Jardiance (Empagliflozin) FDA Approval, Label, Safety, and What's Coming Next

When Was Jardiance FDA Approved, and What Has Changed Since?

Jardiance earned its first FDA approval on August 1, 2014 for glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise. That initial label covered 10 mg once daily, with an option to increase to 25 mg for additional glycemic benefit.

The approval story did not stop there. Boehringer Ingelheim and Eli Lilly built a post-marketing regulatory strategy around outcomes data, and the label has expanded three times since launch.

The Cardiovascular Outcomes Milestone

The EMPA-REG OUTCOME trial, published in the New England Journal of Medicine in 2015, enrolled 7,020 adults with type 2 diabetes and established cardiovascular disease. Empagliflozin reduced the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke by 14% compared with placebo. Cardiovascular death alone fell by 38%. These were the numbers that changed the trajectory of the entire SGLT2 inhibitor class.

For women specifically, the EMPA-REG OUTCOME trial enrolled approximately 28.5% female participants, a proportion that reflects the chronic under-representation of women in cardiovascular outcomes trials. Subgroup analyses suggested the cardiovascular mortality benefit was directionally consistent in women, but the trial was not powered to confirm sex-specific effect sizes. That evidence gap matters clinically and you deserve to know it exists.

Heart Failure Label Expansions

Following the EMPEROR-Reduced trial, the FDA expanded the label in August 2021 to include reducing the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status. The EMPEROR-Preserved trial then supported a further expansion covering heart failure with preserved ejection fraction (HFpEF), which was formally added to the label in May 2022.

HFpEF is disproportionately a women's disease. Women account for roughly 55 to 60% of HFpEF patients, driven by higher rates of hypertension, obesity, and diastolic dysfunction across midlife and beyond. The empagliflozin HFpEF approval is therefore one of the most women-relevant regulatory decisions in the drug's history, even though it is rarely framed that way.

Chronic Kidney Disease Approval

In February 2023, the FDA approved empagliflozin to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease (CKD). This was based on the EMPA-KIDNEY trial, which enrolled patients with CKD across a broad eGFR range, including those without diabetes.

Women with PCOS, type 2 diabetes, or a history of recurrent urinary tract infections carry specific CKD risk profiles. The EMPA-KIDNEY data have not yet been published with sex-stratified primary outcomes as a standalone analysis, which is a gap the research community has noted.

What Does the Current Jardiance Label Say?

The prescribing information, last substantively updated following the CKD approval, covers several areas that matter most to women.

Approved Indications and Doses

The FDA-approved prescribing information lists four indications:

1. Glycemic control in adults with type 2 diabetes (adjunct to diet and exercise): 10 mg once daily in the morning, with or without food; may increase to 25 mg if better glycemic control is needed and tolerated.
2. Reducing cardiovascular death and hospitalization in adults with heart failure (both HFrEF and HFpEF): 10 mg once daily.
3. Reducing risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization in adults with CKD at risk of progression: 10 mg once daily.

The 25 mg dose is approved only for glycemic control, not for the cardiovascular or kidney indications.

Contraindications on the Label

The label lists two absolute contraindications: a history of serious hypersensitivity reactions to empagliflozin, and use during dialysis. It also states that empagliflozin should not be initiated when eGFR is below 20 mL/min/1.73 m² for the glycemic indication, though the cardiorenal indications permit lower eGFR thresholds based on EMPA-KIDNEY data.

Warnings and Precautions Specific to Women

The label's genital mycotic infection warning has particular clinical weight for women. Across pooled phase III trials, genital mycotic infections occurred in approximately 10.0% of women taking empagliflozin versus 1.5% of men, reflecting the anatomical reality that glucosuria creates an environment conducive to Candida overgrowth in the vulvovaginal region. If you have recurrent vulvovaginal candidiasis at baseline, that history should factor into the shared decision-making conversation before starting this drug.

Urinary tract infections are also listed, though the label notes that the rate difference from placebo was modest in trials. Women have a baseline UTI incidence roughly four times that of men across reproductive years, so even modest increases in absolute risk are clinically meaningful.

A practical framework for women by life stage:

| Life Stage | Primary Concern with Empagliflozin | Action | |---|---|---| | Reproductive years (18-40) | Genital yeast infections; contraception if sexually active | Baseline candidiasis history; reliable contraception required | | Trying to conceive | Embryo-fetal toxicity risk | Discontinue before conception if possible | | Pregnancy | Contraindicated from second trimester; avoid in first | Stop immediately; switch to pregnancy-safe agent | | Postpartum / breastfeeding | Unknown lactation transfer; infant kidney development risk | Avoid; choose alternative | | Perimenopause (40-55) | HFpEF risk rises; UTI risk rises post-menopause | Re-evaluate cardiometabolic risk annually | | Post-menopause | HFpEF benefit most relevant; bone density concern | Assess fracture risk at initiation |

Pregnancy, Lactation, and Contraception: What You Must Know

Empagliflozin is contraindicated during the second and third trimesters of pregnancy and should be avoided in the first trimester. This is not a soft recommendation. State it clearly to any prescriber.

Embryo-Fetal Toxicity

The FDA prescribing information carries a clear warning that SGLT2 inhibitors affect renal tubular handling of glucose in the fetal kidney. Animal studies showed adverse renal developmental effects at exposures that, in some species, were comparable to human therapeutic doses. Human prospective data are limited because pregnant women are excluded from trials, which is the fundamental evidence problem.

The FDA drug label recommends discontinuing empagliflozin as soon as pregnancy is detected. For women with type 2 diabetes who become pregnant, insulin remains the standard of care for glycemic management, per ACOG Practice Bulletin guidance on diabetes in pregnancy.

Lactation

There are no adequate human data on empagliflozin transfer into breast milk, the effects on the breastfed infant, or effects on milk production. Animal lactation studies showed drug presence in milk. Because of the potential for serious adverse reactions in the nursing infant, including possible effects on kidney development, the prescribing information advises against using empagliflozin while breastfeeding. If glycemic control is needed postpartum, discuss alternatives with your provider.

Contraception Requirements

Empagliflozin is not classified as a formal teratogen requiring a REMS program or mandatory contraception enrollment, unlike some other women's-health drugs. Still, because unintended pregnancy exposure during organogenesis (weeks 3 to 8) carries real risk before a woman may know she is pregnant, using reliable contraception while taking empagliflozin during reproductive years is a reasonable clinical precaution. Discuss your contraceptive plan with your prescriber, particularly if you have PCOS-related irregular cycles, which can make pregnancy detection slower.

Jardiance Safety Profile: What the Data Actually Show in Women

Safety data from post-market surveillance, the FDA Sentinel system, and published pharmacovigilance add texture to the trial-based label.

Diabetic Ketoacidosis

Euglycemic diabetic ketoacidosis (DKA) is a known class effect of SGLT2 inhibitors. Women with type 1 diabetes who receive empagliflozin off-label (it is not approved for type 1) appear to have a somewhat higher DKA rate than men in observational data, though the mechanistic explanation is still under study. Prolonged fasting, low-carbohydrate diets, and perioperative periods all increase DKA risk on SGLT2 inhibitors, and these are exposures women should discuss with their surgical team before any planned procedure.

Bone Fracture Risk

The EMPA-REG OUTCOME trial reported no significant increase in fracture risk with empagliflozin, which distinguished it from canagliflozin in early class comparisons. Post-menopausal women already face elevated fracture risk from estrogen loss, and bone density assessment before or shortly after starting empagliflozin is reasonable clinical practice for women over 50, even if the label does not require it.

Fournier Gangrene

The FDA issued a safety communication in August 2018 warning about Fournier gangrene (necrotizing fasciitis of the perineum) with the SGLT2 inhibitor class. The case series included both men and women. Any new perineal pain, swelling, or redness while taking empagliflozin warrants immediate evaluation.

Cardiovascular Sex Differences

A 2020 analysis in Circulation examined SGLT2 inhibitor effects by sex across major trials and found that the magnitude of HFpEF benefit may be greater in women, though confidence intervals overlapped substantially. This is an area of active secondary analysis, not settled science.

Empagliflozin and Women's Conditions: PCOS, Perimenopause, and Metabolic Health

Several female-specific conditions make empagliflozin clinically relevant beyond its approved indications, though the evidence ranges from early-stage to modest.

PCOS and Insulin Resistance

PCOS affects approximately 8 to 13% of women of reproductive age worldwide and is characterized by insulin resistance in the majority of cases. Empagliflozin's mechanism of insulin-independent glycosuria makes it theoretically attractive in PCOS, where first-line metformin works through a different pathway.

Small randomized pilot trials have explored SGLT2 inhibitors in PCOS. A 2022 trial published in Fertility and Sterility compared dapagliflozin with metformin in PCOS and found similar improvements in insulin resistance and androgens with fewer gastrointestinal side effects. Empagliflozin-specific PCOS data are sparse. Extrapolating from class-level evidence is reasonable but must be acknowledged as extrapolation, not established practice. Empagliflozin is not FDA-approved for PCOS.

Perimenopause and Metabolic Shift

Perimenopause, typically spanning ages 40 to 55, brings a shift toward visceral adiposity, rising fasting glucose, and increasing cardiovascular risk, even in women who were metabolically healthy before. The declining estrogen of the menopausal transition worsens insulin sensitivity directly.

No prospective randomized trial has enrolled perimenopausal women as its primary population to test empagliflozin's metabolic effects across the transition. That is an honest evidence gap. What exists are subgroup analyses from larger trials showing benefit in women over 50, and observational data showing that SGLT2 inhibitors reduce visceral fat by approximately 10 to 15% over 24 weeks in adults with type 2 diabetes, which may be particularly relevant for women in whom central adiposity rises during the menopausal transition.

Female Pattern Metabolic Disease

Women with type 2 diabetes face higher relative cardiovascular mortality risk compared with similarly diagnosed men, a pattern sometimes called the "female disadvantage" in diabetes outcomes. Data from the AHA suggest that treatments that reduce heart failure hospitalization may close this gap. Empagliflozin's consistent HFpEF benefit is therefore more women-targeted than most cardioprotective agents approved in the past decade.

The Empagliflozin Pipeline: What Is Coming Next

Regulatory activity around empagliflozin continues across several fronts.

Pediatric Label Expansion

The FDA required a pediatric investigation as a condition of adult approval. Boehringer Ingelheim submitted pediatric data, and the FDA granted approval of empagliflozin for type 2 diabetes in pediatric patients aged 10 years and older in March 2023. Adolescent girls with type 2 diabetes, a population in which PCOS frequently co-exists, now have a labeled option, though the genital mycotic infection risk warrants particular counseling in this age group.

Fixed-Dose Combinations

A fixed-dose combination of empagliflozin 10 mg plus linagliptin 5 mg (brand name Glyxambi) received FDA approval and represents the most clinically used combination product. Boehringer Ingelheim and Lilly have pursued additional combination strategies. The regulatory pathway for these products follows standard NDA/sNDA routes with bridging bioequivalence studies.

Cardiovascular Indication Refinements

Post-market studies continue to refine which subpopulations benefit most. The ongoing EMPACT-MI trial examined empagliflozin after acute myocardial infarction and published results in 2024, adding to the growing evidence base for use in broader cardiometabolic settings. Whether sex-stratified analyses from this trial will support label language specifically addressing women remains to be seen.

EMA and Global Regulatory Status

The European Medicines Agency (EMA) approved empagliflozin under the brand name Jardiance with a regulatory history closely paralleling the FDA timeline, including cardiorenal indications. EMA EPAR documents provide European post-marketing pharmacovigilance data that supplement FDA Sentinel findings, particularly for rare adverse events where pooling global data improves signal detection.

Who Jardiance Is Right For (and Not Right For): A Life-Stage View

Likely a Good Fit

• Women with type 2 diabetes and established cardiovascular disease, particularly those over 50 with HFpEF risk factors.
• Post-menopausal women with heart failure and preserved ejection fraction who are not pregnant and do not have active recurrent candidiasis that has not responded to antifungal treatment.
• Women with CKD and proteinuria who meet eGFR thresholds and are not pregnant or breastfeeding.
• Women with type 2 diabetes in perimenopause who have progressed beyond metformin monotherapy and for whom visceral fat reduction and cardiorenal protection are goals.

Requires Careful Conversation First

• Women with a history of recurrent vulvovaginal candidiasis: the yeast infection risk is real and approximately 10% in trials. Prophylactic antifungal strategies exist but add complexity.
• Women with PCOS who are not using reliable contraception: unintended pregnancy while on empagliflozin creates a teratogen-exposure scenario.
• Women who follow very low carbohydrate diets: elevated DKA risk from volume depletion and low insulin secretion warrants close monitoring.

Not Appropriate

• Women who are pregnant or planning pregnancy in the near term.
• Breastfeeding women.
• Women on dialysis.
• Women with type 1 diabetes outside a clinical trial setting (not FDA-approved, elevated DKA risk).

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