Empagliflozin Clinical Trials

What Is Empagliflozin?

Empagliflozin is an FDA-approved medication for patients 10 years of age and older to improve glycemic control in type 2 diabetes, and for the treatment of heart failure and chronic kidney disease. It is sold under the brand name Jardiance. Empagliflozin is an orally-active inhibitor of sodium-glucose co-transporter 2 (SGLT2). This mechanism works by blocking SGLT2 proteins in the kidneys, which are responsible for reabsorbing glucose back into the bloodstream. By inhibiting SGLT2, empagliflozin causes the kidneys to remove more glucose through urine, thereby lowering blood sugar levels.

Beyond its approved uses, empagliflozin is also being investigated for conditions such as obesity, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), and kidney stone prevention.

Uses and Conditions Under Study

Empagliflozin is primarily studied for metabolic and cardiovascular conditions, with a broad range of investigations into its potential benefits.

• Diabetes: Empagliflozin is FDA-approved for improving glycemic control in type 2 diabetes. It is extensively studied across 60 trials for Diabetes Mellitus, Type 2, 30 trials for Type 2 Diabetes, and 21 trials for Type 2 Diabetes Mellitus. Its SGLT2 inhibition helps reduce blood glucose.
• Heart Conditions: The medication is approved for heart failure and is being investigated in 38 trials for Heart Failure and 9 trials for Cardiovascular Diseases. Studies explore its effects on cardiac structure, function, and reducing cardiovascular events, including incident heart failure, even in patients without diabetes.
• Kidney Conditions: Empagliflozin is approved for chronic kidney disease. It is also being studied for its effects on urinary risk factors in individuals with recurrent kidney stones, with 2 trials specifically mentioning kidney stones. Investigations also include its safety and efficacy in dialysis patients, including those with end-stage kidney disease (ESKD).
• Liver Conditions: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are growing health problems linked to metabolic issues. Empagliflozin has shown promise in reducing fat production and deposition in the liver in animal models and is being evaluated in trials for NAFLD.
• Weight Management: Empagliflozin is being studied in 10 trials for Obesity and for its potential role in managing metabolic syndrome, a condition that precedes diabetes and cardiovascular complications. SGLT2 inhibitors can lead to a reduction in body weight.
• Other Conditions: Empagliflozin is also being explored in trials for a variety of other conditions, including gout, bipolar disorder, rheumatoid arthritis, and as an adjunctive therapy in patients hospitalized with COVID-19. Some trials include healthy participants (24 trials) to evaluate pharmacokinetic profiles and safety.

Dosing

Empagliflozin is available in various oral dosage forms, including tablets and film-coated tablets, sometimes in fixed-dose combinations (FDC) with other medications like metformin or linagliptin.

Commonly studied strengths include 10 mg and 25 mg oral tablets. For example, participants in some trials take a 10 mg oral tablet of empagliflozin daily, while others receive 25 mg daily. Lower doses, such as 2.5 mg, and higher doses, such as 50 mg, have also been investigated in specific study arms.

Empagliflozin is typically taken once daily. However, investigational dosing regimens have included thrice-weekly post-hemodialysis dosing for dialysis patients. When combined with other drugs, such as metformin, specific FDC strengths like 12.5 mg empagliflozin/850 mg metformin or 5 mg empagliflozin/500 mg metformin have been studied.

The FDA has approved empagliflozin for patients 10 years of age and older for glycemic control in type 2 diabetes, with specific pediatric dosing regimens being evaluated in trials, such as 10 mg or 25 mg doses for adolescents.

Side Effects

In clinical trials, the most frequently reported side effect for patients taking Empagliflozin was hypoglycaemia (low blood sugar), which occurred in 45.1% of patients, compared to 47.3% on placebo. Other common side effects included:

• Viral upper respiratory tract infection: 12.7% of patients taking Empagliflozin experienced this, compared to 25.9% on placebo.
• Nasopharyngitis (common cold): 8.1% of patients taking Empagliflozin experienced this, compared to 8.5% on placebo.
• Blood ketone body increased: 6.5% of patients taking Empagliflozin experienced this, compared to 3.9% on placebo.
• Hypotension (low blood pressure): 6.3% of patients taking Empagliflozin experienced this, compared to 5.2% on placebo.
• Urinary tract infection: 6.0% of patients taking Empagliflozin experienced this, compared to 5.4% on placebo.

Clinical Trial Results

Clinical trials have investigated the effects of Empagliflozin on blood sugar control, body weight, and its absorption and interactions with other medications.

Blood Sugar Control and Weight Management in Type 2 Diabetes

In a 16-week study (NCT01649297) involving patients with type 2 diabetes already taking metformin, Empagliflozin significantly improved blood sugar levels. Patients taking Empagliflozin 25 mg once daily experienced an average reduction in Fasting Plasma Glucose (FPG) of 22.7 mg/dL, and a reduction in HbA1c (a measure of average blood sugar over 2-3 months) of 0.72 percentage points. In comparison, patients on placebo saw FPG decrease by 0.2 mg/dL and HbA1c decrease by 0.22 percentage points.

Another 24-week study (NCT01719003) in patients new to treatment for type 2 diabetes evaluated Empagliflozin alone or in combination with metformin. Patients taking Empagliflozin 10 mg once daily saw an average FPG reduction of 32.9 mg/dL and an HbA1c reduction of 1.35 percentage points. When Empagliflozin was combined with metformin, the improvements were even greater. For example, patients taking Empagliflozin 12.5 mg twice daily plus metformin 1000 mg twice daily experienced an average FPG reduction of 51.0 mg/dL and an HbA1c reduction of 2.08 percentage points. This combination also led to a significant average body weight reduction of 3.78 kg, compared to a 1.27 kg reduction with metformin 1000 mg twice daily alone.

Drug Absorption and Interactions

A study (NCT01451775) examined how food affects Empagliflozin absorption. It found that taking a 25 mg dose of Empagliflozin with food resulted in slightly lower overall drug exposure (Area Under the Curve, AUC) and peak concentration (Cmax) compared to taking it on an empty stomach. However, no clinically relevant abnormalities were observed, suggesting good tolerability regardless of food intake. Another study (NCT01634100) investigated drug interactions. When Empagliflozin was taken with probenecid, its peak concentration increased from 301 nmol/L (Empagliflozin alone) to 373 nmol/L, and overall exposure (AUC) increased from 2240 nmol*h/L to 3400 nmol*h/L. Similarly, when taken with rifampicin, Empagliflozin's peak concentration increased to 527 nmol/L and AUC to 3020 nmol*h/L.

Fixed-Dose Combination with Metformin

A bioequivalence study (NCT01672788) compared taking Empagliflozin and metformin as a single fixed-dose combination tablet versus taking them as separate tablets. The results showed that the body absorbed Empagliflozin and metformin in very similar amounts and at similar rates whether they were taken together in one tablet or as individual tablets. For instance, the overall exposure (AUC) for Empagliflozin 12.5 mg was 2560 nmol*h/L for the fixed-dose tablet compared to 2530 nmol*h/L for separate tablets, indicating that the fixed-dose combination is bioequivalent.

Currently Recruiting Trials

Where to Participate

• Dallas, Texas (12 sites)
• Jacksonville, Florida (12 sites)
• Miami, Florida (11 sites)
• San Antonio, Texas (11 sites)
• New York, New York (9 sites)
• Chicago, Illinois (9 sites)
• Pittsburgh, Pennsylvania (8 sites)
• Wichita, Kansas (7 sites)
• Nashville, Tennessee (7 sites)
• Baltimore, Maryland (6 sites)

Development Timeline