Sodium/Glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis: An Example of Complementary Evidence for Rare Adverse Events

Alkabbani, Wajd; Pelletier, Ryan; Gamble, John‐Michael

doi:10.1093/aje/kwab052

Cited by 9 publications

(21 citation statements)

References 35 publications

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“…However, these trials were limited by the small number of events and thus these findings do not rule out an increased risk of GTI. 66 Meta-analyses have reported an increased GTI risk associated with ipragliflozin use vs placebo. 7 , 44 For example, Liu et al reported that genital infections were 4.5 times more likely among ipragliflozin users vs placebo.…”

Section: Resultsmentioning

confidence: 99%

“…This also suggests the limitation of RCTs with small sample sizes to precisely estimate the risk of rare adverse events. 66 The totality of the evidence currently suggests about a doubling of risk for diabetic ketoacidosis for SGLT-2 inhibitor users compared to placebo or active comparator. 66 …”

Section: Resultsmentioning

confidence: 99%

“… 66 The totality of the evidence currently suggests about a doubling of risk for diabetic ketoacidosis for SGLT-2 inhibitor users compared to placebo or active comparator. 66 …”

Section: Resultsmentioning

confidence: 99%

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Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date

Alkabbani¹,

Gamble²

2021

DDDT

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Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a novel class of pharmacotherapeutics for type 2 diabetes management that work by reducing renal reabsorption of glucose. Ipragliflozin is a potent, selective SGLT-2 inhibitor used for the management of type 2 diabetes. Objective: The primary aim of this review is to summarize the available evidence on the efficacy and safety of ipragliflozin for the management of type 2 diabetes. We also review the discovery, pharmacokinetic, and pharmacodynamic profile of ipragliflozin. Methods: To inform our review, we searched MEDLINE, International Pharmaceutical Abstracts, and Embase to identify relevant papers to ipragliflozin use in type 2 diabetes. Clinical trial registries were also searched. Results: Findings from randomized clinical trials demonstrate that compared to placebo, ipragliflozin significantly reduces glucose as measured via Hemoglobin A1c and fasting plasma glucose levels. Ipragliflozin is also associated with weight reduction and an improvement in some, but not all, cardiovascular risk markers. Ipragliflozin has a favourable safety profile with a low risk of hypoglycemia and the rates of common adverse events are not significantly different than placebo. Limited data are available to assess rare and long-term adverse effects. Conclusion:Current evidence shows that ipragliflozin is an effective therapeutic option for the management of glucose control in type 2 diabetes. However, no cardiovascular outcome trials have been conducted to date. Real-world observational studies are still needed to accurately capture any possible rare or long-term adverse events.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date

Alkabbani¹,

Gamble²

2021

DDDT

Self Cite

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“…This is particularly relevant in resource-limited settings when patients with limited access to insulin and healthcare systems due to financial constraints present in severe ketoacidosis. The risk of DKA is also increased in patients with renal failure, during pregnancy, and in patients during fasting. , Sodium-glucose cotransporter-2 inhibitors have emerged as a highly effective treatment in patients with diabetes and heart failure with benefits on glycemia, renal function, cardiovascular outcomes, and all-cause mortality. , However, of concern, they have been associated with a twofold increase in the risk of developing ketoacidosis …”

Section: Introductionmentioning

confidence: 99%

“…7,8 However, of concern, they have been associated with a twofold increase in the risk of developing ketoacidosis. 9 The conventional method used to detect ketoacidosis requires a blood sample and access to a laboratory to measure the concentration of serum β-hydroxybutyrate. 10 Noninvasive and minimally invasive techniques, including radio-wave impedance, infrared spectroscopy, optical rotation of polarized light, and biosensors, have been proposed for monitoring blood glucose.…”

Section: Introductionmentioning

confidence: 99%

Breath Analysis for the In Vivo Detection of Diabetic Ketoacidosis

et al. 2022

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Human breath analysis of volatile organic compounds has gained significant attention recently because of its rapid and noninvasive potential to detect various metabolic diseases. The detection of ketones in the breath and blood is key to diagnosing and managing diabetic ketoacidosis (DKA) in patients with type 1 diabetes. It may also be of increasing importance to detect euglycemic ketoacidosis in patients with type 1 or type 2 diabetes or heart failure, treated with sodium-glucose transporter-2 inhibitors (SGLT2-i). The present research evaluates the efficiency of colorimetry for detecting acetone and ethanol in exhaled human breath with the response time, pH effect, temperature effect, concentration effect, and selectivity of dyes. Using the proposed multidye system, we obtained a detection limit of 0.0217 ppm for acetone and 0.029 ppm for ethanol in the detection range of 0.05−50 ppm. A smartphone-assisted unit consisting of a portable colorimetric device was used to detect relative red/green/blue values within 60 s of the interface for practical and real-time application. The developed method could be used for rapid, low-cost detection of ketones in patients with type 1 diabetes and DKA and patients with type 1 or type 2 diabetes or heart failure treated with SGLT2-I and euglycemic ketoacidosis.

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Comparison of statistical methods for integrating real‐world evidence in a rare events meta‐analysis of randomized controlled trials

Yao

Wang

Ren

et al. 2023

Research Synthesis Methods

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Rare events meta‐analyses of randomized controlled trials (RCTs) are often underpowered because the outcomes are infrequent. Real‐world evidence (RWE) from non‐randomized studies may provide valuable complementary evidence about the effects of rare events, and there is growing interest in including such evidence in the decision‐making process. Several methods for combining RCTs and RWE studies have been proposed, but the comparative performance of these methods is not well understood. We describe a simulation study that aims to evaluate an array of alternative Bayesian methods for including RWE in rare events meta‐analysis of RCTs: the naïve data synthesis, the design‐adjusted synthesis, the use of RWE as prior information, the three‐level hierarchical models, and the bias‐corrected meta‐analysis model. The percentage bias, root‐mean‐square‐error, mean 95% credible interval width, coverage probability, and power are used to measure performance. The various methods are illustrated using a systematic review to evaluate the risk of diabetic ketoacidosis among patients using sodium/glucose co‐transporter 2 inhibitors as compared with active‐comparators. Our simulations show that the bias‐corrected meta‐analysis model is comparable to or better than the other methods in terms of all evaluated performance measures and simulation scenarios. Our results also demonstrate that data solely from RCTs may not be sufficiently reliable for assessing the effects of rare events. In summary, the inclusion of RWE could increase the certainty and comprehensiveness of the body of evidence of rare events from RCTs, and the bias‐corrected meta‐analysis model may be preferable.

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Sodium/Glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis: An Example of Complementary Evidence for Rare Adverse Events

Cited by 9 publications

References 35 publications

Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date

Profile of Ipragliflozin, an Oral SGLT-2 Inhibitor for the Treatment of Type 2 Diabetes: The Evidence to Date

Breath Analysis for the In Vivo Detection of Diabetic Ketoacidosis

Comparison of statistical methods for integrating real‐world evidence in a rare events meta‐analysis of randomized controlled trials

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