Common side effects of empagliflozin include genital yeast infections andhypotension, particularly in patients withvolume depletion.[2][16][17] Other symptoms such as nausea and vomiting may occur and seem more pronounced in combination withmetformin.[16][17] Rare but serious adverse events, such as euglycemicdiabetic ketoacidosis (DKA) which may present with hyperventilation, lethargy, or mental status changes have been reported but are infrequent in trials.[16][17] Other serious but rare serious adverse events includeFournier's gangrene, a severe skin infection of the groin, anddiabetic ketoacidosis that may occur even with normal blood glucose levels.[2][18] Use during pregnancy or breastfeeding is not recommended.[19]
Empagliflozin is aSGLT2 inhibitor: a reversibleinhibitor of thesodium glucose co-transporter-2 (SGLT-2). It reduces the kidney's glucose reabsorption and excretes the excess glucose through the urine, thus its place in the treatment of type two diabetes. It is dependent on blood glucose concentrations and theglomerular filtration rate of the kidney. This excretion of glucose in the urine, which does not seem to disturb other blood electrolytes, is accompanied by somediuresis which may be what contributes to many other physiological functions, potentially explaining its place in heart failure treatment.[20][21][22]
In the United States, empagliflozin isindicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure;[12] to reduce the risk of sustained decline ineGFR inchronic kidney disease, hospitalization in adults with chronic kidney disease at risk of progression and cardiovascular death;[12] to reduce the risk of cardiovascular death in adults with type2 diabetes and established cardiovascular disease;[12] and as an adjunct to diet and exercise to improve glycemic control in people aged ten years of age and older with type2 diabetes.[12]
In the European Union, empagliflozin is indicated in people aged ten years of age and older for the treatment of insufficiently controlled type 2 diabetes as an adjunct to diet and exercise;[13] as monotherapy when metformin is considered inappropriate due to intolerance;[13] in addition to other medicinal products for the treatment of diabetes.[13] It is indicated in adults for the treatment of symptomatic chronic heart failure;[13] and it is indicated in adults for the treatment ofchronic kidney disease.[13]
Regardless of the presence of diabetes, Empagliflozin can lower the risk of cardiovascular death and hospitalisation for heart failure, and reduce kidney function decline, when added to standard heart failure treatment in patients with heart failure with a reduced or preserved ejection fraction.[29][30][31]
Empagliflozin isindicated in adults with type2diabetes and established cardiovascular disease to reduce the risk of cardiovascular death; and as an adjunct to diet and exercise to improve glycemic control in adults with type2 diabetes.[12][32][33]
In June 2023, the USFood and Drug Administration (FDA) expanded the indication, as an addition to diet and exercise, to improve blood sugar control in children 10 years and older with type2 diabetes.[34]
Empagliflozin has shown beneficial effects on cardiovascular morbidity and mortality in patients with type 2 diabetes.[35] Additionally, large-scale randomised controlled trials have demonstrated that empagliflozin decreases heart failure hospitalisations and cardiovascular mortality in adults with heart failure, whether they have reduced, mid-range, or preserved left ventricular ejection fraction and regardless of type 2 diabetes status.[15][30] There is evidence from high quality studies that empagliflozin can also help to slow the rate of kidney function decline. Irrespective of diabetes status, benefit was observed in those with mild, moderate or severe loss of kidney function.[36][37] People started on empagliflozin may first see a decrease in kidney function before their glomerular filtration rate stabilises.[38] Greatest benefit was demonstrated in those who had severe loss of kidney function, higher risk of kidney function worsening and background of diabetes.[36]
Empagliflozin helps patients withchronic kidney disease via several complimentary mechanisms:
•Slows kidney function decline: Empagliflozin significantly slows the annual rate of decline in theestimated glomerular filtration rate (eGFR), a key measure of kidney function.
•Reduces risk of major kidney events: Clinical trials have shown that empagliflozin reduces the risk of kidney disease progression, including a sustained drop in eGFR, the need for dialysis or transplant, or death from renal causes.
•Beneficial across patient types: The kidney-protective effects of empagliflozin are consistent in patients with or without diabetes and across different levels of kidney function (eGFR) andalbuminuria (excess protein in the urine).
•Lowerblood pressure: Empagliflozin can cause a modest reduction in blood pressure and weight, which further reduces stress on the kidneys.
•Anti-inflammatory effects: Studies suggest thatSGLT2 inhibitors like empagliflozin may have anti-inflammatory and anti-fibrotic effects, potentially protecting against kidney tissue damage.
The landmarkEMPA-KIDNEY clinical trial demonstrated the broad benefits of empagliflozin for people withCKD.[44]
•Reduced composite risk: Empagliflozin reduced the risk of the composite primary outcome (kidney disease progression or cardiovascular death) by 28% compared to a placebo.
•Decreased hospitalizations: The trial also showed a 14% relative risk reduction for all-cause hospitalizations.
•Consistent benefits: The benefits were observed consistently across different patient groups, including those with low albuminuria who were previously not thought to benefit as much from this class of medication.
While generally well-tolerated, empagliflozin use inCKD patients should be monitored by a healthcare provider.
•InitialeGFR drop: When starting treatment, patients may experience an initial, modest decline in eGFR, which is part of the drug's mechanism. After this initial "dip," the rate of kidney function decline slows significantly.
•Adverse effects: Common side effects include an increased risk ofurinary tract infections and genitalmycotic infections. The risk of dehydration may also increase, especially in elderly patients or those on a low-salt diet.
Empagliflozin increases the risk of genital fungal infections. The risk is highest in people with a prior history of genital fungal infections.[45]
Empagliflozin has been thought to be associated with increased risk ofurinary tract infections. Reviews of clinical trials have shown there is no significant risk of developing urinary tract infections while taking empagliflozin when compared to placebo or other diabetic medications.[46][47]
Empagliflozin reducessystolic anddiastolic blood pressure and can increase the risk oflow blood pressure, which can causefainting and/or falls.[45] The risk is higher in older people, people takingdiuretics, and people with reduced kidney function.[45]
Empagliflozin may cause a temporary decline in kidney function and, in rare cases,acute kidney injury, so it should be used cautiously in patients with kidney impairment. Some evidence suggests it may be safely used in people with significantly reduced kidney function (eGFR ≥ 20 mL/min/1.73 m²) while still providing renal benefits.[48] However, given that this conclusion is largely based on a single major trial, further research is recommended to establish long-term safety and efficacy in this population.[35]
Diabetic ketoacidosis, a rare but potentially life-threatening condition, may occur more commonly with empagliflozin and other SGLT-2 inhibitors.[49][50] While diabetic ketoacidosis is usually associated with elevated blood glucose levels, in people taking SGLT-2 inhibitors diabetic ketoacidosis may be seen with uncharacteristically normal blood glucose levels, a phenomenon called euglycemic diabetic ketoacidosis.[49] The absence of elevated blood glucose levels in people on an SGLT-2 inhibitor may make it more difficult to diagnose diabetic ketoacidosis. The risk of empagliflozin-associated euglycemic diabetic ketoacidosis may be higher in the setting of illness, dehydration, surgery, and/or alcohol consumption.[49] It is also seen in type1 diabetes who take empagliflozin, which notably is an unapproved or "off-label" use of the medication.[50] To lessen the risk of developing ketoacidosis (a serious condition in which the body produces high levels of blood acids called ketones) after surgery, the FDA has approved changes to the prescribing information for SGLT2 inhibitor diabetes medicines to recommend they be stopped temporarily before scheduled surgery. Empagliflozin should each be stopped at least three days before scheduled surgery.[51] Symptoms of diabetic ketoacidosis include nausea, vomiting, abdominal pain, tiredness, and trouble breathing.[51]
Fournier's gangrene, a rare but serious infection of the groin, occurs more commonly in people taking empagliflozin and other SGLT-2 inhibitors.[2][18] Symptoms include feverishness, a general sense of malaise, and pain or swelling around the genitals or in the skin behind them. The infection progresses quickly and urgent medical attention is recommended.[18]
Empagliflozin can increase the risk oflow blood sugar when it is used together with a sulfonylurea or insulin.[52] When used by itself or in addition to metformin it does not appear to increase the risk of hypoglycemia.[53]
Empagliflozin is an inhibitor of thesodium glucose co-transporter-2 (SGLT-2), which is found almost exclusively in theproximal tubules ofnephronic components in the kidneys. SGLT-2 accounts for about 90percent of glucose reabsorption into the blood. Blocking SGLT-2 reduces blood glucose by blockingglucose reabsorption in the kidney and thereby excreting glucose (i.e., blood sugar) via the urine.[54][55][56] Of all the SGLT-2 Inhibitors currently available, empagliflozin has the highest degree of selectivity for SGLT-2 over SGLT-1, SGLT-4, SGLT-5 and SGLT-6.[57]
For cardiovascular death, the FDA based its decision on a postmarketing study it required when it approved empagliflozin in 2014, as an adjunct to diet and exercise to improve glycemic control in adults with type2 diabetes.[23][32] Empagliflozin was studied in a postmarket clinical trial of more than 7,000 participants with type2 diabetes and cardiovascular disease.[32] In the trial, empagliflozin was shown to reduce the risk of cardiovascular death compared to a placebo when added to standard of care therapies for diabetes and atherosclerotic cardiovascular disease.[32]
For heart failure, the safety and effectiveness of empagliflozin were evaluated by the FDA as an adjunct to standard of care therapy in a randomized, double-blind, international trial comparing 2,997 participants who received empagliflozin, 10 mg, once daily to 2,991 participants who received the placebo.[33] The main efficacy measurement was the time to death from cardiovascular causes or need to be hospitalized for heart failure.[33] Of the individuals who received empagliflozin for an average of about two years, 14% died from cardiovascular causes or were hospitalized for heart failure, compared to 17% of the participants who received the placebo.[33] This benefit was mostly attributable to fewer participants being hospitalized for heart failure.[33]
The FDA granted the application for empagliflozin priority review, and approved the additional indication of heart failure in 2022.[33]
As of May 2013, Boehringer and Lilly had submitted applications for marketing approval to theEuropean Medicines Agency (EMA) and the USFood and Drug Administration (FDA).[59] Empagliflozin was approved in the European Union in May 2014,[13] and was approved in the United States in August 2014.[23][24][60] The FDA required four postmarketing studies: a cardiovascular outcomes trial, two studies in children, and a toxicity study in animals related to the pediatric trials.[23][60][needs update]
After the patent expired in 2025, about 37 companies began producinggeneric empagliflozin in India.[61]
A meta-analysis of short-term randomized controlled trials has shown similar efficacy on glycemic control between empagliflozin 10mg and 25mg in people with type2 diabetes. While there may be a higher reduction in HbA1c with higher doses, this difference is more clinically significant when the patients' baseline HbA1c is ≥ 8.5%.[62][63]
Empagliflozin causes moderate reductions in blood pressure and body weight. These effects are likely due to the excretion of glucose in the urine and a slight increase in urinarysodium excretion.[45][64]
In clinical trials, participants with type2 diabetes taking empagliflozin with other diabetic medications lost an average of 2% of their baselinebody weight.[65][66] Empagliflozin use has been associated with clinically meaningful weight loss, with a higher proportion of individuals achieving weight loss greater than 5% of their baseline weight compared to placebo.[67][65][66] The degree of weight loss may vary depending on the dosage (10mg or 25mg).[65][66] While weight loss can contribute to improved glycaemic control, the primary glucose-lowering effect of empagliflozin occurs independently through increased urinary glucose excretion.[35] The same extent of weight loss was also observed in a study with heart failure patients taking empagliflozin.[68]
Empagliflozin has been shown to reduce systolic blood pressure by 3 to 5millimeters of mercury (mmHg) without changes in pulse rate.[65][66][45] A greater percentage of people with uncontrolled blood pressure at baseline, achieved controlled blood pressure (i.e. systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg) after taking empagliflozin at 24 weeks.[66] The effects on blood pressure and body weight are generally viewed as favorable, as many people with type2 diabetes have high blood pressure or are overweight or obese.[53][69]
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