Metformin for Post-Gestational Diabetes

Overseen By Anna Stanhewicz, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Anna Stanhewicz, PhD

Must not be taking: Cardiovascular, Metabolic

Disqualifiers: Prediabetes, Diabetes, Tobacco, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how metformin, a common diabetes medication, can improve blood vessel function in women who had gestational diabetes, a type of diabetes that occurs during pregnancy. The researchers will compare metformin to a placebo (a non-active pill) to evaluate its effectiveness before any disease develops. Women who have experienced gestational diabetes or a healthy pregnancy within the last five years and are not currently pregnant or using tobacco may be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding metformin's effects in people, offering participants a chance to contribute to groundbreaking medical knowledge.

Will I have to stop taking my current medications?

The trial requires that participants do not take any cardiovascular or metabolic medications. If you are on such medications, you would need to stop taking them to join the trial.

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

Research has shown that metformin is generally a safe treatment option. For women with gestational diabetes, metformin helps control blood sugar levels. Compared to insulin, it poses fewer risks, such as low blood sugar in newborns, and reduces the likelihood of newborns needing intensive care. Adults with diabetes who are not pregnant also tolerate it well. Overall, metformin is considered a safe and effective way to manage blood sugar. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for post-gestational diabetes?

Unlike the standard treatments for post-gestational diabetes, which often include lifestyle changes and insulin therapy, Metformin Hydrochloride is a medication typically used to manage blood sugar levels in type 2 diabetes. Researchers are excited about Metformin because it works by improving the body's sensitivity to insulin, potentially offering a more straightforward oral medication option for managing blood sugar levels after pregnancy. This could simplify treatment regimens and improve convenience for new mothers dealing with post-gestational diabetes.

What evidence suggests that metformin might be an effective treatment for post-gestational diabetes?

Research has shown that metformin, which participants in this trial may receive, is a promising treatment for gestational diabetes. It effectively lowers blood sugar levels and improves pregnancy outcomes when combined with insulin. Studies also suggest that metformin reduces the risk of complications for both mothers and babies compared to insulin alone. For example, it lowers the chance of low blood sugar in newborns and reduces the need for neonatal intensive care unit admissions. These findings suggest that metformin might improve blood vessel function in women who had gestational diabetes. ^{2 3 5 6 7}

Who Is on the Research Team?

Anna Stanhewicz, PhD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for women who are between 12 weeks and 5 years postpartum and have had gestational diabetes or a healthy pregnancy. It's not suitable for those outside this timeframe or with other specific health conditions.

Inclusion Criteria

history of GDM or healthy pregnancy

I gave birth between 3 months and 5 years ago.

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 to assess microvascular function improvement

12 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin Hydrochloride

Trial Overview

The study is testing if Metformin Hydrochloride, a common diabetes medication, can improve small blood vessel function in women who've had gestational diabetes compared to a placebo (a substance with no therapeutic effect).

How Is the Trial Designed?

Group I: metformin Active Control 1 Intervention

Group II: placebo Placebo Group 1 Intervention

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

Approved in European Union as Metformin Hydrochloride for:

• Type 2 diabetes
• Polycystic ovary syndrome

Approved in United States as Metformin Hydrochloride for:

• Type 2 diabetes
• Polycystic ovary syndrome
• Gestational diabetes

Approved in Canada as Metformin Hydrochloride for:

• Type 2 diabetes
• Polycystic ovary syndrome

Approved in Japan as Metformin Hydrochloride for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Anna Stanhewicz, PhD

Lead Sponsor

Trials

12

Recruited

460+

Published Research Related to This Trial

In a study of 153 overweight women with prior gestational diabetes, the combination of liraglutide and metformin (MET-LIRA) significantly improved mean blood glucose levels and insulin sensitivity compared to metformin alone (MET-P).

MET-LIRA also led to greater reductions in body weight and central adiposity, as well as decreased triglyceride levels, demonstrating its superior efficacy in managing metabolic health in women with a history of gestational diabetes over 84 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postpartum treatment with liraglutide in combination with metformin versus metformin monotherapy to improve metabolic status and reduce body weight in overweight/obese women with recent gestational diabetes: A double-blind, randomized, placebo-controlled study. Elkind-Hirsch, KE., Shaler, D., Harris, R.[2021]

A study involving 24 healthy male volunteers found that Dialon (Julphar, UAE) and Glucophage (Lipha Pharmaceutical Industries, France) are bioequivalent, meaning they have similar absorption and effectiveness in the body when taken as 500 mg tablets.

The pharmacokinetic parameters, including AUC and C(max), showed no significant differences between the two brands, confirming that Dialon can be used as an alternative to Glucophage for patients requiring metformin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence evaluation of two brands of metformin 500 mg tablets (Dialon & Glucophage)--in healthy human volunteers. Najib, N., Idkaidek, N., Beshtawi, M., et al.[2013]

A retrospective chart review of 471 patients showed that those switched from immediate-release metformin to extended-release metformin (metformin-XR) experienced significantly fewer gastrointestinal side effects, including diarrhea, indicating better tolerability of the extended-release formulation.

The study found that while the overall frequency of gastrointestinal adverse events was similar between both formulations, patients who switched to metformin-XR reported a reduction in gastrointestinal issues, with diarrhea rates dropping from 18.05% to 8.29%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Blonde, L., Dailey, GE., Jabbour, SA., et al.[2021]

In a randomized trial involving patients with type 2 diabetes, both metformin-vidagliptin (MF-VG) and metformin-glimepiride (MF-GP) combinations significantly reduced blood glucose levels and HbA1c after 12 weeks, showing similar efficacy.

Both treatment groups maintained normal liver and kidney function throughout the study, but the MF-GP group experienced numerically more cases of hypoglycemia, indicating a potential safety concern with this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of efficacy and safety of combination of metformin-vidagliptin versus metfromin-glimepiride in most frequently used doses in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy-A randomised open label study. Gupta, S., Khajuria, V., Tandon, VR., et al.[2020]

Metformin is an effective and well-accepted treatment for type 2 diabetes in pregnancy, helping to reduce issues like large-for-gestational-age infants and excessive maternal weight gain.

However, it may lead to smaller fetal sizes and an increased risk of infants being born small-for-gestational-age in some cases, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focus on Metformin: Its Role and Safety in Pregnancy and Beyond. Newman, C., Rabbitt, L., Ero, A., et al.[2023]

In a study of 130 patients with type 2 diabetes treated with Metformin Hydrochloride, gastrointestinal adverse effects were the most common, with diarrhea affecting 30.77% of patients and leading to treatment discontinuation in 3.85%.

No cases of serious complications like lactic acidosis or allergic reactions were reported, indicating that while Metformin is generally safe, monitoring for digestive issues is important in managing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cross-Sectional Study on Adverse Effects of Metformin Hydrochloride on 130 Patients Type 2 Diabetic Admitted to Medical Center and Diabetes Home of Sidi Bel-Abbès]. Sakouhi, M., Matmour, D., Belakhdar, K., et al.[2023]

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]

Metformin is currently the best first-line treatment for type 2 diabetes due to its effectiveness, safety, weight neutrality, and low cost, and it can be combined with other antidiabetic medications.

Sulfonylureas are the preferred choice for combination therapy with metformin, although their effectiveness diminishes more quickly over time compared to other options like glitazones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Metformin role in the treatment of type 2 diabetes in 2008]. Spada, A., Philippe, J.[2013]

Metformin has been shown to effectively reduce the incidence of diabetes after pregnancy (DAP) in women with a history of gestational diabetes mellitus (GDM), although the studies reviewed involved participants who were, on average, 12 years post-GDM pregnancy.

While troglitazone also demonstrated DAP prevention, it was withdrawn from the market due to safety concerns related to liver toxicity, highlighting the importance of safety in pharmacotherapy for DAP prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological intervention for diabetes after pregnancy prevention in women with prior gestational diabetes: A scoping review. Pancer, J., Wu, N., Mahmoud, I., et al.[2020]

The EMERGE trial is a phase III study designed to evaluate the effectiveness and safety of early initiation of metformin in women with gestational diabetes mellitus (GDM), comparing it to a placebo, with a focus on maternal and neonatal outcomes.

This trial will assess key outcomes such as the need for insulin therapy, maternal morbidity, and neonatal health indicators, providing important data on the potential benefits of metformin as a first-line treatment for GDM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised placebo-controlled trial of the effectiveness of early metformin in addition to usual care in the reduction of gestational diabetes mellitus effects (EMERGE): study protocol. Dunne, F., Newman, C., Devane, D., et al.[2022]

Metformin is increasingly being recommended as a first-line treatment for gestational diabetes (GDM), showing similar outcomes to insulin for both mothers and their babies.

Despite its growing acceptance, there are still unresolved concerns regarding the safety and long-term effects of metformin use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The diversity of gestational diabetes: a therapeutic challenge. Qvigstad, E.[2019]

Metformin is an effective oral medication for treating non-insulin-dependent diabetes mellitus (type II diabetes) and does not cause hypoglycemia, which is a common side effect of other diabetes medications like sulfonylureas.

The drug is considered safe when proper precautions are taken, including monitoring liver and kidney function, and it has gained widespread use internationally, recently receiving FDA approval under the brand name Glucophage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. Tanja, JJ., Langlass, TM.[2013]

Metformin remains the first-choice glucose-lowering drug for type 2 diabetes, as other alternatives like sulphonylureas and gliptins have significant adverse effects and lack proven efficacy in preventing diabetes complications.

Many alternative medications, such as sulphonylureas and gliptins, not only lower HbA1c levels modestly but also carry risks of serious side effects, including hypoglycemia, cardiovascular issues, and potential cancer risks, making them less favorable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose-lowering treatment of type 2 diabetes. Part II--Glucose-lowering drugs after metformin: a choice based largely on adverse effects. [2022]

In a study of 107 patients, 19 were diagnosed with metformin-associated lactic acidosis (MALA), primarily occurring in those with acute kidney injury (AKI) due to dehydration and sepsis, highlighting the importance of monitoring kidney function in patients taking metformin.

The overall mortality rate for MALA was 36.8%, with aggressive treatment including renal replacement therapy improving outcomes; however, 46.7% of AKI patients died, emphasizing the need for heightened awareness and education regarding the risks of metformin use in at-risk populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin-associated lactic acidosis (MALA): Is it an underestimated entity? A retrospective, single-center case series. Kim, S., Sarwal, A., Yee, XT., et al.[2023]

In a 24-week study involving 318 patients with type 2 diabetes, adding vildagliptin to a treatment regimen of metformin and glimepiride significantly improved glycaemic control, reducing HbA1c by an average of 1.01% compared to only 0.25% with placebo.

Vildagliptin was well tolerated, showing a low incidence of hypoglycaemia (5.1% vs. 1.9% for placebo) and no significant weight gain, making it a promising option for patients not achieving glycaemic goals with their current medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea. Lukashevich, V., Del Prato, S., Araga, M., et al.[2022]

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