Tests metformin with automated insulin delivery in youth with type 1 diabetes

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for young people with type 1 diabetes who use an automated insulin delivery system, or injections or a manual pump plus a continuous glucose monitor.

Age

12-25 years

Sex

All sexes can join.

Disease stage

Type 1 diabetes. Hemoglobin A1c below 11% (97 mmol/mol). No diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS) in the past 30 days. Pubertal (Tanner stage 2 or higher).

Earlier treatment

Must have used an automated insulin delivery system, or multiple daily insulin injections or a manual insulin pump, plus a continuous glucose monitor for more than 6 months.

Main reasons for not taking part

• Blood pressure above 140/90 mm Hg
• Hemoglobin below 9 g/dL
• Kidney problems: estimated glomerular filtration rate below 60 mL/min/1.73 m2, serum creatinine above 1.2 mg/dL (106 µmol/L), or past acute kidney injury
• Use of other diabetes medicines besides insulin
• Seafood or iodine allergy, or pregnancy or breast feeding

The registry criteria, word for word

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

• Are you between 12 and 25 years old?YesNo

What the trial wants to find out

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.

The 3 groups in the trial

• Metformin plus automated insulin delivery systemExisting treatment, for comparison

  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.

  Treatment: Metformin Hcl 1000Mg Tab, Aminohippurate Sodium 20 % Injection, and Iohexol 300 Mg/mL Injectable Solution

• Placebo plus automated insulin delivery systemPlacebo, for comparison

  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.

  Treatment: Aminohippurate Sodium 20 % Injection, Iohexol 300 Mg/mL Injectable Solution, and Placebo

• Multiple daily insulin injections or manual insulin pump plus continuous glucose monitorOther group

  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.

  Treatment: Aminohippurate Sodium 20 % Injection and Iohexol 300 Mg/mL Injectable Solution