Apply to Trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

60 Participants Needed

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

Recruiting at 3 trial locations

Overseen ByLucy Hall, MS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Kalie Tommerdahl

Must be taking: Insulin

Must not be taking: ACE inhibitors, ARBs, NSAIDs

Disqualifiers: Hypertension, Anemia, Kidney disease, others

Approved in 3 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how metformin (also known as Glucophage, Fortamet, Glumetza, Riomet, Riomet ER, Axpinet, Diagemet, Glucient, Metabet), combined with automated insulin delivery systems, might improve heart and kidney health in people with type 1 diabetes. It compares how the body processes insulin and how blood vessels function when using metformin with these systems. Participants are youth who have had type 1 diabetes for more than six months and are already using insulin delivery systems. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that participants do not use anti-diabetic agents other than insulin, ACE inhibitors, ARBs, diuretics, daily NSAIDs or aspirin, sulfonamides, procaine, thiazosulfone, or probenecid. If you are taking other anti-diabetic medications, you may need to stop them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that automated insulin delivery (AID) systems are generally safe and effective for people with type 1 diabetes. These systems manage blood sugar levels without causing major side effects by using an insulin pump and a glucose monitor to track and adjust insulin levels.

Metformin, a drug often used for type 2 diabetes, has also been studied for type 1 diabetes. Studies have found that metformin can improve how the body uses insulin and may help keep blood vessels flexible in young people with type 1 diabetes. This suggests it might benefit heart and kidney health, but more studies are needed to confirm this.

While both treatments have been studied separately, combining them remains new. This trial is in its early stages, and researchers are still collecting initial safety data. However, since the FDA has already approved metformin for another use, it is generally considered safe.¹ ² ³ ⁴ ⁵

Why are researchers excited about this trial's treatments?

Metformin, commonly known for treating type 2 diabetes, is being explored for type 1 diabetes in combination with automated insulin delivery. Unlike typical treatments that rely on multiple daily insulin injections or manual insulin pumps, this approach leverages metformin's potential to enhance insulin sensitivity and improve blood sugar control. Researchers are excited because this combination could offer better glucose management and possibly reduce cardiovascular risks, providing a more comprehensive treatment for individuals with type 1 diabetes.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

Research has shown that metformin helps the body use insulin more effectively and maintains blood vessel flexibility, which is crucial for heart health in young people with type 1 diabetes. In this trial, some participants will receive metformin alongside an automated insulin delivery system. Automated insulin delivery systems have proven to control blood sugar levels better than other insulin treatments. They help maintain blood sugar within the desired range, reducing the risk of complications. Combining metformin with these automated systems might enhance these benefits, potentially improving heart and kidney health further. This trial studies whether this combination can better manage diabetes-related health issues.² ⁶ ⁷ ⁸ ⁹

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I am between 12 and 21 years old.

I haven't had recent severe diabetic complications.

I have been using an insulin pump or taking multiple daily insulin shots and a continuous glucose monitor for over 6 months.

See 4 more

Exclusion Criteria

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

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

I have anemia.

See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or placebo for 4 months while using automated insulin delivery systems or multiple daily injections with continuous glucose monitoring

16 weeks

Regular visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

Metformin Hcl

Trial Overview 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.

How Is the Trial Designed?

3Treatment groups

Experimental Treatment

Active Control

Placebo Group

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

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.

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 addition 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 addition to assessments of cardiovascular and endothelial function.

Metformin Hcl is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Glucophage for:

Type 2 diabetes mellitus
Polycystic ovary syndrome

Approved in United States as Glucophage for:

Type 2 diabetes mellitus

Approved in Canada as Glucophage for:

Type 2 diabetes mellitus

Find a Clinic Near You

Who Is Running the Clinical Trial?

Kalie Tommerdahl

Lead Sponsor

Trials

Recruited

60+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The combination tablet of sitagliptin and metformin (Janumet) has been approved by the FDA for patients with Type 2 diabetes who need better glycemic control, either when taking these medications separately or together.

Sitagliptin has been demonstrated to be safe and effective at a daily dose of 100 mg, and its combination with metformin is believed to enhance glycemic control through complementary mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janumet: a combination product suitable for use in patients with Type 2 diabetes.Reynolds, JK., Neumiller, JJ., Campbell, RK.[2019]

In a study of 100 patients with type-1 diabetes and poor glycaemic control, metformin treatment for one year did not significantly improve HbA1c levels compared to placebo, indicating no enhancement in glycaemic control.

However, metformin was associated with a significant reduction in total daily insulin doses and body weight, suggesting potential benefits in insulin management and weight control for patients with type-1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study.Lund, SS., Tarnow, L., Astrup, AS., et al.[2022]

GLP-1 receptor agonists (RAs) like exenatide and liraglutide have been shown to effectively lower glycated hemoglobin (A1C) levels and promote weight loss in patients with type 2 diabetes, making them beneficial treatment options alongside metformin.

These medications have a low risk of causing hypoglycemia and can improve cardiovascular risk factors, although they may cause nausea initially, which tends to decrease over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatments and strategies for type 2 diabetes: can we do better with GLP-1 receptor agonists?Peterson, G.[2018]

Citations

1.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC11429521/

Comparative effectiveness trial of metformin versus insulin for ...Aim 1: We hypothesise that metformin is not inferior or worse than insulin by an absolute margin or difference of more than 8% in the composite ...

2.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC12017971/

Efficacy of automated insulin delivery systems in people with ...The comparative efficacy of automated insulin delivery (AID) systems and other treatment options for type 1 diabetes, accounting for the certainty of evidence ...

3.clinicaltrials.govclinicaltrials.gov/study/NCT05065372?term=Diabetes%20type%201%20and%20artificial%20pancreas&aggFilters=funderType:nih%20fed,status:rec&viewType=Table&rank=2

MANATEE-T1D: Metformin ANd AutomaTEd Insulin ...We have shown that metformin improved peripheral insulin sensitivity and vascular stiffness in youth with type 1 diabetes on multiple daily insulin injections ...

4.researchgate.netresearchgate.net/publication/381544922_Real-world_glycaemic_outcomes_of_automated_insulin_delivery_in_type_1_diabetes_A_meta-analysis

Real‐world glycaemic outcomes of automated insulin ...Aim To evaluate the real‐world effectiveness of automated insulin delivery (AID) systems in patients with type 1 diabetes (T1D).

5.e-dmj.orge-dmj.org/journal/view.php?number=2893

Efficacy and Safety of Automated Insulin Delivery Systems ...In conclusion, AID systems significantly improve glucose control in patients with T1DM compared to other insulin-based treatments. Greater ...

6.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC11960199/

Efficacy and Safety of Automated Insulin Delivery Systems in ...Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (–1.80% vs. –0.86%, P=0.031) and ...

7.accessdata.fda.govaccessdata.fda.gov/cdrh_docs/pdf16/p160017b.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)The consequences of falsely high glucose reading on the continuous glucose monitor would be potential over-delivery of insulin via automated ...

8.touchendocrinology.comtouchendocrinology.com/diabetes/journal-articles/review-of-automated-insulin-delivery-systems-for-type-1-diabetes-and-associated-time-in-range-outcomes/

Review of Automated Insulin Delivery Systems for Type 1 ...Safety and glycemic outcomes during the MiniMed™advanced hybrid closed-loop system pivotal trial in adolescents and adults with type 1 diabetes.

9.diabetesjournals.orgdiabetesjournals.org/care/article/47/Supplement_1/S158/153955/9-Pharmacologic-Approaches-to-Glycemic-Treatment

9. Pharmacologic Approaches to Glycemic TreatmentAutomated insulin delivery (AID) systems are safe and effective for people with type 1 diabetes. Randomized controlled trials and real-world ...

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