin monotherapy in drug-naive subjects with Type 2 diabetes

Kutoh

Wada

Murayama³

et al. 2018

Indian J Endocr Metab

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Objectives:The aim of this project is to compare the effect of canagliflozin monotherapy on metabolic parameters between responders and nonresponders with this drug. This study is a prospective, unblinded, observational study.Subjects and Methods:Drug-naïve patients with type 2 diabetes mellitus received only 50–100 mg/day canagliflozin for 3 months (n = 39). They were divided into two groups according to the novel “A1c index” to assess glycemic efficacies; responders (n = 24) and nonresponders (n = 15).Results:At baseline, glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) were significantly higher and homeostatic model assessment (HOMA)-B and body mass index (BMI) were significantly lower in responders. In both groups, similar, significant reductions of BMI (−1.9% with responder and −1.8% with nonresponder) and HOMA-R (−35.8% for responder and –31.5% for nonresponder) were observed. However, differences were seen with other parameters as follows: 1) responders: significant reductions of HbA1c (10.95%–8.44%), FBG (−29.6%) or free fatty acid (FFA) (−16.2%), and significant increases of HOMA-B (79.7%) were observed. 2) Nonresponders: significant reductions of serum uric acid (UA) (−8.6%) levels were seen. Significant correlations were observed between the baseline levels of serum UA and those of HOMA-B (R = 0.7259). However, this link became uncorrelated with the treatment with canagliflozin.Conclusions:These results suggest that (1) responders with canagliflozin have lower BMI and beta-cell function. Reductions of body weight with canagliflozin were not associated with its glycemic efficacy, (2) reduced FFA levels and enhanced insulin sensitivity/beta-cell function could be a potential mechanism of good glycemic efficacy of canagliflozin, and (3) serum UA might be involved in modulating beta-cell function during canagliflozin treatment.

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Canagliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, for the Management of Type 2 Diabetes

Cited by 6 publications

References 54 publications

Canagliflozin: a sodium glucose co‐transporter 2 inhibitor for the treatment of type 2 diabetes mellitus

Canagliflozin: a sodium glucose co‐transporter 2 inhibitor for the treatment of type 2 diabetes mellitus

What's next after metformin? focus on sulphonylurea: add-on or combination therapy

Characterization of metabolic parameters in responders and nonresponders treated with canagliflozin monotherapy in drug-naive subjects with Type 2 diabetes

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