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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

12 Years - 25 Years

Healthy Volunteers

Not accepted

Interventions

• Metformin Hcl 1000Mg Tab — DRUG
  Agent used to modify insulin sensitivity
• Aminohippurate Sodium 20 % Injection — DRUG
  Diagnostic aid/agent used to measure renal plasma flow and calculate renal vascular resistance
• Iohexol 300 Mg/mL Injectable Solution — DRUG
  Diagnostic aid/agent used to measure glomerular filtration rate
• Placebo — DRUG
  Identical to Metformin Hcl 1000Mg Tab but without metabolic effects

Study Details

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.

Key Dates

Start date

Jul 1, 2022

Status verified

Jun 2025

Primary completion

Mar 1, 2027

Completion

Jul 31, 2027

Study Design

Enrollment

60 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Metformin plus automated insulin delivery system
  Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with metformin and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function.
• Placebo Comparator: Placebo plus automated insulin delivery system
  Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with a placebo pill which is identical in appearance to the metformin pill and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function.
• Other: Multiple daily insulin injections or manual insulin pump plus continuous glucose monitor
  Participants with type 1 diabetes using multiple daily injections or an insulin pump in manual mode plus a continuous glucose monitor will not be randomized to receive medication treatment but will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function.

Primary Outcome Measure

Renal vascular resistance [ Time Frame: 4 months ]

Central Contacts

• Kalie Tommerdahl, MD
  (206) 616-9015
  [email protected]

Locations (2)

Find similar trials in Aurora, CO

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