What side effects are associated with this type of intervention?

Common treatments for Type 1 Diabetes include insulin therapy and metformin. Insulin therapy can cause hypoglycemia, weight gain, and injection site reactions. Metformin, which improves insulin sensitivity and may modulate renal vascular resistance, can cause gastrointestinal side effects such as nausea, diarrhea, and abdominal discomfort. It is contraindicated in patients with renal impairment due to the risk of lactic acidosis. Combining metformin with automated insulin delivery systems may offer additional benefits but requires careful monitoring for side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Type 1 Diabetes that focus on improving insulin sensitivity and potentially modulating renal vascular resistance. Metformin, although primarily used for Type 2 Diabetes, has shown benefits in improving insulin sensitivity and vascular stiffness in youth with Type 1 Diabetes. Automated insulin delivery systems, which combine an insulin pump, continuous glucose monitor, and control algorithm, have also been studied for their potential to improve glycemic control and reduce hypoglycemia. These systems, particularly when combined with metformin, may positively impact renal vascular resistance and cardiometabolic function.

What other types of research exist?

Promising alternatives to Metformin for Type 1 Diabetes patients include GLP-1 receptor agonists (e.g., liraglutide), SGLT2 inhibitors (e.g., empagliflozin, canagliflozin), and DPP-4 inhibitors (e.g., sitagliptin, linagliptin). These medications have shown potential in improving glycemic control and may offer additional renal and cardiovascular benefits.

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Biguanide

Metformin + Automated Insulin Delivery for Type 1 Diabetes (MANATEE-T1D Trial)

Phase 1

Recruiting

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 12-21 years

No recent episodes of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS)

Must not have

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

Anemia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 months

Summary

This trial tests a device that automatically adjusts insulin levels and a medication called metformin in young people with type 1 diabetes. The goal is to see if this combination can better manage blood sugar and improve heart and kidney health. The use of metformin along with insulin therapy has been suggested as a means of improving diabetes control and alleviating weight gain in type 1 diabetes.

Who is the study for?

This trial is for young people aged 12-21 with type 1 diabetes who use an automated insulin delivery system or injections plus a glucose monitor. They should weigh over 54 kg, have a BMI above the 5th percentile, and not have had recent severe diabetic complications. Participants must not be pregnant, taking certain medications (like ACE inhibitors), or have high blood pressure, kidney issues, or seafood/iodine allergies.

What is being tested?

The MANATEE-T1D study tests if metformin can improve kidney function and insulin sensitivity in youth with type 1 diabetes using automated insulin systems versus those on standard injections. It's a randomized trial where some get metformin and others get a placebo for four months to see effects on renal resistance and cardiometabolic health.

What are the potential side effects?

Metformin may cause digestive upset like nausea or diarrhea, vitamin B12 deficiency with long-term use, and rarely lactic acidosis—a serious condition requiring immediate medical attention. The contrast agents used could cause allergic reactions or affect thyroid function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 12 and 21 years old.

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I haven't had recent severe diabetic complications.

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I weigh more than 54 kg and my BMI is above the 5th percentile for my age and sex.

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I am a young person with type 1 diabetes confirmed by pancreatic antibody.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My kidney function is reduced, shown by tests or past kidney injury.

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I have anemia.

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I am not taking any diabetes medication except insulin, or specific blood pressure, water pills, daily pain relievers, or certain antibiotics.

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I am not pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Glomerular filtration rate

Renal vascular resistance

Secondary study objectives

Arterial stiffness

Endothelial function

Insulin sensitivity

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Multiple daily insulin injections plus continuous glucose monitorExperimental Treatment2 Interventions

Participants with type 1 diabetes using multiple daily injections 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 additional to assessments of cardiovascular and endothelial function.

Group II: Metformin plus automated insulin delivery systemActive Control3 Interventions

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 additional to assessments of cardiovascular and endothelial function.

Group III: Placebo plus automated insulin delivery systemPlacebo Group3 Interventions

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 additional to assessments of cardiovascular and endothelial function.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Insulin therapy is essential for Type 1 Diabetes patients as it replaces the insulin their bodies can no longer produce, helping to regulate blood glucose levels. Metformin, typically used for Type 2 Diabetes, is being studied for its potential benefits in Type 1 Diabetes. It improves insulin sensitivity, which can help lower blood glucose levels and reduce insulin requirements. Additionally, metformin may modulate renal vascular resistance, potentially offering cardiovascular and renal benefits. Understanding these mechanisms is crucial for optimizing treatment plans and reducing the risk of complications in Type 1 Diabetes patients.

The Mystery of Diabetic Cardiomyopathy: From Early Concepts and Underlying Mechanisms to Novel Therapeutic Possibilities.