Recruiting
Phase 1

Metformin & Insulin Delivery

Sponsor:

Kalie Tommerdahl

Code:

NCT05065372

Conditions

Type 1 Diabetes

Diabetic Kidney Disease

Cardiovascular Diseases

Endothelial Dysfunction

Insulin Sensitivity

Eligibility Criteria

Sex: All

Age: 12 - 25

Healthy Volunteers: Not accepted

Interventions

Metformin Hcl 1000Mg Tab

Aminohippurate Sodium 20 % Injection

Iohexol 300 Mg/mL Injectable Solution

Placebo

Study Details

Brief 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

Study ID

NCT05065372

Start date

Jul 1, 2022

Status verified date

Jun, 2025

Completion date

Jul 31, 2027

Anticipated

Primary completion date

Mar 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 12 - 25

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

Metformin Hcl 1000Mg Tab

Agent used to modify insulin sensitivity

Aminohippurate Sodium 20 % Injection

Diagnostic aid/agent used to measure renal plasma flow and calculate renal vascular resistance

Iohexol 300 Mg/mL Injectable Solution

Diagnostic aid/agent used to measure glomerular filtration rate

Placebo

Identical to Metformin Hcl 1000Mg Tab but without metabolic effects

Primary outcome measure

  • Renal vascular resistance [ Time Frame: 4 months ]
  • Glomerular filtration rate [ Time Frame: 4 months ]

Central Contacts and Locations

Central contacts

Kalie Tommerdahl, MD

(206) 616-9015ktomme@uw.edu

Locations

Seattle Children's Hospital

Recruiting

Seattle, Washington, United States, 98102

Contacts

Kalie Tommerdahl, MD

(206) 616-9015ktomme@uw.edu

Principal Investigator:

Kalie Tommerdahl, MD

More Information

Sponsor

Kalie Tommerdahl

Last update posted

Jun 13, 2025

Last verified

Jun, 2025

Keywords

  • Type 1 diabetes
  • Youth
  • Insulin sensitivity
  • Cardiovascular function
  • Diabetic kidney disease

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-25. This information was provided to ClinicalTrials.gov by Kalie Tommerdahl on 2025-06-13. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.