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

Trial Summary

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.

What evidence supports the effectiveness of the drug empagliflozin for weight loss?

Empagliflozin, a drug used to treat type 2 diabetes, has been shown to help reduce body weight by promoting the loss of calories through urine. In studies, it has also been found to lower blood pressure and provide heart and kidney protection, which may indirectly support weight management. ^{1 2 3 4 5}

Is empagliflozin safe for humans?

Empagliflozin (Jardiance) is generally safe for humans, but it can cause some side effects like genital infections, especially in women, and a slight increase in mild urinary tract infections. It may also lead to low blood pressure and fluid loss, so monitoring is important, especially for those at risk. ^{1 2 3 5 6}

How does the drug empagliflozin differ from other treatments for obesity?

Empagliflozin is unique because it works by preventing the kidneys from reabsorbing glucose, leading to its excretion in urine, which not only helps control blood sugar levels but also promotes weight loss by eliminating calories. This mechanism is different from other weight loss treatments that may focus on appetite suppression or fat absorption. ^{2 3 7 8 9}

What is the purpose of this trial?

The study will assign participants to take either the medication, empagliflozin or a placebo for 12 weeks. The goal of the study is to determine the effects of empagliflozin on arterial health in Veterans with obesity.

Research Team

Jaume Padilla Parellada, PhD

Principal Investigator

Harry S. Truman Memorial, Columbia, MO

Eligibility Criteria

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

I have diabetes.

History of recurrent UTIs or mycotic genital infections

I have an active cancer other than minor skin cancers.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 (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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. [2022]

2. Belgium pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2021]

4. England 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. [2023]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

9. England pubmed.ncbi.nlm.nih.gov

▼ Empagliflozin, diabetes and outcomes. [2017]