Empagliflozin for Obesity-Related Inflammation
(SADIE2 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
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.12345
Is empagliflozin generally safe for humans?
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.14689
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.
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Trial 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 (Anti-diabetic agent)
Trial OverviewThe 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
2Treatment groups
Active Control
Placebo Group
Group I: Empagliflozin ArmActive Control1 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 ArmPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Vanderbilt University Medical CenterNashville, TN
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Who Is Running the Clinical Trial?
Vanderbilt University Medical CenterLead Sponsor
References
Diabetes Drug Now Approved for Heart Failure. [2023]The diabetes drug empagliflozin (Jardiance) is now approved to reduce the risk of cardiovascular death and hospitalization in adults with heart failure, even if they do not have diabetes.Nurses and NPs should monitor patients for adverse effects, especially fluid deficits.
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]Label="WHAT IS THIS SUMMARY ABOUT?" NlmCategory="UNASSIGNED">This is a summary of the article describing the EMPEROR-Reduced study of empagliflozin, which was published in the New England Journal of Medicine. Empagliflozin (brand name Jardiance®) is a new drug therapy for the treatment of chronic heart failure. Chronic heart failure is a long-term condition where the heart cannot pump enough blood around the body, leading to symptoms such as shortness of breath, fatigue and build-up of too much water in the body (fluid retention). It also increases the risk for premature death.
Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. [2020]Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes.
[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. [2022]Empagliflozin is a new inhibitor of sodiumglucose cotransporters type 2 (SGLT2) for the treatment of type 2 diabetes mellitus (T2DM). Its specific action inhibits glucose reabsorption in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(Ic)), independently of insulin. Furthermore, calorie urinary loss promotes weight reduction and osmotic diuresis lowers arterial blood pressure. The efficacy of empagliflozin increases according to the level of hyperglycaemia but decreases in patients with renal insufficiency. In 24 to 104-week controlled trials versus placebo, empagliflozin reduces HbA(1c) (approximately 0.8%), without hypoglycaemia (except in patients already treated with insulin or sulphonylureas). This improvement in glucose control is rather similar to that observed with active comparators (metformin, glimepiride or sitagliptin), with the advantage for empagliflozin of reducing body weight (approximately 2 kg) and blood pressure (systolic approximately 4 mm Hg and diastolic approximately 2 mm Hg). Empagliflozin has shown a cardiovascular protection in the EMPA-REG OUTCOME trial. Mycotic genital infections occur more frequently, especially in women, while a negligible increase in mild urinary tract infections may be observed. The risk of hypotension and volume depletion is low, although it should be carefully checked in more fragile and at risk patients. Empagliflozin (Jardiance), which is commercialized at the doses of 10 mg and 25 mg once daily, is indicated for the treatment of T2DM and reimbursed in Belgium with conditions as add-on to a background glucose-lowering therapy.
▼ Empagliflozin, diabetes and outcomes. [2017]The prevalence of type 2 diabetes is rising, and in 2015 more than 5% of adults in the UK were affected by this condition.(1,2) Management of type 2 diabetes includes encouraging lifestyle changes (increased exercise, modification of diet and smoking cessation) alongside the provision of medication to minimise long-term complications and manage blood sugar control while avoiding unwanted effects of drug treatment.(3) Of particular importance, people with type 2 diabetes are at increased risk of cardiovascular disease, and therefore the aims of treatment also include modification of associated risk factors.(2-5)▼ Empagliflozin (Jardiance-Boehringer Ingelheim) is the third sodium-glucose co-transporter-2 (SGLT2) inhibitor licensed for use in the UK. It was launched in August 2014, and acts in a similar way to the other SGLT2 inhibitors, ▼ dapagliflozin and ▼ canagliflozin, by inhibiting renal glucose resorption and promoting glycosuria.(6) It is indicated for the treatment of type 2 diabetes in adults to improve glycaemic control, as monotherapy when metformin cannot be used, and in combination with other glucose-lowering drugs including insulin. Here we review the evidence for empagliflozin and discuss the results of a recent study that assessed cardiovascular outcomes.
The dual role of empagliflozin: Cardio renal protection in T2DM patients. [2022]Empagliflozin (Jardiance®) is an insulin independent antihyperglycemic agent used in treatment of T2D.The drug is a sodium glucose cotransporter-2 (SGLT2) inhibitor approved in USA and Europe and other countries of the world. As empagliflozin demonstrates cardioprotective and Reno protective properties its prime target are patients having CVD and CKD complicated by T2D. This review sheds light on mechanism of action of the drug and with the help of clinical outcomes establishes the use of empagliflozin in T2D patients. Although empagliflozin is a well-tolerated and easy to administer drug, it has some side effects and contraindications which are discussed in the article to help the reader weigh its beneficial effects against its adverse effect and understand its use in clinical medicine.
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]To evaluate the pharmacokinetic properties and safety of empagliflozin, and the bioequivalence of test formulation empagliflozin tablet compared with the brand-name drug Jardiance (reference formulation) after single oral administration under fasting and fed conditions in healthy Chinese subjects.
SGLT2 inhibitors: new reports. [2019]A significant decrease in cardiovascular mortality has been reported with use of the SGLT2 inhibitor empagliflozin (Jardiance) to treat patients with type 2 diabetes who have established cardiovascular disease. The mechanism of this reduction is unclear, and these results may not apply to patients with type 2 diabetes and less advanced cardiovascular disease. Whether the increase in fractures reported with canagliflozin (Invokana) could also occur with empagliflozin remains to be established. All SGLT2 inhibitors are only modestly effective for treatment of diabetes.
Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization. [2019]Obesity-associated low-grade inflammation underlies insulin resistance and associated metabolic comorbidities, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease. Excessive ectopic fat deposition in obesity causes disorders of energy homeostasis and low-grade chronic inflammation in metabolic tissues. In particular, obesity-induced recruitment and activation of adipose tissue macrophages play a key role in the pathogenesis of insulin resistance and T2D. Therefore, treatment options for energy metabolism and macrophage polarization in obese subjects are needed. Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion by inhibiting renal glucose reabsorption, thereby having subsequent anti-hyperglycemic effects and reducing body weight. We recently reported that the SGLT2 inhibitor empagliflozin increases fat utilization and browning in white adipose tissue and attenuates obesity-induced inflammation and insulin resistance by activating M2 macrophages. Thus, this review focuses on the beneficial effects of empagliflozin in energy homeostasis and obesity-related inflammation and insulin resistance.