Effects of SGLT-2 inhibitors on diabetic ketoacidosis: A meta-analysis of randomised controlled trials

Monami, Matteo; Nreu, Besmir; Zannoni, Stefania; Lualdi, Carlotta; Mannucci, Edoardo

doi:10.1016/j.diabres.2017.04.017

Cited by 96 publications

(67 citation statements)

References 16 publications

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“…A recent literature review analysed RCTs, cohort studies, case reports and pharmacovigilance database studies53: DKA incidence was less than 1/1000 in RCTs (in line with data from an MA54) and 1.6/1000 person‐years in cohort studies. In case reports and in pharmacovigilance databases, duration of SGLT2‐I treatment before DKA onset was extremely variable; overall, DKA is a rare adverse event during SGLT2‐I therapy, with fatal episodes representing 1.6% of all reported cases 55.…”

Section: Observational Findings: What's Missing?mentioning

confidence: 67%

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Raschi

Poluzzi

Fadini

et al. 2018

Diabetes Obesity Metabolism

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Sodium glucose co‐transporter‐2 inhibitors have attracted the interest of the scientific community following the results from dedicated cardiovascular outcome trials, which demonstrated remarkable reduction in all‐cause mortality and other cardiovascular (CV) endpoints with empagliflozin and canagliflozin. These impressive results raised further expectations on real world data from large observational cohort studies. They were designed to address the possible existence of a class effect, and the uncertainty on whether this benefit can be extended from secondary to primary CV prevention of patients with type 2 diabetes. In this review, we collated data from existing observational studies (including the celebrated CVD‐REAL cohorts) and critically appraised results and methodological issues with the aim of providing clinical insight, including unsettled aspects, and proposing a research agenda for future investigations.

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Section: Observational Findings: What's Missing?mentioning

confidence: 67%

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Raschi

Poluzzi

Fadini

et al. 2018

Diabetes Obesity Metabolism

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show abstract

“…An increase in the risk of diabetic ketoacidosis was also observed by Fralick et al in > 76,000 commercially insured T2D patients in the United States taking SGLT2 inhibitors compared to those using DPP4 inhibitors (hazard ratio for diabetic ketoacidosis, 2.2 95% CI 1.4-3.6) 95 . In contrast, a separate meta-analysis of completed clinical trials in >10,000 T2D patients reported a reduction in risk of diabetic ketoacidosis, while a third administrative database analysis in >150,000 T2D patients reported an overall neutral risk of diabetic ketoacidosis, highlighting that more data are needed to better understand this rare but potentially serious risk 105–107 .…”

Section: Sglt2 Inhibition and Potential Side Effectsmentioning

confidence: 93%

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure

et al. 2017

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Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin – a sodium glucose co-transporter 2 (SGLT2) inhibitor. The CANVAS trial subsequently reported a reduction in 3-point MACE (major adverse cardiovascular events) and HF hospitalization risk. While SGLT2 inhibition may have potential application beyond T2D, including HF, the mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, as well as decreases in blood pressure, arterial stiffness and afterload, thereby improving subendocardial blood flow in patients with HF. SGLT2 inhibition is also associated with preservation of renal function. Based on data from mechanistic studies and clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use of SGLT2 inhibition in patients with HF with and without T2D. Accordingly, in this review, we summarize key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence which support the rationale for the use of SGLT2 inhibitors in HF patients with T2D. Since presumably these favorable effects occur independent of blood-glucose lowering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at risk of HF, such as in patients with coronary artery disease or hypertension. Finally, we provide a detailed overview and summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors.

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“…However, a meta-analysis in 2017 compared 72 trials of sodium-glucose cotransporter 2 inhibitors that reported information about DKA and found no significant increased risk for ketoacidosis with inhibitor use either individually or given as a class of molecules (12).…”

Section: Discussionmentioning

confidence: 99%

Steroid-Induced Diabetic Ketoacidosis in a Patient with Type 2 Diabetes Mellitus

Tiwari

Al-Robeh

Sharma

et al. 2018

AACE Clinical Case Reports

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Effects of SGLT-2 inhibitors on diabetic ketoacidosis: A meta-analysis of randomised controlled trials

Cited by 96 publications

References 16 publications

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Observational research on sodium glucose co‐transporter‐2 inhibitors: A real breakthrough?

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure

Steroid-Induced Diabetic Ketoacidosis in a Patient with Type 2 Diabetes Mellitus

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