Effects of Diabetes Medications on Adrenal Function and Intestinal Microbiota

Complementary Effects of New Diabetes Medications on Adrenal Function and Intestinal Microbiota

The primary aim of this observational study is to describe the effects of glucagon-like peptide-1 (GLP-1) receptor agonists and Sodium-Glucose Co-transporter 2 inhibitors ( SGLT-2 inhibitors) on adrenal function. Secondary endpoint is change in intestinal microbiota.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: GLP-1 receptor agonist; Drug: SGLT2 inhibitor

Detailed Description

This is an observational study conducted in patients with type 2 diabetes starting treatment with either GLP-1 receptor agonist or sodium-glucose cotransporter-2 (SGLT-2) inhibitor.

Planned study cohort consists of 60 patients: 30 patients starting GLP-1 receptor agonist treatment and 30 patients starting SGLT-2 inhibitor treatment. All patients must have metformin as background therapy. All other diabetes medications are allowed.

Patients are tested before starting treatment, at 1 month (stool sample only), 3 months and 12 months after starting treatment. The primary endpoint is change in overnight urinary aldosterone corrected for creatinine.

Secondary endpoint is change in intestinal microbiota composition.

• Study Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

• Study Contact: Name: Vallo Volke, MD, PhD; Phone Number: +37256489216; Email: vallo.volke@ut.ee

Study Locations

• Estonia
  • Tartu, Estonia
    • Tartu University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes who need treatment intensification with SGLT-2 inhibitor or GLP-1 receptor agonist.

Description

Inclusion Criteria:

• Age > 18 years
• Type 2 diabetes
• HbA1c < 10%
• BMI >32
• Daily dose of metformin 1,5 g or more.
• No change in diabetes treatment at least 90 days before starting the study.
• Never used SGLT-2 inhibitors or/and GLP-1 receptor agonist.
• Tested negative to glutamic acid decarboxylase 65 autoantibodies.

Exclusion Criteria:

• Pregnancy and lactation.
• Use of systemic antibiotic treatment < 60 days before starting the study.
• Use of spironolactone < 60 days before starting the study.
• Use of oral contraceptives or hormonal replacement therapy.
• Use of immunosuppressive drug
• Heart failure New York Heart Association III-IV
• Severe liver disease.
• Malignant disease.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
GLP-1 receptor agonist treatment; Patients starting treatment with any molecule belonging to the class of GLP-1 receptor agonist.	Drug: GLP-1 receptor agonist; Treatment with GLP-1 agonist for up to 1 year.
SGLT-2 inhibitor treatment; Patients starting treatment with any molecule belonging to the class of SGLT-2 inhibitors.	Drug: SGLT2 inhibitor; Treatment with SGLT2 inhibitor for up to 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary aldosterone at 3 months	Overnight urinary aldosterone compared to pretreatment level.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gastrointestinal microbiota.	Fecal microbiota will be compared to pre-treatment sample.	At 1 month after starting treatment, at 3 months and 12 months.
Urinary aldosterone at 12 months	Overnight urinary aldosterone at 12 months compared to pretreatment level.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum adrenocorticotropic hormone	Change in adrenocorticotropic hormone in serum compared to pretreatment level.	At 3 months and 12 months.
Plasma cortisol	Change in plasma cortisol compared to pretreatment level	At 3 months and 12 months.
Urinary cortisol	Change in overnight urinary cortisol compared to pretreatment level.	At 3 months and 12 months.
Plasma aldosterone	Change in plasma aldosterone compared to pretreatment level.	At 3 months and 12 months.
Plasma renin	Change in plasma renin compared to pretreatment level.	At 3 months and 12 months.
Serum sodium	Change in serum sodium compared to pretreatment level.	At 3 months and 12 months.
Serum potassium	Change in serum potassium compared to pretreatment level.	At 3 months and 12 months.
Glycated hemoglobin A1c	Change in glycated hemoglobin A1c compared to pretreatment level.	At 3 months and 12 months.
Ceruloplasmin	Change in plasma ceruloplasmin compared to pretreatment level.	At 3 months and 12 months.
Ferritin	Change in plasma ferritin compared to pretreatment level.	At 3 months and 12 months.

Collaborators and Investigators

• Sponsor: University of Tartu
• Investigators: Principal Investigator: Vallo Volke, MD, PhD, University of Tartu, Institute of Biomedicine and Translational Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2019
• Primary Completion (Actual): January 23, 2023
• Study Completion (Actual): January 23, 2023

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: November 4, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 19, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: SGLT-2 inhibitor; GLP-1 receptor agonist
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors
• Other Study ID Numbers: 290/T-20

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