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The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Body Composition in Type 2 Diabetes Mellitus: A Narrative Review.

ABSTRACT: Body composition is related to cardiometabolic disorders and is a major driver of the growing incidence of type 2 diabetes mellitus (T2DM). Altered fat distribution and decreased muscle mass are related to dysglycemia and impose adverse health-related outcomes in people with T2DM. Hence, improving body composition and maintaining muscle mass is crucial in T2DM. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering medications gaining popularity because of their cardiorenal-protective effects and weight-lowering characteristics. However, reports on myopathy secondary to SGLT2 inhibitor treatment raised a safety concern. The importance of maintaining muscle mass in people with T2DM necessitates further investigation to explore the impact of novel medications on body composition. In this review, we discussed current evidence on the impact of SGLT2 inhibitors on body composition in people with T2DM.

SUBMITTER: Jahangiri S

PROVIDER: S-EPMC10597985 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Body Composition in Type 2 Diabetes Mellitus: A Narrative Review.

Jahangiri Soodeh S Malek Mojtaba M Kalra Sanjay S Khamseh Mohammad E ME

Diabetes therapy : research, treatment and education of diabetes and related disorders 20231014 12

Body composition is related to cardiometabolic disorders and is a major driver of the growing incidence of type 2 diabetes mellitus (T2DM). Altered fat distribution and decreased muscle mass are related to dysglycemia and impose adverse health-related outcomes in people with T2DM. Hence, improving body composition and maintaining muscle mass is crucial in T2DM. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering medications gaining popularity because of their cardiorenal ...[more]

PMID: 37837581

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Project description:Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The 'SGLT2i Prescribing Tool for T2DM Management', previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care.

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:BackgroundPatients 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.MethodsWe 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.ResultsFive 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.ConclusionsRisk 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 registrationURL: https://www.clinicaltrials.gov. Unique identifiers: NCT01107886 and NCT01730534.

Dataset Information

The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Body Composition in Type 2 Diabetes Mellitus: A Narrative Review.

Publications

The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Body Composition in Type 2 Diabetes Mellitus: A Narrative Review.

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