A Phase 3 interventional study of Metformin and Placebo oral tablet in Aging, Insulin Sensitivity and Chronic Disease, sponsored by Oklahoma Medical Research Foundation. Completed at 2 sites in United States. Open to participants aged 40 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by Oklahoma Medical Research Foundation · Phase 3, Interventional, and Prevention
Among 120 studies testing metformin in Insulin Resistance — 8 open to participants now, 11 under way, 2 of them phase 3. Metformin · Insulin Resistance.
Among the 120 studies testing metformin in Insulin Resistance, this one is the 22nd largest by enrollment of the 119 interventional ones, is the only one that started in 2020, is one of 20 in phase 3, and was the 98th registered.
2,969 studies on the registry are indexed under Insulin Resistance; 338 are open to participants now.
This study's enrollment of 166 is above the median of 40 across 2,369 interventional studies indexed under Insulin Resistance.
Browse Insulin Resistance studies →8 of the 120 studies testing metformin in Insulin Resistance are open now, in 5 countries. Each count lists the studies.
Metformin: first FDA approval 1995 (GLUCOPHAGE), first EMA approval 2003. What it is approved for, and how studies give it, is on its page →
Of the 244 Insulin Resistance studies recruiting now, 54 (22%) set no upper age limit and 158 (65%) stop at 75 or younger; 30 take children under 18; 113 take healthy volunteers.
This study: 40 Years to 75 Years · all sexes · healthy volunteers too.
The full table on the hub →120 studies; the count open now beside each. This study's row is marked.
First in 2000; this study’s year is marked. 1 started in 2020.
Median enrollment 60 across the 119 interventional studies. Of the 89 that completed or were terminated, 30 (34%) have results posted.
2 of 120 have an industry lead sponsor. The 10 most frequent:
Oklahoma Medical Research Foundation is the lead sponsor of 15 studies on the registry; 2 are open to participants now.
Oklahoma Medical Research Foundation has 1 study filed under Insulin Resistance — fewer than ten, so there is no comparison to draw.
4 of the studies testing metformin in Insulin Resistance that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07297290Phase 3University Of Nigeria Teaching HospitalEffect of Metformin Use on Weight Loss in Obese, Non-diabetic People (MOWRI) | 2027-03-31 |
| NCT03107884University of UtahRole of Metformin on Muscle Health of Older Adults | 2026-11-01 |
| NCT05065372Kalie TommerdahlMANATEE-T1D: Metformin ANd AutomaTEd Insulin Delivery System Effects on Renal Vascular Resistance, Insulin Sensitivity, and Cardiometabolic Function in Youth With Type 1 Diabetes | 2027-03-01 |
| NCT07770711Dicle UniversityInositol and Metformin Administration in Mediterranean Diet and Low-Carbohydrate Diets in Women With PCOS | 2027-09 |
Among the 120 studies testing metformin in Insulin Resistance, from their registry updates:
Aging is the number one risk factor for the majority of chronic diseases. There are no pharmaceutical treatments to slow aging and prolong healthspan. The anti-diabetic drug metformin is considered a likely pharmaceutical candidate to slow aging. In this study, the investigators hypothesize that metformin treatment in subjects free of type 2 diabetes will improve insulin sensitivity and glucoregulation in insulin resistant individuals, but will decrease insulin sensitivity and glucoregulation in insulin sensitive subjects. Further, the investigators hypothesize that long-term metformin treatment will remodel mitochondria in a way that decreases mitochondrial function in subjects that are insulin sensitive, but improves mitochondrial function in subjects that are insulin resistant. The investigators will use a dual-site, 12- week drug intervention trial performed in a double-blind, placebo-controlled manner on 148 subjects recruited from two separate sites (Oklahoma Medical Research Foundation (OMRF) and University of Wisconsin-Madison (UWM)). After consent and initial subject screening for chronic disease, subjects will be stratified to insulin sensitive (IS) or insulin resistant (IR) groups. Over a 12- week intervention, half of each group will take metformin and half will take a placebo. Pre- and post--intervention, subjects will complete a series of procedures to assess insulin sensitivity, glucose regulation, and biomarkers of aging. The same subjects will provide a skeletal muscle biopsy pre-- and post-intervention to assess the change in mitochondrial function and mitochondrial remodeling with and without metformin treatment. By completion of this project, the investigators expect to provide evidence that helps further delineate who may benefit from metformin treatment to slow aging.
Although there is epidemiological support for health benefits of metformin in patient populations, it is not clear if these protective effects extend to those free of disease. Therefore, there is a need to perform human studies determining which subjects free of chronic disease benefit from metformin treatment. Retrospective analysis of a randomized, double-blinded clinical trial in our lab revealed that subjects who were insulin sensitive had no effect or negative effects on insulin sensitivity when taking metformin during an exercise training program. These data suggest that in some subjects, metformin has detrimental metabolic outcomes that could accelerate aging. There are data both in support of and refuting that metformin inhibits mitochondrial complex I action and/or mitochondrial remodeling. The overall objective of this trial is to determine if subjects currently free of disease benefit from metformin treatment. There are two critical questions that remain unanswered in human subjects: 1) does antecedent metabolic health influence responses to metformin, and 2) does long-term treatment with metformin lead to mitochondrial remodeling and changes in function. To better understand the translational potential of a clinically relevant dose of metformin for the prevention of chronic conditions, this proposal aims to determine how antecedent metabolic health affects the response to metformin treatment, and identify the relationship between skeletal muscle mitochondrial remodeling and mitochondrial function with metformin treatment. The hypotheses are that: 1) metformin treatment in subjects free of Type 2 diabetes will improve insulin sensitivity and glucoregulation in insulin resistant individuals, but will decrease insulin sensitivity and glucoregulation in insulin sensitive subjects, and 2) long-term metformin treatment will remodel mitochondria in a way that decreases mitochondrial function in subjects that are insulin sensitive, but improves mitochondrial function in subjects that are insulin resistant. To test these hypotheses, a 12-week randomized, double-blind clinical trial will be performed in subjects 40-75 yrs of age, free of disease, and stratified by insulin sensitivity (insulin sensitive and insulin resistant). Pre- and post-training assessments include the hyperinsulinemic- euglycemic clamp to measure hepatic and peripheral insulin sensitivity, continuous glucose monitoring to determine glucoregulation, and proposed blood-based biomarkers of aging. Further, the use of novel stable isotope labeling with proteomic analysis will determine individual and complex-specific mitochondrial remodeling. This approach will be combined with analysis of protein modification and turnover to comprehensively analyze mitochondrial effects of metformin treatment in skeletal muscle. By completion of this project, it is expected that there will be evidence that helps further delineate who may benefit from metformin treatment to slow aging.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
Drug: Metformin
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate). The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
Drug: Placebo oral tablet
The investigators use a "ramp up" dosing protocol in which the amount of metformin (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day, which is a standard clinical dose (1500-2000 mg/day). If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
Drug: Metformin
Subjects assigned to the placebo group will receive visually identical pills (silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate). The same dosing schedule will be followed as for metformin. The investigators use a "ramp up" dosing protocol in which the amount of placebo (Hunter Pharmacy) will begin at 500 mg/day in week 1, increase to 1000 mg/day in week 2, and then to 1500 mg/day in week 3, as tolerated. At week 3 and for the remaining 9 weeks, the dose will remain at 1500 mg/day. If a subject has gastrointestinal discomfort with 1500 mg/day the dose, the investigators will lower the dose to 1000 mg/day. The investigators will split the dose with 1/2 given in the a.m. and 1/2 in the p.m. and taken with meals to minimize GI discomfort.
Drug: Placebo oral tablet
Metformin (Hunter Pharmacy) following a "ramp up" dosing protocol with a targeted dose of 1500 mg/day for 12 weeks.
Also known as: Glucophage, Glucophage extended-release, Fortamet, Glumetza, Riomet
Silicified microcrystalline cellulose, Micosolle®, K30 povidone, sodium starch glycolate, and magnesium stearate
Also known as: Placebo
Mean Change in Insulin Sensitivity Index
Insulin Sensitivity Index = M / I x 1000. M = Glucose disposal rate (mg/min), normalized to fat-free mass (kg). I = insulin concentration (mU/L) during steady state of the clamp (based on glucose infusion rate). We rely on the delta (post-pre) of the insulin sensitivity index as our primary outcome. Positive delta values indicate improved insulin sensitivity (a positive outcome), while negative delta values indicate lower insulin sensitivity (a negative outcome). Insulin sensitivity cannot be physiologically zero or negative. Maximum negative change insulin sensitivity index = -52.31 mg/kg FFM/min/mU/L. Maximum positive insulin sensitivity index = 42.32 mg/kg FFM/min/mU/L.
Time frame: Change from baseline to 12 weeks
Mean Change in Mitochondrial Function of the Electron Transport System Measured by Complex I Activity
Mitochondrial respiration was measured using permeabilized muscle fibers from the vastus lateralis using high-resolution respirometry. We rely on the delta (change from post-pre) of the Complex I mitochondrial respiratory capacity. Positive values indicate an increase in mitochondrial respiratory capacity and improved outcomes, while negative values indicate a reduction in mitochondrial respiratory capacity and a negative outcome. There is no minimum or maximum reported for mitochondrial respiratory capacity of CI, but mitochondrial respiratory capacity of CI cannot physiologically be zero or negative. We and others have previously reported maximal complex I linked oxidative phosphorylation at approximately 250 pmol/mg of tissue/s in ultra-endurance athletes.
Time frame: Change from baseline to 12 weeks
Mean Change in Daily Average Glucose Measure
We measured blood glucose using a Dexcom Continuous Glucose Monitor (CGM) over seven days. We rely on the delta (change from pre to post) in mean glucose (mg/dL) levels. Positive values indicate an increase in blood glucose and a negative outcome, while negative values indicate a reduction in mean blood glucose and a positive outcome. Glucose values of 70-140 mg/dL generally represent a normal physiological range; values below 70 mg/dL indicate hypoglycemia excursions, while values above 180 mg/dL indicate hyperglycemia excursions.
Time frame: Change from baseline to 12 weeks
Mean Change in Blood-based Biomarker Measures of Aging
This blood-based biomarker panel, developed by LeBrasseur and colleagues, measures changes in senescence-associated secretory phenotype proteins. This panel is associated with chronological age, biological age, and adverse clinical outcomes. Changes in the protein levels of biomarkers reflect changes in biological age. A greater abundance in these biomarkers is associated with greater frailty or biological aging. We rely on the delta (change from post-pre) of the biological markers. A positive value is associated with a negative outcome, while a negative value is associated with a positive outcome.
Time frame: Change from baseline to 12 weeks
Participants were recruited from 2 sites: The Oklahoma Medical Research Foundation/University of Oklahoma Health Sciences Center and the University of Wisconsin-Madison.
| Milestone | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant |
|---|---|---|---|---|
| Started | 48 | 31 | 52 | 35 |
| Homa-ir based population - completed | 27 | 20 | 33 | 21 |
| Re-distribution of subjects for insulin sensitivity index-based analyses population | 24 | 23 | 27 | 27 |
| Completed | 27 | 20 | 33 | 21 |
| Not completed | 21 | 11 | 19 | 14 |
| Withdrew: Lost to follow-up | 7 | 8 | 5 | 2 |
| Withdrew: Investigator decision | 10 | 0 | 7 | 0 |
| Withdrew: Failed inclusion criteria | 4 | 3 | 5 | 12 |
| Withdrew: Withdrawal by subject | 0 | 0 | 2 | 0 |
Insulin Sensitivity Index = M / I x 1000. M = Glucose disposal rate (mg/min), normalized to fat-free mass (kg). I = insulin concentration (mU/L) during steady state of the clamp (based on glucose infusion rate). We rely on the delta (post-pre) of the insulin sensitivity index as our primary outcome. Positive delta values indicate improved insulin sensitivity (a positive outcome), while negative delta values indicate lower insulin sensitivity (a negative outcome). Insulin sensitivity cannot be physiologically zero or negative. Maximum negative change insulin sensitivity index = -52.31 mg/kg FFM/min/mU/L. Maximum positive insulin sensitivity index = 42.32 mg/kg FFM/min/mU/L.
| mg/kg Fat Free Mass/min/mU/L | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant |
|---|---|---|---|---|
| Mean Change in Insulin Sensitivity Index | -6.3 ± 17.9 | 1.8 ± 8.8 | -4.5 ± 9.7 | 2.1 ± 4.8 |
Mitochondrial respiration was measured using permeabilized muscle fibers from the vastus lateralis using high-resolution respirometry. We rely on the delta (change from post-pre) of the Complex I mitochondrial respiratory capacity. Positive values indicate an increase in mitochondrial respiratory capacity and improved outcomes, while negative values indicate a reduction in mitochondrial respiratory capacity and a negative outcome. There is no minimum or maximum reported for mitochondrial respiratory capacity of CI, but mitochondrial respiratory capacity of CI cannot physiologically be zero or negative. We and others have previously reported maximal complex I linked oxidative phosphorylation at approximately 250 pmol/mg of tissue/s in ultra-endurance athletes.
| pmol/mg/s | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant |
|---|---|---|---|---|
| Mean Change in Mitochondrial Function of the Electron Transport System Measured by Complex I Activity | 0.99 ± 15.95 | 0.48 ± 11.79 | -5.98 ± 22.27 | -2.57 ± 13.67 |
We measured blood glucose using a Dexcom Continuous Glucose Monitor (CGM) over seven days. We rely on the delta (change from pre to post) in mean glucose (mg/dL) levels. Positive values indicate an increase in blood glucose and a negative outcome, while negative values indicate a reduction in mean blood glucose and a positive outcome. Glucose values of 70-140 mg/dL generally represent a normal physiological range; values below 70 mg/dL indicate hypoglycemia excursions, while values above 180 mg/dL indicate hyperglycemia excursions.
| Change in Average Daily Glucose (mg/DL) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant |
|---|---|---|---|---|
| Mean Change in Daily Average Glucose Measure | 0.3 ± 9.3 | 0.8 ± 16.9 | -0.4 ± 10.6 | -8.3 ± 11.1 |
This blood-based biomarker panel, developed by LeBrasseur and colleagues, measures changes in senescence-associated secretory phenotype proteins. This panel is associated with chronological age, biological age, and adverse clinical outcomes. Changes in the protein levels of biomarkers reflect changes in biological age. A greater abundance in these biomarkers is associated with greater frailty or biological aging. We rely on the delta (change from post-pre) of the biological markers. A positive value is associated with a negative outcome, while a negative value is associated with a positive outcome.
| Protein Expression (relative units) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant |
|---|---|---|---|---|
| MMP-1 | 386 ± 929 | -651 ± 1681 | 80 ± 530 | 609 ± 1343 |
| MPO | -9442 ± 44571 | 1720 ± 94137 | 59345 ± 176257 | -31943 ± 139016 |
| IL-6 | 0.14 ± 1.12 | -0.06 ± 1.00 | 0.73 ± 3.5 | -0.02 ± 1.10 |
| PAI-1 | 1151 ± 27000 | -12129 ± 38693 | -3444 ± 27222 | 16407 ± 38436 |
| Eotaxin | 10 ± 58 | -14 ± 31 | 2 ± 34 | 16 ± 40 |
| ActivinA | -11 ± 41 | -6 ± 42 | -22 ± 54 | -10 ± 57 |
| ADAMTS13 | -7161 ± 1032212 | 30842 ± 131318 | 13147 ± 81801 | 920 ± 167172 |
| FAS | 2 ± 562 | -151 ± 349 | -43 ± 577 | 792 ± 3619 |
| GDF-15 | 67 ± 126 | 21 ± 57 | 95 ± 77 | 168 ± 202 |
| ICAM-1 | 1338 ± 17293 | -5364 ± 16876 | -1724 ± 12356 | 1124 ± 31718 |
| INFg | -0.02 ± 1.3 | -0.16 ± 0.61 | 0.03 ± 1.44 | -0.04 ± 0.49 |
| IL-15 | 0.01 ± 0.92 | -1.13 ± 4.8 | 3.70 ± 16.68 | -14.9 ± 51.38 |
| IL-7 | -0.31 ± 6.24 | -3.18 ± 7.35 | -1.34 ± 7.19 | 1.34 ± 9.91 |
| IL-8 | 0.28 ± 2.91 | -0.58 ± 2.94 | 0.33 ± 2.59 | 1.07 ± 2.09 |
| MCP-1 | 6 ± 54 | 11 ± 32 | -5 ± 47 | 14 ± 52 |
| MDC | -11 ± 67 | -33 ± 87 | 5 ± 103 | 98 ± 328 |
| MMP-2 | -569 ± 23803 | -5747 ± 21459 | -9175 ± 19076 | 1578 ± 29394 |
| MMP-7 | 82 ± 212 | -96 ± 477 | 135 ± 191 | 279 ± 370 |
| MMP-9 | 3721 ± 5553 | -3602 ± 61421 | 25103 ± 60279 | -10826 ± 53765 |
| Osteoactivin | -334 ± 1184 | -323 ± 1169 | -234 ± 1295 | -531 ± 1869 |
| Osteopontin | 336 ± 5519 | 374 ± 5069 | 1369 ± 3596 | 1955 ± 10590 |
| PARC | -491 ± 6054 | -4167 ± 11225 | 1466 ± 7506 | 1926 ± 17278 |
| PDGF-AA | -8587 ± 26863 | -8889 ± 26841 | 3295 ± 17592 | 9499 ± 25431 |
| PDGF-AB | 28 ± 116 | -287 ± 1172 | 117 ± 1460 | 561 ± 1415 |
| PLA2G7 | -2817 ± 14312 | -248 ± 46249 | 17230 ± 50079 | -7747 ± 31756 |
| RAGE | -167 ± 245 | 13 ± 310 | -125 ± 156 | -6 ± 359 |
| RANTES | -1395 ± 16663 | -358 ± 23741 | -1233 ± 17146 | 5279 ± 16267 |
| SOST | 18 ± 71 | 6 ± 47 | 16 ± 50 | 9 ± 69 |
| SPARC | 38039 ± 316563 | -122037 ± 435422 | -1425 ± 22653 | 103686 ± 410690 |
| TNF RI | 8 ± 95 | -18 ± 133 | 40 ± 114 | 27 ± 132 |
| TNF RII | -40 ± 215 | 136 ± 514 | 72 ± 246 | 15 ± 279 |
| TNF-a | 0.47 ± 3.19 | -0.03 ± 2.35 | -0.14 ± 3.03 | -0.65 ± 8.08 |
| uPAR | -20 ± 57 | -27 ± 67 | -16 ± 52 | 11 ± 74 |
| VEGF | -14 ± 26 | -39 ± 99 | 6 ± 50 | 6 ± 62 |
Collected over From enrollment until completion of the study, up to 16 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/47 (0%) | 0/47 (0%) | 25/47 (53.2%) |
| Metformin | 0/54 (0%) | 0/54 (0%) | 37/54 (68.5%) |
| Event | Placebo | Metformin |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 8/47 | 19/54 |
| NauseaGastrointestinal disorders | 7/47 | 10/54 |
| HeadacheNervous system disorders | 1/47 | 8/54 |
| Abdominal discomfortGastrointestinal disorders | 2/47 | 6/54 |
| DizzinessNervous system disorders | 1/47 | 6/54 |
| AnorexiaMetabolism and nutrition disorders | 1/47 | 5/54 |
| ConstipationGastrointestinal disorders | 1/47 | 4/54 |
| VesiclesSkin and subcutaneous tissue disorders | 3/47 | 3/54 |
| DyspepsiaGastrointestinal disorders | 1/47 | 3/54 |
| HypoglycaemiaMetabolism and nutrition disorders | 2/47 | 3/54 |
Subjects were re-assigned based on GIR (mg/kg FFM/min/mU/L) which is reflected here.
| Age, Customized(Years) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| Age | 57 ± 8 | 57 ± 10 | 57 ± 9 | 56 ± 10 | 57 ± 10 |
| Sex: Female, Male(Participants) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| Female | 10 | 18 | 18 | 15 | 61 |
| Male | 14 | 5 | 9 | 12 | 40 |
| Race (NIH/OMB)(Participants) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 1 | 3 | 0 | 2 | 6 |
| Asian | 1 | 1 | 0 | 2 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 0 | 2 | 3 |
| White | 18 | 17 | 26 | 20 | 81 |
| More than one race | 2 | 2 | 1 | 1 | 6 |
| Unknown or Not Reported | 1 | 0 | 0 | 0 | 1 |
| Ethnicity (NIH/OMB)(Participants) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 0 | 0 | 2 |
| Not Hispanic or Latino | 23 | 22 | 27 | 27 | 99 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Body Mass Index (BMI)(kg/(m^2)) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| Mean | 27.4 ± 4.8 | 31.9 ± 6.4 | 28.0 ± 6.3 | 32.2 ± 6.5 | 29.9 ± 6.3 |
| Precent Body Fat(%) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| Mean | 34.14 ± 12.78 | 42.52 ± 7.05 | 36.61 ± 10.13 | 40.18 ± 7.36 | 37.61 ± 10.35 |
| Fat Mass(kg) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| Mean | 38.3 ± 18.1 | 36.1 ± 10.8 | 29.4 ± 12.7 | 37.4 ± 12.8 | 32.8 ± 14.2 |
| Fat Free Mass(kg) | Placebo - Insulin Sensitive | Placebo - Insulin Resistant | Metformin - Insulin Sensitive | Metformin - Insulin Resistant | Total |
|---|---|---|---|---|---|
| Mean | 54.0 ± 9.7 | 48.1 ± 8.3 | 51.0 ± 13.1 | 54.7 ± 11.9 | 52.1 ± 11.2 |
4 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Results from the trial will be disseminated through presentations at professional meetings and through peer-reviewed publications. Data and other resources will be shared as required by NIH Resource Sharing policies.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: De-identified data will be shared following the publication of the primary manuscripts for each specific aim from the trial by the trial investigators.
Access criteria: Researchers interested in accessing de-identified data will contact the trial principal investigators to complete data use agreements and paper/presentation proposals needed for consideration of the proposed research.
Ran from Jul 2020 to primary completion in Mar 2025, 55 months.
Results were first posted in Jul 2026, 1 year 3 months after primary completion. A results delay was requested in Mar 2026.
Of 44 phase 3 interventional studies under Insulin Resistance, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 53. This study's 55 months is above that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is completed, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Metformin
Oklahoma Medical Research Foundation