Metformin for Prediabetes

Recruiting at 1 trial location

Overseen By Diana I Jalal, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Diana Jalal

Must not be taking: Metformin, Vitamin C, others

Disqualifiers: Smoking, Hypertension, Diabetes, others

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: 7

Duration: 12 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not currently use metformin or any medications that are contraindicated (not recommended) for use with metformin. You also cannot take vitamin C supplements. If you are on any of these, you would need to stop them to participate.

What data supports the effectiveness of the drug Metformin for prediabetes?

While the provided research focuses on treatments for type 2 diabetes, Metformin is commonly used to help manage blood sugar levels and is often prescribed for prediabetes to prevent the progression to type 2 diabetes. It works by improving the body's response to insulin and reducing sugar production in the liver. ^{1 2 3 4 5}

Is metformin safe for humans?

Metformin, including its extended-release forms like Glumetza, has been shown to be well-tolerated in clinical trials for type 2 diabetes, with no increase in adverse effects at higher doses. However, it should not be used by people with kidney problems. ^{2 6 7 8 9}

How does the drug Metformin differ from other treatments for prediabetes?

Metformin is unique because it is often the first drug considered for prediabetes due to its favorable safety, tolerability, efficacy, and cost profile. Unlike some other treatments, it is specifically recommended for certain subgroups of prediabetes patients and has been shown to effectively lower fasting plasma glucose levels. ^{10 11 12 13 14}

What is the purpose of this trial?

The goal of this clinical trial is to investigate whether metformin improves vascular function in individuals with prediabetes. The main questions it aims to answer are: 1. Does metformin improve large conduit artery endothelial function in individuals with prediabetes? 2. Does metformin improve microvascular endothelial function in individuals with prediabetes? Researchers will compare metformin to a placebo to see if metformin improves vascular function in prediabetes. The trial duration is 12 weeks. Participants will take metformin or a placebo once a day for 2 weeks. After 2 weeks, participants will take metformin or a placebo twice a day for the remaining 10 weeks. There will be a screening visit, two baseline visits, a 4-week safety visit, and two 12-week end-of-study visits. Adherence will be calculated from pill count and adverse events will be quantified via a questionnaire.

Research Team

Diana I Jalal, MD

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for individuals with prediabetes, a condition where blood sugar levels are higher than normal but not high enough to be type 2 diabetes. Participants should not have started any new cardiovascular or glucose-lowering medications within the last three months.

Inclusion Criteria

Prediabetes defined as an HbA1c between 5.7% and 6.4%

Able to provide informed consent

Exclusion Criteria

I have a history of diabetes, heart issues, liver disease, or severe kidney disease.

Uncontrolled hypertension (Systolic blood pressure >140 mmHg)

I am not taking any medications that can't be used with metformin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline

Two baseline visits to establish initial vascular function measurements

2 visits

2 visits (in-person)

Treatment

Participants receive metformin or placebo once a day for 2 weeks, then twice a day for 10 weeks

12 weeks

4-week safety visit, 2 end-of-study visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Metformin

Trial Overview The study tests if metformin, a common diabetes medication, can improve blood vessel function in people with prediabetes. It compares the effects of metformin against a placebo over 12 weeks, with doses increasing after the first two weeks.

Participant Groups

Group I: Metformin Experimental Treatment 1 Intervention

Participants will receive metformin 850 mg PO once a day for 2 weeks. After 2 weeks, participants will receive metformin 1700 mg PO once a day for the remaining 10 weeks.

Group II: Placebo Placebo Group 1 Intervention

Patients will receive placebo pill identical in appearance and taste to the supplement

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

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Diana Jalal

Lead Sponsor

Trials

3

Recruited

150+

Findings from Research

Saxagliptin significantly reduces glycosylated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM), with reductions ranging from -0.72% to -0.90% compared to -0.27% with placebo, based on data from 11 Phase III clinical trials.

Saxagliptin is well tolerated, with common side effects including upper respiratory infections and urinary tract infections, and it does not increase cardiovascular risk compared to other treatments, making it a safe option for managing T2DM, especially in combination with other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. Kania, DS., Gonzalvo, JD., Weber, ZA.[2022]

In a 16-week study involving 169 adults with type 2 diabetes, all three medications (colesevelam, rosiglitazone, and sitagliptin) improved blood sugar control, as measured by reductions in HbA1c levels.

Colesevelam not only improved glycemic control but also significantly reduced LDL-cholesterol levels, while rosiglitazone and sitagliptin were associated with increases in LDL-cholesterol, highlighting colesevelam's unique benefit in managing both blood sugar and cholesterol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of colesevelam, rosiglitazone, or sitagliptin on glycemic control and lipid profile in patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy. Rigby, SP., Handelsman, Y., Lai, YL., et al.[2021]

GLP-1 receptor agonists, like liraglutide and exenatide, effectively lower blood sugar levels in type 2 diabetes patients by enhancing insulin production in a glucose-dependent manner, leading to reductions in HbA1c levels by -0.79% to -1.12%.

These medications not only help manage blood sugar without causing hypoglycemia but also promote weight loss and improve cardiovascular risk factors, making them a safe and effective option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 (GLP-1) receptor agonists: Differentiating the new medications. Unger, JR., Parkin, CG.[2021]

GLP-1 receptor agonists (GLP-1RAs) are effective injectable medications for adults with type 2 diabetes, significantly improving blood sugar levels and aiding in weight loss by enhancing insulin release and reducing appetite.

These medications have a low risk of causing hypoglycemia and are recommended as second-line treatments alongside other diabetes medications, making them a valuable option for managing type 2 diabetes effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

User's guide to mechanism of action and clinical use of GLP-1 receptor agonists. Shaefer, CF., Kushner, P., Aguilar, R.[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]

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]

Janumet(TM), a combination of sitagliptin and metformin, is FDA-approved for patients with type 2 diabetes who are not adequately controlled on either medication alone, highlighting its efficacy in improving glycemic control.

Sitagliptin, at a daily dose of 100 mg, is safe and effective, and when combined with metformin, it may provide complementary benefits for better blood sugar management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes. Reynolds, JK.[2021]

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]

Glumetz (M-ER) is a newly approved extended-release formulation of metformin that provides effective and sustained glycemic control with once-daily dosing, showing similar bioavailability to immediate-release metformin taken twice daily.

In clinical trials lasting 24 weeks, M-ER demonstrated good efficacy and was well tolerated, with continued glycemic control maintained in an additional 24-week open-label extension study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. Schwartz, SL., Gordi, T., Hou, E., et al.[2013]

Patients with impaired fasting glucose and impaired glucose tolerance are classified as having 'prediabetes', which significantly increases their risk of developing diabetes and cardiovascular diseases.

Various medications, including metformin and glitazones, have shown effectiveness in improving blood sugar levels in prediabetes, but none are currently recommended by professional organizations for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug therapy in prediabetes. Mukhopadhyay, P., Chowdhury, S.[2013]

Prediabetes is a significant health concern that increases the risk of developing type 2 diabetes (T2DM) and associated complications, but it can be effectively managed through lifestyle changes and medications.

Various treatments, including lifestyle interventions, medications like metformin and GLP-1 receptor agonists, and even bariatric surgery, have been shown to prevent or delay the progression from prediabetes to T2DM, highlighting the importance of individualized management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating prediabetes: why and how should we do it? Braga, T., Kraemer-Aguiar, LG., Docherty, NG., et al.[2019]

Lifestyle interventions, including modest weight loss and increased physical activity, are safe and effective for patients with prediabetes, significantly reducing the risk of developing type 2 diabetes and cardiovascular disease.

Thiazolidinediones (TZDs) are the most effective oral medications for delaying the onset of type 2 diabetes in prediabetic patients, reducing the risk by up to 80%, while metformin is recommended as a first-line treatment due to its favorable safety and efficacy profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of prediabetes. Matfin, G., Pratley, RE.[2023]

Long-acting insulin analogs like insulin glargine and insulin detemir, along with GLP-1 mimetics such as liraglutide and exenatide, are effective treatment options for patients with type 2 diabetes who are not achieving optimal blood sugar control with oral medications.

The review highlights the need for more comparative studies to better understand how to integrate GLP-1 therapies with established insulin treatments in managing type 2 diabetes, particularly for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of basal insulin and glucagon-like peptide-1 agonists in the therapeutic management of type 2 diabetes--a comprehensive review. Garg, SK.[2015]

In a study of 686 subjects with prediabetes, prolonged-release metformin (metformin XR) effectively reduced fasting plasma glucose levels, normalizing them in 43% of participants after 12 weeks.

Metformin XR was well tolerated, with gastrointestinal side effects being the most common, supporting its use as a safe treatment option for managing prediabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of the efficacy of prolonged-release metformin in people with prediabetes. Hostalek, U., Zilahi, Z.[2020]

References

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

Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. [2022]

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

Effects of colesevelam, rosiglitazone, or sitagliptin on glycemic control and lipid profile in patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy. [2021]

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

Glucagon-like peptide-1 (GLP-1) receptor agonists: Differentiating the new medications. [2021]

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

User's guide to mechanism of action and clinical use of GLP-1 receptor agonists. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

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

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

Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Janumet: a combination product suitable for use in patients with Type 2 diabetes. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. [2013]

10. India pubmed.ncbi.nlm.nih.gov

Drug therapy in prediabetes. [2013]

11. Italy pubmed.ncbi.nlm.nih.gov

Treating prediabetes: why and how should we do it? [2019]

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

Advances in the treatment of prediabetes. [2023]

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

The role of basal insulin and glucagon-like peptide-1 agonists in the therapeutic management of type 2 diabetes--a comprehensive review. [2015]

14. England pubmed.ncbi.nlm.nih.gov

Observational study of the efficacy of prolonged-release metformin in people with prediabetes. [2020]