Is dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a treatment option for patients with heart failure?
Lakeisha Williams, PharmD, MSPH and Tori Wiley, PharmD respond-Cardiovascular disease and diabetes continue to be clinical and public health challenges. More than 30 million Americans are living with type 2 diabetes (T2DM), and approximately 6.2 million are living with heart failure (HF).1,2 Patients with T2DM have a twofold risk of developing HF, and patients with T2DM have cardiovascular outcomes, hospitalization rates, healthcare expenditures, and prognoses that are worse compared with those without T2DM.3
As a result, clinicians may find it challenging to treat patients with these comorbidities. Irrespective of T2DM, SGLT2 inhibitors are recommended for patients with HF with reduced ejection fraction (HFrEF) to reduce hospitalizations and cardiovascular mortality.4 Since the clinician's role is to weigh options to maximize patient outcomes, this article presents dapagliflozin as a therapy option to assist patients in lowering blood glucose levels and managing HF.
Mechanism of action
Dapagliflozin is an SGLT2 inhibitor that effectively lowers A1C up to 2.1% by reducing glucose reabsorption in the kidneys and promoting urinary glucose excretion.5 It also reduces sodium reabsorption, which may be linked to lower cardiac preload and afterload, downregulated sympathetic activity, and decreased intraglomerular pressure.5
Indications and contraindications
SGLT2 inhibitors currently available for T2DM, such as dapagliflozin, have several clinical benefits.6,7 Dapagliflozin reduced the risk of cardiovascular death and hospitalization for HF in adults with HFrEF (New York Heart Association class II-IV) with and without T2DM.8-10 Dapagliflozin has also been shown, as monotherapy and in combination with other agents, such as metformin, pioglitazone, glimepiride, sitagliptin, or insulin, to decrease plasma N-terminal pro-B-type natriuretic peptide levels, induce weight loss, and reduce BP.5 Although dapagliflozin is used as an adjunct to diet and exercise to improve glycemic control in patients with T2DM, it is also indicated to reduce the risk of sustained estimated glomerulus filtration rate decline, end-stage kidney disease, cardiovascular death, and hospitalization for HF in adults with chronic kidney disease at risk for progression, as well as reduce the risk of hospitalization for HF in adults with T2DM and established cardiovascular disease or multiple cardiovascular risk factors.5 Dapagliflozin has not been FDA-approved for use in patients with HF with mildly reduced ejection fraction and HF with preserved ejection fraction.11 Contraindications include a history of serious hypersensitivity reaction to dapagliflozin and patients requiring dialysis.5
Dosage and administration
Dapagliflozin is supplied in 5 mg and 10 mg tablets. The recommended dose of dapagliflozin in patients with HF and no contraindications is 10 mg taken orally once daily, with or without food.5
Warnings, adverse reactions, safety precautions
Dapagliflozin may cause intravascular volume depletion, which may lead to symptomatic hypotension.5 This risk increases in older adults, patients with impaired renal function, or patients taking loop diuretics. Clinicians should assess renal function and correct volume depletion before initiating dapagliflozin. They should also discuss the importance of hydration. Reports of ketoacidosis were identified in patients with type 1 diabetes taking any SGLT-2 inhibitor, including dapagliflozin. Therefore, dapagliflozin should not be prescribed in patients with type 1 diabetes or patients with ketoacidosis.5
Hypoglycemia risk also increases in patients taking dapagliflozin combined with insulin or an insulin secretagogue, such as sulfonylureas or glinides.5 However, severe hypoglycemia and diabetic ketoacidosis (DKA) were observed only in patients with diabetes. Temporary discontinuation of dapagliflozin should be considered before scheduled surgery or in settings of fluid loss.12
Necrotizing fasciitis of the perineum (Fournier's gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, has also been identified in postmarketing trials in patients taking SGLT-2 inhibitors, including dapagliflozin.5 Patients should be encouraged to promptly report signs or symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise.5
Common adverse reactions to dapagliflozin include nasopharyngitis, urinary tract infections, and mycotic infections in females.5 Other adverse reactions include increased urination, nausea, constipation, back pain, and genital mycotic infections in males.5
Dapagliflozin's safety and efficacy have not been established in pediatric patients under 18 years of age.5 Patients should be instructed to not use dapagliflozin during pregnancy because of the potential risk to a fetus especially during the second and third trimesters and breastfeeding. Patients should also be instructed that since SGLT2 inhibitors, including dapagliflozin, increase urinary glucose excretion and lead to positive urine glucose tests, monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Patients should use alternative methods to monitor glycemic control.5
Patients with HF must understand that add-on therapy of an SGLT2 inhibitor is recommended irrespective of having T2DM (see Patient education). Dapagliflozin has shown clinical benefits in both populations.
Patient education5
* Teach patients about the medication, including indications, dosage and administration, and adverse reactions.
* Patients should take a missed dose as soon as they realize one was missed. However, they should skip the missed dose if it is almost time for the next dose. In addition, they should not take two doses of dapagliflozin simultaneously.
* Hydration is important; patients should report signs and symptoms of dehydration, including feeling dizzy, faint, lightheaded, or weak, especially with standing.
* Females should be made aware of the signs and symptoms of vaginal yeast infections to report, including vaginal odor, vaginal discharge, and vaginal itching.
* Males should be aware of the signs and symptoms of yeast infection of the skin around the penis to report, including penile redness, itching, or swelling; penile rash; foul-smelling discharge from the penis; or pain in the skin around the penis.
* Patients with T2DM should know the signs and symptoms of hypoglycemia, such as headache, shaking, and sweating, and DKA such as nausea, vomiting, and difficulty breathing and what to do should they occur.
* All patients should know the signs and symptoms of a urinary tract infection to report, such as urinary burning, frequency, urgency, and blood in the urine.
* Patients should seek medical attention immediately if they have signs and symptoms of necrotizing fasciitis of the perineum, including fever, malaise, pain or tenderness, swelling, or redness of skin in the area between and around the anus and genitals.
* Assess potential barriers to medication adherence, including adverse reactions, cost, health literacy, language and cultural barriers, cognitive abilities, and social determinants of health.13,14
* Assist patients with medication costs by submitting prior authorizations to patient insurance companies while supporting uninsured patients using the drug manufacturer's prescription savings program, formulary finder, and other prescription discount coupons.
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