Empagliflozin for Arterial Stiffness

(ERASE-Aging Trial)

Overseen By Andrea Atkins, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Missouri-Columbia

Must not be taking: Hormone replacement, Nitrate medications

Disqualifiers: Diabetes, Cardiovascular disease, Cancer, 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: 4

Duration: 12 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

Randomized placebo-controlled clinical trial in a cohort of males (n=40) and females (n=40), 60-80 years of age, with the hypothesis that SGLT2 inhibition with empagliflozin (10mg/day for 12 weeks) reduces aging-related arterial stiffening.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have a stable anti-hypertensive medication regimen for at least 90 days if you are using such medications.

What data supports the effectiveness of the drug empagliflozin for improving arterial stiffness?

Empagliflozin has been shown to improve arterial stiffness in patients with type 2 diabetes, and it also reduces the risk of cardiovascular events and hospitalizations in people with heart failure. This suggests it may be effective in improving arterial health. ^{1 2 3 4 5}

Is empagliflozin generally safe for humans?

Empagliflozin, also known as Jardiance, is generally considered safe for humans and is used to treat conditions like heart failure and type 2 diabetes. However, it is important to monitor for side effects such as fluid deficits (loss of body fluids) and potential bone fractures. ^{1 2 4 6 7}

How does the drug empagliflozin differ from other treatments for arterial stiffness?

Empagliflozin is unique because it is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that not only helps manage blood sugar levels in type 2 diabetes but also offers cardiovascular and renal protection, which may benefit conditions like arterial stiffness. Its ability to lower blood pressure and promote weight loss further distinguishes it from other treatments. ^{1 2 5 6 8}

Eligibility Criteria

This trial is for men and women aged 60-80 who experience arterial stiffness as they age. Participants must be able to consent, have a specific measure of arterial stiffness (carotid femoral PWV >9.5 m/s), and if taking blood pressure medication, it should be stable for at least 90 days.

Inclusion Criteria

My heart to leg artery pulse speed is over 9.5 m/s.

I am capable of understanding and agreeing to the study's procedures.

I am between 60 and 80 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10mg of Empagliflozin or placebo daily for 12 weeks

12 weeks

Visits at baseline, week 4, week 8, and week 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Empagliflozin

Trial Overview The study tests whether Empagliflozin (10mg daily) can reduce arterial stiffening associated with aging compared to a placebo. It's a randomized controlled trial involving 80 participants over the course of 12 weeks.

Participant Groups

Group I: Empagliflozin Experimental Treatment 1 Intervention

10mg Empagliflozin daily for 12 weeks

Group II: Placebo Placebo Group 1 Intervention

10mg Placebo daily for 12 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?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Findings from Research

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 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 EMPA-REG OUTCOME trial involving 7020 patients with type 2 diabetes and atherosclerotic cardiovascular disease, empagliflozin significantly reduced the risk of major adverse cardiovascular events by 22% compared to placebo, indicating its efficacy in lowering cardiovascular complications.

Empagliflozin also led to a 42% reduction in hospital admissions for heart failure and an 17% reduction in all-cause hospital admissions, demonstrating its potential to improve overall patient outcomes in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial. McGuire, DK., Zinman, B., Inzucchi, SE., et al.[2022]

In a study of 58 patients with type 2 diabetes, empagliflozin significantly improved arterial stiffness, as shown by reductions in central systolic blood pressure and pulse pressure after 6 weeks of treatment compared to placebo.

The improvement in arterial stiffness was linked to changes in inflammatory markers (hsCRP) and blood pressure, suggesting that empagliflozin may exert its vascular benefits through anti-inflammatory mechanisms rather than changes in glucose metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial. Bosch, A., Ott, C., Jung, S., 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 (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]

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®) 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]

References

1. 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]

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

Diabetes Drug Now Approved for Heart Failure. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial. [2022]

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

How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial. [2020]

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

SGLT2 inhibitors: new reports. [2019]

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. England pubmed.ncbi.nlm.nih.gov

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