Use of Empagliflozin to Treat Prediabetes - a Randomized, Double-blind, Placebo-controlled 13-week Intervention Trial
Overview
- Phase
- Phase 4
- Intervention
- Empagliflozin
- Conditions
- PreDiabetes
- Sponsor
- Oregon State University
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Insulin-stimulated glucose disposal
- Status
- Active, Not Recruiting
- Last Updated
- 3 months ago
Overview
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.
Investigators
Sean Newsom
Associate Professor, Kinesiology
Oregon State University
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)
Arms & Interventions
Empagliflozin
Participants will be provided 10-25mg empagliflozin per day for 13 weeks.
Intervention: Empagliflozin
Multivitamin-Placebo
Participants will be provided 1 multivitamin-placebo per day for 13 weeks.
Intervention: Multivitamin-Placebo
Outcomes
Primary Outcomes
Insulin-stimulated glucose disposal
Time Frame: Insulin-stimulated glucose disposal is measured before the start of the intervention (baseline) and during week 13 of the intervention.
The glucose infusion rate to maintain glycemia during insulin clamp, using plasma enrichment of glucose isotope tracer to determine changes in rates of insulin-stimulated glucose disposal
Secondary Outcomes
- Whole-body fat oxidation(Whole-body fat oxidation is measured before the start of the intervention (baseline) and during week 13 of the intervention.)
- Skeletal muscle insulin signaling(Skeletal muscle insulin signaling is measured before the start of the intervention (baseline) and during week 13 of the intervention.)
- Oral glucose tolerance(Oral glucose tolerance is measured before the start of the intervention (baseline) and during week 12 of the intervention.)
- Fasting plasma glucose concentration(Fasting plasma glucose is measured before the start of the intervention (baseline) and during week 13 of the intervention.)
- Skeletal muscle lipids(Skeletal muscle lipids are measured before the start of the intervention (baseline) and during week 13 of the intervention.)
- Skeletal muscle mitochondrial respiratory function(Skeletal muscle mitochondrial respiratory function is measured before the start of the intervention (baseline) and during week 13 of the intervention.)
- Skeletal muscle energetic stress(Skeletal muscle energetic stress is measured before the start of the intervention (baseline) and during week 13 of the intervention.)