Empagliflozin for Prediabetes

Overseen By Matthew M Robinson, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Oregon State University

Must not be taking: Glucose-lowering, MAO inhibitors, beta-blockers, diuretics

Disqualifiers: Regular exercise, pregnancy, smoking, major metabolic, 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: 10

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the diabetes drug empagliflozin (also known as Jardiance) affects muscle health in people with prediabetes. Researchers aim to determine if the drug can help control blood sugar and improve muscle metabolism, which involves how the body uses energy. Participants will take either the drug or a placebo (a pill with no active drug) for 13 weeks. Individuals who are overweight or obese, with stable weight and slightly elevated blood sugar, might be suitable for this study. As a Phase 4 trial, this study involves an FDA-approved drug and seeks to understand its benefits for more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, especially glucose-lowering medications and some others like beta-blockers and diuretics, to participate in this trial.

What is the safety track record for empagliflozin?

Research shows that empagliflozin is generally safe for people with type 2 diabetes. The FDA has approved this drug for treating type 2 diabetes, indicating a good safety record. Studies have found that while empagliflozin can increase the risk of diabetic ketoacidosis (a serious condition where the body makes too many acids), it is linked to lower risks of kidney injury and low blood sugar.

In people with advanced chronic kidney disease, empagliflozin did not present new safety issues and might even help prevent some complications. These findings suggest that empagliflozin could be safe for people with prediabetes, as it is being tested in this trial. Always consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Empagliflozin is unique because it targets prediabetes by reducing blood sugar levels through a mechanism called SGLT2 inhibition. Unlike traditional treatments for prediabetes, which often focus on lifestyle changes or medications that increase insulin sensitivity, empagliflozin works by helping the kidneys remove excess glucose from the body. Researchers are excited about this treatment because it offers a novel approach that could complement existing therapies, potentially leading to more effective management of prediabetes. Additionally, empagliflozin's ability to lower blood sugar without relying on insulin production might offer benefits for patients who struggle with other options.

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

Research shows that empagliflozin helps control blood sugar levels in people with type 2 diabetes. Studies have found that it lowers A1C levels, reflecting average blood sugar over time. Empagliflozin also aids in weight loss, though the effect is small. It can reduce the risk of heart problems like heart attacks and strokes. In this trial, participants will receive either empagliflozin or a multivitamin-placebo. For those with prediabetes, empagliflozin might help prevent the development of full diabetes by improving how the body handles sugar and fats. These benefits suggest it could manage blood sugar and improve overall health for people with prediabetes. ^{1 3 4 6 7}

Who Is on the Research Team?

Sean A Newsom, Ph.D.

Principal Investigator

Oregon State University

Are You a Good Fit for This Trial?

This trial is for overweight or obese adults with prediabetes, defined by specific blood sugar levels. Participants should have a BMI between 26-45 and stable weight. They can't join if they smoke, are pregnant, take certain medications (like glucose-lowering drugs), have major health issues like heart disease or diabetes, exercise regularly, or have allergies to empagliflozin.

Inclusion Criteria

You have a body mass index (BMI) between 26 and 45.

Your blood sugar levels are within a certain range when you haven't eaten for a while, or your HbA1c levels are within a specific range.

Your weight has not changed by more than 10 pounds in the past 3 months.

Exclusion Criteria

You are currently smoking or using nicotine, or have quit for less than a year.

You are allergic to lidocaine.

I am not taking any diabetes, depression, blood pressure, or water pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either empagliflozin or a multivitamin-placebo for 13 weeks to assess changes in glucose metabolism and skeletal muscle health

13 weeks

9 visits (in-person)

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 improves blood sugar regulation in skeletal muscle among those at risk for diabetes. It compares the effects of empagliflozin against a placebo (multivitamin) on how the body and muscles handle glucose.

How Is the Trial Designed?

Group I: Empagliflozin Experimental Treatment 1 Intervention

Participants will be provided 10-25mg empagliflozin per day for 13 weeks.

Group II: Multivitamin-Placebo Placebo Group 1 Intervention

Participants will be provided 1 multivitamin-placebo per day for 13 weeks.

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?

Oregon State University

Lead Sponsor

Trials

51

Recruited

8,300+

Samaritan Health Services

Collaborator

Trials

5

Recruited

270+

Published Research Related to This Trial

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 56-year-old man with type 2 diabetes presented in diabetic ketoacidosis (DKA) despite only mild hyperglycemia, highlighting a rare complication associated with the use of empagliflozin (Jardiance®).

This case emphasizes the need for emergency physicians to recognize that DKA can occur in patients on SGLT-2 inhibitors like empagliflozin, even when blood sugar levels are not severely elevated, which can complicate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-glucose Cotransporter-2 Induced Diabetic Ketoacidosis with Minimal Hyperglycemia. Gammons, DT., Counselman, FL.[2020]

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 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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9506669/

Empagliflozin Ameliorates Progression From Prediabetes ... The purpose of this paper is to demonstrate how EMPA ameliorates progression from prediabetes to diabetes and improves hepatic lipid metabolism.

2. pro.boehringer-ingelheim.com pro.boehringer-ingelheim.com/us/products/jardiance/t2d/efficacy

T2D Efficacy Data | Jardiance® (empagliflozin) tablets Explore the efficacy and clinical trial data of JARDIANCE in reducing A1C levels for adults with type 2 diabetes. See Safety, Prescribing Info, & Med Guide.

3. 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 ...

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

Empagliflozin, Cardiovascular Outcomes, and Mortality in ... In conclusion, patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin had significantly lower rates of ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38509341/

Effectiveness and safety of empagliflozin: final results from ... Empagliflozin relative to DPP-4i was associated with risk reductions of MI or stroke, HHF, MACE and the composite of cardiovascular ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9210861/

Safety of Empagliflozin in Patients With Type 2 Diabetes ... Use of empagliflozin in patients with type 2 diabetes and advanced CKD raised no new safety concerns and may have beneficial effects on the development of ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1262363622000994

Empagliflozin cardiovascular and renal effectiveness and ... For safety outcomes, initiation of empagliflozin was associated with a lower risk of acute kidney injury, increased risk of diabetic ketoacidosis, and similar ...