SGLT2 inhibitors trials

The cardiorenal protection

Independent of glucose-lowering effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors to avoid interfering with the glucose reducing medications taken by a patient.

EMPA-REG Outcome trial 2015

Empagliflozin significantly lowered the risk for cardiovascular death and all-cause mortality in adults with type 2 diabetes and established history of cardiovascular disease.

CANVAS program 2017

Patients with type 2 diabetes at elevated risk for cardiovascular ailment assigned to canagliflozin saw a 33% reduction in the risk ofhospitalization for heart failure and were 40% less likely to experience renal decline versus those assigned placebos.

DECLARE-TIMI 58 trial 2018

Dapagliflozin in patients with type 2 diabetes mellitus, compared with placebo led to a significant 17% renal risk reduction in co-primary efficacy endpoint of a composite of cardiovascular death or hospitalization for heart failure.

CREDENCE trial 2019

Canagliflozin safely decreased the risk of kidney failure and prevented cardiovascular events in patients with type 2 diabetes and chronic kidney disease.

DAPA-HF trial

In heart failure patients, with or without diabetes, treatment with SGLT2 inhibitors reduced the risk for worsening heart failure and cardiovascular death when added to standard therapy;

• In the prevention of heart failure in patients with type 2 diabetes.
• Of treatment of heart failure with diminished ejection fraction in patients with diabetes and nondiabetics.

Guidelines

European Society of Cardiology

Recommends SGLT2 inhibitors to lower the risk of hospitalization for heart failure in patients with type 2 diabetes mellitus.

American Diabetes Association

Advises SGLT2 inhibitors in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease (ASCVD), multiple ASCVD risk factors or diabetic kidney disease to lessen the risk for major adverse events and heart failure hospitalization.

Interdisciplinary communication is needed

• Cardiologists need to talk to diabetologist about the importance of treating heart failure.
• Diabetologists need to help cardiologists understand how to use these and other effective oral hypoglycemic agents that reduce cardiovascular risk.

References

1. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457-71.
2. Oku A, et al. T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999;48(9):1794-800.
3. Pabel S, et al. Empagliflozin directly improves diastolic function in human heart failure. Eur J Heart Fail. 2018;20(12):1690-700.
4. Vasilakou D, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(4):262-74.
5. Dobkowski D. Braunwald: SGLT2 inhibitors have influenced cardiovascular care regardless of diabetes status. HealioNews. April 26, 2020.
6. Gunawan F, et al. Relative frequency of cardiology vs. endocrinology visits by type 2 diabetes patients with cardiovascular disease in the USA: implications for implementing evidence-based use of glucose-lowering medications. Cardiovasc Endocrinol Metab. 2020;9(2):56-9.
7. Zoler ML. SGLT2 inhibitors developed for T2D, now belong to cardiologists and nephrologists. Medscape. July 2020.