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Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus.

ABSTRACT: BACKGROUND:Sodium-glucose cotransporter (SGLT) 2 inhibitors were recently approved as glucose-lowering interventions in people with type 2 diabetes mellitus (T2DM). Potential beneficial or harmful effects of SGLT 2 inhibitors in people at risk for the development of T2DM are unknown. OBJECTIVES:To assess the effects of SGLT 2 inhibitors focusing on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose or moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of ongoing for information about additional trials. The date of the last search of all databases was January 2016. SELECTION CRITERIA:Randomised controlled trials (RCTs) of any duration comparing SGLT 2 inhibitors with any glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS:Two review authors read all abstracts, assessed quality and extracted data independently. We resolved discrepancies by consensus or the involvement of a third author. MAIN RESULTS:We could not include any RCT in this systematic review. One trial was published in two abstracts, but did not provide separate information of the participants with impaired glucose tolerance, impaired fasting glucose or both. We identified two ongoing trials, both evaluating the effects of dapagliflozin (and metformin) in people at risk for the development of type 2 diabetes and a follow-up of 24 to 26 weeks. Both trials will mainly report on surrogate outcome measures with some data on adverse effects and health-related quality of life. AUTHORS' CONCLUSIONS:Due to lack of data it is not possible to conclude whether SGLT 2 inhibitors prevent or delay the diagnosis of T2DM and its associated complications.

SUBMITTER: Hemmingsen B

PROVIDER: S-EPMC6486006 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus.

Hemmingsen Bianca B Krogh Jesper J Metzendorf Maria-Inti MI Richter Bernd B

The Cochrane database of systematic reviews 20160421

<h4>Background</h4>Sodium-glucose cotransporter (SGLT) 2 inhibitors were recently approved as glucose-lowering interventions in people with type 2 diabetes mellitus (T2DM). Potential beneficial or harmful effects of SGLT 2 inhibitors in people at risk for the development of T2DM are unknown.<h4>Objectives</h4>To assess the effects of SGLT 2 inhibitors focusing on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glu ...[more]

PMID: 27101360

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Project description:Diabetic kidney disease (DKD) occurs in approximately 20-40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (-?21.0%, confidence interval [CI]?-?34.1 to?-?5.2, p?=?0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52-0.86; p?=?0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48-0.64, p?<?0.0001) with SGLT2i, irrespective of baseline estimated glomerular filtration rate. Thus, there is emerging evidence that SGLT2i may be used to curb the mortality and improve the quality of life in patients with DKD. However, clinicians need to effectively select candidates for SGLT2i therapy. In this consensus statement, we have qualitatively synthesized evidence demonstrating the renal effects of SGLT2i and proposed recommendations for optimal use of SGLT2i to effectively manage and delay progression of DKD.

Project description:BACKGROUND:Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor. METHODS:We developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of P<0.001 were included in the risk score. We externally validated the score in 8578 patients with T2DM in the placebo arm of DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58). The relative and absolute risk reductions in HHF with the sodium-glucose cotransporter-2 inhibitor dapagliflozin were assessed by baseline HHF risk. RESULTS:Five clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0-7 points) using these predictors identified a >20-fold gradient of HHF risk (P for trend <0.001) in both the derivation and validation cohorts, with C indices of 0.81 and 0.78, respectively. Although relative risk reductions with dapagliflozin were similar for patients across the risk scores (25%-34%), absolute risk reductions were greater in those at higher baseline risk (1-sided P for trend=0.04), with high-risk (2 points) and very-high-risk (?3 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively. CONCLUSIONS:Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01107886 and NCT01730534.

Dataset Information

Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus.

Publications

Sodium-glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus.

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