Empagliflozin for Obesity-Related Inflammation

(SADIE2 Trial)

Overseen By Mona Mashayekhi, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Anti-diabetics, Glucocorticoids, Anticoagulants, others

Disqualifiers: Type 1 diabetes, Cardiovascular disease, Neurologic disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether empagliflozin, a medication commonly used for diabetes, can reduce inflammation associated with obesity. Researchers aim to understand how this inflammation might impact heart health. Participants will receive either the drug or a placebo (a pill with no active medication) to compare effects. Ideal candidates are individuals with obesity who plan to undergo weight loss surgery and have conditions such as high blood pressure or high blood sugar. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you have not used certain medications recently, like SGLT2 inhibitors in the last 3 months or anti-diabetic medications other than a stable dose of metformin or a sulfonylurea in the last month. If you are on these medications, you may need to stop them before joining the trial.

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

Research has shown that empagliflozin, a medication commonly used for type 2 diabetes, is generally safe. The FDA has approved it for diabetes, and it is also used for heart failure, so doctors understand its mechanism. Studies indicate that empagliflozin can reduce the risk of death from heart issues. However, it may cause side effects, such as increased urination due to fluid loss. Its safety for treating inflammation related to obesity remains under investigation. Overall, empagliflozin is well-tolerated, but potential risks should be considered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for obesity-related inflammation focus on lifestyle changes or medications that suppress appetite or alter fat metabolism. However, empagliflozin works differently by targeting the kidneys to increase glucose excretion, which can indirectly reduce inflammation. This gives it a unique angle compared to the typical appetite or metabolism-focused therapies. Researchers are excited about empagliflozin because it is already FDA-approved for other conditions, indicating a strong safety profile, and it offers a novel mechanism that could benefit people with obesity-related issues beyond just weight loss.

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

In this trial, participants will receive either empagliflozin or a placebo. Research has shown that empagliflozin, a medication approved for type 2 diabetes, may help reduce inflammation related to obesity. Studies have found that it lowers the buildup of certain immune cells, decreasing inflammation in the body. It also aids in weight loss and reduces waist size, both important for managing obesity. Additionally, empagliflozin boosts energy use and helps convert white fat into brown fat, enhancing the body's ability to burn fat. These effects suggest that empagliflozin could effectively address inflammation linked to obesity. ^{2 3 6 7 8}

Who Is on the Research Team?

Mona Mashayekhi, MD, PhD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with metabolic syndrome, defined by high blood pressure, elevated triglycerides, low HDL cholesterol, high fasting blood sugar or large waist circumference. Participants must have a BMI ≥ 35 kg/m2 and be planning obesity surgery within the next 90-150 days. Exclusions include alcohol/drug abuse history, pregnancy/breastfeeding without contraception, type 1 diabetes or recent SGLT2 inhibitor use.

Inclusion Criteria

You have three or more of the following: high blood pressure, high triglycerides, low HDL cholesterol, high blood sugar, or a large waist size.

Exclusion Criteria

My diabetes is not well-managed, with an HbA1c level of 9% or higher.

I am not pregnant or breastfeeding and use effective birth control or am surgically sterilized.

I have advanced liver disease with cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the SGLT2 inhibitor empagliflozin or placebo for 12 weeks

12 weeks

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 whether Empagliflozin (a drug that lowers blood sugar) can reduce inflammation in fat tissue and improve heart-related functions in obese patients. It's a randomized controlled trial where participants will either receive Empagliflozin or a placebo to compare effects.

How Is the Trial Designed?

Group I: Empagliflozin Arm Active Control 1 Intervention

Empagliflozin is an FDA-approved SGLT2 inhibitor used for the treatment of type 2 diabetes, with off-label use for diabetic kidney disease and for heart failure with reduced ejection fraction even in those without diabetes. To ensure blinding, empagliflozin will be over-encapsulated in identical gelatin capsules as placebo.

Group II: Placebo Arm Placebo Group 1 Intervention

Placebo consists of gelatin capsules.

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?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Empagliflozin, an SGLT2 inhibitor, helps reduce obesity-related inflammation and insulin resistance by promoting the activation of M2 macrophages, which are beneficial for metabolic health.

This medication also enhances fat utilization and promotes browning of white adipose tissue, contributing to improved energy homeostasis and potential weight loss in obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization. Xu, L., Ota, T.[2019]

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 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) is a new medication classified as an SGLT2 inhibitor, specifically designed to help manage blood sugar levels in individuals with type-2 diabetes.

This medication not only aids in lowering blood glucose but also has potential benefits for heart health, making it a promising option for patients with diabetes at risk for cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. Ndefo, UA., Anidiobi, NO., Basheer, E., et al.[2020]

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]

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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5478253/

SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization ... Our results indicate that empagliflozin attenuates obesity-related inflammation by decreasing macrophage accumulation and causing an M2-dominant phenotypic ...

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

Empagliflozin reverses obesity and insulin resistance ... Conclusions Treatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated ...

3. withpower.com withpower.com/trial/phase-2-inflammation-8-2023-5c406

Empagliflozin for Obesity-Related Inflammation In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8117073/

Empagliflozin therapy and insulin resistance-associated ... Preclinical and clinical studies of empagliflozin in patients with T2D have demonstrated significant improvements of body weight, waist circumference, insulin ...

5. nature.com nature.com/articles/s41598-019-51648-1

Empagliflozin and Dulaglutide are Effective against Obesity ... Empagliflozin and dulaglutide could be a promising therapy for obesity-induced asthma and showed additive effects in combination.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11806693/

The real-world safety profile of empagliflozin Our study uncovered a yearly increase in the number of adverse event reports associated with empagliflozin, beginning in 2014 and maintaining a ...

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

Empagliflozin, Cardiovascular Outcomes, and Mortality in ... As compared with placebo, empagliflozin resulted in a significantly lower risk of death from cardiovascular causes (hazard ratio, 0.62; 95% CI, ...

8. 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 ...