SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials

Zelniker, Thomas A; Wiviott, Stephen D.; Raz, Itamar; Im, KyungAh; Goodrich, Erica L.; Bonaca, Marc P.; Mosenzon, Ofri; Kato, Eri; Furtado, Remo H M; Bhatt, Deepak L.; Leiter, Lawrence A.; McGuire, Darren K.; Wilding, John; Sabatine, Marc S.

doi:10.1016/s0140-6736(18)32590-x

Cited by 2,239 publications

(2,029 citation statements)

References 36 publications

Supporting

Mentioning

1,834

Contrasting

Unclassified

105

Order By: Relevance

“…With consistent evidence of the beneficial effects of SGLT‐2is on CV risk and their strengthened position in guidelines, it is of high importance to understand the actual patient profiles in these CVOTs and, thereby, how representative of a general T2D population the included patient populations actually are . From the present analysis, it is clear that the main inclusion criteria, determining the baseline CV risk in the respective CVOT, are closely correlated to how representative of a general T2D population the trials are in comparison with each other.…”

Section: Discussionmentioning

confidence: 75%

“…Patients with type 2 diabetes are at increased risk of mortality and cardiovascular (CV) disease . Recent cardiovascular outcome trials (CVOTs) have shown clinically important results in reducing CV risk when using sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is), and further studies are upcoming . The generalizability of the results of clinical trials to common clinical practice is recognized as a major issue.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study

Birkeland

Bodegård

Norhammar

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aims Enrollment criteria vary substantially among cardiovascular outcome trials (CVOTs) of sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is), which impacts the relationship between a trial population and the general type 2 diabetes (T2D) population. The aim of this study was to evaluate the representativeness of four SGLT‐2i CVOTs of a general T2D population. Methods T2D patients from Germany, The Netherlands, Norway and Sweden were included in the study. Given the available data per country, key inclusion and exclusion criteria were defined by diagnoses, procedures and drug treatments to facilitate comparability among countries. Representativeness was determined by dividing the number of patients fulfilling the key enrolment criteria of each CVOT (CANVAS, DECLARE‐TIMI 58, EMPA‐REG OUTCOME, VERTIS‐CV) by the total T2D population. Results In 2015, a total T2D population of 803 836 patients was identified in Germany (n = 239 485), in The Netherlands (n = 36 213), in Norway (n = 149 782) and in Sweden (n = 378 356). These populations showed a 25% to 44% cardiovascular (CV) disease baseline prevalence and high CV‐preventive drug use (>80%). The general T2D population had less prevalent CV disease and patients were slightly older than those included in the CVOTs. The DECLARE‐TIMI 58 trial had the highest representativeness, 59% compared to the general T2D population, and this representativeness was almost 2‐, 3‐ and 4‐fold higher compared to the CANVAS (34%), EMPA‐REG OUTCOME (21%) and VERTIS‐CV (17%) trials, respectively. Conclusions In large T2D populations within Europe, consistent patterns of representativeness of CVOTs were found when applying the main enrolment criteria. The DECLARE‐TMI 58 trial had the highest representativeness, indicating that it included and examined patients who are most representative of the general T2D patients in the studied countries.

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study

Birkeland

Bodegård

Norhammar

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…A meta-analysis of these major trials released, at the same time as DECLARE-TIMI 58 concluded that “SGLT-2 inhibitors have moderate benefits on atherosclerotic MACE that seem confined to patients with established atherosclerotic CVD. However, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerotic CVD or a history of heart failure” [52]. …”

Section: A Review Of the Evidencementioning

confidence: 99%

Managing Cardiovascular Risk in Type 2 Diabetes: What Do the Cardiovascular Outcome Trials Mean for Australian Practice?

et al. 2019

View full text Add to dashboard Cite

Understanding the implications of cardiovascular (CV) outcomes data of glucose-lowering agents on the management of type 2 diabetes mellitus can be challenging for many primary practitioners. Amongst different classes of diabetes medications assessed for CV safety, several agents within the sodium-glucose transport protein-2 inhibitor and glucagon-like peptide-1 receptor agonists classes have demonstrated CV risk reduction. Applying the trial findings to patients typically seen in clinical practice, such as those with established CV disease and those with multiple CV risk factors without established CV disease, requires further clarity. To bridge this gap in our current knowledge, the aim of this review was to utilise expert-driven opinions on common case scenarios and practical recommendations on the most appropriate choice of agents, according to an individual patient’s clinical risk profile (CV and kidney disease), treatment preference and reimbursement environment from an Australian perspective.Funding: Boehringer Ingelheim Australia.

show abstract

“…Cholesterol lowering, hypertension management, smoking cessation programs, and bariatric surgery have shown significant benefits in reducing cardiovascular adverse events among patients with T2D. Although conventional antihyperglycemic therapy have failed to improve long‐term macrovascular outcomes, two new classes of antidiabetic medications, glucagon‐like peptide‐1 receptor agonists (GLP1ra) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), appear to exert macrovascular benefit among patients with T2D independent of their glycemic effect …”

Section: Introductionmentioning

confidence: 99%

Opportunities for improving use of evidence‐based therapy in patients with type 2 diabetes and cardiovascular disease

Gao

Peterson

Pagidipati

2019

Clinical Cardiology

View full text Add to dashboard Cite

Evidence‐based therapy that target hyperlipidemia, hypertension, smoking cessation, and weight loss have demonstrated significant benefits in reducing cardiovascular risks and related events. Although the benefit of intensively lowering blood glucose is unclear, newer antidiabetic drugs (glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors) have shown cardiovascular benefits in addition to their antihyperglycemic effect. Yet, studies suggest that recent use of evidence‐based therapy and management of cardiovascular risk among individuals with type 2 diabetes (T2D) and cardiovascular disease (CVD) remains largely suboptimal. The following narrative review first identifies barriers to translating research evidence to clinical practice at the levels of provider, health system, patient, and cost. Then it synthesizes previous implementation strategies that addressed multifaceted barriers and attempted to improve care for patients with T2D and CVD. In conclusion, team‐based care coordination, reminding systems in combination to pharmacist consultation and patient education, provider education compatible with clinical workflow, and coupled incentives between providers and patients appeared to be effective in reducing cardiovascular risks for patients with T2D and CVD, though the scalability and long‐term clinical effect of these strategies as well as the possibility of interventions involving payers and health systems remain uncertain.

show abstract

SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials

Cited by 2,239 publications

References 36 publications

How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study

How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study

Managing Cardiovascular Risk in Type 2 Diabetes: What Do the Cardiovascular Outcome Trials Mean for Australian Practice?

Opportunities for improving use of evidence‐based therapy in patients with type 2 diabetes and cardiovascular disease

Contact Info

Product

Resources

About