Companies: Bristol-Myers Squibb and AstraZeneca
Pharmacologic class: Sodium-glucose cotransporter 2 (SGLT2) inhibitor
Active ingredient: Dapagliflozin 5 mg, 10 mg; tablets
Indication: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitation of use: not for treating type 1 diabetes mellitus or diabetic ketoacidosis.
Pharmacology: Dapagliflozin inhibits the SGLT2, which reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion.
Clinical trials: Farxiga was studied as monotherapy and in combination with metformin (Fortamet, Glucophage, Glumetza, Riomet), pioglitazone (Actos), glimepiride (Amaryl), sitagliptin (Januvia), or insulin. Farxiga was also compared with glipizide (Glucotrol) added on to metformin.
In a 24-week monotherapy study, 558 treatment-naïve patients with inadequately controlled diabetes were randomized to Farxiga 5 mg or 10 mg once daily in either the morning or evening, or placebo. At week 24, Farxiga 10 mg in the morning provided significant improvements in hemoglobin (Hb)A1c and fasting plasma glucose (FPG) compared with placebo. The Farxiga 10 mg dose demonstrated a difference from placebo of −0.7 (95% CI: −1.0, −0.4; P <0.0001) for HbA1c reduction and −24.7 (95% CI: −35.7, −13.6; P <0.0001) for reduction of FPG.
In two 24-week active-controlled studies, the safety and efficacy of Farxiga 5 mg or 10 mg in combination with metformin extended-release (XR) was studied in 1,241 treatment-naïve patients with inadequately controlled type 2 diabetes.
In one study, 638 patients were randomized to Farxiga 10 mg + metformin XR, Farxiga 10 mg + placebo, or metformin XR + placebo. The Farxiga 10 mg + metformin XR combination provided statistically significant improvements in HbA1c (−0.5 difference from Farxiga, 95% CI: −0.7, −0.3; −0.5 difference from metformin XR, 95% CI: −0.8, −0.3; P <0.0001) and FPG (−13.9 difference from Farxiga, 95% CI: −20.9, −7.0; −25.5 difference from metformin XR, 95% CI: −32.6, −18.5; P <0.0001) compared with either monotherapy treatment and significant reduction in body weight compared with metformin XR alone.
Farxiga 10 mg as monotherapy also showed a statistically significant reduction in body weight when compared with metformin XR alone and was non-inferior to metformin XR monotherapy in lowering HbA1c. Farxiga as an add-on to a sulfonylurea, thiazolidinedione, DPP-4 inhibitor, or insulin also showed statistically significant improvements in HbA1c, two-hour postprandial glucose, FPG, and weight loss.
For more clinical trial data, see full labeling.
Adults: Take in the morning. Initially 5mg once daily; if tolerated and need additional glycemic control, may increase to 10 mg once daily. Renal impairment: if estimated glomerular filtration rate (eGFR) <60, do not initiate. Discontinue if eGFR falls persistently <60.
Children: <18 years: not established.
Contraindications: Severe renal impairment, end-stage renal disease, or on dialysis.
Warnings/Precautions: Correct volume depletion before starting therapy. Monitor for signs/symptoms of hypotension (especially elderly, patients with renal impairment, or patients on diuretics). Evaluate renal function prior to starting and monitor periodically thereafter. Increased risk of genital mycotic infections; monitor and treat if occurs. Monitor for increases in LDL; treat if occur. Active bladder cancer: do not use. Severe hepatic impairment. Elderly. Pregnancy (Category C). Nursing mothers: not recommended.
Interactions: Concomitant insulin or insulin secretagogue: consider a lower dose of insulin/insulin secretagogue to reduce risk of hypoglycemia. Hypotension with concomitant loop diuretics.
Adverse reactions: Female genital mycotic infections, nasopharyngitis, urinary tract infections, back pain, increased urination; volume depletion and renal impairment.
How supplied: Tabs—30, 90, 500
For more information, call 855.332.7944 or visit www.Farxiga.com.