Empagliflozin for Obesity

(EMPA Trial)

Overseen By Katherine M Burr

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: GLP-1 analogs, SGLT2 inhibitors

Disqualifiers: Diabetes, Cardiovascular disease, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of the medication empagliflozin (also known as Jardiance) on artery health in Veterans with obesity. Participants will take either empagliflozin or a placebo (a pill with no active drug) daily for 12 weeks. The trial aims to determine if empagliflozin can improve conditions related to stiff arteries, which can affect blood circulation. Veterans who may qualify have obesity, some evidence of artery stiffening, and no history of diabetes, heart disease, or uncontrolled high blood pressure. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as GLP-1 analogs, SGLT2 inhibitors, hormone replacement therapy, weight loss drugs, and anticoagulants. If you are on anti-hypertensive medication, your regimen should not have changed in the last 90 days.

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

Previous studies have shown that empagliflozin is safe. Research indicates it can aid in small reductions in weight and waist size, suggesting it is often well-tolerated. More importantly, studies have demonstrated that empagliflozin can improve heart and kidney health in people with type 2 diabetes. It has also proven safe for individuals with obesity. These studies reported no major safety concerns, making it a promising option for further research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Empagliflozin is unique because it targets obesity by inhibiting the sodium-glucose co-transporter 2 (SGLT2), a mechanism typically used in diabetes treatments to help the body excrete excess glucose through urine. Unlike standard obesity treatments that often focus on appetite suppression or fat absorption, empagliflozin offers a novel approach by addressing glucose metabolism. Researchers are excited about this treatment because it may provide a dual benefit for weight management and improved glucose control, potentially offering a fresh alternative for people struggling with obesity.

What evidence suggests that empagliflozin might be an effective treatment for obesity?

Research has shown that empagliflozin, which participants in this trial may receive, can aid weight loss in people with type 2 diabetes. Studies indicate it can result in a modest weight loss of up to 3.2%. Additionally, empagliflozin may enhance heart health by reducing the risk of heart attacks and strokes. It also increases calorie burning and supports the conversion of unhealthy white fat to healthier brown fat. While these findings are promising, most studies have concentrated on individuals with diabetes rather than those with obesity alone. ^{2 6 7 8 9}

Who Is on the Research Team?

Jaume Padilla Parellada, PhD

Principal Investigator

Harry S. Truman Memorial, Columbia, MO

Are You a Good Fit for This Trial?

This trial is for Veterans with obesity to explore how a medication, empagliflozin, might improve arterial health. Participants will be randomly assigned to receive either the actual medication or a placebo for 12 weeks.

Inclusion Criteria

I am between 30 and 60 years old.

Body mass index (BMI) 30-45 kg/m2

My tests show my arteries are stiffer than normal for my age.

Exclusion Criteria

History of recurrent UTIs or mycotic genital infections

I have an active cancer other than minor skin cancers.

I have diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 10mg empagliflozin or placebo daily for 12 weeks

12 weeks

Visits at baseline, week 4, week 8, and week 12

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 is testing the effects of empagliflozin on arterial stiffness in obese Veterans compared to a placebo. The main goal is to see if this medication can make arteries healthier and more flexible.

How Is the Trial Designed?

Group I: Empagliflozin Experimental Treatment 1 Intervention

12 week treatment with 10mg empagliflozin daily

Group II: Placebo Placebo Group 1 Intervention

12 week treatment with 10mg placebo daily

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of Missouri-Columbia

Collaborator

Trials

387

Recruited

629,000+

Published Research Related to This Trial

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]

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 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]

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]

A study involving 60 healthy Chinese subjects demonstrated that the test formulation of empagliflozin is bioequivalent to the brand-name drug Jardiance, showing similar pharmacokinetic properties under both fasting and fed conditions.

Both formulations of empagliflozin were generally well tolerated, indicating a good safety profile for the drug in the tested populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. Chen, G., Zhang, D., Du, A., et al.[2021]

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 (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, 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4768401/

Empagliflozin reduces body weight and indices of adipose ... Empagliflozin significantly reduced weight and adiposity indices with the potential to improve cardiometabolic risk among patients with type 2 diabetes mellitus ...

2. nature.com nature.com/articles/s41598-024-83820-7

Effect of empagliflozin on weight in patients with ... Many studies indicate that using empagliflozin results in a mild weight reduction (less than 3.2%)8–11, and achieving greater weight loss ...

3. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/new-retrospective-data-showed-empagliflozin-reduced-a1c-body-weight-and-markers-abdominal-fat-adults

New Data Showed Empagliflozin Reduced T2D Symptoms A1c was significantly reduced from a baseline of 7.97 percent by 0.65 percent with empagliflozin · Body weight was significantly reduced, from a ...

4. drc.bmj.com drc.bmj.com/content/7/1/e000783

Empagliflozin reverses obesity and insulin resistance ... Results · Empagliflozin reduced weight gain and increased energy expenditure in HFD-fed mice · Empagliflozin promoted fat browning in DIO mice.

5. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.14593

Effectiveness and safety of empagliflozin in routine care ... The primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12182543/

Impact of Empagliflozin on Cardiovascular Outcomes and ... Empagliflozin significantly improved cardiovascular and renal outcomes in Chinese populations with obesity and T2DM, with sustained benefits observed over 6 ...

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

Empagliflozin, Cardiovascular Outcomes, and Mortality in ... Over the course of the study, empagliflozin, as compared with placebo, was associated with small reductions in weight, waist circumference, uric ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/14740338.2022.2062322

Safety and effectiveness of empagliflozin according to body ... In the safety analysis set of patients, empagliflozin treatment was associated with significant overall reductions from baseline over time in body weight. At ...

9. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.14415

Effect of empagliflozin on cardiorenal outcomes and mortality ... In the EMPA-REG OUTCOME trial in T2D patients, the SGLT2 inhibitor empagliflozin reduced the risk of CV death by 38%, hospitalization for ...