Farxiga (Dapagliflozin): What to Expect Week by Week in Your First Month

What Happens in the First Days

Dapagliflozin blocks the sodium-glucose cotransporter 2 in the kidney, so glucose that would normally be reabsorbed leaves in urine, and water follows it, which is an osmotic diuresis [1]. The tablet is taken once daily, with or without food; a high-fat meal can lower the peak blood level by up to 50% without changing overall exposure [1].

Blood levels peak about 2 hours after a dose and the half-life is about 12.9 hours [1]. Glucose excretion continues for about 3 days after the last tablet [1].

What the Label Records, With Rates

In 12 pooled placebo-controlled trials lasting 12 to 24 weeks (placebo N=1,393; 5 mg N=1,145; 10 mg N=1,193), the rates were [1]:

• Female genital yeast infections: 1.5% on placebo, 8.4% on 5 mg, 6.9% on 10 mg
• Male genital yeast infections: 0.3% on placebo, 2.8% on 5 mg, 2.7% on 10 mg
• Urinary tract infection: 3.7%, 5.7%, 4.3%
• Increased urination: 1.7%, 2.9%, 3.8%
• Nasopharyngitis: 6.2%, 6.6%, 6.3%

The reactions seen in 5% or more of patients were female genital yeast infections, nasopharyngitis and urinary tract infections [1]. Volume depletion, reported as dehydration, hypovolemia, orthostatic hypotension or hypotension, occurred in 0.4% of placebo patients, 0.6% on 5 mg and 0.8% on 10 mg in the 12-trial pool, and in 2.4% vs 2.5% in DECLARE-TIMI 58 [1]. These are cumulative rates over 12 to 24 weeks, not week-one rates [1].

What to Watch For From the First Dose

The label's warnings apply from the start, not from week four [1].

• Ketoacidosis. Blood glucose at presentation can be below 250 mg/dL. Nausea, vomiting, abdominal pain, general malaise and shortness of breath are signs that need immediate medical attention. The label says to discontinue Farxiga if ketoacidosis is suspected [1]. In DECLARE-TIMI 58, diabetic ketoacidosis occurred in 0.3% on dapagliflozin vs 0.1% on placebo [2]. Farxiga is not recommended for glycemic control in type 1 diabetes, where it significantly increases ketoacidosis risk [1].
• Surgery and prolonged fasting. The label says to withhold Farxiga for at least 3 days, if possible, before such a procedure, and to resume once the patient is clinically stable and eating again [1].
• Volume depletion. Risk is higher with an eGFR under 60 mL/min/1.73 m2, older age and loop diuretics, and can appear as symptomatic hypotension or acute transient changes in creatinine. The label says to assess volume status and kidney function before starting in those groups, and to monitor afterwards [1].
• Genital and perineal infection. The label says to evaluate immediately for pain, tenderness, redness or swelling in the genital or perineal area with fever or malaise, for necrotizing fasciitis of the perineum (Fournier gangrene); if suspected, it says to discontinue Farxiga and promptly begin medical and surgical treatment [1].
• Hypersensitivity. A history of serious hypersensitivity to dapagliflozin or an excipient is the only contraindication; anaphylaxis and angioedema have occurred [1].

Blood Sugar and Weight

At 24 weeks, monotherapy lowered HbA1c by 0.9 points on 10 mg and 0.8 points on 5 mg, against 0.2 points on placebo; HbA1c came in under 7% for 50.8% of the 10 mg group, 44.2% of the 5 mg group and 31.6% of the placebo group [1]. Starting alongside metformin XR produced a 2.0-point HbA1c fall, against 1.5 points with dapagliflozin alone and 1.4 with metformin XR alone, from a baseline near 9.0% [1].

Dapagliflozin has no weight-management indication; its approved uses are chronic kidney disease, heart failure and blood sugar control in type 2 diabetes [1].

Interactions That Matter From Day 1

• Insulin and sulfonylureas. The risk of hypoglycemia rises; a lower dose of the insulin or the secretagogue may be required [1].
• Diuretics. Additive volume depletion, with loop diuretic users at higher risk. In the DECLARE-TIMI 58 loop-diuretic subgroup, volume-depletion events were 6.6% on dapagliflozin vs 6.1% on placebo [1].
• Lithium. Dapagliflozin may decrease serum lithium; the label says to monitor lithium more often when starting and with dose changes [1].
• Glucose monitoring. Urine glucose tests will be positive and 1,5-anhydroglucitol measurements are unreliable; the label says to use another method to track control [1].
• Rifampin and mefenamic acid. Rifampin lowers dapagliflozin AUC by 22% and mefenamic acid raises it by 51%; the label recommends no dose adjustment for either [1]. In vitro, dapagliflozin neither inhibited nor induced the major CYP enzymes [1].

For Heart Failure or Kidney Disease

The dose for these indications is 10 mg once daily. The label says to use the usual dose at an eGFR of 25 or higher and not to start below 25, though patients already taking it may continue if eGFR later falls below that [1]. DAPA-HF, in 4,744 adults with an ejection fraction of 40% or less, found worsening heart failure or cardiovascular death in 16.3% on dapagliflozin vs 21.2% on placebo over a median of 18.2 months (HR 0.74, 95% CI 0.65 to 0.85) [3]. DELIVER, in 6,263 adults with an ejection fraction above 40%, found 16.4% vs 19.5% over a median of 2.3 years (HR 0.82, 0.73 to 0.92) [5]. DAPA-CKD, in 4,304 adults with chronic kidney disease, found the kidney composite in 9.2% vs 14.5% over a median of 2.4 years (HR 0.61, 0.51 to 0.72; number needed to treat 19) [4].