The Effects of Mirabegron and Tadalafil on Glucose Tolerance in Prediabetics

The investigator hypothesizes that treatment with the ß3 agonist mirabegron results in improved glucose metabolism, including a reversal of prediabetes in obese, insulin-resistant human research participants, and this is further improved by combination therapy with tadalafil. The investigator will comprehensively analyze glucose homeostasis in prediabetic patients treated for 14 weeks with mirabegron, tadalafil or both drugs as compared to a placebo.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Pre-diabetes
• Intervention / Treatment: Drug: Mirabegron 50 MG; Drug: Tadalafil 10 MG; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Philip Kern, M.D.; Phone Number: 859-218-1394; Email: pake222@uky.edu
• Study Contact Backup: Name: Zach Leicht; Phone Number: 859-218-1397; Email: zachary.leicht@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky
      • Principal Investigator: Philip Kern, M.D.
      • Contact: Zach Leicht; Phone Number: 859-218-1397; Email: zachary.leicht@uky.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Hemoglobin A1C between 5.7 and 6.4
• Body mass index between 27 and 45

Exclusion Criteria:

• Diabetes
• Chronic use of any antidiabetic medications
• Any unstable medical condition
• Use of steroids or daily use of NSAIDS
• History of chronic inflammatory conditions
• Use of anticoagulants
• Contraindications to the use of mirabegron or tadalafil
• Any condition deemed risky by the study physician

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mirabegron (M); Drug will be administered for 12 weeks after baseline procedures.	Drug: Mirabegron 50 MG; Mirabegron 50 mg/day will be administered for 14 weeks.
Experimental: Tadalafil (T); Drug will be administered for 12 weeks after baseline procedures.	Drug: Tadalafil 10 MG; Tadalafil 10 mg/day will be administered for 14 weeks after baseline procedures.
Experimental: Mirabegron and Tadalafil (MT); Both drugs will be administered for 12 weeks after baseline procedures.	Drug: Mirabegron 50 MG; Mirabegron 50 mg/day will be administered for 14 weeks.; Drug: Tadalafil 10 MG; Tadalafil 10 mg/day will be administered for 14 weeks after baseline procedures.
Placebo Comparator: Placebo (P)	Drug: Placebo; Placebo will be administered for 14 weeks after baseline procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral glucose tolerance test	Participants will complete a standard oral glucose tolerance test using 75 g of glucose at baseline and blood glucose will be measured.	Baseline
Oral glucose tolerance test	Participants will complete a standard oral glucose tolerance test using 75 g of glucose at 14 weeks and blood glucose will be measured.	14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin A1C	Participant hemoglobin A1C will be evaluated at baseline.	Baseline
Hemoglobin A1C	Participant hemoglobin A1C will be evaluated at 14 weeks.	14 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fat biopsy	Beiging of fat as measured in the lab by histochemistry.	Baseline
Fat biopsy	Beiging of fat as measured in the lab by histochemistry.	14 weeks
Muscle biopsy	Fiber type, as measured in the lab by histochemistry.	Baseline
Muscle biopsy	Fiber type, as measured in the lab by histochemistry.	14 weeks

Collaborators and Investigators

• Sponsor: Philip Kern
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Philip Kern, M.D., University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 21, 2021

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Mirabegron; Tadalafil
• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Overweight; Hyperglycemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Glucose Intolerance; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Indole Alkaloids; Heterocyclic Compounds, 3-Ring; Carbolines; Tadalafil; mirabegron
• Other Study ID Numbers: 55665; R01DK128033 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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