Farxiga Sexual Function Impact: What Dapagliflozin Does (and Doesn't Do) to Libido, Erectile Function, and Genital Health

Does dapagliflozin lower libido or cause erectile dysfunction?

The Farxiga label's Table 1 lists adverse reactions reported in at least 2% of adults with type 2 diabetes across 12 placebo-controlled trials. Erectile dysfunction and low libido do not appear in it [5]. The table covers 1,393 people on placebo, 1,145 on dapagliflozin 5 mg and 1,193 on 10 mg, treated for 12 to 24 weeks [5]. Its genital and urinary entries are female genital mycotic infections, male genital mycotic infections, urinary tract infections and discomfort with urination [5].

A 2% cutoff will not capture uncommon events, so the table cannot rule out a small effect on sexual function either way.

What dapagliflozin measurably changes

Dapagliflozin blocks the sodium-glucose cotransporter 2 in the kidney, so more glucose leaves the body in urine, causing an osmotic diuresis [5]. Glucose lowering depends on kidney function and fades at low eGFR, while the heart and kidney benefits appear with or without diabetes [5].

Three changes have been measured directly:

• HbA1c. In a 24-week monotherapy trial described in the label, HbA1c fell 0.9 points on 10 mg and 0.8 on 5 mg, against 0.2 on placebo [5].
• Weight. In a 24-week trial of 182 adults with type 2 diabetes taking metformin, placebo-corrected total body weight fell 2.08 kg (95% CI -2.84 to -1.31) [6].
• Blood pressure. A review of dapagliflozin's cardiovascular risk-factor effects describes blood pressure reductions consistent with modest diuresis and weight loss [7].

Diabetes itself is tied to sexual problems. A review of diabetes and sexual dysfunction reports a threefold higher risk of erectile dysfunction in diabetic than nondiabetic men, and a generally higher but less consistent prevalence of female sexual dysfunction [8]. The Massachusetts Male Aging Study, a community-based survey of men aged 40 to 70 near Boston, found complete impotence rose from 5% to 15% between ages 40 and 70 and, after adjustment for age, correlated with heart disease, hypertension and diabetes [9]. These are background risks in the people who take the drug.

Genital yeast infections: the effect the label does quantify

The label says dapagliflozin increases urinary glucose excretion and increases the risk of genitourinary infections, including genital mycotic infections, in both men and women [5]. A pooled analysis of 12 placebo-controlled trials relates these infections to glucosuria [10]. In the label's 12-trial pool, genital mycotic infections were reported in 8.4% of women on 5 mg and 6.9% on 10 mg, against 1.5% on placebo, and in 2.8% of men on 5 mg and 2.7% on 10 mg, against 0.3% on placebo [5]. Female genital mycotic infections are among the three most common adverse reactions in the label, alongside nasopharyngitis and urinary tract infection [5].

In the pooled analysis (4,545 patients: 3,152 on dapagliflozin, 1,393 on placebo), diagnosed genital infections occurred in 4.1% on 2.5 mg, 5.7% on 5 mg and 4.8% on 10 mg, against 0.9% on placebo [10]. Most were mild or moderate and responded to standard antimicrobial treatment, discontinuation because of them was rare, and there was no clear dose-response [10].

The label notes that people with a history of genitourinary infections are more likely to develop one on dapagliflozin, and it says to monitor for signs and symptoms and treat promptly [5]. Urinary tract infections are reported separately, at 3.7% on placebo, 5.7% on 5 mg and 4.3% on 10 mg [5], a much smaller gap than for genital yeast infections.

Fournier's gangrene

The label's warnings section covers necrotizing fasciitis of the perineum (Fournier's gangrene), a rare, life-threatening infection that requires urgent surgical intervention [5]. Reported cases have required hospitalization, and serious outcomes have included multiple surgeries and death [5]. The label says to immediately evaluate pain or tenderness, erythema, or swelling in the genital or perineal area accompanied by fever or malaise for necrotizing fasciitis, and, if it is suspected, to discontinue dapagliflozin and promptly start medical and/or surgical treatment [5].

Medicines and tests that interact with dapagliflozin

The label's clinically relevant interactions are few [5]:

• Insulin and insulin secretagogues such as sulfonylureas raise hypoglycemia risk, and the label says a lower dose of the insulin or secretagogue may be needed.
• Lithium concentrations may fall, and the label says to monitor lithium more often at initiation and with dose changes.
• Urine glucose tests will be positive and the 1,5-anhydroglucitol assay is unreliable, so the label says to use another method to monitor glycemic control.

In vitro, dapagliflozin neither inhibited nor induced the major CYP enzymes, and it is unlikely to affect the pharmacokinetics of medicines that are P-gp, OCT2, OAT1 or OAT3 substrates [5]. The label's interaction table does not list any medicine used for sexual function [5].