Dapagliflozin Clinical Trials

What Is Dapagliflozin?

Dapagliflozin is an FDA-approved medication for the treatment of diabetes and heart failure. It is a type of drug known as a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Dapagliflozin works by preventing the kidneys from reabsorbing glucose back into the bloodstream. This leads to increased glucose excretion in the urine, which helps lower blood glucose levels. This mechanism can also contribute to weight reduction.

Beyond its approved uses, dapagliflozin is being investigated for a wide range of other conditions. These include chronic kidney disease, autosomal dominant polycystic kidney disease, non-alcoholic fatty liver disease, obesity, and various cardiovascular complications.

Uses and Conditions Under Study

Dapagliflozin is being studied for its potential benefits across several health areas, with clinical trials exploring its effects on various conditions:

• Diabetes: Dapagliflozin is FDA-approved for diabetes. It is extensively studied for Type 2 Diabetes, with 58 trials specifically mentioning this condition, along with other related terms like Diabetes Mellitus (57 trials) and Type 2 Diabetes Mellitus (51 trials). As an SGLT2 inhibitor, it helps manage blood sugar by increasing glucose excretion through the kidneys.
• Heart Conditions: The medication is FDA-approved for Heart Failure, a condition with 38 trials investigating dapagliflozin. Researchers are also exploring its use in complications following Fontan operations, acute myocardial infarction (AMI), and to protect against cardiotoxicity from certain cancer treatments.
• Kidney Conditions: Dapagliflozin is being studied for various kidney diseases, including Chronic Kidney Diseases (18 trials) and Chronic Kidney Disease (11 trials). It is also under investigation for autosomal dominant polycystic kidney disease (ADPKD), cystinuria, nephrotic syndrome, and lupus nephritis, where it may help slow the loss of kidney function and reduce proteinuria.
• Liver Conditions: Studies are underway for Non-alcoholic Fatty Liver Disease (NAFLD), with 10 trials listed, and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Dapagliflozin may help improve lipid homeostasis and reduce fat accumulation in the liver.
• Weight Management and Metabolic Health: With 10 trials for Obesity, dapagliflozin is being explored for its role in weight reduction. It is also studied for prediabetes, metabolic syndrome, hypertension, and polycystic ovary syndrome, where it may help improve metabolic parameters.
• Other Conditions: Dapagliflozin is also being investigated for conditions such as Long COVID, stage IA lung adenocarcinoma, large vessel vasculitis, and sleep-disordered breathing in heart failure patients.

Dosing

Dapagliflozin is primarily available as an oral tablet. The most commonly studied and approved strength is 10 mg, typically administered once daily. For example, some trials specify taking one tablet of dapagliflozin once a day for durations such as 12 months or 24 weeks. It is often taken orally, sometimes specified as before breakfast.

Various strengths have been studied in clinical trials, ranging from very low doses such as 0.001 mg, 0.01 mg, 0.1 mg, 0.3 mg, 1 mg, 2.5 mg, and 5 mg, up to higher investigational doses like 20 mg and 150 mg. These different strengths are explored for various conditions, including type 2 diabetes, heart failure, chronic kidney disease, obesity, and hypertension.

Dapagliflozin is also studied in fixed-dose combinations with other medications, such as metformin, saxagliptin, gemigliptin, and pioglitazone. These combinations are often taken as a single tablet, sometimes with specific instructions regarding fasting or fed conditions. For instance, a fixed-dose combination of gemigliptin/dapagliflozin/metformin 50/10/1000 mg has been studied under both fasting and fed conditions. While specific pediatric doses are not detailed, dapagliflozin is being investigated in younger populations for conditions like brain cancer in patients aged 6-10 years and 11-21 years, as part of combination chemotherapy regimens.

Side Effects

In clinical trials, the most common side effect reported for Dapagliflozin was hypoglycemia (low blood sugar). Approximately 26.1% of patients taking Dapagliflozin experienced hypoglycemia, compared to 20.0% of those on placebo. Other common side effects included:

• Nasopharyngitis (common cold symptoms): 5.2% of patients on Dapagliflozin experienced this, compared to 4.4% on placebo.
• Headache: 5.1% of patients on Dapagliflozin, compared to 4.6% on placebo.
• Influenza (flu): 4.9% of patients on Dapagliflozin, compared to 4.2% on placebo.
• Diarrhea: 3.9% of patients on Dapagliflozin, compared to 3.0% on placebo.
• Urinary tract infection: 4.1% of patients on Dapagliflozin, compared to 4.0% on placebo.

Some serious conditions were observed less frequently in patients taking Dapagliflozin compared to placebo. For example, cardiac failure occurred in 4.3% of Dapagliflozin patients versus 6.1% on placebo, and acute kidney injury occurred in 1.2% of Dapagliflozin patients compared to 1.5% on placebo.

Clinical Trial Results

Clinical trials have evaluated the effectiveness of Dapagliflozin in managing type 2 diabetes, both as a standalone treatment and in combination with other medications.

Monotherapy Trials

In a pilot study (NCT00357370) over 12 weeks, Dapagliflozin showed improvements in blood sugar control. Patients taking Dapagliflozin 20 mg experienced a mean decrease in fasting plasma glucose (FPG) of 9.64 mg/dL, while those on placebo saw an increase of 17.80 mg/dL. Hemoglobin A1C (HbA1c) levels also decreased by 0.69% with Dapagliflozin 20 mg and 0.61% with Dapagliflozin 10 mg, compared to an increase of 0.09% on placebo. Additionally, patients on Dapagliflozin 10 mg or 20 mg reduced their mean total daily insulin dose by 1.35 and 0.83 units/day, respectively, while placebo patients increased their dose by 1.69 units/day. In this study, 15 participants on either 10 mg or 20 mg of Dapagliflozin achieved an HbA1c decrease of at least 0.5% from baseline, compared to 3 participants on placebo.

Another phase III study (NCT00528372) involving patients whose type 2 diabetes was not well controlled with diet and exercise, demonstrated further benefits. After 24 weeks, patients taking Dapagliflozin 10 mg once daily saw their FPG levels decrease by 28.8 mg/dL (morning dose) or 29.6 mg/dL (evening dose), compared to a 4.1 mg/dL decrease on placebo. HbA1c levels decreased by 0.89% (10 mg morning dose) or 0.79% (10 mg evening dose) with Dapagliflozin, versus 0.23% on placebo. More patients achieved an HbA1c below 7.0% with Dapagliflozin 10 mg (50.8% for morning dose, 51.6% for evening dose) compared to 31.6% on placebo. Patients taking Dapagliflozin 10 mg also experienced a mean weight reduction of 3.16 kg (morning dose) or 3.05 kg (evening dose), while placebo patients lost 2.19 kg.

Combination Therapy with Metformin

When Dapagliflozin was added to metformin therapy (NCT00528879), patients experienced significant improvements over 24 weeks. FPG levels decreased by 23.5 mg/dL with Dapagliflozin 10 mg plus metformin, compared to a 6.0 mg/dL decrease with placebo plus metformin. HbA1c levels decreased by 0.84% with Dapagliflozin 10 mg plus metformin, versus 0.30% with placebo plus metformin. A greater percentage of patients achieved an HbA1c below 7.0% with Dapagliflozin 10 mg plus metformin (40.6%) compared to placebo plus metformin (25.9%). Patients also experienced greater weight loss, with a mean reduction of 2.86 kg for Dapagliflozin 10 mg plus metformin, compared to 0.89 kg for placebo plus metformin.

In a study comparing Dapagliflozin plus metformin XR to metformin XR alone (NCT00643851), the combination therapy showed superior results. After 24 weeks, FPG decreased by 61.0 mg/dL with Dapagliflozin 5 mg plus metformin XR, compared to 33.6 mg/dL with metformin XR alone. HbA1c levels decreased by 2.05% with the combination, versus 1.35% with metformin XR alone. The combination also led to a mean weight reduction of 2.66 kg, compared to 1.29 kg with metformin XR alone. 52.4% of patients on Dapagliflozin 5 mg plus metformin XR achieved an HbA1c below 7.0%, compared to 34.6% on metformin XR alone.

Comparison with Glipizide

A study (NCT00660907) directly compared Dapagliflozin plus metformin with glipizide plus metformin. Both treatments resulted in a similar mean reduction in HbA1c levels (0.52%). However, patients on Dapagliflozin plus metformin experienced a mean weight reduction of 3.22 kg, while those on glipizide plus metformin gained 1.44 kg. Importantly, the incidence of hypoglycemia was significantly lower with Dapagliflozin plus metformin (3.5%) compared to glipizide plus metformin (40.8%). 33.3% of patients on Dapagliflozin plus metformin achieved a body weight reduction of at least 5%, versus only 2.5% on glipizide plus metformin.

Currently Recruiting Trials

Dapagliflozin, a medication known as an SGLT2 inhibitor, is currently being investigated in numerous clinical trials to explore its potential benefits across a wide range of health conditions. These studies aim to understand how dapagliflozin can help patients with various kidney, heart, and metabolic disorders, and even in some cancer and neurological conditions.

One ongoing Phase 4 study, NCT07405216, is examining the efficacy and safety of dapagliflozin in adolescents with early stages of chronic kidney disease and albuminuria. This trial, sponsored by Centenario Hospital Miguel Hidalgo, seeks to enroll 200 participants in Mexico, where CKD is highly prevalent among young people.

For patients with advanced kidney disease, the Oman Ministry of Health is sponsoring a study (NCT07491042) to assess the impact of six-month dapagliflozin treatment in 38 individuals with end-stage kidney disease on chronic peritoneal dialysis. Yale University is conducting a Phase 2 trial (NCT07273838) with 130 participants to determine if adding SGLT2 inhibitors to usual care is safe and effective for hospitalized patients with heart failure and acute kidney injury.

In cardiovascular health, two Phase 3 trials are underway in Mexico. NCT07297589, sponsored by Instituto Mexicano del Seguro Social, is enrolling 136 participants with ST-elevation myocardial infarction (STEMI) to study the effects of dapagliflozin and semaglutide on epicardial fat. Another trial from the same sponsor, NCT07295223, is recruiting 44 patients with acute myocardial infarction to evaluate the effect of these agents on inflammation.

Beyond traditional indications, dapagliflozin is being explored for unique conditions. Washington University School of Medicine is sponsoring a Phase 2 study (NCT07174687) involving 70 participants to assess the safety and tolerability of dapagliflozin 10 mg daily for 12 months in individuals with geographic atrophy, a severe form of dry age-related macular degeneration. An early Phase 1 trial (NCT07235280) at Jonsson Comprehensive Cancer Center is testing the safety of dapagliflozin given prior to surgery in 48 patients with stage IA lung adenocarcinoma.

Further demonstrating its broad research scope, a Phase 1/2 study (NCT07239011) by Tanta University is investigating dapagliflozin in 60 participants with depression. AstraZeneca is sponsoring large Phase 3 trials, including NCT06677060, which plans to enroll 11,300 participants to investigate heart failure and cardiovascular death with a combination of baxdrostat and dapagliflozin.

Other notable trials include NCT07187570, a Phase 3 study with 1,600 participants in Sweden evaluating dapagliflozin's effect on atrial fibrillation recurrence, and NCT06642272, a large Phase 4 pragmatic trial with 17,200 participants comparing the effectiveness of empagliflozin and dapagliflozin for diabetes, chronic kidney disease, and heart failure.

Where to Participate

Clinical trials for dapagliflozin are actively recruiting participants across a wide geographic area, with study sites located in 17 countries and 48 states within the United States. This extensive network ensures diverse patient populations can contribute to advancing medical knowledge.

Top recruiting cities in the United States include:

• Dallas, Texas (7 sites)
• Houston, Texas (6 sites)
• San Antonio, Texas (6 sites)
• Columbus, Ohio (6 sites)
• Los Angeles, California (6 sites)
• Kansas City, Missouri (6 sites)
• Atlanta, Georgia (6 sites)
• Cincinnati, Ohio (6 sites)
• Chicago, Illinois (6 sites)
• Miami, Florida (5 sites)

Eligibility for these trials is broad, welcoming participants aged between 6 and 130 years. Studies are open to individuals of all genders, and many trials also include healthy volunteers and children, depending on the specific research objectives.

Development Timeline

The journey of dapagliflozin began with its first clinical trial on December 8, 2005, marking the start of extensive research into its therapeutic potential. Since then, a total of 552 trials have been conducted or are ongoing, involving a remarkable 1,282,981 participants.

Early development initially explored conditions such as IBS-C and hyperphosphatemia, but the drug's pipeline rapidly expanded. AstraZeneca has been a primary driver of this research, sponsoring 119 trials. Over time, the focus broadened significantly to include major indications like Type 2 Diabetes Mellitus, Heart Failure, and Chronic Kidney Diseases, which are now central to dapagliflozin's clinical use and ongoing studies.

The development has progressed through all phases, with a substantial number of studies in advanced stages: 175 Phase 4 trials, 128 Phase 3 trials, and 82 Phase 2 trials. There have also been 68 Phase 1 trials, alongside studies spanning combined phases (Phase 1/2, Phase 2/3) and those not yet assigned a phase. This progression reflects a comprehensive investigation into dapagliflozin's efficacy and safety across a growing spectrum of conditions, including various forms of heart disease, kidney diseases, and even exploratory studies in areas like breast cancer, depression, and eye conditions, with the latest trial starting on April 29, 2026.