Empagliflozin for Type 2 Diabetes

Overseen By Aurora Merovci, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: GLP-1 RA, DPP-4i, TZD, insulin

Disqualifiers: Proliferative retinopathy, eGFR < 60, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called empagliflozin (also known as Jardiance) to assess its effects on fat breakdown and ketone production in people with type 2 diabetes. Researchers aim to understand how this drug differs in breaking down fats and producing glucose in the liver. The trial compares empagliflozin alone to a version that includes controlling pancreatic activity. People with type 2 diabetes who manage their condition with diet, metformin, or certain other medications might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

If you are taking medications like GLP-1 RA, DPP-4i, TZD, or insulin, you will need to stop them to participate in this trial. However, if you are on a stable dose of sulfonylurea, metformin, or statins, you can continue taking them.

Is there any evidence suggesting that empagliflozin is likely to be safe for humans?

Research shows that empagliflozin is generally safe for people with type 2 diabetes. Studies have found that those taking empagliflozin face a lower risk of kidney problems and low blood sugar compared to other treatments. However, the risk of diabetic ketoacidosis (DKA), a serious condition where the body produces too many blood acids called ketones, is higher. Despite these risks, empagliflozin lowers the risk of death from heart-related issues. Various studies have tested the treatment and consider it tolerable, but awareness of these risks is important when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Empagliflozin is unique because it targets type 2 diabetes by blocking the reabsorption of glucose in the kidneys, a mechanism of action not found in traditional treatments like metformin or insulin. This process helps to lower blood sugar levels by allowing excess glucose to be excreted in the urine, potentially offering a novel approach to managing blood glucose levels. Researchers are excited about empagliflozin because it not only helps control blood sugar but may also provide benefits for heart and kidney health, which are crucial concerns for individuals with type 2 diabetes.

What evidence suggests that empagliflozin might be an effective treatment for type 2 diabetes?

Research shows that empagliflozin, which participants in this trial may receive, effectively benefits people with type 2 diabetes by improving heart health and controlling blood sugar levels. One study found that people taking empagliflozin experienced fewer heart problems compared to those taking a placebo, a pill with no active medicine. Another study demonstrated that it lowers A1C levels, an important measure of long-term blood sugar control. Additionally, it aids in weight loss when combined with other treatments. Overall, strong evidence supports that empagliflozin helps manage type 2 diabetes and reduces the risk of heart issues. ^{5 6 7 8 9}

Who Is on the Research Team?

Ralph A DeFronzo, MD

Principal Investigator

University of Texas Health Science Center San Antonio

Are You a Good Fit for This Trial?

This trial is for adults aged 30-75 with Type 1 or Type 2 diabetes, a BMI of 21-45, and good kidney function (eGFR >60). Participants should be in good health, not on heavy exercise programs, and have stable weight. They can be treated with diet or certain diabetes medications but not insulin or drugs affecting glucose metabolism. Women must use contraception if able to bear children.

Inclusion Criteria

I have been on a stable dose of statin for at least 3 months.

Your kidney function, measured by eGFR, is higher than 60 ml/min/1.73m2.

I am being treated with diet, sulfonylurea, metformin, or both.

Exclusion Criteria

I am not currently taking GLP-1 RA, DPP-4i, TZD, or insulin for diabetes.

I do not have proliferative retinopathy or kidney issues (eGFR ≥ 60).

I am not on medication that affects my blood sugar, except for SU/MET.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo baseline measurements and a 4-week run-in period to stabilize insulin doses and monitor glucose levels

4 weeks

Weekly visits for monitoring

Treatment

Participants receive empagliflozin and/or pioglitazone, with regular monitoring of plasma insulin, glucose, and ketone levels

10 weeks

Bi-weekly visits for monitoring and blood tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The study tests the effects of Empagliflozin—a drug that helps control blood sugar—on various metabolic processes in diabetics. Some participants will receive the actual medication while others will get a placebo for comparison. The study also looks at how this drug affects fat breakdown and stress hormone levels.

How Is the Trial Designed?

Group I: Empagliflozin Experimental Treatment 1 Intervention

Empagliflozin 25 mg/day

Group II: Placebo/Control Group Placebo Group 1 Intervention

Placebo control

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established cardiovascular disease, although the exact mechanism for this benefit is not yet understood.

There is uncertainty regarding whether empagliflozin may also increase the risk of fractures, a concern raised with another SGLT2 inhibitor, canagliflozin (Invokana), and all SGLT2 inhibitors are noted to have only modest effectiveness in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

Empagliflozin (Jardiance®) is an effective treatment for type 2 diabetes (T2D) that works by inhibiting the sodium glucose cotransporter-2 (SGLT2), and it also offers cardioprotective and renoprotective benefits, making it particularly suitable for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD).

While empagliflozin is generally well-tolerated and easy to administer, it does have some side effects and contraindications that need to be considered, highlighting the importance of evaluating its benefits against potential risks in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. Shafiq, A., Mahboob, E., Samad, MA., et al.[2022]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

Empagliflozin effectively reduces blood sugar levels in patients with type 2 diabetes by preventing glucose reabsorption, leading to a loss of about 70 grams of glucose per day, which also contributes to weight loss.

In addition to its blood sugar-lowering effects, empagliflozin has been shown to slightly decrease blood pressure and has been approved for use in the European Union since May 2014, often in combination with other diabetes medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. Prázný, M., Slíva, J.[2018]

Empagliflozin, an SGLT2 inhibitor, is effective in improving blood sugar control in adults with type 2 diabetes, especially when metformin is not suitable.

In addition to managing diabetes, empagliflozin also aims to reduce cardiovascular risks associated with the condition, highlighting its dual role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

▼ Empagliflozin, diabetes and outcomes. [2017]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1504720

Empagliflozin, Cardiovascular Outcomes, and Mortality in ... In conclusion, patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin had significantly lower rates of ...

2. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/t2d/efficacy

T2D Efficacy Data | Jardiance® (empagliflozin) tablets Explore the efficacy and clinical trial data of JARDIANCE in reducing A1C levels for adults with type 2 diabetes. See Safety, Prescribing Info, & Med Guide.

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.068613

Comparative Cardiovascular Effectiveness of Empagliflozin ... Empagliflozin and dapagliflozin initiators had no differences in 6-year cardiovascular outcomes in adults with treated type 2 diabetes.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0168822721004824

Long-term effectiveness and safety of quadruple ... Quadruple combination therapy with either empagliflozin or dapagliflozin showed a positive long-term effect in the glycemic control and body weight reduction.

5. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/jardiance-empagliflozin-tablets-reduce-risk-cv-death-boehringer-ingelheim-us

Jardiance® (empagliflozin) Tablets Reduce Risk of CV Death The landmark EMPA-REG OUTCOME trial demonstrated that Jardiance reduced the risk of cardiovascular death by 38 percent versus placebo in people ...

6. diabetesjournals.org diabetesjournals.org/care/article/45/6/1445/145036/Safety-of-Empagliflozin-in-Patients-With-Type-2

Safety of Empagliflozin in Patients With Type 2 Diabetes and ... Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of ...

7. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/jardiance-empagliflozin-analysis-reinforces-established-safety-profile

Jardiance® (empagliflozin) T2D Analysis on Safety Profile The landmark EMPA-REG OUTCOME trial demonstrated that Jardiance reduced the risk of cardiovascular death by 38 percent versus placebo in people ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01131676

Study Details | NCT01131676 | BI 10773 (Empagliflozin) ... The aim of the present study is to investigate the safety of BI 10773 treatment in patients with Type 2 Diabetes Mellitus and high cardiovascular risk.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38509341/

Effectiveness and safety of empagliflozin: final results from ... Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression ...