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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall purpose of this study is to identify how empagliflozin (a drug commonly used to treat type 2 diabetes) impacts skeletal muscle metabolic health among adults with prediabetes. Our aims are to: 1) Test the ability of empagliflozin to improve regulation of glucose metabolism (i.e., blood sugar) among overweight and obese individuals at risk for diabetes, and 2) Identify mechanisms to explain how empagliflozin may improve skeletal muscle glucose metabolism. We hypothesize empagliflozin will improve regulation of glucose metabolism due to changes in whole-body and skeletal muscle metabolism (e.g., increased rates of whole-body fat oxidation, evidence of impaired skeletal muscle mitochondrial respiratory function and increased energetic stress, lower accumulation of skeletal muscle lipids and improved skeletal muscle insulin signaling compared with placebo treatment).

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 data supports the effectiveness of the drug empagliflozin for prediabetes?

Empagliflozin, known as Jardiance, is effective in lowering blood sugar levels and reducing body weight in people with type 2 diabetes, and it also offers heart and kidney protection. While it is not specifically studied for prediabetes, its benefits in managing blood sugar and reducing cardiovascular risks in diabetes may suggest potential benefits for prediabetes as well. ^{1 2 3 4 5}

Is empagliflozin (Jardiance) safe for humans?

Empagliflozin (Jardiance) is generally well-tolerated, but it can cause some side effects like genital infections, urinary tract infections, and a rare condition called diabetic ketoacidosis (a serious diabetes complication). It is important for patients to be monitored for fluid deficits and other adverse effects, especially if they have heart failure or are at risk of low blood pressure. ^{1 2 4 5 6}

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

Empagliflozin is unique because it works by preventing the kidneys from reabsorbing glucose, leading to its excretion in urine, which helps lower blood sugar levels and reduce body weight. Unlike many other diabetes treatments, it also offers heart and kidney protection, making it beneficial for patients with cardiovascular and kidney issues. ^{2 4 5 7 8}

Research Team

Sean A Newsom, Ph.D.

Principal Investigator

Oregon State University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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]

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]

References

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

▼ Empagliflozin, diabetes and outcomes. [2017]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Belgium pubmed.ncbi.nlm.nih.gov

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

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

Sodium-glucose Cotransporter-2 Induced Diabetic Ketoacidosis with Minimal Hyperglycemia. [2020]

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

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]