Glucose Intolerance, Metabolic Syndrome (MetS)
Conditions
Keywords
MetS, Metabolic Syndrome, Metformin, Insulin Sensitivity, Metabolic Flexibility, OGTT
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.
Interventions
BEHAVIORALTemporary Metformin Withdrawal
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.
Sponsors
University of Castilla-La Mancha
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in glycated hemoglobin | From enrolment to the end of the intervention, 14 days. | HbA1c will be measured in blood and reported as percentage of total hemoglobin. |
| Percentage of time in range assessed by continuous glucose monitoring | From enrolment to the end of the intervention, 14 days. | 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. |
| Change in respiratory exchange ratio response during the oral glucose tolerance test | From enrolment to the end of the intervention, 14 days. | 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. |
| Change in plasma triglycerides | From enrolment to the end of the intervention, 14 days. | Plasma triglyceride concentration will be measured in blood before each OGTT. |
| Change in total cholesterol | From enrolment to the end of the intervention, 14 days. | Total cholesterol concentration will be measured in blood before each OGTT. |
| Change in HDL-cholesterol | From enrolment to the end of the intervention, 14 days. | HDL-cholesterol concentration will be measured in blood before each OGTT. |
| Change in LDL-cholesterol | From enrolment to the end of the intervention, 14 days. | LDL-cholesterol concentration will be measured in blood before each OGTT. |
| Change in estimated glomerular filtration rate | From enrolment to the end of the intervention, 14 days. | The estimated glomerular filtration rate will be calculated from serum creatinine and reported in mL/min/1.73 m². |
| Change in serum creatinine | From enrolment to the end of the intervention, 14 days. | Serum creatinine concentration will be measured in blood before each OGTT. |
| Change in urinary albumin-to-creatinine ratio | From enrolment to the end of the intervention, 14 days. | The urinary albumin-to-creatinine ratio will be measured in urine before each OGTT. |
Countries
Spain
Contacts
CONTACTRicardo Mora-Rodriguez, Prof.
CONTACTDiego Mora-Gonzalez, Msc.
Outcome results
None listed