Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes

Giugliano, Dario; Longo, Miriam; Scappaticcio, Lorenzo; Caruso, Paola; Esposito, Katherine

doi:10.1186/s12933-021-01213-w

Cited by 29 publications

(24 citation statements)

References 78 publications

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“…All trials from the DAPA-HF with dapagliflozin, the EMPEROR-Reduced trial with empagliflozin, CANVAS with canagliflozin, the VERTIS-CV trial with ertugliflozin, and the SCORED trial with sotagliflozin consistently had a similar effect of the SGLT2 inhibitor on HF [125,126,[129][130][131]. A meta-analysis of trials that evaluated the effect of SGLT2 inhibitors on HF showed a 32% reduction in the risk of hospitalization for HF in the group with SGLT2 inhibitors [11].…”

Section: Glucose-lowering Medication and CV Outcomes In T2dmmentioning

confidence: 98%

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Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes

Yun

2021

Metabolism

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With the advances in diabetes care, the trend of incident cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) has been decreasing over past decades. However, given that CVD is still a major cause of death in patients with diabetes and that the risk of CVD in patients with T2DM is more than twice that in those without DM, there are still considerable challenges to the prevention of CVD in diabetes. Accordingly, there have been several research efforts to decrease cardiovascular (CV) risk in T2DM. Large-scale genome-wide association studies (GWAS) and clinical cohort studies have investigated the effects of factors, such as genetic determinants, hypoglycaemia, and insulin resistance, on CVD and can account for the unexplained CV risk in T2DM. Lifestyle modification is a widely accepted cornerstone method to prevent CVD as the first-line strategy in T2DM. Recent reports from large CV outcome trials have proven the positive CV effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with high CVD risk. Overall, current practice guidelines for the management of CVD in T2DM are moving from a glucocentric strategy to a more individualised patient-centred approach. This review will discuss the current epidemiologic trends of CVD in T2DM and the risk factors linking T2DM to CVD, including genetic contribution, hypoglycaemia, and insulin resistance, and proper care strategies, including lifestyle and therapeutic approaches.

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Section: Glucose-lowering Medication and CV Outcomes In T2dmmentioning

confidence: 98%

“…For instance, there is abundant evidence that lifestyle changes can effectively improve CV risk and prevent CVD events [7][8][9][10]. Furthermore, recent trials have shown that the use of newer antidiabetic medications can lead to a marked risk reduction of CVD in T2DM with high CVD risk [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes

Yun

2021

Metabolism

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“…The objective of the current study is to update previous meta‐analyses, adding data from the other completed placebo‐controlled cardiovascular (CV) and kidney outcomes trials of SGLT‐2is in patients with T2D, specifically dapagliflozin with DAPA‐CKD EMPEROR‐R (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction) and DAPA‐HF (Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure) trials, and sotaglifozin with SCORED (Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease) trial 7–9 . We focused on the effect of SGLT‐2is on major adverse cardiovascular events (MACE) and composite renal outcomes, leaving out their effect on hospitalization for heart failure, which has already been addressed 10 …”

Section: Introductionmentioning

confidence: 99%

Sodium‐glucose co‐transporter‐2 inhibitors for the prevention of cardiorenal outcomes in type 2 diabetes: An updated meta‐analysis

Giugliano

Longo

Caruso

et al. 2021

Diabetes Obesity Metabolism

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A meta-analysis of cardiorenal outcomes of sodium-glucose co-transporter-2 inhibitors (SGLT-2is) available in Europe or the United States in patients with type 2 diabetes (T2D) is presented. An electronic search up to 6 January 2021 was conducted to determine eligible trials. A total of eight cardiorenal outcomes trials of SGLT-2is (empagliflozin, canagliflozin, dapagliflozin, ertugliflozin and sotagliflozin) were identified, with 65,587 patients. Data were analysed using a random effects model. Overall, SGLT-2is were associated with a 12% reduced risk of major adverse cardiovascular events (MACE; HR = 0.88; 95% CI, 0.83-0.93; Q statistic, p = .19), with no significant heterogeneity (p for interaction = .465) between subgroups of patients with or without cardiovascular disease (CVD). The risk of the composite renal outcome was significantly reduced by treatment with SGLT-2is (HR = 0.61, 95% CI, 0.54-0.70), with no significant heterogeneity of associations with outcome (I 2 = 37%, p = .11), and no difference in the risk between patients with or without CVD (p for interaction = .665). SGLT-2is have moderate benefits on MACE and major benefits on the progression of diabetic kidney disease.

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“…However, some previous reviews have identified anti-obesity effects of SGLT-2 inhibitors 32 , 33 . Among the studies included in the present meta-analysis, only canagliflozin caused a significant reduction in the incidence of MACE in the obesity sub-group of CREDENCE and CANVAS, while other SGLT-2 inhibitors did not 13 , 14 , 16 – 18 , and hypotheses have been proposed to explain this inconsistency in the effects of SGLT-2 inhibitors on the incidence of MACE 34 . In particular, SGLT-2 inhibitors differ in their selectivity for SGLT-2 and SGLT-1 35 .…”

Section: Discussionmentioning

confidence: 83%

Systematic review and meta-analysis for prevention of cardiovascular complications using GLP-1 receptor agonists and SGLT-2 inhibitors in obese diabetic patients

Uneda

Kawai

Yamada

et al. 2021

Sci Rep

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Patients with type 2 diabetes mellitus (T2DM) and obesity are at high risk of developing cardiovascular disease (CVD). Both glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter (SGLT-2) inhibitors have been shown to prevent CVD in T2DM patients. Additionally, the two drugs reduce body mass. However, it is unknown which drug is more effective at reducing the risk of CVD in such patients. We searched Medline, EMBASE, and Cochrane Library records to February 20, 2021 and performed a network meta-analysis to compare the efficacy with which the drugs reduced the risk of major adverse cardiovascular events (MACE). We included 102,728 patients in 12 studies containing data of obesity subgroup analyses. In T2DM patients with obesity, GLP-1 RAs significantly reduced the risk of MACE versus placebo (relative risk, RR [95% confidence interval, CI]: 0.88 [0.81–0.96]), whereas SGLT-2 inhibitors showed a tendency (RR [95% CI]: 0.91 [0.83–1.00]). In an indirect comparison, GLP-1 RAs were not associated with a significant difference in MACE compared with SGLT-2 inhibitors (RR [95% CI]: 0.97 [0.85–1.09]). Thus, GLP-1 RAs are effective at preventing MACE than placebo in T2DM patients with obesity, although further studies are warranted to conclude their superiority to SGLT-2 inhibitors.

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Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes

Cited by 29 publications

References 78 publications

Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes

Current trends in epidemiology of cardiovascular disease and cardiovascular risk management in type 2 diabetes

Sodium‐glucose co‐transporter‐2 inhibitors for the prevention of cardiorenal outcomes in type 2 diabetes: An updated meta‐analysis

Systematic review and meta-analysis for prevention of cardiovascular complications using GLP-1 receptor agonists and SGLT-2 inhibitors in obese diabetic patients

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