Here is an interesting challenge for you. Given below are the details for a patient with a history of CAD and cardiomyopathy who is also referred for T2DM management. Which therapy will you choose to lower the possibility of HF exacerbation?

Case details

A 65-year-old man with a history of coronary artrery disease and ischaemic cardiomyopathy was referred to the endocrinologist for management of type II diabetes mellitus. History was not suggestive of any of microvascular complications. The patient presently on sitagliptin 100 mg/day and insulin 18 units at night. His HbA1c was 7.5% with normal kidney functions. He had a history of hospitalisation last month for volume overload due to heart failure exacerbation.

What is the basis of the treatment?

The management is based on the results of trials of SGLT inhibitors in cardiac patients such as DECLARE-TIMI 58. DECLARE-TIMI 58 is the biggest SGLT2 inhibitor trial to date.

DECLARE-TIMI 58

This is the only SGLT2 inhibitor CV outcome trial to date with baseline data on LV ejection fraction. This was a double-blind International randomised control trial with more than 17000 patients with high cardiovascular risk factors who were randomised to dapagliflozin (DAPA) 10 mg daily or placebo added to standard therapy. The median follow-up was for.2 years. Primary outcome was composite of death or hospitalisation for heart failure.

Result

• In diabetes mellitus and elevated cardiac risk patients, Dapagliflozin effectively reduced the likelihood of cardiovascular mortality and heart failure in HfrEF patients relative to others with HFrEF. dapa vs placebo (P= 0.046)
• HFrEF: 38% reduced risk (HR 0.62)
• Without HFrEF: 12% reduced risk (HR 0.88). CV death: Significantly lower with HFrEF (P= 0.012). All-cause mortality: Significantly lower with HFrEF (P= 0.016)

Other significant cardiovascular outcome trials for SGLT2 inhibitors include:

• EMPA-REG OUTCOME (empagliflozin)
• CANVAS (canagliflozin)
• DECLARE-TIMI 58 (dapagliflozin)
• CREDENCE (canagliflozin (+renal outcomes])
• DAPA-HF (dapagliflozin, heart failure)

The crux results of all these trials suggest decreased rates for heart failure hospital admission in patients with type 2 diabetes mellitus and HFrEF patients irrespective of diabetes.

Recommendations from guidelines

Leading specialist associations and societies have advised the use of SGLT2 inhibitors irrespective of glycaemic status in clinical care recommendations for patients with current cardiac disease, heart failure, and kidney disease.

American Diabetes Association

Sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist is recommended as part of the glucose-lowering regimen in patients with type 2 DM with cardiac disease and established renal disease irrespective of HbA1C.

American Heart Association and American College of Cardiology

The guideline states that in patients with an elevated cardiovascular risk, GLP-1 receptor agonist or an SGLT2 inhibitor is shown to enhance cardiovascular outcomes irrespective of HbA1c. If heart failure or chronic kidney disease dominates the clinical picture, an SGLT2 inhibitor is preferred.

European Society of Cardiology/ European Association for the Study of Diabetes

Glucose-lowering treatment for patients with diabetes in the form of SGLT2 inhibitors such as empagliflozin, canagliflozin, or dapagliflozin can be used to reduce the risk of heart failure hospitalisation and diabetic kidney disease. Empagliflozin is recommended in patients with prevalent CVD, to reduce the risk of death.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Monish S Raut is a Consultant in Cardiothoracic Vascular Anaesthesiology. His area of expertise is perioperative management and echocardiography with numerous publications in various national and international indexed journals.