Dapagliflozin is a once-daily oral drug that blocks sodium-glucose cotransporter 2 (SGLT2) in the kidney, so glucose that would normally be reabsorbed is passed in the urine. It is sold by AstraZeneca as Farxiga in the US and as Forxiga in the European Union. It was first approved to lower blood sugar in type 2 diabetes, and large outcome trials later led to approvals for heart failure and chronic kidney disease (CKD), including in people without diabetes.
The single most important fact for readers of this site: like the rest of its class, dapagliflozin raises hematocrit (the share of blood made up of red cells). Testosterone does the same, and observational studies link the combination to higher rates of erythrocytosis (an abnormally high red cell count). The broader class, including canagliflozin and empagliflozin, is covered on the SGLT2 inhibitors page; this page focuses on dapagliflozin.
This page summarizes what the FDA label, the major randomized trials and published studies report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Sodium-glucose cotransporter 2 (SGLT2) inhibitor (“gliflozin”) |
| Brands / approval | Farxiga (US, initial approval 2014); Forxiga (EU, authorized November 2012) |
| Route | Oral tablet, once daily, with or without food |
| Strengths | 5 mg and 10 mg tablets |
| Labeled dose | 5–10 mg once daily for blood sugar; 10 mg once daily for heart failure, CKD and heart failure risk reduction |
| Half-life (label) | ≈12.9 h after a single 10 mg dose |
| Key mechanism fact | About 70 g of glucose per day lost in urine at 5–10 mg in type 2 diabetes |
| Boxed warning | None |
| US status | Prescription only; not a controlled substance |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Dapagliflozin is a C-glucoside: a glucose-like ring joined by a carbon–carbon bond to a chlorinated diphenylmethane group. Its formula is C₂₁H₂₅ClO₆ and its molecular weight is 408.9 g/mol (PubChem). The tablet contains it as dapagliflozin propanediol monohydrate, a co-crystal with propylene glycol and water (FDA label).
SGLT2 sits in the proximal tubule of the kidney and does most of the work of pulling filtered glucose back into the blood. By blocking it, dapagliflozin makes the kidney excrete glucose. The label states that 5 or 10 mg per day in people with type 2 diabetes produced about 70 g of urinary glucose per day at week 12, and that excretion was near maximal at 20 mg.
Blocking SGLT2 also sends more sodium further down the tubule. According to the label, this may lower the load on the heart before and after each beat, reduce sympathetic nervous activity, and lower pressure inside the kidney’s filters through a feedback loop (tubuloglomerular feedback). These effects do not depend on blood sugar, which is the usual explanation for why the heart and kidney benefits also appear in people without diabetes.
Pharmacokinetics
| Parameter | Value (FDA label) |
|---|---|
| Time to peak (fasting) | Usually within 2 h |
| Oral bioavailability | 78% (10 mg dose) |
| Effect of a high-fat meal | Peak level down by up to 50%, total exposure unchanged |
| Protein binding | ≈91% |
| Main metabolic route | Glucuronidation by UGT1A9 to an inactive 3-O-glucuronide; CYP enzymes play a minor role |
| Excretion | 75% of a radiolabeled dose in urine, 21% in feces; under 2% excreted unchanged in urine |
| Terminal half-life | ≈12.9 h |
| Offset of effect | Urinary glucose loss returns to near baseline about 3 days after stopping 10 mg |
Kidney function changes both exposure and effect. At steady state, people with type 2 diabetes and mild, moderate or severe kidney impairment had 45%, 100% and 200% higher drug exposure, but their 24-hour urinary glucose loss was 42%, 80% and 90% lower than in people with normal kidney function. This is why the label does not recommend dapagliflozin for blood sugar control when eGFR (estimated glomerular filtration rate, a measure of kidney function) is under 45 mL/min/1.73 m², while the heart and kidney indications still apply at lower eGFR.
Approved medical use
The current FDA label lists four indications (FDA label):
- to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death and hospitalization for heart failure in adults with CKD at risk of progression;
- to reduce the risk of CV death, hospitalization for heart failure and urgent heart failure visits in adults with heart failure;
- to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and either established CV disease or multiple CV risk factors;
- as an adjunct to diet and exercise to improve blood sugar control in adults and children aged 10 years and older with type 2 diabetes.
The label’s limitations of use say it is not recommended for blood sugar control in type 1 diabetes, and not expected to work for CKD caused by polycystic kidney disease or in people needing recent immunosuppressive therapy for kidney disease.
| Indication | Labeled dosing | Kidney function notes |
|---|---|---|
| Blood sugar control, type 2 diabetes | Start 5 mg once daily; may increase to 10 mg | Not recommended if eGFR under 45 |
| CKD, heart failure, heart failure risk in type 2 diabetes | 10 mg once daily | Starting not recommended if eGFR under 25; may continue if eGFR falls below 25 |
Other labeled instructions:
- check kidney function and volume status before starting, and correct dehydration first;
- withhold for at least 3 days, if possible, before surgery or procedures with prolonged fasting, and restart once the person is stable and eating.
What the research shows
Blood sugar and body weight
In a 24-week placebo-controlled monotherapy trial in treatment-naive adults with type 2 diabetes, dapagliflozin 10 mg lowered HbA1c (a 2–3 month average of blood sugar) by 0.9 percentage points from a baseline of 8.0%, versus 0.2 with placebo; the placebo-adjusted difference was −0.7 (95% CI −1.0 to −0.4) (FDA label).
In a 24-week trial of initial therapy in 638 patients, combining dapagliflozin 10 mg with extended-release metformin worked better than either drug alone:
| Arm | HbA1c change | Body weight change |
|---|---|---|
| Dapagliflozin 10 mg + metformin XR | −2.0 | −3.3 kg |
| Dapagliflozin 10 mg alone | −1.5 | −2.7 kg |
| Metformin XR alone | −1.4 | −1.4 kg |
Dapagliflozin alone was non-inferior to metformin for HbA1c in that trial. Baseline HbA1c was about 9% in all arms.
To see what the weight loss is made of, a 24-week double-blind trial added dapagliflozin 10 mg or placebo to metformin in 182 adults with type 2 diabetes and measured body composition by DXA (dual-energy X-ray absorptiometry) (Bolinder et al., JCEM 2012). Placebo-corrected changes were −2.08 kg body weight (95% CI −2.84 to −1.31) and −1.48 kg fat mass (95% CI −2.22 to −0.74), and MRI in a subset showed reductions in both visceral and subcutaneous fat. The authors concluded that the weight loss came predominantly from fat. In the 102-week extension, weight and fat mass reductions were maintained, and no meaningful changes in bone turnover markers or bone mineral density were seen (Bolinder et al., Diabetes Obes Metab 2014).
DECLARE-TIMI 58: cardiovascular outcomes in type 2 diabetes
DECLARE-TIMI 58 randomized 17,160 adults with type 2 diabetes who had, or were at risk of, atherosclerotic CV disease to dapagliflozin 10 mg or placebo, with a median follow-up of 4.2 years (Wiviott et al., NEJM 2019). Most participants (10,186) did not have established atherosclerotic disease.
| Outcome | Dapagliflozin | Placebo | Hazard ratio (95% CI) |
|---|---|---|---|
| MACE (CV death, heart attack, ischemic stroke) | 8.8% | 9.4% | 0.93 (0.84–1.03) |
| CV death or hospitalization for heart failure | 4.9% | 5.8% | 0.83 (0.73–0.95) |
| Hospitalization for heart failure | 2.5% | 3.3% | 0.73 (0.61–0.88) |
| CV death | 2.9% | 2.9% | 0.98 (0.82–1.17) |
| Renal composite | 4.3% | 5.6% | 0.76 (0.67–0.87) |
| Death from any cause | 6.2% | 6.6% | 0.93 (0.82–1.04) |
Dapagliflozin met the safety criterion (no increase in MACE) but did not reduce MACE. The benefit on the combined endpoint came from fewer heart failure hospitalizations. This trial is the basis for the heart failure risk-reduction indication in type 2 diabetes.
DAPA-HF and DELIVER: heart failure
DAPA-HF randomized 4,744 patients with heart failure and an ejection fraction (the share of blood the left ventricle pumps out per beat) of 40% or less to dapagliflozin 10 mg or placebo on top of standard therapy, for a median of 18.2 months (McMurray et al., NEJM 2019). The trial enrolled patients with and without type 2 diabetes.
| Outcome (DAPA-HF) | Dapagliflozin | Placebo | Hazard ratio (95% CI) |
|---|---|---|---|
| Worsening heart failure or CV death (primary) | 16.3% | 21.2% | 0.74 (0.65–0.85) |
| First worsening heart failure event | 10.0% | 13.7% | 0.70 (0.59–0.83) |
| CV death | 9.6% | 11.5% | 0.82 (0.69–0.98) |
| Death from any cause | 11.6% | 13.9% | 0.83 (0.71–0.97) |
Results were similar in patients with and without diabetes. Adverse events related to volume depletion, kidney dysfunction and hypoglycemia did not differ between groups.
DELIVER extended this to 6,263 patients with an ejection fraction above 40%, followed for a median of 28 months (Solomon et al., NEJM 2022). According to the label, the primary composite of CV death, heart failure hospitalization or urgent heart failure visit was reduced (hazard ratio 0.82, 95% CI 0.73–0.92), driven by fewer heart failure events; the CV death component alone was not significantly reduced (0.88, 95% CI 0.74–1.05). The label reports that the effect on this composite was consistent across the range of ejection fractions studied in the two trials.
DAPA-CKD: chronic kidney disease
DAPA-CKD randomized 4,304 adults with an eGFR of 25–75 mL/min/1.73 m² and significant albumin in the urine to dapagliflozin 10 mg or placebo, on top of an ACE inhibitor or ARB in 97% of patients (Heerspink et al., NEJM 2020). About two-thirds had type 2 diabetes. The trial was stopped early for efficacy after a median of 2.4 years.
| Outcome (DAPA-CKD) | Dapagliflozin | Placebo | Hazard ratio (95% CI) |
|---|---|---|---|
| ≥50% eGFR decline, kidney failure, or renal or CV death (primary) | 9.2% | 14.5% | 0.61 (0.51–0.72) |
| Kidney-specific composite (no CV death) | — | — | 0.56 (0.45–0.68) |
| CV death or hospitalization for heart failure | — | — | 0.71 (0.55–0.92) |
| Death from any cause | 4.7% | 6.8% | 0.69 (0.53–0.88) |
The number needed to treat to prevent one primary outcome event over the trial was 19 (95% CI 15–27). Effects were similar with and without type 2 diabetes.
Hematocrit and red blood cells
The rise in hematocrit is a consistent, labeled effect. In a pool of 13 placebo-controlled glycemic trials, mean hematocrit at week 24 changed by +2.30 percentage points with dapagliflozin 10 mg versus −0.33 with placebo, and hematocrit over 55% was reported in 1.3% versus 0.4% of patients (FDA label). The increase started in week 1 and peaked around week 16.
This is not only fluid loss concentrating the blood. In a 12-week randomized placebo-controlled trial in 52 obese adults with type 2 diabetes, dapagliflozin 10 mg raised hemoglobin and hematocrit, lowered hepcidin (a hormone that restricts iron supply to the bone marrow) and ferritin, and produced a transient rise in erythropoietin; no such changes occurred with placebo (Ghanim et al., JCEM 2020). In DAPA-HF, anemia at baseline (hematocrit under 39% in men, under 36% in women) resolved in 62.2% of patients on dapagliflozin versus 41.1% on placebo (Docherty et al., Eur J Heart Fail 2021).
A 2026 network meta-analysis of 136 randomized trials (102,882 participants) found that SGLT2 inhibitors as a class raise hemoglobin, hematocrit, red cell count and erythropoietin, but rated the certainty of evidence low to very low and could not establish clear differences between individual drugs (Sridharan & Sivaramakrishnan, Diabetes Metab Syndr 2026).
Combined with testosterone
Testosterone also stimulates red cell production (see testosterone cypionate). No randomized trial has tested dapagliflozin together with testosterone. The available evidence is observational and reports SGLT2 inhibitors as a class:
- Case reports. Two men with hypogonadism and type 2 diabetes developed erythrocytosis on testosterone plus an SGLT2 inhibitor (Motta et al., JCEM 2019). A separate series described 5 men on long-term testosterone who developed erythrocytosis after empagliflozin was added; it resolved after testosterone was stopped or reduced, or after phlebotomy (Schumacher & Gosmanov, J Investig Med High Impact Case Rep 2022).
- US veterans cohort. Among 53,971 people with type 2 diabetes, those on both an SGLT2 inhibitor and testosterone had higher adjusted odds of a new hematocrit over 54% within a year than those on an SGLT2 inhibitor alone (OR 3.80, 95% CI 2.27–6.11) or testosterone alone (OR 2.49, 95% CI 1.51–3.59). Topical versus injectable testosterone did not change this (Gosmanov et al., J Endocrinol Invest 2024).
- Israeli cohort. In 5,235 men with type 2 diabetes and hypogonadism who started testosterone, hematocrit, hemoglobin and red cell count rose significantly in those also on an SGLT2 inhibitor, and the odds of hematocrit over 54% were higher than in men not on one (OR 4.85, 95% CI 3.06–7.69) (Kabha et al., Endocrinol Diabetes Metab 2025).
A 2025 review notes that SGLT2 inhibitors are now prescribed widely for heart and kidney disease regardless of blood sugar, so co-prescription with testosterone is becoming more common. It lists re-evaluating the testosterone indication, addressing other risk factors, switching to transdermal testosterone and lowering the testosterone dose as management options, and advises against routine venesection (blood removal) except in clonal disease (Tramontana et al., Endocr Connect 2025).
Side effects and risks
Dapagliflozin has no boxed warning. Its only labeled contraindication is a history of serious hypersensitivity to dapagliflozin or the tablet’s ingredients; anaphylaxis and angioedema have been reported (FDA label). The label notes that no new adverse reactions emerged in DAPA-HF, DELIVER or DAPA-CKD, and that severe hypoglycemia and diabetic ketoacidosis occurred only in patients with diabetes.
Common adverse reactions
From the label’s pool of 12 placebo-controlled glycemic trials (12–24 weeks):
| Adverse reaction | Placebo | 5 mg | 10 mg |
|---|---|---|---|
| Genital fungal infection, women | 1.5% | 8.4% | 6.9% |
| Genital fungal infection, men | 0.3% | 2.8% | 2.7% |
| Urinary tract infection | 3.7% | 5.7% | 4.3% |
| Increased urination | 1.7% | 2.9% | 3.8% |
| Nasopharyngitis | 6.2% | 6.6% | 6.3% |
| Back pain | 3.2% | 3.1% | 4.2% |
Genital and urinary infections
Glucose in the urine feeds yeast and bacteria. The most common genital infections were vulvovaginal yeast infections in women and balanitis (inflammation of the head of the penis) in men. People with a past genital fungal infection were much more likely to get one on treatment: 25.0% on 10 mg versus 10.0% on placebo, compared with 5.0% versus 0.8% in those without such a history. In DECLARE, genital infections that led to stopping the drug or were serious occurred in 0.9% versus 0.1% (Wiviott et al., NEJM 2019).
Serious infections are rare but listed as warnings: urosepsis, kidney infection (pyelonephritis) and Fournier’s gangrene, a necrotizing infection of the perineum that has required multiple surgeries and caused deaths. The label says to evaluate immediately anyone with pain, tenderness, redness or swelling in the genital or perineal area together with fever or malaise.
Ketoacidosis
SGLT2 inhibitors can cause ketoacidosis (a dangerous build-up of acids from fat breakdown), and the label warns that blood sugar may be only mildly raised, for example under 250 mg/dL, which can delay diagnosis. In DECLARE, diabetic ketoacidosis occurred in 27 of 8,574 patients on dapagliflozin and 12 of 8,569 on placebo. Fatal cases have been reported after marketing.
Triggers named in the label include:
- reduced or missed insulin doses;
- acute illness with fever;
- reduced calorie intake or a ketogenic diet;
- surgery;
- volume depletion;
- alcohol abuse.
Urinary glucose loss lasts about 3 days after stopping, but postmarketing reports describe ketoacidosis or glucosuria lasting longer than 6 days and up to 2 weeks after stopping an SGLT2 inhibitor. The drug is not recommended for blood sugar control in type 1 diabetes, where the risk is markedly higher.
Volume depletion and kidney function
Dapagliflozin causes an osmotic diuresis (extra urine driven by glucose), which can lead to dehydration, low blood pressure on standing, or acute kidney injury; some postmarketing cases needed dialysis. Risk is higher in older adults, people with eGFR under 60 and those on loop diuretics. In DECLARE, volume depletion events occurred in 2.5% on dapagliflozin and 2.4% on placebo overall, and in 6.6% versus 6.1% among patients on loop diuretics.
Starting the drug causes a small, expected rise in serum creatinine and drop in eGFR within about two weeks, which then stabilizes. The label says changes that do not follow this pattern should be investigated as possible kidney injury.
Hypoglycemia
Dapagliflozin rarely causes low blood sugar on its own, but the risk rises when it is added to insulin or a sulfonylurea. In a 24-week add-on to insulin trial, glucose under 54 mg/dL occurred in 23.0% on 10 mg versus 21.8% on placebo; on metformin alone, no such episodes were recorded in any arm.
Lipids and other lab effects
In the 13-trial pool, LDL cholesterol rose 2.9% with dapagliflozin 10 mg versus a 1.0% fall with placebo at week 24. The label also notes:
- urine glucose tests will be positive, so they cannot be used to monitor blood sugar;
- the 1,5-anhydroglucitol (1,5-AG) blood test is unreliable on SGLT2 inhibitors.
Interactions and special populations
- Insulin and sulfonylureas. May need lower doses to avoid hypoglycemia.
- Lithium. SGLT2 inhibitors may lower lithium levels; the label advises more frequent lithium monitoring.
- Testosterone. Not a labeled interaction, but both raise hematocrit (see above).
- Pregnancy. Not recommended in the second and third trimesters, based on kidney changes in rats exposed during kidney development.
- Breastfeeding. Not recommended.
Monitoring
The label and the studies above point to these checks:
| What | Why |
|---|---|
| Kidney function (eGFR) | Before starting and as clinically indicated; an early small dip is expected |
| Volume status and blood pressure | Before starting, especially in older adults and people on diuretics |
| Ketones when ill, fasting or around surgery | Ketoacidosis can occur with near-normal glucose |
| Signs of genital or urinary infection | Common; rarely severe (Fournier’s gangrene) |
| Hematocrit, if also on testosterone | Observational data link the combination to hematocrit over 54% |
Legal status and use outside medicine
In the US, dapagliflozin is a prescription drug and is not a controlled substance. It is not named on the WADA 2026 Prohibited List. The list’s S5 class bans named diuretics plus “other substances with a similar chemical structure or similar biological effect(s)”, and SGLT2 inhibitors are not among the named examples.
Interest outside its approved uses usually centers on fat loss and on heart and kidney protection. The weight loss in trials was modest (about 2 kg more than placebo at 24 weeks in the DXA study) and the outcome benefits were shown in people with diabetes, heart failure or CKD, not in healthy or athletic populations.
Key takeaways
- Kidney glucose blocker with heart and kidney outcomes. Dapagliflozin makes the kidney excrete about 70 g of glucose a day and is FDA-approved for type 2 diabetes, heart failure and CKD.
- Outcome trials are strong in their populations. It cut heart failure hospitalization in DECLARE-TIMI 58, worsening heart failure or CV death in DAPA-HF (HR 0.74), and the kidney composite in DAPA-CKD (HR 0.61); it did not reduce MACE in DECLARE.
- Hematocrit rises. The label reports a mean rise of 2.3 points, partly from true red cell production. Observational studies link SGLT2 inhibitors plus testosterone to more erythrocytosis than either alone.
- Infections and ketoacidosis are the key risks. Genital yeast infections are common, Fournier’s gangrene is rare but serious, and ketoacidosis can occur at near-normal blood sugar.
- Weight loss is modest. About 2 kg more than placebo at 24 weeks, mostly fat; it is not approved for weight loss.
Sources
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- European Medicines Agency. Forxiga (dapagliflozin): EPAR. EMA.
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