Jardiance Side Effects: Potentially Permanent Adverse Events Women Need to Know

What Is Empagliflozin and Why Do Women Use It?

Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that blocks glucose reabsorption in the kidney, causing roughly 60-90 grams of glucose per day to be excreted in the urine. The FDA approved Jardiance for glycemic control in type 2 diabetes (T2D) in 2014, for heart failure in 2021, and for chronic kidney disease in 2023.

Women use this drug across several overlapping conditions. PCOS increases insulin resistance, making T2D and prediabetes more common in reproductive-age women. Perimenopause accelerates metabolic decline. Heart failure with preserved ejection fraction (HFpEF) disproportionately affects postmenopausal women. This drug lands in a lot of women's medicine cabinets.

The landmark EMPA-REG OUTCOME trial enrolled 7,020 patients and demonstrated a 38% relative reduction in cardiovascular death with empagliflozin 10 mg or 25 mg versus placebo in adults with T2D and established cardiovascular disease. Women made up only about 29% of that trial. That enrollment gap matters for interpreting sex-specific risk data.

Common Side Effects: Higher Burden in Women

Most women on Jardiance tolerate it, but two side effects occur significantly more often in women than in men.

Genital Mycotic Infections

The most reported side effect in women is vulvovaginal candidiasis. In the EMPA-REG OUTCOME trial and pooled phase III data, genital mycotic infections occurred in approximately 10-14% of women compared with roughly 4% of men. The glycosuria (sugar in the urine) that makes the drug work also feeds Candida species in the vagina and vulva.

Women who experience recurrent or severe episodes may need:

• Longer courses of topical azole antifungals (7-14 days rather than a single dose)
• Oral fluconazole for severe infections
• Dose review with their prescriber if infections are monthly

Women with diabetes already have a baseline elevated risk of vulvovaginal candidiasis. Empagliflozin compounds that risk. Postmenopausal women on vaginal estrogen therapy may have some mucosal protection, but this has not been studied in a controlled trial specific to SGLT2 inhibitors.

Urinary Tract Infections

Pooled empagliflozin trial data show UTI incidence of approximately 8-12% in women, compared with 3-4% in men. Postmenopausal women are already at elevated UTI risk due to hypoestrogenic urogenital atrophy. Adding chronic glycosuria creates a nutrient-rich urinary environment for bacteria.

Women in perimenopause or postmenopause who have a history of recurrent UTIs should discuss this compounded risk with their clinician before starting empagliflozin. Local vaginal estrogen can reduce UTI recurrence in postmenopausal women independent of empagliflozin use, and the combination is worth considering.

Genital Itching and Irritation

Even without a confirmed infection, genital pruritis (itching) and irritation from the glucose-laden urine occurs in a meaningful minority of women. Good perineal hygiene, moisture-wicking underwear, and rinsing after urination can reduce severity. These symptoms are not permanent but can significantly affect quality of life and sexual comfort.

Potentially Permanent Side Effect: Fournier's Gangrene

This is the side effect women ask about most and understand least. Fournier's gangrene is a necrotizing fasciitis (flesh-eating infection) of the perineum and genitalia. It is rare. It is life-threatening. In women who survive, it can cause permanent disfigurement of the vulva, perineum, and surrounding structures.

What the FDA Data Show

In 2018, the FDA issued a Drug Safety Communication warning that 12 cases of Fournier's gangrene had been identified among SGLT2 inhibitor users reported to the FDA Adverse Event Reporting System (FAERS) between March 2013 and May 2018. All 12 required surgery. Some required multiple debridements (removal of dead tissue). One patient died. In a matched historical cohort using other antidiabetic drugs, the FDA identified only 6 cases over a 35-year period, suggesting a real signal above background.

A 2019 FAERS analysis by Bersoff-Matcha et al. Published in Annals of Internal Medicine identified 55 cases across all SGLT2 inhibitors through January 2019, including 19 women. Women represented roughly 35% of cases despite making up a minority of SGLT2 inhibitor prescriptions at the time, suggesting women may not be at lower risk than men for this complication.

Why This Can Be Permanent

Necrotizing fasciitis spreads along fascial planes at a rate of up to 2-3 centimeters per hour without treatment. Surgical debridement is the only effective treatment, and the tissue removed does not regenerate. Women who develop Fournier's gangrene may require:

• Removal of labia majora or minora tissue
• Perineal reconstruction
• Colostomy in severe cases involving the rectum
• Multiple surgeries over months

The functional and psychological consequences, including effects on sexual function and body image, can be permanent.

Warning Signs Every Woman Should Know

Seek emergency care immediately if you develop any of these while on Jardiance:

• Pain, tenderness, or swelling in the genitals or perineum that is out of proportion to what you can see
• Redness or warmth spreading from the genitals toward the inner thighs
• Fever over 38.3°C (101°F) with genital symptoms
• Any skin that appears dark, blistered, or crepitant (crackling sensation under the skin)

Delay in diagnosis is the main driver of worse outcomes. Do not wait for a telehealth appointment if these symptoms appear.

Diabetic Ketoacidosis: A Serious Risk With Female-Specific Nuances

Empagliflozin is associated with euglycemic diabetic ketoacidosis (DKA), a form of DKA in which blood glucose may be only mildly elevated (sometimes below 200 mg/dL) while life-threatening acidosis develops. The FDA issued a safety communication on this in 2015.

Women With PCOS Face Elevated DKA Risk

PCOS affects an estimated 8-13% of reproductive-age women worldwide and is characterized by insulin resistance, hyperandrogenism, and ovulatory dysfunction. Women with PCOS who also carry type 1 diabetes misdiagnosed as type 2, or who have latent autoimmune diabetes in adults (LADA), are at elevated risk if prescribed empagliflozin without an appropriate diagnostic workup. SGLT2 inhibitors are not approved for type 1 diabetes, and euglycemic DKA risk in that population is substantially higher.

Even in true type 2 diabetes, women with PCOS who follow low-carbohydrate or ketogenic diets, which are commonly recommended for PCOS management, face additional DKA risk on SGLT2 inhibitors. The combination of carbohydrate restriction and SGLT2-mediated glucose dumping creates the conditions for ketone accumulation even when blood glucose remains near normal.

Perimenopause and Insulin Shifts

Estrogen has direct effects on beta-cell insulin secretion and peripheral insulin sensitivity. As estrogen falls during perimenopause, insulin secretory capacity and sensitivity both decline. A woman whose glycemic control was stable on empagliflozin may find her metabolic state shifts unpredictably during the perimenopausal transition. Clinicians should increase monitoring frequency during this period, not decrease it.

Surgical and Fasting Risk

The FDA and the American Diabetes Association recommend holding empagliflozin at least 3-4 days before any elective surgery or prolonged fasting. Women undergoing gynecological procedures (hysterectomy, myomectomy, laparoscopy for endometriosis, oocyte retrieval) must inform their surgical team they are taking this drug. Post-surgical DKA cases have been reported following procedures where the drug was continued.

Kidney and Volume Effects

Acute Kidney Injury

The FDA added a warning for acute kidney injury (AKI) to SGLT2 inhibitor labeling in 2016. Empagliflozin causes an initial dip in eGFR due to hemodynamic changes in the glomerulus. This is reversible when the drug is stopped, but if a woman becomes volume-depleted (from vomiting, diarrhea, excessive heat, or aggressive diuresis with a loop diuretic), AKI can follow.

Women who also take ACE inhibitors, ARBs, or NSAIDs for conditions like lupus nephritis or menstrual pain face additive kidney risk. This combination is sometimes called the "triple whammy" for nephrotoxicity.

Volume Depletion in Smaller-Bodied Women

Empagliflozin has a mild diuretic effect. Women, on average, have a smaller circulating blood volume than men. This means the absolute volume loss from SGLT2-induced glycosuria and osmotic diuresis can represent a larger proportion of total volume in a petite woman than in a larger man. Symptoms of dehydration, including dizziness, lightheadedness on standing (orthostatic hypotension), and fatigue, may be more pronounced.

Women on blood pressure medications, particularly in summer months or during fever, should discuss sick-day rules with their clinician. Standard advice is to hold empagliflozin if unable to eat or drink normally for more than 24 hours.

Bone and Fracture Risk: What We Know in Women

The CANVAS trial of canagliflozin, a related SGLT2 inhibitor, showed a significant increase in fracture risk. The EMPA-REG OUTCOME trial did not show this signal with empagliflozin, but the trial was not designed or powered to detect fracture outcomes.

Women over 50 are already at elevated fracture risk, and postmenopausal women lose bone rapidly in the years following menopause. The North American Menopause Society (NAMS) guidelines recommend baseline DEXA scanning for women at risk. If you are a postmenopausal woman with osteopenia or osteoporosis being prescribed empagliflozin, a bone health plan should be part of your care, even if the drug-specific fracture data are not as alarming as with canagliflozin.

Lower Limb Amputation: Signal vs. Noise

Canagliflozin carries an FDA black box warning for lower limb amputation risk based on the CANVAS trial. Empagliflozin does not carry this warning, and the EMPA-REG OUTCOME trial did not show a significant amputation signal. Women with peripheral arterial disease or severe diabetic neuropathy should still have their lower extremities assessed regularly, as this is standard diabetes care, but the amputation concern is less pressing with empagliflozin specifically than with canagliflozin.

Pregnancy, Lactation, and Contraception: Required Reading

Jardiance is contraindicated during the second and third trimester of pregnancy. This is not a relative contraindication. Stop the drug.

Pregnancy Category and Human Data

The FDA has removed the A/B/C/D/X letter categories and replaced them with narrative labeling. The current Jardiance prescribing information states that animal studies showed adverse renal effects in offspring when empagliflozin was administered during organogenesis at doses relevant to human exposure. Rat studies at 13 times the maximum recommended human dose showed renal pelvic dilatation and tubular dilatation in offspring, effects that were irreversible in some animals.

Human data during the second and third trimester are limited, but the mechanism is concerning: fetal kidneys begin active urine production by weeks 10-12 and are the primary source of amniotic fluid thereafter. SGLT2 inhibition in the fetal kidney may impair this function, leading to oligohydramnios (low amniotic fluid) with potentially permanent renal consequences for the baby.

The first trimester risk is less certain in humans. Animal teratogenicity data at recommended doses were not conclusive, but no adequate and well-controlled human trials have been conducted. The conservative clinical standard is to avoid empagliflozin throughout pregnancy.

Contraception Requirement

Women of reproductive age prescribed empagliflozin should use effective contraception. If planning a pregnancy, empagliflozin should be discontinued before conception attempts. Discuss transition to a pregnancy-compatible glucose-lowering regimen (insulin is the standard of care in T2D during pregnancy) with your clinician at least one to three months before attempting conception.

Lactation

The Jardiance label advises against breastfeeding during treatment. Empagliflozin is excreted in rat milk at levels approximately 11 times the maternal plasma concentration. Human lactation transfer data are absent. Given the potential for renal effects in a nursing infant whose kidneys are still developing, the precautionary recommendation is to avoid breastfeeding while taking this drug.

Women who are breastfeeding and require glucose-lowering medication should discuss insulin or, in some cases, metformin (which has more lactation data) with their clinician.

PCOS and Fertility

Women with PCOS using empagliflozin off-label for insulin resistance or weight management (neither an FDA-approved indication in isolation) need a specific conversation framework before prescribing:

1. Is this woman actively trying to conceive? If yes, empagliflozin is not appropriate.
2. Is she using reliable contraception? Document this before prescribing.
3. Does she have LADA or type 1 misdiagnosed as type 2? Check C-peptide and anti-GAD antibodies before prescribing, as SGLT2 inhibitors in true type 1 carry high DKA risk.
4. If she has PCOS and follows a ketogenic diet, has she been counseled specifically on euglycemic DKA?

This four-point check is not part of any current published PCOS guideline, but it reflects the gaps that ASRM and ACOG leave open regarding SGLT2 inhibitor use in reproductive-age women with PCOS.

Who This Drug Is Right For (and Who Should Think Twice)

Women Who Tend to Benefit Most

• Postmenopausal women with T2D and established cardiovascular disease (EMPA-REG OUTCOME showed cardiovascular mortality benefit)
• Women with T2D and heart failure with reduced ejection fraction (HFrEF) per EMPEROR-Reduced trial data
• Women with T2D and CKD (eGFR 20-44 mL/min/1.73m² now labeled per EMPA-KIDNEY trial)
• Women who need modest weight reduction alongside glycemic control

Women Who Should Approach With Caution or Avoid

• Pregnant women in any trimester (avoid; contraindicated in 2nd/3rd)
• Breastfeeding women (avoid)
• Women with a history of recurrent vulvovaginal candidiasis (consider alternative agents)
• Women with recurrent UTIs, particularly postmenopausal women without vaginal estrogen
• Women on low-carbohydrate or ketogenic diets (elevated DKA risk)
• Women with PCOS who may have undiagnosed LADA
• Women with eGFR <20 mL/min/1.73m² (reduced efficacy and increased risk)
• Women with frequent episodes of DKA or hyperosmolar hyperglycemic state

Evidence Gaps Specific to Women

The clinical trial evidence base for empagliflozin is substantial by pharmaceutical standards, but women were consistently underrepresented. In EMPA-REG OUTCOME, women were 29% of participants. In EMPEROR-Reduced, women were 24% of enrollees. In EMPA-KIDNEY, women made up approximately 33% of the cohort.

Sex-disaggregated subgroup analyses in these trials generally showed direction-consistent benefit in women, but they were not powered to detect whether the magnitude of benefit, or the pattern of harm, differs meaningfully by sex. What we call "women's data" from these trials is largely extrapolation from male-dominant populations. The infection data (yeast, UTIs) are an exception, where female-specific rates are consistently reported.

A 2021 analysis in Diabetes Care found that the glycemic efficacy of SGLT2 inhibitors was modestly lower in women than in men (HbA1c reduction approximately 0.1-0.2% less), possibly related to differences in SGLT2 expression density or renal glucose handling by sex. The clinical relevance of this small difference is uncertain, but it represents one of the few sex-specific pharmacodynamic findings published for this drug class.

Monitoring While on Jardiance: A Women's Checklist

Monitoring empagliflozin effectively in women means paying attention to the right parameters at the right intervals.

• eGFR and serum creatinine: At baseline, at 3 months, then every 6-12 months
• Urinalysis with culture: If any UTI symptoms arise. Do not assume pyuria from glycosuria alone
• Ketones (blood or urine): If nausea, vomiting, abdominal pain, or altered mentation develops, even if fingerstick glucose is near normal
• Blood pressure and orthostatic vitals: At each visit, especially in women on antihypertensives or diuretics
• Genital exam: Self-examination; report any unusual pain, swelling, or skin change in the perineum without delay
• Bone density (DEXA): Per standard osteoporosis screening guidelines for women 65+ or younger postmenopausal women with risk factors
• Pregnancy test: Before prescribing or renewing in women of reproductive age

If you are perimenopausal and your glycemic control has become unpredictable, bring this up at your next visit. Hormonal shifts during the menopausal transition may require dose adjustment or a switch to a different agent.