The US Food and Drug Administration has reported that dapagliflozin has been approved to reduce the risk of kidney function loss, kidney impairment, cardiovascular mortality, and heart failure hospitalisation in adults with a chronic renal disease that is at risk of progression. This article highlights the usage of this SGLT2 drug along with considerations for patients with diabetes.

Usage approval for dapagliflozin

Dapagliflozin, which was approved about a year ago for the management of heart failure with decreased ejection fraction (HFrEF) in adults with and without type 2 diabetes, is also the first SGLT2 inhibitor to be approved for the management of CKD. In more than 20 years, this is the most important breakthrough in the management of chronic kidney disease.

Effect of SGLT2 on kidney diseases

“Chronic kidney disease is a major public health concern, and there is an unfulfilled demand for treatments that delay disease progression and enhance outcomes. Dapagliflozin certification for the management of progressive kidney failure is a significant move forward in assisting patients dealing with kidney disease”, stated FDA’s Center for Drug Evaluation and Research. Dapagliflozin is one of the few agents that has captivated the public's interest in recent years. Some predicted that, with the SGLT2 inhibitor class forging paths in heart failure and chronic kidney disease, this approval will be a foregone conclusion based on evidence from several clinical trials.

The new approval for dapagliflozin is for lowering the incidence of kidney function loss, kidney damage, premature mortality, and hospitalisation for heart failure in adults with chronic renal disease who are at risk of disease worsening, based on the findings of the DAPA-CKD trial, which was initially proposed at ESC 2020. In the phase 3 experiment, 4304 patients were randomly assigned to receive dapagliflozin or placebo in a 1:1 ratio. The study's primary endpoint was a 50% reduction in renal function, worsening to renal disease, or coronary or kidney mortality, and the findings showed that dapagliflozin was correlated with a 39% reduction in the study's primary endpoint. The decline was observed in both diabetic and non-diabetic patients, with declines of 36 per cent in diabetic patients and 50 per cent in non-diabetic patients, according to trial investigators.

Effect of dapagliflozin in diabetic patients

Dapagliflozin has not been studied in patients with autosomal dominant or recessive polycystic kidney disease (characterised by multiple cysts) or those who need or have recently utilized immunosuppressive medication to support kidney disease.

Patients who have had severe hypersensitivity responses to the drug in the past or who are on dialysis should avoid taking dapagliflozin. In diabetic patients, by taking dapagliflozin severe, life-threatening cases of Fournier's gangrene have been reported. If patients are still taking dapagliflozin, they should consider lowering their insulin or insulin secretagogue dosage to minimise the chance of hypoglycemia (low blood sugar). Dehydration, severe urinary tract infections, vaginal yeast infections, and metabolic acidosis or ketoacidosis are also possible side effects of dapagliflozin (acid build-up in the blood). Before beginning dapagliflozin, patients should have their volume status and kidney function checked.

Dapagliflozin was first licenced in 2014 to help people with type 2 diabetes boost their glycaemic control in addition to diet and exercise.

Using dapagliflozin

For approval, dapagliflozin earned fast track, breakthrough therapy, and priority review designations. Fast track is intended to speed up the discovery and evaluation of medications to cure chronic illnesses or meet an unmet medical need. Breakthrough therapy classification is meant to speed up the discovery and evaluation of medications that are intended to treat a dangerous disorder and early clinical data suggests that the medication may show a meaningful difference over current therapy on the clinically significant outcome(s). Priority assessment focuses on emphasis and energy on drug applications that, if approved, will include major changes in the safety or efficacy of medication, diagnosis, or prevention of severe conditions over normal applications.

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 is a practising super specialist from New Delhi.