Metformin for Type 1 Diabetes and Obesity

Overseen By HI Team

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Heba M. Ismail

Must not be taking: Antibiotics, Steroids, Metformin, others

Disqualifiers: Type 2 diabetes, Infections, Immunocompromise, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

114 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how metformin, a common diabetes medication, might help manage weight in young people with type 1 diabetes (T1D) who are overweight or obese. Researchers aim to understand the role of the gut microbiome (the bacteria in the stomach) in T1D and its potential link to weight. The study consists of two parts: one group will take metformin for six months, while another group will have their gut bacteria analyzed based on their weight category. Young people with T1D who are either overweight or lean and have not previously used metformin might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used metformin before.

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research shows that metformin is generally safe and well-tolerated for people with type 1 diabetes and obesity. Studies have found that metformin can be safely used with insulin. The most common side effects, such as stomach upset or diarrhea, are usually mild and often improve as the body adjusts to the medication.

Metformin is also often used to help prevent diabetes and can aid in weight loss when taken regularly, with effects lasting for at least 10 years. Additionally, the FDA has approved metformin for type 2 diabetes, indicating a well-established safety record.

Some studies have shown that metformin can slightly reduce body mass index (BMI), a measure of body fat based on height and weight. However, when added to insulin for overweight teenagers with type 1 diabetes, it did not significantly improve blood sugar control after six months.

In summary, while metformin is not a miracle solution for weight loss or diabetes management, its safety profile is promising for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for type 1 diabetes, which often focus on insulin management, metformin is unique because it targets insulin sensitivity and has the potential to address obesity. Metformin is well-known as a treatment for type 2 diabetes, where it works by improving how the body responds to insulin and reducing glucose production in the liver. Researchers are excited about using metformin for type 1 diabetes and obesity because it might help manage weight and improve metabolic health in young people with type 1 diabetes, offering a dual benefit that standard insulin therapies don't typically address.

What evidence suggests that metformin might be an effective treatment for type 1 diabetes and obesity?

Research has shown that metformin can help people with Type 1 Diabetes (T1D) and obesity lose weight. One study found that T1D patients who took metformin lost weight, even though their blood sugar levels didn't change much. In this trial, one group of participants will receive metformin to evaluate its effects on weight management. Metformin is already a safe and effective treatment for Type 2 Diabetes and might help reduce insulin resistance in overweight T1D patients. While it may not greatly affect blood sugar control, it could be helpful for managing weight. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for obese and lean youths aged 11-18 with Type 1 Diabetes (T1D). They should not have participated in other research trials within the last 3 months, had infections or antibiotic treatments in the past month, used metformin, or have chronic gastrointestinal diseases including celiac disease. Those with monogenic diabetes forms or immune-compromise conditions are also excluded.

Inclusion Criteria

I am between 11-18 years old, obese, and have Type 1 Diabetes.

Exclusion Criteria

Participation in any research intervention trials within the past 3 months

I have not had an infection or taken antibiotics in the last month.

I have a genetic form of diabetes or Type 2 diabetes confirmed by tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin for 6 months to assess changes in gut microbiome and metabolic markers

6 months

Visits at baseline, Month 3, and Month 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study investigates how obesity affects young people with T1D by looking at their gut bacteria. It's testing whether Metformin, a common Type 2 diabetes medication, can help manage T1D in obese youth by altering their gut microbiome.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

This is a group of 30 youth with type 1 diabetes and overweight/obesity who will receive metformin for 6 months.

Group II: Comparison of microbiome by BMI Category Active Control 1 Intervention

The gut microbiome and metabolites of 42 lean and 42 overweight/obese youth with type 1 diabetes will be evaluated cross-sectionally.

Who Is Running the Clinical Trial?

Heba M. Ismail

Lead Sponsor

Trials

1

Recruited

110+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 150 patients with type 2 diabetes, extended-release metformin showed comparable efficacy to Glucophage (standard metformin) over 12 weeks, with no significant differences in fasting plasma glucose or HbA1c levels between the two treatments.

Both treatments had mild adverse effects, primarily gastrointestinal, with a slightly higher rate in the extended-release metformin group, but no serious adverse events were reported, indicating that both options are safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of extended-release metformin in treatment of type 2 diabetes mellitus]. Zhang, JP., Yang, WY., Hong, TP., et al.[2022]

Weight loss is crucial in preventing and managing Type 2 diabetes, and pharmacological treatments should not only promote weight loss but also improve insulin sensitivity.

Metformin is highlighted as the first-line medication for obese diabetic patients because it effectively reduces insulin resistance and improves blood sugar control without causing weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of the obese diabetic patient. Scheen, AJ., Lefebvre, PJ.[2018]

In a study of 126 overweight and obese patients with type 2 diabetes, dulaglutide (DU) showed a significant and sustained reduction in HbA1c levels over 18 months, with a mean decrease of -0.85% at 6 months, indicating its effectiveness as an add-on therapy to metformin.

Dulaglutide was associated with a higher percentage of patients achieving glycemic targets (HbA1c ≤ 7.0%) compared to liraglutide (LIRA) at 18 months, with 64.8% of DU patients reaching this target versus 42.6% for LIRA, highlighting its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes. Mirabelli, M., Chiefari, E., Tocci, V., et al.[2021]

In a study of 113 women with type 1 diabetes, both long-acting insulin analogues, detemir and glargine, provided comparable glycaemic control throughout pregnancy, with similar HbA1c levels and rates of severe hypoglycaemia.

The study found that while pregnancy outcomes were generally similar, women using glargine had a lower prevalence of large for gestational age infants compared to those using detemir, suggesting a potential advantage of glargine in this aspect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes: comparison of glycaemic control and pregnancy outcome. Callesen, NF., Damm, J., Mathiesen, JM., et al.[2015]

GLP-1 receptor agonists, such as liraglutide and semaglutide, effectively manage type 2 diabetes by improving glucose control, promoting weight loss, and reducing cardiovascular disease risk, with higher doses leading to better outcomes.

Tirzepatide, a dual agonist targeting GLP-1 and GIP receptors, has shown superior reductions in blood sugar and body weight compared to other treatments, and is currently being tested for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A new era for glucagon-like peptide-1 receptor agonists]. Neuville, MF., Paquot, N., Scheen, AJ.[2023]

Long-acting GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective anti-obesity medications that can lead to significant weight loss, with semaglutide showing an average weight loss of 11.6% after one year, compared to 5.5% with liraglutide.

Both medications are generally well tolerated, with similar safety profiles, though they can cause transient gastrointestinal issues; ongoing long-term studies are needed to further evaluate their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. Christensen, RM., Juhl, CR., Torekov, SS.[2020]

The review highlights that while there are many innovative drugs being developed for type 2 diabetes, several have faced serious safety issues, leading to their withdrawal or halting of development.

It discusses the current state of treatments, including glitazones, incretin mimetics, SGLT-2 inhibitors, and new experimental drugs, emphasizing the need for better methods to predict and differentiate drug-related adverse events from natural disease occurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes]. Schindler, C., Barthel, A., Fischer, S., et al.[2021]

Weight reduction is crucial for managing obesity in both Type 1 and Type 2 diabetes, with various medications available to aid in weight loss, including orlistat and incretin analogues like exenatide and liraglutide.

Incretin analogues, particularly those administered every one to two weeks, are highlighted as a key strategy for treating obese Type 2 diabetics, potentially even in combination with insulin, while bariatric surgery can also lead to remission of Type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of obese diabetics. Svacina, S.[2016]

Metformin extended release (ER) provides effective glycaemic control with once-daily dosing, showing similar effectiveness to twice-daily dosing of immediate-release formulations over a 24-week period in clinical trials.

The metformin ER formulation was well tolerated at doses of 1500 and 2000 mg/day, with no increase in adverse events, indicating its safety for patients managing their blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin extended release for the treatment of type 2 diabetes mellitus. Schwartz, SL., Wu, JF., Berner, B.[2019]

Citations

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Weight Management in Patients with Type 1 Diabetes and ... ... T1D and obesity [59, 60]. In a recent randomized control trial, patients with T1D using metformin had significant improvements in body ...

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The effects of metformin in type 1 diabetes mellitus - PMC These results were independent of blood lipid improvement or weight loss, although on average weight remained decreased with metformin-insulin ...

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Effect of Metformin Added to Insulin on Glycemic Control ... Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months.

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Optimizing metformin therapy in practice: Tailoring therapy in ... Metformin is the first-line medication for type 2 diabetes. It is effective and safe, provided some caution is taken in specific populations.

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Recommendations for Practical Use of Metformin, a Central ... In individuals with type 1 diabetes and overweight/ obesity, metformin may have an adjuvant role in reducing insulin resistance (50). Several ...

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An Updated Systematic Review and Meta‐Analysis on the ... This updated meta‐analysis evaluates the efficacy and safety of metformin as add‐on therapy to insulin in patients with type 1 diabetes.

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Long-Term Safety, Tolerability, and Weight Loss Associated ... Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of ...

8. publications.aap.org publications.aap.org/pediatrics/article/147/3/e20201610/77087/Efficacy-and-Safety-of-Metformin-for-Obesity-A

Efficacy and Safety of Metformin for Obesity: A Systematic ... Metformin was modestly efficacious at decreasing BMI (range of mean changes: −2.70 to 1.30) compared with a placebo (range of mean changes: −1.12 to 1.90).