Metabolic Syndrome (MetS)METMSNCT07659444
Metformin Withdrawal In Metabolic Syndrome
A study testing Temporary Metformin Withdrawal in people with Metabolic Syndrome (MetS) and Glucose Intolerance, run by University of Castilla-La Mancha at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metabolic Syndrome (MetS), Glucose Intolerance
- What is being tested?
- Temporary Metformin Withdrawal
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteSpain
- Study dates
- 5 Apr 2026to 30 Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of 14-Day Metformin Withdrawal on OGTT-Derived Insulin Sensitivity in Adults With Metabolic Syndrome: A Randomized Controlled Trial
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:
Read more
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 (taking placebo pills instead). 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
- Being tested
- Temporary Metformin Withdrawal
- Keywords
- MetS, Metabolic Syndrome, Metformin, Insulin Sensitivity, Metabolic Flexibility, OGTT
- Medical subject headings
- Metabolic Syndrome, Glucose Intolerance, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temporary Metformin WithdrawalBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| METFOR WITHDRAW | Experimental | Participants in this arm will stop their Metformin treatment for 14 days (sucrose placebo pills). Receives: Behavioral: Temporary Metformin Withdrawal |
| CONTROL | Active comparator | Participants in this arm will continue with their Metformin treatment for 14 days. Receives: Behavioral: Temporary Metformin Withdrawal |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: From enrolment to the end of the intervention, 14 days.
Secondary outcomes (10)
Change in glycated hemoglobin
HbA1c will be measured in blood and reported as percentage of total hemoglobin.
Measured: From enrolment to the end of the intervention, 14 days.
Percentage of time in range assessed by continuous glucose monitoring
Time in range will be defined as the percentage of time with sensor glucose between 70 and 180 mg/dL during the 14-day intervention period.
Measured: From enrolment to the end of the intervention, 14 days.
Change in respiratory exchange ratio response during the oral glucose tolerance test
Respiratory exchange ratio (RER) will be assessed by indirect calorimetry during the oral glucose tolerance test. The response will be calculated using the pre-specified respiratory exchange ratio values obtained during the test.
Measured: From enrolment to the end of the intervention, 14 days.
Change in plasma triglycerides
Plasma triglyceride concentration will be measured in blood before each OGTT.
Measured: From enrolment to the end of the intervention, 14 days.
Change in total cholesterol
Total cholesterol concentration will be measured in blood before each OGTT.
Measured: From enrolment to the end of the intervention, 14 days.
Change in HDL-cholesterol
HDL-cholesterol concentration will be measured in blood before each OGTT.
Measured: From enrolment to the end of the intervention, 14 days.
Change in LDL-cholesterol
LDL-cholesterol concentration will be measured in blood before each OGTT.
Measured: From enrolment to the end of the intervention, 14 days.
Change in estimated glomerular filtration rate
The estimated glomerular filtration rate will be calculated from serum creatinine and reported in mL/min/1.73 m².
Measured: From enrolment to the end of the intervention, 14 days.
Change in serum creatinine
Serum creatinine concentration will be measured in blood before each OGTT.
Measured: From enrolment to the end of the intervention, 14 days.
Change in urinary albumin-to-creatinine ratio
The urinary albumin-to-creatinine ratio will be measured in urine before each OGTT.
Measured: From enrolment to the end of the intervention, 14 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2026
- Study start5 Apr 2026
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic Syndrome (MetS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a participant-blinded, randomized, parallel-group clinical trial. Participants are randomly assigned to either temporarily discontinue metformin for 14 days or continue their usual metformin treatment. To achieve the blinded placebo situation, at the begining of the study participants turned in theri prescribed metformin pills to the team's physician. He embedded those pills or sucrose placebo into opaque empty capsules and placed them into two different alphanumerically labeled prescription bottles. The doctor provided pill bottles containing either a placebo or metformin to the subject in a randomized order only known to him. The doctor collected the empty pill bottles at the end of each 14 days to ensure treatment compliance.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Castilla-La Mancha
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07659444
- Sponsor's protocol ID
- METMS
- Acronym
- METMS
- Status last verified
- Jun 2026
- First submitted
- 9 Jun 2026
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of 14-Day Metformin Withdrawal on OGTT-Derived Insulin Sensitivity in Adults With Metabolic Syndrome: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07659444
- Acronym / sponsor ID
- METMS / METMS
- Conditions
- Metabolic Syndrome (MetS), Glucose Intolerance
- Keywords
- MetS, Metabolic Syndrome, Metformin, Insulin Sensitivity, Metabolic Flexibility, OGTT
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of Castilla-La ManchaUniversity, hospital or other
- Study start
- 5 Apr 2026 (actual)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 22 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (taking placebo pills instead). 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- This is a participant-blinded, randomized, parallel-group clinical trial. Participants are randomly assigned to either temporarily discontinue metformin for 14 days or continue their usual metformin treatment. To achieve the blinded placebo situation, at the begining of the study participants turned in theri prescribed metformin pills to the team's physician. He embedded those pills or sucrose placebo into opaque empty capsules and placed them into two different alphanumerically labeled prescription bottles. The doctor provided pill bottles containing either a placebo or metformin to the subject in a randomized order only known to him. The doctor collected the empty pill bottles at the end of each 14 days to ensure treatment compliance.
| Arm | Type | Receives |
|---|---|---|
| METFOR WITHDRAW | Experimental | Behavioral: Temporary Metformin WithdrawalParticipants in this arm will stop their Metformin treatment for 14 days (sucrose placebo pills). |
| CONTROL | Active comparator | Behavioral: Temporary Metformin WithdrawalParticipants in this arm will continue with their Metformin treatment for 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Temporary Metformin WithdrawalParticipants 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. | Behavioural | CONTROL, METFOR WITHDRAW |
Primary outcome
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Time frame: From enrolment to the end of the intervention, 14 days.
HOMA-IR will be calculated from fasting plasma glucose and fasting insulin concentrations. Higher values indicate greater insulin resistance.
Change in Matsuda Insulin Sensitivity Index
Time frame: From enrolment to the end of the intervention, 14 days.
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.
Mean sensor glucose during the intervention period
Time frame: From enrolment to the end of the intervention, 14 days.
Mean glucose concentration will be assessed using continuous glucose monitoring (CGM) during the 14-day intervention period.
10 secondary outcomes
Change in glycated hemoglobin
Time frame: From enrolment to the end of the intervention, 14 days.
Percentage of time in range assessed by continuous glucose monitoring
Time frame: From enrolment to the end of the intervention, 14 days.
Change in respiratory exchange ratio response during the oral glucose tolerance test
Time frame: From enrolment to the end of the intervention, 14 days.
Change in plasma triglycerides
Time frame: From enrolment to the end of the intervention, 14 days.
Change in total cholesterol
Time frame: From enrolment to the end of the intervention, 14 days.
Change in HDL-cholesterol
Time frame: From enrolment to the end of the intervention, 14 days.
Change in LDL-cholesterol
Time frame: From enrolment to the end of the intervention, 14 days.
Change in estimated glomerular filtration rate
Time frame: From enrolment to the end of the intervention, 14 days.
Change in serum creatinine
Time frame: From enrolment to the end of the intervention, 14 days.
Change in urinary albumin-to-creatinine ratio
Time frame: From enrolment to the end of the intervention, 14 days.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Individual participant dataSharing planned: Undecided. Upon reasonable request
Related trials for Metabolic Syndrome (MetS)
Recruiting
Multi-omics Dissection of Gut Microbiome Engraftment During FMT
Recurrent C. Difficile (rCDI), Ulcerative Colitis (UC)
Recruiting
Effect of Resistance Exercises on Serum IGF-1 Levels in Knee Osteoarthritis
Osteoarthritis (Knee), Metabolic Syndrome (MetS)
Recruiting
Preoperative Oral Carbohydrate Loading and Gastrointestinal Recovery After Bariatric Surgery in Metabolic Syndrome
Metabolic Syndrome (MetS)
Recruiting
Effectiveness of the Personalized Responses & Integrated Systems for Metabolism (PRISM) on Improving Insulin Resistance Among Adults With Metabolic Syndrome: A Pilot Study (PRISM-I)
Metabolic Syndrome (MetS)
Recruiting
Duodenal-jejunal Bypass Sleeve (DJBS) for Obesity and Metabolic Syndrome
Obesity, Metabolic Syndrome (MetS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Temporary Metformin Withdrawal in people with Metabolic Syndrome (MetS) and Glucose Intolerance, run by University of Castilla-La Mancha at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (time frame: From enrolment to the end of the intervention, 14 days.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.