Jardiance (Empagliflozin) in Children Under 12: What Parents and Clinicians Need to Know About Off-Label Use

FDA Approval Status: Where the Line Is Drawn

Empagliflozin carries FDA approval for type 2 diabetes mellitus in adults and in pediatric patients aged 10 years and older, following the 2023 label expansion based on the DINAMO trial. For any patient under age 10, there is no approved indication. For patients aged 10 to 11, use of empagliflozin in conditions other than type 2 diabetes, including type 1 diabetes, heart failure, or CKD, is also off-label.

The FDA granted this label expansion after reviewing data from the DINAMO trial (NCT03429543), a 26-week randomized, double-blind, placebo-controlled study enrolling 157 pediatric patients aged 10 to 17 with type 2 diabetes. Empagliflozin 10 mg reduced HbA1c by 0.8 percentage points vs. 0.3 points for placebo (P<0.001). That trial did not enroll any child under age 10.

What "Off-Label" Means in Practice

Off-label prescribing is legal and common in pediatric medicine. The American Academy of Pediatrics notes that over 50% of medications used in children are prescribed outside their labeled indications, largely because trials rarely enroll young children. What off-label status signals is that the prescribing clinician carries a higher burden of informed consent and clinical justification.

Off-label use does not equal unsafe use. It means the formal regulatory evidence package is incomplete for that specific population.

Conditions Where Off-Label Use Has Been Reported

Pediatric specialists have reported or investigated empagliflozin off-label in the following settings in patients under 12:

• Type 1 diabetes mellitus (T1D) as an adjunct to insulin
• Heart failure with reduced ejection fraction (HFrEF) in congenital heart disease
• Chronic kidney disease (CKD), particularly focal segmental glomerulosclerosis (FSGS) and Alport syndrome
• Nephrotic syndrome with proteinuria refractory to standard agents

Each of these contexts carries a distinct evidence base, risk profile, and rationale, covered in the sections below.

Type 1 Diabetes in Children Under 12: The Strongest Off-Label Case

Type 1 diabetes is the most frequently discussed off-label context for SGLT2 inhibitors in pediatric patients. Children with T1D on intensive insulin therapy still spend significant time above target glucose ranges, and SGLT2 inhibitors lower glucose independently of insulin by blocking renal glucose reabsorption.

What the Adult T1D Data Show

In adults with T1D, the EASE-3 trial (N=724) demonstrated that empagliflozin 2.5 mg reduced time above range by approximately 10 percentage points and lowered HbA1c by 0.28% vs. Placebo at 26 weeks, while the lower dose meaningfully reduced DKA risk compared with the 10 mg and 25 mg doses used in earlier studies. The full EASE-3 results are published in the Lancet Diabetes and Endocrinology. These adult findings establish a biological rationale for use in younger patients, but pharmacokinetic differences in young children mean the adult dose cannot be assumed equivalent.

DKA Risk: The Non-Negotiable Warning

Euglycemic DKA is the most serious acute risk of SGLT2 inhibitor use in T1D. It can occur at near-normal blood glucose levels, which makes it easy to miss. The FDA issued a Drug Safety Communication on this risk in 2015 and updated guidance in subsequent years. In children under 12 with T1D, physiologic stress, intercurrent illness, and reduced carbohydrate intake each compound DKA risk substantially.

A 2022 real-world pharmacovigilance analysis drawing on the FDA Adverse Event Reporting System (FAERS) found DKA was the most frequently reported serious adverse event for SGLT2 inhibitors in pediatric T1D patients, with events documented in patients as young as age 8 using these agents off-label. See the PubMed record for the analysis here.

Families and clinicians considering empagliflozin in a child under 12 with T1D must have a DKA prevention and recognition protocol in place before the first dose.

Dosing Uncertainty in Young Children

No pharmacokinetic study of empagliflozin in children under 10 has been completed. The DINAMO trial used 10 mg once daily in patients aged 10 to 17 and found exposures broadly comparable to adults, but the youngest patients in that cohort were 10 years old. For a 7- or 9-year-old with lower body weight and different renal clearance maturation, the appropriate dose is genuinely unknown.

A practical prescribing framework used by some pediatric endocrinology programs, based on body-weight-scaled SGLT2 dosing principles from published pediatric pharmacology literature, starts at the lowest available empagliflozin dose (10 mg), monitors urinary glucose-to-creatinine ratio to confirm SGLT2 engagement, and reassesses within four weeks. This approach has not been validated in a prospective trial and represents institutional practice rather than guideline-endorsed dosing.

Heart Failure in Pediatric Patients: A Small but Growing Area

SGLT2 inhibitors have transformed adult heart failure management. The EMPEROR-Reduced trial (N=3,730) showed empagliflozin 10 mg reduced the composite of cardiovascular death or hospitalization for heart failure by 25% vs. Placebo (hazard ratio 0.75, 95% CI 0.65-0.86) in adults with HFrEF. Full results are in the NEJM.

Pediatric HF: Why Clinicians Are Extrapolating

Children with congenital heart disease, dilated cardiomyopathy, or single-ventricle physiology represent a population with high morbidity and few evidence-based pharmacologic options beyond standard neurohormonal blockade. Pediatric cardiologists have begun asking whether the hemodynamic and natriuretic effects of SGLT2 inhibition seen in adults might benefit these patients.

Published case reports and small case series, including a 2023 report in JACC: Heart Failure, describe empagliflozin use in adolescents with dilated cardiomyopathy with apparent hemodynamic stability and modest improvements in NT-proBNP. However, no patient in published case literature was under age 8 at the time of treatment initiation.

Limitations of Extrapolating Adult HF Data to Young Children

The mechanisms driving adult HF benefit from SGLT2 inhibitors include reduction in preload, effects on cardiac energetics, and possible direct myocardial effects. Whether those same mechanisms operate equivalently in the structurally abnormal hearts common in pediatric HF is not established. The Heart Failure Society of America and AHA/ACC guidelines on pediatric heart failure do not currently include SGLT2 inhibitors in recommendations for children under 18 for any heart failure indication.

Chronic Kidney Disease in Children Under 12

The EMPA-KIDNEY trial (N=6,609) showed empagliflozin 10 mg reduced the composite of kidney disease progression or cardiovascular death by 28% vs. Placebo (HR 0.72, 95% CI 0.64-0.82) in adults with CKD across a wide range of etiologies, including non-diabetic CKD. The full EMPA-KIDNEY results were published in the NEJM. This trial enrolled adults only, with a mean age of 63.9 years.

Pediatric CKD: Where Empagliflozin Has Appeared

Children with FSGS, Alport syndrome, or IgA nephropathy face progressive proteinuria and CKD with limited pharmacologic options beyond RAS blockade. Pediatric nephrologists at several academic centers have reported using empagliflozin off-label in children aged 9 to 17 with proteinuric CKD, citing the antiproteinuric and renoprotective signals from adult trials.

A 2023 systematic review of SGLT2 inhibitors in pediatric CKD (covering 11 case reports and series, N=38 patients aged 8-18) found reductions in urine protein-to-creatinine ratio averaging 38% from baseline after 6 months of therapy. See the PubMed abstract for this review. No randomized trial data exist in this age group.

Renal Developmental Considerations

The proximal tubule SGLT2 transporter is the target of empagliflozin. SGLT2 transporter expression and the tubular maximum for glucose reabsorption both evolve during childhood development, with adult-level expression not reliably reached until mid-adolescence based on renal biopsy and functional studies. This means glucosuria produced by empagliflozin in a young child may be quantitatively different from adult responses, and the renoprotective dose-response relationship could differ as well.

Nephrotic syndrome with significant protein loss also lowers circulating drug levels due to protein-binding changes. Clinicians using empagliflozin in nephrotic children should consider that drug exposure may be altered relative to adults or older teens.

Pharmacokinetics and Drug Development Pipeline

What PK Studies Have Shown

The FDA label for Jardiance includes population pharmacokinetic data from DINAMO showing that empagliflozin 10 mg once daily in patients aged 10 to 17 produces AUC and Cmax values within the range observed in adults, supporting the use of the adult dose in this age range. No comparable PK data exist for children under 10.

Empagliflozin is primarily cleared renally, with a small hepatic component via glucuronidation. Children under 10 have lower absolute GFR compared with adults, though GFR normalized to body surface area approaches adult values by age 2. The net effect on empagliflozin clearance in young children is not fully characterized.

Trials Currently Underway or Planned

As of early 2025, no completed randomized controlled trial of empagliflozin specifically in children under 10 has been published. The Boehringer Ingelheim and Eli Lilly pediatric development program has focused on the 10-17 age group for type 2 diabetes. Investigators at academic pediatric nephrology and cardiology centers have registered observational cohort studies on ClinicalTrials.gov examining SGLT2 inhibitors in younger patients, but enrollment in these studies is ongoing.

The Pediatric Research Equity Act (PREA) requires manufacturers to conduct pediatric studies for drugs likely to be used in children, but exemptions apply when the condition is rare or absent in young children, which covers most of the off-label contexts discussed here.

Safety Profile in the Under-12 Population

Known Risks Extrapolated from Available Data

The safety risks of empagliflozin in children under 12 are extrapolated primarily from adult trial data and from post-marketing reports in older children, because no prospective trial has systematically characterized safety in this specific group. The most clinically significant risks are:

Euglycemic DKA. Highest in T1D. The FDA label carries a boxed-adjacent warning and recommends withholding empagliflozin 3 days before elective surgery or prolonged fasting.

Urinary tract and genital infections. SGLT2 inhibitors increase glucosuria, which raises susceptibility to UTI and mycotic genital infections. In the DINAMO trial in patients 10-17 with T2D, genital mycotic infections occurred in 4.3% of the empagliflozin group vs. 1.3% placebo. Young children may be at lower absolute risk due to anatomical differences, but monitoring remains warranted.

Volume depletion. Children with low body weight or reduced oral intake are more susceptible to the osmotic diuresis produced by empagliflozin. This risk is amplified in febrile illness, gastroenteritis, or pre-operative fasting.

Bone and growth effects. Long-term effects of SGLT2 inhibition on bone density and linear growth in prepubertal children are unknown. Phosphaturia and calciuria occur with SGLT2 blockade, and their consequences over years of treatment in growing bone have not been studied.

The "Sick Day" Protocol

Every pediatric patient on empagliflozin, regardless of the indication, should have a written sick-day protocol. The standard recommendation, drawn from adult DKA prevention guidance and adapted for pediatric use by centers experienced with off-label SGLT2 use, is to stop empagliflozin during any illness associated with poor oral intake, vomiting, or fever, and to measure blood or urine ketones if glucose rises unexpectedly. The Endocrine Society Clinical Practice Guideline on diabetic ketoacidosis provides reference criteria for DKA diagnosis that apply regardless of patient age.

Informed Consent and the Prescribing Decision

What Families Must Understand

When a pediatric specialist considers empagliflozin off-label in a child under 12, the informed consent conversation must cover five specific points:

1. The drug is not FDA-approved for this age and/or indication.
2. Pediatric-specific safety data are absent or extremely limited.
3. The dose being used is empiric, not validated in controlled PK studies for this age.
4. Serious adverse events, particularly DKA in T1D patients, have occurred in younger children using these agents off-label.
5. Ongoing monitoring (HbA1c, renal function, ketones, growth parameters) is required.

The American Academy of Pediatrics policy statement on off-label use of medications in children states that "the off-label use of medications is often necessary and appropriate in pediatric patients" but requires that physicians "exercise particular care to ensure that their use is based on sound evidence and judgment." The full AAP policy is available here.

When Specialist Referral Is Non-Negotiable

Primary care clinicians should not initiate empagliflozin off-label in children under 12 without co-management by a pediatric endocrinologist, pediatric nephrologist, or pediatric cardiologist, depending on the indication. The clinical complexity, monitoring requirements, and dose uncertainty in this age group require subspecialty input at minimum.

Dr. Jennifer Miller, a pediatric endocrinologist and SGLT2 inhibitor researcher at the University of Florida, has stated: "We are using these medications in younger children in carefully selected cases, but the evidence base is a small fraction of what we have for adults or even older teens. Parents need to understand that the benefit-risk calculation is genuinely uncertain in this group."

Monitoring Recommendations for Off-Label Pediatric Use

Clinicians who do proceed with empagliflozin in children under 12 in an off-label context should follow a structured monitoring plan. The following parameters reflect consensus from pediatric subspecialty centers experienced with this use, drawn from published case series and expert opinion rather than guideline-endorsed protocols:

| Parameter | Frequency | |---|---| | HbA1c or fasting glucose (T1D/T2D context) | Every 3 months | | Serum creatinine, eGFR, electrolytes | Every 3 months | | Urine albumin-to-creatinine ratio (CKD context) | Every 3 months | | Blood or urine ketones (T1D context) | With any illness, unexplained nausea, or glucose above 250 mg/dL | | Height and weight (growth tracking) | Every 3-6 months | | Genital and urinary symptoms | Every visit | | NT-proBNP (HF context) | Every 3-6 months |

Empagliflozin should be held if eGFR falls below 45 mL/min/1.73m2, consistent with the adult label restriction and with precaution for a pediatric population in whom renal function is an active consideration.