Use of Empagliflozin to Treat Prediabetes

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

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).

Study Overview

• Status: Recruiting
• Conditions: PreDiabetes; Prediabetic State; Overweight and Obesity
• Intervention / Treatment: Drug: Empagliflozin; Drug: Multivitamin-Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sean A Newsom, Ph.D.; Phone Number: (541) 737-1613; Email: sean.newsom@oregonstate.edu
• Study Contact Backup: Name: Matthew M Robinson, Ph.D.; Phone Number: (541) 737-1126; Email: matthew.robinson@oregonstate.edu

Study Locations

• United States
  • Oregon
    • Corvallis, Oregon, United States, 97331
      • Recruiting
      • Oregon State University
      • Contact: Matthew M Robinson, Ph.D.; Phone Number: (541) 737-1126; Email: matthew.robinson@oregonstate.edu
      • Contact: Sean A Newsom, Ph.D.; Phone Number: 541-737-1613; Email: sean.newsom@oregonstate.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin; Participants will be provided 10-25mg empagliflozin per day for 13 weeks.	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.; Other Names: Jardiance
Placebo Comparator: Multivitamin-Placebo; Participants will be provided 1 multivitamin-placebo per day for 13 weeks.	Drug: Multivitamin-Placebo; Participants will take 1 multivitamin per day for 13 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Oregon State University
• Collaborators: Samaritan Health Services
• Investigators: Principal Investigator: Sean A Newsom, Ph.D., Oregon State University

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2022
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Body Weight; Hyperglycemia; Prediabetic State; Glucose Intolerance; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: OregonSU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The current study is a pilot and feasibility project. IPD will not be made publicly available, save for publication and reporting requirements. Individual requests for data will be addressed by the Principal Investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No