MANATEE-T1D: Metformin ANd AutomaTEd Insulin Delivery System Effects on Renal Vascular Resistance, Insulin Sensitivity, and Cardiometabolic Function in Youth With Type 1 Diabetes
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Metformin Hcl 1000Mg Tab, Aminohippurate Sodium 20 % Injection, Iohexol 300 Mg/mL Injectable Solution, Placebo.
- Who it may be relevant to
- Registry conditions: Type 1 Diabetes, Diabetic Kidney Disease, Cardiovascular Diseases, Endothelial Dysfunction. Basic parameters: 12 years — 25 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Diabetic kidney disease and cardiovascular disease remain the leading causes of morbidity and mortality in people with type 1 diabetes and are exacerbated with longer duration of diabetes and time outside goal glycemic range. Yet, type 1 diabetes is a complex disease with pathophysiology that extends beyond beta-cell injury and insulin deficiency to include insulin resistance and renal vascular resistance, factors that accelerate cardiovascular disease risk. We have shown that metformin improved peripheral insulin sensitivity and vascular stiffness in youth with type 1 diabetes on multiple daily insulin injections or standard insulin pumps. However, metformin's effect on kidney and endothelial outcomes, and the effects of type 1 diabetes technologies, with or without metformin, on any cardiovascular or kidney outcome, remains unknown. Automated insulin delivery systems combine an insulin pump, continuous glucose monitor, and control algorithm to modulate background insulin delivery and decrease peripheral insulin exposure while improving time in target range and reducing hypoglycemia. We hypothesize that automated insulin delivery systems, particularly when combined with metformin, may modulate renal vascular resistance and insulin sensitivity, thereby impacting cardiometabolic function. MANATEE-T1D is a randomized, double-blind, placebo-controlled trial of 4 months of metformin 2,000 mg daily in 40 youth aged 12-25 years with type 1 diabetes on automated insulin delivery systems vs. 20 control youth with type 1 diabetes on multiple daily injections plus a continuous glucose monitor or an insulin pump in manual mode plus a continuous glucose monitor which will assess for changes in calculated renal vascular resistance and gold standard measures of whole-body and adipose insulin sensitivity, arterial stiffness, and endothelial function.
Interventions
- Drug Metformin Hcl 1000Mg Tab
Agent used to modify insulin sensitivity - Drug Aminohippurate Sodium 20 % Injection
Diagnostic aid/agent used to measure renal plasma flow and calculate renal vascular resistance - Drug Iohexol 300 Mg/mL Injectable Solution
Diagnostic aid/agent used to measure glomerular filtration rate - Drug Placebo
Identical to Metformin Hcl 1000Mg Tab but without metabolic effects
Primary outcome measures
- Renal vascular resistance [Time frame: 4 months]
- Glomerular filtration rate [Time frame: 4 months]
Secondary outcome measures (2)
- Arterial stiffness [Time frame: 4 months]
- Insulin sensitivity [Time frame: 4 months]
Eligibility criteria
Inclusion criteria
- T1D and using an automated insulin delivery system or multiple daily insulin injections/manual insulin pump plus continuous glucose monitor for > 6 months
- Age 12-25 years
- Use of an automated insulin delivery system or multiple daily insulin injections plus a continuous glucose monitor or an insulin pump in manual mode plus a continuous glucose monitor for > 6 months
- Hemoglobin A1c < 11%
- No recent episodes of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS) (within 30 days)
- Pubertal (Tanner stage ≥ 2)
- Weight > 54 kg and BMI > 5th percentile for age and sex
Exclusion criteria
- Blood pressure > 140/90 mm Hg
- Hemoglobin < 9 g/dL
- Estimated glomerular filtration rate < 60 mL/min/1.73 m2 or serum creatinine > 1.2 mg/dL or history of urinary albumin to creatinine ratio ≥ 300mg/g or history of acute kidney injury
- Use of anti-diabetic agents except insulin, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB's), diuretics, daily non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin, sulfonamides, procaine, thiazosulfone or probenecid
- Seafood or iodine allergy
- Pregnancy or breast feeding for females
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Double blind
- Primary purpose
- Treatment
Study locations
United States · 2 centers
- Children's Hospital Colorado/University of Colorado Anschutz Medical Campus — Aurora
- Seattle Children's Hospital — Seattle
Identifiers
NCT: NCT05065372 · 21-3483 · K23HL159292