Use of Empagliflozin to Treat Prediabetes

Overweight and Obesity Clinical Trial

Official title:

Use of Empagliflozin to Treat Prediabetes - a Randomized, Double-blind, Placebo-controlled 13-week Intervention Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05426525
• Other study ID #: OregonSU
• Status: Recruiting
• Phase: Phase 4
• Start date: October 13, 2022
• Est. completion date: April 2025

Study information

• Verified date: June 2023
• Source: Oregon State University
• Contact: Sean A Newsom, Ph.D.
• Phone: (541) 737-1613
• Email: sean.newsom[@]oregonstate.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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)

Related Conditions & MeSH terms

• Glucose Intolerance
• Overweight
• Overweight and Obesity
• PreDiabetes
• Prediabetic State

Intervention

Drug:
• Empagliflozin
Participants will take 10mg empagliflozin per day for 2 weeks. Absent contraindications, dosing will be increased to 25 mg empagliflozin per day for the next 11 weeks.
• Multivitamin-Placebo
Participants will take 1 multivitamin per day for 13 weeks.

Locations

Country	Name	City	State
United States	Oregon State University	Corvallis	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Oregon State University	Samaritan Health Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin-stimulated glucose disposal	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	Insulin-stimulated glucose disposal is measured before the start of the intervention (baseline) and during week 13 of the intervention.
Secondary	Oral glucose tolerance	The change in blood glucose concentration in response to a 75g glucose beverage	Oral glucose tolerance is measured before the start of the intervention (baseline) and during week 12 of the intervention.
Secondary	Fasting plasma glucose concentration	The change in fasting plasma glucose concentration	Fasting plasma glucose is measured before the start of the intervention (baseline) and during week 13 of the intervention.
Secondary	Whole-body fat oxidation	Indirect calorimetry will be used to determine the change in whole-body rate of fat oxidation during basal and insulin-stimulated conditions	Whole-body fat oxidation is measured before the start of the intervention (baseline) and during week 13 of the intervention.
Secondary	Skeletal muscle insulin signaling	Immunoblotting to determine the change in activation of insulin signaling proteins in skeletal muscle collected at basal and during insulin-stimulated conditions	Skeletal muscle insulin signaling is measured before the start of the intervention (baseline) and during week 13 of the intervention.
Secondary	Skeletal muscle lipids	Mass spectrometry lipidomic analysis of skeletal muscle to determine changes in muscle lipid content	Skeletal muscle lipids are measured before the start of the intervention (baseline) and during week 13 of the intervention.
Secondary	Skeletal muscle mitochondrial respiratory function	Changes in skeletal muscle mitochondrial respiratory capacity measured using high-resolution respirometry	Skeletal muscle mitochondrial respiratory function is measured before the start of the intervention (baseline) and during week 13 of the intervention.
Secondary	Skeletal muscle energetic stress	Immunoblotting to determine changes in activation of AMPK and related signaling proteins pathways	Skeletal muscle energetic stress is measured before the start of the intervention (baseline) and during week 13 of the intervention.