Clinical trial NCT05426525: Use of Empagliflozin to Treat Prediabetes
Official title: Use of Empagliflozin to Treat Prediabetes - a Randomized, Double-blind, Placebo-controlled 13-week Intervention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: PreDiabetes
Prediabetic State
Overweight and Obesity
Lead sponsor: Oregon State University
Sponsor class: OTHER
Collaborators: name: Samaritan Health Services
First posted: 2022-06-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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).

Detailed description: The overall study design is a 13-week, double-blind, placebo-controlled intervention trial, testing the ability of empagliflozin to improve glucose metabolism among overweight and obese individuals at risk for diabetes (compared with a multivitamin-placebo). The study involves metabolic testing before and during the intervention to identify changes in outcomes as a function of the intervention and to ensure participant safety. The study involves 9 visits to the Samaritan Athletic Medicine Center on the campus of Oregon State University in Corvallis, Oregon. Full completion of the study is anticipated to take \~4 months. The project is being completed in collaboration with physicians at Samaritan Health Services.

Eligibility criteria: Inclusion Criteria:

* BMI 26-45 kg/m2
* Weight stable (± 10 lbs in previous 3 months)
* Fasting blood glucose \<126 mg/dL or HbA1c \<6.5% (\<48mmol/mol)

Exclusion Criteria:

* Regular moderate-vigorous exercise (≥30 min/session on ≥2 days per week)
* Pregnancy, planning to become pregnant or nursing
* Lidocaine allergy
* Current or recent smoking or nicotine use (≤ 1-year abstention)
* Medications including glucose lowering medications and supplements (SGLT2 inhibitors, GLP1 agonists, sulfonylurea, insulin, TZDs); mono-amine oxidase inhibitors; beta-blockers; diuretics
* Major metabolic or cardiovascular conditions (e.g., type 1 diabetes, Crohn's disease, untreated hypo- or hyperthyroid, cancer, coronary artery disease, tachycardia, prior bariatric surgery, peripheral vascular disease, liver diseases (e.g., cirrhosis)
* Diagnosed type 2 diabetes. In absence of diagnosis, two separate samples with test results of fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5% (48 mmol/mol).
* Contraindications/precautions for empagliflozin (impaired renal function (EGR\<60), history of: empagliflozin hypersensitivity, ketoacidosis, hypotension, recurring urinary tract or genital mycotic infections, amputation)

Primary outcomes:
measure: Insulin-stimulated glucose disposal
timeFrame: Insulin-stimulated glucose disposal is measured before the start of the intervention (baseline) and during week 13 of the intervention.
Secondary outcomes:
measure: Oral glucose tolerance
timeFrame: Oral glucose tolerance is measured before the start of the intervention (baseline) and during week 12 of the intervention.
measure: Fasting plasma glucose concentration
timeFrame: Fasting plasma glucose is measured before the start of the intervention (baseline) and during week 13 of the intervention.
measure: Whole-body fat oxidation
timeFrame: Whole-body fat oxidation is measured before the start of the intervention (baseline) and during week 13 of the intervention.
measure: Skeletal muscle insulin signaling
timeFrame: Skeletal muscle insulin signaling is measured before the start of the intervention (baseline) and during week 13 of the intervention.
measure: Skeletal muscle lipids
timeFrame: Skeletal muscle lipids are measured before the start of the intervention (baseline) and during week 13 of the intervention.
measure: Skeletal muscle mitochondrial respiratory function
timeFrame: Skeletal muscle mitochondrial respiratory function is measured before the start of the intervention (baseline) and during week 13 of the intervention.
measure: Skeletal muscle energetic stress
timeFrame: Skeletal muscle energetic stress is measured before the start of the intervention (baseline) and during week 13 of the intervention.
Other outcomes:
Locations:
city: Corvallis
country: United States
facility: Oregon State University
state: Oregon
Study officials:
affiliation: Oregon State University
name: Sean A Newsom, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: