Empagliflozin for Prediabetes
(PREVNT Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Charles George VA Medical Center
Must not be taking: Antihyperglycemics, Weight loss agents
Disqualifiers: Diabetes, Pregnancy, Neurogenic bladder, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
Prediabetes effects 96 million people 18 years of age or older. It is important to identify treatment options to slow or prevent progression to diabetes. It is also critical to assess the potential of medications like sodium glucose transporter 2 inhibitors to reduce the risk of cardiovascular events and kidney complications, both common and costly complications of diabetes. This is a 12-week, open-label pilot feasibility study assessing the use of empagliflozin in prediabetes.
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.
What data supports the effectiveness of the drug empagliflozin for prediabetes?
Is empagliflozin generally safe for humans?
Empagliflozin has been studied for safety in people with type 2 diabetes, showing no major effects on breathing, brain, or heart function in animal studies. Some side effects include weight loss, increased urination, and changes in kidney function, but it was not found to cause cancer in most animals tested.678910
How does the drug empagliflozin differ from other treatments for prediabetes?
Eligibility Criteria
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 am between 35 and 60 years old.
Able to read and speak English
I have prediabetes with an HbA1c between 5.7% and 6.5% or fasting glucose between 100-125 mg/dL.
Exclusion Criteria
I am taking medication for type 2 diabetes or using a weight loss drug/supplement.
Veterans unable to complete informed consent process (Veterans with impaired decision-making ability or who require use of a legally authorized representative)
I have been diagnosed with diabetes.
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Trial Timeline
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
Treatment Details
Interventions
- Empagliflozin (Sodium Glucose Transporter 2 Inhibitor)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Standard Care plus empagliflozinExperimental Treatment2 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 CareActive Control1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Charles George VA Medical CenterAsheville, NC
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Who Is Running the Clinical Trial?
Charles George VA Medical CenterLead Sponsor
References
Prediction of the Effects of Empagliflozin on Cardiovascular and Kidney Outcomes Based on Short-Term Changes in Multiple Risk Markers. [2022]Aims: The EMPA-REG OUTCOME trial demonstrated that the sodium-glucose cotransporter-2 inhibitor (SGLT2) empagliflozin reduces the risk of cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes. We previously developed the parameter response efficacy (PRE) score, which translates drug effects on multiple short-term risk markers into a predicted long-term treatment effect on clinical outcomes. The main objective of this study was to assess the accuracy of the PRE score in predicting the efficacy of empagliflozin in reducing the risk of CV and kidney outcomes. Methods: Short-term (baseline to 6-months) changes in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), urinary-albumin-creatinine-ratio (UACR), hemoglobin, body weight, high-density-lipoprotein (HDL) cholesterol, low-density-lipoprotein (LDL) cholesterol, uric acid, and potassium were determined among 7020 patients with type 2 diabetes and established CV disease in the EMPA-REG OUTCOME trial. The beta-coefficients, derived from a Cox proportional hazards model in a pooled database consisting of 6355 patients with type 2 diabetes, were applied to the short-term risk markers in the EMPA-REG OUTCOME trial to predict the empagliflozin-induced impact on CV (defined as a composite of non-fatal myocardial infarction, non-fatal stroke, or CV death) and kidney (defined as a composite of doubling of serum creatinine or end-stage kidney disease) outcomes. Results: Empagliflozin compared to placebo reduced HbA1c (0.6%), SBP (4.2 mmHg), UACR (13.0%), body weight (2.1 kg), uric acid (20.4 μmol/L), and increased hemoglobin (6.6 g/L), LDL-cholesterol (0.1 mmol/L) and HDL-cholesterol (0.04 mmol/L) (all p<0.01). Integrating these effects in the PRE score resulted in a predicted relative risk reduction (RRR) for the CV outcome of 6.4% (95% CI 1.4-11.7), which was less than the observed 14.7% (95% CI 1.3-26.4%) RRR. For the kidney outcome, the PRE score predicted a RRR of 33.4% (95% CI 26.2-39.8); the observed RRR was 46.9% (95% CI 26.8-61.5). In a subgroup of 2,811 patients with UACR ≥30 mg/g at baseline, the PRE score predicted RRR was 40.8% (95% CI 31.2-49.1) vs. the observed RRR of 40.8% (95% CI 12.4-60.0) for the kidney outcome. Conclusions: Integrating multiple short-term risk marker changes in the PRE score underestimated the effect of empagliflozin on CV and kidney outcomes, suggesting that the currently used risk markers do not fully capture the effect of empagliflozin. In patients with increased albuminuria, the PRE score adequately predicted the effect of empagliflozin on kidney outcomes.
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. [2022]We assessed the glucose-lowering efficacy of adding empagliflozin versus dose escalating existing medications in patients with uncontrolled type 2 diabetes (T2D).
Empagliflozin: a review of its use in patients with type 2 diabetes mellitus. [2021]Oral empagliflozin (Jardiance(®)), a sodium glucose cotransporter-2 (SGLT2) inhibitor, is a convenient once-daily treatment for adult patients with type 2 diabetes mellitus. By inhibiting reabsorption of glucose from the proximal tubules in the kidney via inhibition of SGLT2, empagliflozin provides a novel insulin-independent mechanism of lowering blood glucose. In several phase III trials (≤104 weeks' duration; typically 24 weeks' duration) and extension studies (typically ≥76 weeks' treatment), empagliflozin monotherapy or add-on therapy to other antihyperglycaemics, including insulin, improved glycaemic control and reduced bodyweight and systolic blood pressure in adult patients with type 2 diabetes. In a large phase III trial, as add-on therapy to metformin, empagliflozin was shown to be noninferior to glimepiride at 52 and 104 weeks and superior to glimepiride at 104 weeks, in terms of reductions in glycated haemoglobin level (primary endpoint). Empagliflozin was well tolerated by participants in these clinical trials, with most adverse events being mild or moderate in intensity. Empagliflozin treatment appeared to have no intrinsic risk of hypoglycaemia, although hypoglycaemia occurred more frequently when empagliflozin was coadministered with insulin and/or a sulfonylurea. With its insulin-independent mechanism of action, empagliflozin monotherapy or combination therapy with other antidiabetic drugs, including insulin, provides a useful addition to the therapeutic options for the management of type 2 diabetes. This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.
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. [2022]This open-label, prospective study evaluated the effectiveness and safety of empagliflozin as add-on therapy in inadequately controlled type 2 diabetes (T2D) patients (glycated haemoglobin [HbA1c], 7.5-12%) who were already using three other types of orally active antidiabetic agents. A total of 268 T2D patients were enrolled and divided into two groups, empagliflozin (EMPA 25 mg/d, n = 142) or insulin glargine (INS, n = 126), respectively. After the treatment period of 24 weeks, HbA1c and fasting plasma glucose (FPG) were significantly reduced (HbA1c, P = 0.004; FPG, P = 0.008, respectively) in the EMPA group compared to the INS group. Also, EMPA treatment evoked a significant reduction in body weight (P
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. [2023]To compare the effectiveness and safety of empagliflozin and dulaglutide in patients with type 2 diabetes (T2D) inadequately controlled by oral triple therapy.
Safety and Tolerability of Empagliflozin in Patients with Type 2 Diabetes. [2022]The aim of this analysis was to establish the safety profile and tolerability of empagliflozin in patients with type 2 diabetes mellitus (T2DM) according to pooled data from several clinical trials.
Post-Authorization Safety Study of Hospitalization for Acute Kidney Injury in Patients with Type 2 Diabetes Exposed to Dapagliflozin in a Real-World Setting. [2023]Dapagliflozin is a sodium-glucose cotransporter 2 inhibitor approved to treat type 2 diabetes mellitus (T2DM), among other conditions. When dapagliflozin was approved in Europe for treating T2DM (2012), potential safety concerns regarding its effect on kidney function resulted in this post-authorization safety study to assess hospitalization for acute kidney injury (hAKI) among dapagliflozin initiators in a real-world setting.
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. [2020]Empagliflozin is a new, emerging oral hypoglycemic agent (OHA) which has shown significant benefits in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease. In this analysis, our aim was to systematically compare the adverse drug events (ADEs) associated with a low (10 mg) versus a high (25 mg) dose of empagliflozin as (1) monotherapy, (2) as an add-on to other OHAs, and (3) as an add-on specifically to metformin, in patients who were treated for T2DM.
Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin. [2018]Empagliflozin, a selective inhibitor of the renal tubular sodium-glucose cotransporter 2, was developed for treatment of type 2 diabetes mellitus. Nonclinical safety of empagliflozin was studied in a battery of tests to support global market authorization. Safety pharmacology studies indicated no effect of empagliflozin on measures of respiratory or central nervous system function in rats or cardiovascular safety in telemeterized dogs. In CD-1 mouse, Wistar Han rat, or beagle dogs up to 13, 26, or 52 weeks of treatment, respectively, empagliflozin exhibited a toxicity profile consistent with secondary supratherapeutic pharmacology related to glucose loss and included decreased body weight and body fat, increased food consumption, diarrhea, dehydration, decreased serum glucose and increases in other serum parameters reflective of increased protein catabolism, gluconeogenesis, and electrolyte imbalances, and urinary changes such as polyuria and glucosuria. Microscopic changes were consistently observed in kidney and included tubular nephropathy and interstitial nephritis (dog), renal mineralization (rat) and tubular epithelial cell karyomegaly, single cell necrosis, cystic hyperplasia, and hypertrophy (mouse). Empagliflozin was not genotoxic. Empagliflozin was not carcinogenic in female mice or female rats. Renal adenoma and carcinoma were induced in male mice only at exposures 45 times the maximum clinical dose. These tumors were associated with a spectrum of nonneoplastic changes suggestive of a nongenotoxic, cytotoxic, and cellular proliferation-driven mechanism. In male rats, testicular interstitial cell tumors and hemangiomas of the mesenteric lymph node were observed; both tumors are common in rats and are unlikely to be relevant to humans. These studies demonstrate the nonclinical safety of empagliflozin.
Efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. [2022]To assess the efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes (T2D).
Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. [2022]Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus (T2DM).
Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence. [2018]To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).
[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.
Modulatory effect of empagliflozin on cellular parameters of endocrine pancreas in experimental pre-diabetes. [2019]The effect of empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), on the structure of endocrine pancreas in pre-diabetes (Pre-DM) is not yet elucidated. In the current study the relatively enlarged islets of Langerhans seen in the Pre-DM group was restored to control size by administration of EMPA. In addition the disbalance in the percentage of β-cells and α-cells in islets of the Pre-DM was corrected in the Pre-DM + EMPA group with reversal of the significantly increased islet mass, β-cell mass and neogenesis. Administrating EMPA in Pre-DM decreased level of caspase-3, increased that of Bcl-2 to control level and reduced the significantly increased inflammatory cytokines to levels approximated to those of the control group. In Pre-DM + EMPA group, EMPA had efficiently restored the significantly impaired glucose hemostasis to levels nearly similar to those of the control animals. This may indicate that the modulatory effect of EMPA on cells of the islets in Pre-DM is associated with a local pleotropic effect on inflammatory cytokines.