Dapagliflozin, a drug originally developed to treat diabetes, shows benefit in patients in heart failure.
Dapagliflozin belongs to a relatively new class of drugs, the sodium-glucose co-transporter-2 inhibitors, for treating type 2 diabetes mellitus. This new class of drugs reduces blood glucose levels by reducing the reabsorption of glucose in the kidneys. Clinical trials treating patients with sodium-glucose co-transporter-2 inhibitors found that in addition to being an effective treatment for type 2 diabetes, they also had positive effects on the cardiovascular health of study participants. Keeping the cardiovascular benefits in mind, scientists at the University of Glasgow studied if dapagliflozin treatment can benefit all patients with cardiovascular disease, including those who did not suffer from diabetes. The results of their Phase 3 clinical trial were published in The New England Journal of Medicine.
The study included 4,744 patients who were diagnosed with heart failure and with reduced ability of the heart to pump out blood. Of these, 45% of participants also suffered from Type 2 diabetes. The researchers chose a placebo-controlled trial design wherein study participants were randomly assigned to receive either dapagliflozin (10 mg once daily) or a matching placebo (control treatment that has no therapeutic effect), in addition to their normal treatment regimen. The researchers then monitored for signs of worsening heart failure such as hospitalizations, or need for urgent treatment for heart failure, or death due to cardiovascular events.
Over a follow-up period that averaged around 18 months, the researchers found that the number of patients with worsened heart failure were lower in the group treated with dapagliflozin (16.3%) as compared to the placebo group (21.2%). This translates into a 26% reduced risk of heart failure in patients treated with dapagliflozin.
Further detailed analyses revealed that the dapagliflozin treatment reduced the risk of ‘first worsening heart failure event’ by 30% and an 18% lower risk of death due to cardiovascular causes. The common adverse effects observed were dehydration, low blood pressure, fainting, kidney dysfunction, and low blood sugar levels. These adverse effects were observed in approximately 7% of the study participants with no difference in frequency of adverse effects observed in either groups. As explained by Professor McMurray, who led the study, “Adverse events rarely required the discontinuation of treatment. There was no notable excess of any serious adverse event in the dapagliflozin group.”
The reduced risk associated with dapagliflozin treatment was similar in patients with diabetes to those patients without diabetes. The significance of this finding was noted by Professor McMurray, “The most important finding of all is the benefit in patients without diabetes. This shows dapagliflozin is truly a treatment for heart failure and not just a drug for diabetes.” He concluded that “The trial shows that dapagliflozin reduces death and hospitalization, and improves health-related quality of life, in patients with heart failure and reduced ejection fraction, with and without diabetes. The clinical implications are potentially huge-few drugs achieve these results in heart failure and dapagliflozin does even when added to excellent standard therapy.”
Written by Bhavana Achary, Ph.D
McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O’Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Sep 19
Press release retrieved from https://www.eurekalert.org/pub_releases/2019-09/d-nrs091919.php
Information on dapagliflozin – https://www.diabetes.co.uk/diabetes-medication/sglt2-inhibitors.html
Image by Raman Oza from Pixabay