Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern

Gelaye, Alehegn; Haidar, Abdallah; Kassab, Christina; Kazmi, Syed Omar; Sinha, Prabhat

doi:10.1155/2016/1656182

Cited by 22 publications

(26 citation statements)

References 9 publications

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“…We retrieved a total of 105 episodes of DKA in patients receiving SGLT2i from May 2014 to April 2017 . Demographic characteristics, type of diabetes and type of SGLT2i are reported in Table .…”

Section: Review Of the Literaturementioning

confidence: 99%

Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

Bonora

Avogaro

Fadini

2017

Diabetes Obesity Metabolism

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Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are increasingly used for the treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1 diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2is may cause diabetic ketoacidosis (DKA). We report details on 2 new cases of SGLT2i-associated DKA and review the literature for similar cases within randomized controlled trials (RCTs), cohort studies and single reports. We searched the medical literature for reports of SGLT2i-associated DKA cases. A quantitative analysis of frequency and clinical characteristics is reported. The 2 narrative cases illustrate that SGLT2i-associated DKA can occur in patients with T1D incorrectly diagnosed as T2D, perhaps without the presence of obvious DKA precipitating factors. The incidence of SGLT2i-associated DKA was less than 1/1000 in randomized controlled trials and 1.6/1000 person-years in cohort studies. We retrieved detailed data on 105 SGLT2i-associated DKA case reports, wherein 35% showed glucose levels of less than 200 mg/dL and 22% were not associated with typical triggers. In case reports and in pharmacovigilance databases, duration of SGLT2i treatment before DKA onset was extremely variable. Fatal SGLT2i-associated DKA episodes were found only in pharmacovigilance databases and represented 1.6% of all reported cases. DKA is a rare adverse event during SGLT2i therapy. Predisposing and precipitating factors are still incompletely understood, although a minority of cases lacked typical DKA triggers. More narrative case series and cohort studies are needed to better understand the true risk and the spectrum of this adverse event.

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Section: Review Of the Literaturementioning

confidence: 99%

Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

Bonora

Avogaro

Fadini

2017

Diabetes Obesity Metabolism

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“…SGLT 2 inhibitor is the newest class of anti diabetic medications approved recently by the US food and drug agency to be used in conjunction with diet and exercise for treatment of type 2 diabetes mellitus [1]. Canagliflozin, dapagliflozin and empaglifilozin are the SGLT-2 inhibitors currently approved by the FDA [2].…”

Section: Discussionmentioning

confidence: 99%

“…The most common adverse reactions associated with canagliflozin are genital mycotic infections, urinary tract infections, osmotic diuresis, and reduced intravascular volume [1] but FDA revised the labels more recently to include warnings and precautions about the risks of ketoacidosis with SGLT 2 inhibitors [6].…”

Section: Discussionmentioning

confidence: 99%

“…In March 2013, first Sodium-glucose co-transporter-2 (SGLT-2) inhibitor, canagliflozin, was approved for the treatment of type 2 diabetes mellitus by the US food and drug agency (FDA) (1). SGLT-2 inhibitors reversibly inhibit the SGLT-2 located in the proximal convoluted tubule of the kidney where 90% of filtered sodium and glucose is reabsorbed.…”

Section: Introductionmentioning

confidence: 99%

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A Case of Euglycemic Diabetic Ketoacidosis due to Canagliflozin Complicated by Takotsubo Cardiomyopathy

Khan¹,

Khalid²,

Marwat³

et al. 2018

AJMCR

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Sodium-glucose co-transporter-2 (SGLT-2) inhibitor is the latest class of anti diabetic medication that improves glycemic control in insulin independent fashion by increasing urinary loss of filtered glucose. Since its introduction in 2013, several cases of euglycemic DKA have been reported in patients being treated with SGLT-2 inhibitors. Blood glucose levels in range lower than expected for DKA makes the diagnosis challenging if clinical suspicion for euglycemic DKA is not high. We report a case of a patient being treated with canagliflozin who presented with DKA, AKI and mild hyperglycemia that was complicated by stress-induced cardiomyopathy.

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“…Some cases of DKA in T2DM patients were euglycemic 58–60. Other cases of DKA were associated with off-label use of SGLT2 inhibitors in patients with type 1 diabetes mellitus 58,61,62. SGLT2 inhibitor clinical trials reported low frequencies of DKA in T2DM: canagliflozin events by treatment group were 0.07% (4/5,337), 0.11% (6/5,350), and 0.03% (2/6,909) for 100 mg, 300 mg, and comparator, respectively;63 dapagliflozin events were <0.1% in >18,000 patients (no further details stated);64 and DKA events with empagliflozin by treatment group were 2 events for 10 mg and 1 event for 25 mg, vs 5 events for placebo (N>13,000 T2DM patients; treatment group sizes not stated) 64.…”

Section: Summary Of Mechanisms Efficacy and Safetymentioning

confidence: 99%

Sodium-glucose cotransporter 2 inhibitors combined with dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: a review of current clinical evidence and rationale

Yassin

Aroda

2017

DDDT

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Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial cardiometabolic disorder. Almost half of adults with diabetes fail to achieve their recommended glucose control target. This has prompted some clinicians to advocate the use of more intensive initial therapy, including the use of combination therapy to target multiple physiologic defects in diabetes with the goal of achieving and sustaining glucose control. Numerous options exist for combining the various classes of glucose-lowering agents in the treatment of T2DM. This report reviews the mechanism, rationale, and evidence from clinical trials for combining two of the newer drug classes, namely, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors, and considers the possible role of such dual therapy in the management of T2DM.

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Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern

Cited by 22 publications

References 9 publications

Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: An updated review of the literature

A Case of Euglycemic Diabetic Ketoacidosis due to Canagliflozin Complicated by Takotsubo Cardiomyopathy

Sodium-glucose cotransporter 2 inhibitors combined with dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: a review of current clinical evidence and rationale

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