Empagliflozin for Prediabetes

(PREVNT Trial)

Overseen By Beth Greck, PharmD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Charles George VA Medical Center

Must not be taking: Antihyperglycemics, Weight loss agents

Disqualifiers: Diabetes, Pregnancy, Neurogenic bladder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how empagliflozin, a medication, might help people with prediabetes avoid progressing to diabetes and reduce the risk of heart and kidney issues. It compares two groups: one receiving standard care with lifestyle education and another receiving the same care plus empagliflozin. The trial is open to individuals diagnosed with prediabetes, where blood sugar is higher than normal but not high enough to be considered diabetes. Participants should not already be on diabetes medication or weight loss supplements. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

If you are currently taking any medication for type 2 diabetes or weight loss, you will need to stop those before joining the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that empagliflozin is likely to be safe for humans?

Research has shown that empagliflozin is generally safe for people with type 2 diabetes. Studies have found a higher chance of developing diabetic ketoacidosis (DKA), but the risks of kidney injury, low blood sugar, and disease progression are lower. In individuals with serious kidney problems, empagliflozin did not cause new safety issues and might even benefit kidney health. These findings suggest that empagliflozin is mostly safe, though some risks require close monitoring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about empagliflozin for prediabetes because it offers a novel approach by targeting the kidneys to reduce blood sugar levels. Unlike standard treatments like lifestyle changes and medications that primarily focus on insulin sensitivity or secretion, empagliflozin works by blocking a protein that helps the kidneys reabsorb glucose, allowing more sugar to be excreted in urine. This mechanism not only helps in managing blood sugar but also has the potential to improve kidney function and support weight loss, making it a promising option for those at risk of developing diabetes.

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

Research has shown that empagliflozin can slow the progression of diabetes in individuals with prediabetes. One study demonstrated that it improved the liver's ability to manage fat, benefiting those with prediabetes. Participants taking empagliflozin often lost weight, aiding in blood sugar control. Empagliflozin has also improved insulin use in the body, facilitating lower blood sugar levels. In this trial, one group will receive standard care plus empagliflozin, while another will receive standard care alone. These findings suggest that empagliflozin may effectively manage prediabetes and prevent further health issues. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for veterans aged 35-60 with prediabetes, able to read and speak English. They must have an HbA1c level between 5.7% and 6.5%, or fasting glucose of 100-125 mg/dL. Participants cannot be on diabetes medications, weight loss drugs, or have a history of severe reactions to SGLT2i medications.

Inclusion Criteria

I have prediabetes with an HbA1c between 5.7% and 6.5% or fasting glucose between 100-125 mg/dL.

I am between 35 and 60 years old.

Exclusion Criteria

I cannot take SGLT2i drugs due to past reactions or have taken them in the last 6 months.

Veterans unable to complete informed consent process (Veterans with impaired decision-making ability or who require use of a legally authorized representative)

I am taking medication for type 2 diabetes or using a weight loss drug/supplement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lifestyle education and monitoring of HbA1c, kidney function, weight, and blood pressure. The experimental group also receives empagliflozin 10mg daily.

12 weeks

3 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 Empagliflozin's effectiveness in slowing down the progression from prediabetes to diabetes over a period of 12 weeks compared to standard lifestyle education alone. It also examines its potential in reducing cardiovascular and kidney risks associated with diabetes.

How Is the Trial Designed?

Group I: Standard Care plus empagliflozin Experimental Treatment 2 Interventions

Participants in this arm will receive lifestyle education to manage pre-diabetes as well as the monitoring of HbA1c, kidney function, weight, and blood pressure. They will also receive empagliflozin 10mg daily.

Group II: Standard Care Active Control 1 Intervention

Participants in this arm will receive lifestyle education to manage pre-diabetes as well as the monitoring of HbA1c, kidney function, weight, and blood pressure.

Who Is Running the Clinical Trial?

Charles George VA Medical Center

Lead Sponsor

Trials

1

Recruited

60+

Published Research Related to This Trial

In a study involving over 34,000 person-years of real-world exposure, dapagliflozin was associated with a significantly lower incidence of hospitalization for acute kidney injury (hAKI) compared to other glucose-lowering drugs, indicating a safer profile for kidney function.

The adjusted incidence rate ratios showed that dapagliflozin users had a 30% reduced risk of hAKI, supporting its safety and efficacy in treating type 2 diabetes mellitus without compromising kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Authorization Safety Study of Hospitalization for Acute Kidney Injury in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting. Johannes, CB., Beachler, DC., Layton, JB., et al.[2023]

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]

In a study of 268 patients with inadequately controlled type 2 diabetes, adding empagliflozin (25 mg/day) significantly reduced HbA1c and fasting plasma glucose levels compared to insulin glargine after 24 weeks.

Empagliflozin also led to notable improvements in body weight and systolic blood pressure, while having fewer hypoglycemic events compared to insulin, indicating it is a safe and effective add-on therapy for glycemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of empagliflozin-based quadruple therapy compared with insulin glargine-based therapy in patients with inadequately controlled type 2 diabetes: An observational study in clinical practice. Ku, EJ., Lee, DH., Jeon, HJ., et al.[2022]

In a 24-week trial involving 152 patients with type 2 diabetes, empagliflozin was found to significantly reduce HbA1c levels more than dulaglutide, with a mean treatment difference of -0.27%.

Empagliflozin also led to a significant weight loss of -1.72 kg, while both treatments were reported to have no serious adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucometabolic control of once-weekly dulaglutide switched from DPP4 inhibitor versus daily empagliflozin add-on in patients with type 2 diabetes inadequately controlled with metformin, sulfonylurea, and DPP4 inhibitor: A randomised trial. Lee, EY., Cho, JH., Lee, WJ., et al.[2023]

Empagliflozin (Jardiance) is an effective once-daily treatment for type 2 diabetes that works by inhibiting glucose reabsorption in the kidneys, leading to improved blood sugar control, weight loss, and reduced blood pressure, as shown in phase III trials lasting up to 104 weeks.

In a large trial, empagliflozin was found to be noninferior to glimepiride and even superior at 104 weeks in lowering glycated hemoglobin levels, with a good safety profile and minimal risk of hypoglycemia, especially when not used with insulin or sulfonylureas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin: a review of its use in patients with type 2 diabetes mellitus. Scott, LJ.[2021]

In a systematic review of 8 trials involving 8514 patients with type 2 diabetes, empagliflozin at both 10 mg and 25 mg showed no significant differences in adverse drug events, indicating similar safety profiles for both dosages.

While the overall incidence of adverse effects was comparable between the two doses, female patients experienced a higher rate of genital and urinary tract infections regardless of the empagliflozin dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Drug Events Associated with Low-Dose (10 mg) Versus High-Dose (25 mg) Empagliflozin in Patients Treated for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Dai, X., Luo, ZC., Zhai, L., et al.[2020]

Empagliflozin (EMPA) effectively restored the size and cellular balance of the islets of Langerhans in pre-diabetic subjects, correcting the enlarged islet mass and the disbalance of β-cells and α-cells.

The treatment with EMPA not only improved glucose homeostasis in pre-diabetes but also reduced inflammation and apoptosis markers, suggesting a protective effect on pancreatic cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulatory effect of empagliflozin on cellular parameters of endocrine pancreas in experimental pre-diabetes. Abdel-Hamid, AAM., Firgany, AEL.[2019]

The EMPA-REG OUTCOME trial with 7020 patients showed that empagliflozin significantly reduces cardiovascular and kidney risks in type 2 diabetes, with observed reductions in HbA1c, blood pressure, and body weight.

The PRE score, which predicts long-term treatment effects based on short-term risk markers, underestimated empagliflozin's impact on cardiovascular and kidney outcomes, indicating that current markers may not fully capture its benefits, although it performed well in patients with higher albuminuria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of the Effects of Empagliflozin on Cardiovascular and Kidney Outcomes Based on Short-Term Changes in Multiple Risk Markers. Tye, SC., de Vries, ST., Wanner, C., et al.[2022]

In a 6-month study of patients with uncontrolled type 2 diabetes, adding empagliflozin significantly reduced HbA1c levels more than increasing doses of existing medications, indicating its superior glucose-lowering efficacy.

Empagliflozin not only improved blood sugar control but also led to reductions in blood pressure, body weight, and fat mass, while maintaining lean body mass, showcasing its additional metabolic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea. Shin, Y., Moon, JH., Chin, HJ., et al.[2022]

Empagliflozin, a medication for type 2 diabetes, showed similar maximum plasma concentrations in individuals with normal kidney function and those with varying degrees of renal impairment, indicating consistent absorption regardless of kidney health.

The study found that empagliflozin was well tolerated across all levels of renal impairment, with no need for dose adjustments, suggesting it is a safe option for patients with kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Macha, S., Mattheus, M., Halabi, A., et al.[2022]

Empagliflozin is an effective oral medication for type 2 diabetes that works independently of insulin, showing improvements in blood glucose levels, body weight, and blood pressure across various patient populations.

It has been found to be well tolerated with no increased risk of hypoglycemia compared to placebo, making it a safe option for managing diabetes either alone or in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence. White, JR.[2018]

Empagliflozin, at doses of 10 mg and 25 mg, was found to be well tolerated in over 9000 patient-years of exposure, with no significant increase in adverse events compared to placebo.

The drug did not increase the risk of hypoglycemia except in patients also taking sulfonylurea or insulin, and while there was a higher incidence of genital infections with empagliflozin, serious complications were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes. Kohler, S., Salsali, A., Hantel, S., et al.[2022]

Empagliflozin, a medication for type 2 diabetes, showed a generally safe profile in nonclinical studies, with no adverse effects on respiratory or central nervous system functions and no cardiovascular issues in tested animals.

While empagliflozin caused some kidney-related changes and weight loss due to its mechanism of action (promoting glucose loss), it was not genotoxic or carcinogenic at normal doses, indicating a manageable safety profile for potential human use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin. Bogdanffy, MS., Stachlewitz, RF., van Tongeren, S., et al.[2018]

In a study involving 269 Japanese patients with type 2 diabetes, adding empagliflozin (10 mg or 25 mg) to insulin treatment resulted in significant reductions in HbA1c levels after 16 weeks, which were maintained up to 52 weeks.

Empagliflozin also led to improvements in fasting plasma glucose and body weight, with a similar safety profile to placebo, although there was a slightly higher incidence of mild hypoglycemia in the empagliflozin groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Sone, H., Kaneko, T., Shiki, K., et al.[2022]

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. nature.com nature.com/articles/s41598-024-83820-7

Effect of empagliflozin on weight in patients with ... In conclusion the weight, BMI, and waist circumference of patients decreased following the administration of empagliflozin. Weight reduction was ...

3. diabetesjournals.org diabetesjournals.org/care/article/45/2/398/139008/Empagliflozin-Improves-Insulin-Sensitivity-of-the

Empagliflozin Improves Insulin Sensitivity of the ... Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity, a favorable response that could contribute to ...

4. 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.

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

Empagliflozin, Cardiovascular Outcomes, and Mortality in ... The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the ...

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

Effectiveness and safety of empagliflozin: final results from ... Regarding the safety outcomes, empagliflozin was associated with an increased risk of DKA and lower risks of AKI, hypoglycaemia and progression ...

7. diabetesjournals.org diabetesjournals.org/care/article/45/6/1445/145036/Safety-of-Empagliflozin-in-Patients-With-Type-2

Safety of Empagliflozin in Patients With Type 2 Diabetes and ... 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01131676

Study Details | NCT01131676 | BI 10773 (Empagliflozin) ... The aim of the present study is to investigate the safety of BI 10773 treatment in patients with Type 2 Diabetes Mellitus and high cardiovascular risk.