Pharm
Empagliflozin
search
Empagliflozin
, Jardiance
See Also
SGLT2 Inhibitor
Type II Diabetes Medications
Canagliflozin
Dapagliflozin
Ertugliflozin
Sotagliflozin
Bexagliflozin
Indications
Type 2 Diabetes Mellitus
Management
FDA approved for age 10 years and older
Comorbid
Chronic Kidney Disease
or
Microalbuminuria
Comorbid
Congestive Heart Failure
Like
GLP-1 Agonist
s,
SGLT2 Inhibitor
s have moved to first-line agents for their effects on conditions comorbid to Diabetes
SGLT2 Inhibitor
s (as with
GLP-1 Agonist
s) may assist with weight loss in
Obesity
SGLT2 Inhibitor
s (as with
GLP-1 Agonist
s) decrease
Cardiovascular Risk
Best evidence for Empagliflozin (Jardiance)
SGLT2 Inhibitor
s (as with
GLP-1 Agonist
s) decrease
Chronic Kidney Disease
progression
Best evidence for Empagliflozin (Jardiance),
Canagliflozin
(
Invokana
),
Dapagliflozin
(
Farxiga
)
Contraindications
Type 1 Diabetes Mellitus
Renal dysfunction with GFR <30 ml/min (previously <45 ml/min)
Other relative contraindications (use with caution)
Diabetic Ketoacidosis
(relative contraindication)
Osteoporosis
or
Osteopenia
(low
Bone Mineral Density
)
Diabetic Foot Wound
(
Neuropathic Foot Ulcer
)
Other contraindications due to lack of efficacy (from Empagliflozin labeling)
Polycystic Kidney Disease
Chronic Kidney Disease
requiring IV
Immunosuppression
(or equivalent to
Prednisone
45 mg/day)
Perioperative status (or prolonged
Fastin
g,
Dehydration
)
Hold for at least 3 to 4 days before major surgery
Mechanism
Sodium-Glucose Transporter 2
(SGLT2)
SGLT2 acts in the
Kidney
s to resorb
Glucose
at the proximal tubules
SGLT2 mediates 90% of renal
Glucose
reabsorption from the tubules
SGLT2 Inhibitor
s
Blocks SGLT2, Allowing more
Glucose
to remain in the urine without reabsorption
Results in osmotic diuresis
Efficacy is lower when GFR is decreased
Medications
Empagliflozin (Jardiance)
Dosing
Empagliflozin is FDA approved for age 10 years and older (as of 2023)
AM dosing is recommended due to
Diuretic
effect
Avoid in
Dehydration
Taken 30 minutes before first meal of day
Start: 10 mg orally daily
Next: May increase to 25 mg orally daily
Pharmacokinetics
SGLT2 Inhibitor
s share similar
Pharmacokinetics
Rapid absorption and peak activity within 2 hours
Efficacy
Lower efficacy in moderate to severe renal
Impairment
Class Effects
May lower weight up to 4 to 7 pounds (via diuresis)
May lower
Blood Pressure
by 3-5 mmHg (via similar mechanism to weight)
Lowers
Hemoglobin A1C
0.5 to 1%
Glucose
lowering effect decreases with lower GFR
Low risk of
Hypoglycemia
Decreases
Cardiovascular Risk
Decreases
Chronic Kidney Disease
progression
Empagliflozin (Jardiance) specific effects
Heart Failure with Reduced Ejection Fraction
Jardiance is associated with a decreased hospitalization and CV death rate when taken over 16 months (NNT 14)
Packer (2020) N Engl J Med 383:1413-24 [PubMed]
Heart Failure with Preserved Ejection Fraction
Appears effective in reducing hospitalizations even in non-Diabetic patients with
HFpEF
However, best effect in reduced Ejection Fraction (even mild reduction of 40-50% EF)
Anker (2021) N Engl J Med [PubMed]
Modest reduction in overall mortality (NNT 39) and cardiovascular death (NNT 45) over 3 years
Invokana
may also lower cardiovascular event risk (NNT 333), but unlike Jardiance does not reduce mortality
Zinman (2015) N Engl J Med 373(22):2117-28 +PMID:26378978 [PubMed]
May slow
Diabetic Nephropathy
when combined with
ACE Inhibitor
or ARB
May reduce hypoalbuminuria (NNT 20), but marginal effect on delaying
Dialysis
(NNT 333)
Wanner (2016) N Engl J Med 375(4):323-34 [PubMed]
Reduces progression of
Chronic Kidney Disease
and its cardiovascular complications (including death)
(2023) N Engl J Med 388(2):117-27 +PMID: 36331190 [PubMed]
Adverse Effects
Perioperative Recommendations
See
Preoperative Guidelines for Medications Prior to Surgery
Stop
SGLT2 Inhibitor
s 3 days before surgery (due to
Euglycemic Ketoacidosis
risk)
Restart
SGLT2 Inhibitor
s post-operatively when oral intake returns to normal
Urinary Tract Infection
Genital yeast infection
Number needed to harm (NNH) 17 in women, 40 in men
Fournier's Gangrene
https://www.fda.gov/Drugs/DrugSafety/ucm617360.htm
Euglycemic Ketoacidosis
See
Euglycemic Ketoacidosis
Presents with
Anion Gap Metabolic Acidosis
(
Ketoacidosis
despite normal
Serum Glucose
)
Diuretic
effect
Risk of
Dehydration
,
Orthostatic Hypotension
Risk of
Acute Kidney Injury
(see below)
Acute Kidney Injury
Seen with
Canagliflozin
(
Invokana
) and
Dapagliflozin
(
Farxiga
), but likely a class effect due to diuresis
Higher risk when combined with
ACE Inhibitor
s (and ARBs),
NSAID
s and
Diuretic
s and esp. in elderly
Avoid
Hypovolemia
, and consider lowering
Diuretic
dose when on
SGLT2 Inhibitor
Check
Serum Creatinine
before initiating agent, 10-14 days later and again with dose increase
Stop and hold the SGLT2 Inhibitor
Serum Creatinine
rises >30%
Resources
http://www.fda.gov/Drugs/DrugSafety/ucm505860.htm
Hyperkalemia
When used in combination with
ACE Inhibitor
s,
Angiotensin Receptor Blocker
s or
Potassium
Sparing
Diuretic
s
May also decrease
Serum Potassium
LDL Cholesterol
increase (4-8 mg/dl)
Bladder Cancer
increased risk
Associated only with
Farxiga
Fracture
s
Upper extremity
Fracture
s most common (and not caused by major
Trauma
)
Number needed to harm 125 for one additional
Fracture
with
Invokana
over 18 months of use
Invokana
and for those with
Renal Insufficiency
,
Farxiga
, have been associated with increased risk
Unknown mechanism (possibly decreased
Bone Mineral Density
, increased
Fall Risk
)
http://www.fda.gov/Drugs/DrugSafety/ucm461449.htm
Acute Pancreatitis
Amputation Risk
Canagliflozin
associated with increased risk of amputations
Relative Risk
: 2.0 (risk of 6 amputations per 1000 on
Canagliflozin
)
May be a
SGLT2 Inhibitor
class effect (unclear mechanism)
See
Amputation Prevention in Diabetes Mellitus
FDA Drug Safety Communication
https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm
Safety
Avoid in
Lactation
Pregnancy
Unknown safety in first trimester
Avoid in second and third trimester
Monitoring
Renal Function
Resources
Empagliflozin
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=faf3dd6a-9cd0-39c2-0d2e-232cb3f67565
References
(2020) Presc Lett 27(12): 68
(2020) Presc Lett 27(5): 26
(2018) Presc Lett 25(2)
(2016) Presc Lett 23(2): 8-9
(2014) Presc Lett 21(10): 57
(2013) Presc Lett 20(5): 28
Tomaszewski (2022) Crit Dec Emerg Med 36(11): 32
Nisly (2013)Am J Health-Syst Pharm 70 (4):311-9 [PubMed]
Stenlof (2013) Diabetes Obes Metab 15(4): 372-82 [PubMed]
Vaughan (2024) Am Fam Physician 109(4): 333-42 [PubMed]
Type your search phrase here