NCT05065372

MANATEE-T1D: Metformin ANd AutomaTEd Insulin Delivery System Effects on Renal Vascular Resistance, Insulin Sensitivity, and Cardiometabolic Function in Youth With Type 1 Diabetes

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Kalie Tommerdahl · Academic / Other
• Sex: All
• Age: 12 Years – 25 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Type 1 Diabetes
• Diabetic Kidney Disease
• Cardiovascular Diseases
• Endothelial Dysfunction
• Insulin Sensitivity

Interventions

Type	Name	Description
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

Timeline

• Start date: 2022-07-01
• Primary completion: 2027-03-01
• Completion: 2027-07-31
• First posted: 2021-10-04
• Last updated: 2025-06-13

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study