Metformin Withdrawal In Metabolic Syndrome

NCT07659444 | Recruiting

• 1 other identifier: METMS
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to investigate how a short-term interruption of metformin treatment affects insulin sensitivity, glucose control, and metabolic flexibility in adults with metabolic syndrome who are taking metformin as part of their usual medical treatment. Temporary interruptions in metformin treatment may occur in real-life situations, such as missed doses, medication access problems, travel, or planned short-term discontinuation for clinical reasons. This study aims to understand whether stopping metformin for 14 days leads to rapid changes in glucose metabolism or whether the effects of previous metformin treatment may persist during a short period without the medication. The main questions it aims to answer are: Does stopping metformin for 14 days worsen glucose control or insulin sensitivity measured by oral glucose tolerance tests, HbA1c, and continuous glucose monitoring? Does stopping metformin for 14 days affect metabolic flexibility, measured by indirect calorimetry during the oral glucose tolerance test? Does stopping metformin for 14 days affect blood lipids, liver and inflammatory markers, red blood cell parameters, kidney function markers, fasting lactate levels, blood pressure, or heart rate? Researchers will compare participants who stop metformin for 14 days with participants who continue their usual metformin treatment to see whether temporary metformin discontinuation affects insulin sensitivity, glucose control, metabolic flexibility, and other cardiometabolic markers. Participants in the metformin discontinuation group will stop taking metformin for 14 days. They will attend study visits on day 0, day 4, day 7, and day 14. At each visit, they will complete an oral glucose tolerance test, have blood samples taken, and undergo indirect calorimetry measurements before and after the glucose drink. Blood pressure and heart rate will also be measured during the test. Participants will wear a continuous glucose monitor throughout the 14-day period to track glucose levels and help detect any potentially unsafe increase in blood glucose. Participants in the usual-treatment group will continue taking metformin as prescribed. They will attend study visits on day 0 and day 14. At each visit, they will complete an oral glucose tolerance test, have blood samples taken, and undergo indirect calorimetry, blood pressure, and heart rate measurements during the test. At the study visits, researchers will assess glucose and insulin responses, HbA1c, continuous glucose monitoring data, metabolic flexibility, blood lipid profile, liver and inflammatory markers, red blood cell parameters, kidney function markers, fasting lactate levels, blood pressure, and heart rate.

Conditions

Metabolic Syndrome (MetS); Glucose Intolerance

Keywords

MetS; Metabolic Syndrome; Metformin; Insulin Sensitivity; Metabolic Flexibility; OGTT

Outcome Measures

Primary Outcomes (3)

• Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

  HOMA-IR will be calculated from fasting plasma glucose and fasting insulin concentrations. Higher values indicate greater insulin resistance.

  From enrolment to the end of the intervention, 14 days.

• Change in Matsuda Insulin Sensitivity Index

  The Matsuda Insulin Sensitivity Index will be calculated from glucose and insulin concentrations obtained during the oral glucose tolerance test. Higher values indicate greater whole-body insulin sensitivity.

  From enrolment to the end of the intervention, 14 days.

• Mean sensor glucose during the intervention period

  Mean glucose concentration will be assessed using continuous glucose monitoring (CGM) during the 14-day intervention period.

  From enrolment to the end of the intervention, 14 days.

Secondary Outcomes (10)

• Change in glycated hemoglobin

  From enrolment to the end of the intervention, 14 days.

• Percentage of time in range assessed by continuous glucose monitoring

  From enrolment to the end of the intervention, 14 days.

• Change in respiratory exchange ratio response during the oral glucose tolerance test

  From enrolment to the end of the intervention, 14 days.

• Change in plasma triglycerides

  From enrolment to the end of the intervention, 14 days.

• Change in total cholesterol

  From enrolment to the end of the intervention, 14 days.

Study Arms (2)

METFOR WITHDRAW

EXPERIMENTAL

Participants in this arm will stop their Metformin treatment for 14 days.

Behavioral: Temporary Metformin Withdrawal

CONTROL

ACTIVE COMPARATOR

Participants in this arm will continue with their Metformin treatment for 14 days.

Behavioral: Temporary Metformin Withdrawal

Interventions

Temporary Metformin Withdrawal BEHAVIORAL

Participants assigned to this intervention will temporarily stop taking their usual metformin treatment for 14 days. During this period, participants will undergo oral glucose tolerance tests and blood sampling on day 0, day 4, day 7, and day 14. They will also wear a continuous glucose monitoring device throughout the 14-day period to monitor glucose levels during metformin discontinuation.

CONTROL; METFOR WITHDRAW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Currently treated with metformin as part of their usual medical care for at least 12 months before enrolment.
• Diagnosis of metabolic syndrome according to established clinical criteria, based on the presence of at least three of the following components: increased waist circumference, elevated triglycerides, reduced HDL cholesterol, elevated blood pressure or antihypertensive treatment, and elevated fasting glucose or treatment for dysglycemia.
• Stable metformin dose for at least 3 months before enrolment.
• Willing and medically able to temporarily discontinue metformin for 14 days if assigned to the metformin discontinuation group.
• Able and willing to undergo repeated oral glucose tolerance tests, venous catheter placement, repeated blood sampling, indirect calorimetry measurements, blood pressure measurements, and heart rate measurements.
• willing to wear a continuous glucose monitoring device during the study period.
• Preserved kidney function at baseline, defined as estimated glomerular filtration rate ≥60 mL/min/1.75 m² and urine albumin-to-creatinine ratio \<30 mg/g, or values considered clinically acceptable by the study physician.
• No previous history of clinically significant diabetes-related complications, including diabetic retinopathy, diabetic foot disease, severe peripheral neuropathy, or diabetic kidney disease.

You may not qualify if:

• Diagnosis of type 1 diabetes.
• Current treatment with insulin or other glucose-lowering medications.
• Previous history of severe hypoglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state, or other acute diabetes-related metabolic complications.
• Uncontrolled diabetes or clinically unsafe glycemic status at screening, defined as HbA1c above 8.0 %, fasting plasma glucose above 160 mg/dl, or any other glycemic value considered unsafe by the study physician.
• Known allergy or intolerance to materials used in the continuous glucose monitoring device, adhesive patches, venous catheter, or study procedures.

Sponsors & Collaborators

• University of Castilla-La Mancha: lead

Study Sites (1)

University of Castilla-La Mancha

Toledo, Toledo, 45071, Spain

RECRUITING

MeSH Terms

Conditions

Metabolic Syndrome; Glucose Intolerance; Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperglycemia

Central Study Contacts

Ricardo Mora-Rodriguez, Prof.

CONTACT

675424515; Ricardo.Mora@uclm.es

Diego Mora-Gonzalez, Msc.

CONTACT

634596243; Diego.Mora@uclm.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, randomized, parallel-group clinical trial. Participants are randomly assigned to either temporarily discontinue metformin for 14 days or continue their usual metformin treatment. Because participants know whether they are taking or not taking metformin, the study is not blinded.

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: June 22, 2026
• Study Start: April 5, 2026
• Primary Completion: July 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: June 22, 2026

Record last verified: 2026-06

Locations

ES (1)