Empagliflozin for Obesity-Related Inflammation

(SADIE2 Trial)

Overseen By Mona Mashayekhi, MD

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

Trial Summary

What is the purpose of this trial?

Obesity is associated with increased cardiometabolic disease risk due, in part, to heightened chronic inflammation arising from adipose tissue. There are no current targeted therapies to prevent or reverse the chronic inflammation of obesity, and a better understanding of these inflammatory pathways in humans is key to future therapeutic interventions. This trial will determine both the anti-inflammatory potential of the SGLT2 inhibitor empagliflozin, and the contribution of adipose inflammation to surrogate measures of cardiovascular disease in a randomized controlled trial of obese patients.

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.

What data supports the effectiveness of the drug empagliflozin for obesity-related inflammation?

Empagliflozin, also known as Jardiance, has been shown to reduce the risk of cardiovascular death and hospitalization in people with heart failure, and it helps manage blood sugar levels in type 2 diabetes, which can also lead to weight loss and lower blood pressure. These effects suggest it may help with conditions related to obesity, although direct evidence for obesity-related inflammation is not provided. ^{1 2 3 4 5}

Is empagliflozin generally safe for humans?

Empagliflozin, also known as Jardiance, is generally well-tolerated and has been used safely in people with type 2 diabetes and heart failure. However, it can have side effects, such as fluid deficits, and its safety in other conditions like obesity-related inflammation is still being studied. ^{1 5 6 7 8}

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

Empagliflozin is unique because it not only helps reduce blood sugar levels by increasing glucose excretion through urine but also promotes fat browning and reduces inflammation in obesity by activating certain immune cells (M2 macrophages). This dual action on energy metabolism and inflammation makes it different from other treatments. ^{1 4 6 8 9}

Research Team

Monda Mashayekhi, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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.

I am between 18 and 70 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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 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, 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]

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]

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) 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, 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]

References

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

Diabetes Drug Now Approved for Heart Failure. [2023]

2. 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]

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

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. [2020]

4. Belgium pubmed.ncbi.nlm.nih.gov

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

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

▼ Empagliflozin, diabetes and outcomes. [2017]

6. England pubmed.ncbi.nlm.nih.gov

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

7. 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]

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

SGLT2 inhibitors: new reports. [2019]

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

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