Metformin for Type 1 Diabetes and Obesity

Overseen By Heba M Ismail

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?

Obesity prevalence in persons with T1D has increased, which further complicates management and risk for complications. The proposed study is relevant to public health because it helps us understand the role of the gut microbiome in disease pathophysiology in T1D youth with obesity as well as potential mechanisms to modify disease.

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 metformin safe for humans?

Metformin, including its extended-release form, is generally well-tolerated in humans, with studies showing it provides effective blood sugar control without increasing the frequency or severity of side effects at higher doses. ^{1 2 3 4 5}

How does the drug metformin differ from other treatments for type 1 diabetes and obesity?

Metformin is unique because it helps improve insulin sensitivity and control blood sugar without causing weight gain, and it may even promote some weight loss, which is beneficial for obese patients with type 1 diabetes. Unlike insulin therapy, which often leads to weight gain, metformin offers a weight-neutral or weight-reducing option. ^{2 6 7 8 9}

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 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 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

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of extended-release metformin in treatment of type 2 diabetes mellitus]. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes]. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Metformin extended release for the treatment of type 2 diabetes mellitus. [2019]

5. Switzerland 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Treatment of obese diabetics. [2016]

7. Belgium pubmed.ncbi.nlm.nih.gov

[A new era for glucagon-like peptide-1 receptor agonists]. [2023]

8. England 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. [2015]

9. France pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of the obese diabetic patient. [2018]