Heart failure (HF) develops earlier in patients with type 2 diabetes mellitus (T2D) than in those without T2D and goes undiagnosed in many patients. T2D causes RAAS activation, arterial stiffness, fluid expansion, hypertension, and renal hyperfiltration, which all contribute to early cardiac dysfunction. HF is the most frequent diagnosis associated with 30-day readmission. The disease cost a projected $31 billion in 2012 and is projected to increase 127% by 2030, therefore SGLT2 inhibitor (SGLT2i) treatments such as FARXIGA® (dapagliflozin) are not only effective in improving patient outcomes, but in greatly reducing health care costs as well, according to presenters of a science and innovation theater at AMCP Nexus 2019.
FARXIGA® is indicated for use as an adjunct to diet and exercise to control blood sugar in adults with T2D. The goal of this treatment is to reduce the risk of HF hospitalization in adults with T2D, cardiovascular disease, or multiple cardiovascular risk factors. FARXIGA® is not recommended for patients with type 1 diabetes mellitus or for treating diabetic ketoacidosis. Contraindications include previous adverse experience with FARXIGA®, severe renal impairment, end-stage renal disease, or patients on dialysis.
DECLARE is the largest cardiovascular outcomes trial with an SGLT2i to study hospitalization for heart failure (hHF) risk reduction in both primary and secondary prevention patients. In DECLARE’s patient population of 17,160 T2D patients aged > 40 years, FARXIGA® met the primary safety endpoint vs. placebo for the composite of CV death, MI, or ischemic stroke (MACE) (HR=0.93; 95% CI, 0.84 to 1.03, P<0.001 for noninferiority). The researchers also saw a 22% RRR for hHF in patients with established CVD (HR=0.78; 95% CI, 0.63 to 0.97; 1.2% ARR).
Potential risks associated with FARXIGA® include intravascular volume contraction that can result in symptomatic hypotension. This should be addressed by assessing and correcting the volume status before initiating FARXIGA® in patients with impaired renal function, elderly patients, or patients on loop diuretics.
FARXIGA® also comes with an elevated risk for ketoacidosis, which has been reported in patients with type 1 and type 2 diabetes receiving the treatment. Some of these cases have resulted in death. Patients presenting signs and symptoms of metabolic acidosis for ketoacidosis should be assessed regardless of their blood glucose levels. If ketoacidosis is suspected, FARXIGA® should be discontinued and the patient should be treated promptly. Urosepsis, pyelonephritis, hypoglycemia, necrotizing fasciitis of the perineum (Fournier’s gangrene), and genital mycotic infection are among other precautions to consider when prescribing FARXIGA®. There are also potential risks to the fetus associated with FARXIGA®, particularly in the second and third trimesters, and the treatment is not recommended when breastfeeding.
Science and Innovation Theater:
AstraZeneca. Thinking Glycemia and Beyond: The Importance of Managing Heart Failure Risks in Type 2 Diabetes. Presented at: AMCP Nexus 2019; October 29 – Nov 1; National Harbor, MD.