Metformin + Glipizide for Diabetes

(SUGAR-MGH Trial)

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must not be taking: Diabetes meds, Glucocorticoids

Disqualifiers: Pregnancy, Liver disease, Kidney disease, CAD, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how genetic differences affect responses to two common type 2 diabetes medications, metformin and glipizide. Researchers aim to determine if specific gene variations alter the effectiveness of these drugs in managing blood sugar levels. The trial involves administering both medications and monitoring changes in blood glucose levels. Individuals at risk of developing diabetes or with conditions like high blood sugar, PCOS, or obesity may be suitable for this study. Participants should not currently be on diabetes medication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a unique opportunity to contribute to groundbreaking research.

Will I have to stop taking my current medications?

If you are currently taking any medications for diabetes or medications that affect blood sugar levels, you will need to stop taking them to participate in this trial. The trial does not specify a washout period, but you should discuss this with the study team.

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

Research shows that both glipizide and metformin are generally safe when used alone or together to manage type 2 diabetes. Studies have found that using these drugs together can effectively lower blood sugar levels. However, some possible side effects require attention.

Low blood sugar, or hypoglycemia, is a common concern. This can occur if meals are skipped, alcohol is consumed, or exercise is increased. Regularly checking blood sugar levels while taking these medications is important.

Regarding overall safety, research suggests that metformin is linked to a lower risk of major heart problems compared to glipizide. This makes metformin a popular choice for people with diabetes who also have heart concerns.

Both drugs are widely used and well-tolerated by many people. However, as with any medication, discussing any concerns with a healthcare provider is important. They can help ensure the treatment is safe and effective. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for diabetes focus on either increasing insulin sensitivity or boosting insulin production. But this combination of Metformin and Glipizide offers a dual approach: Metformin enhances insulin sensitivity, making the body's cells more responsive to insulin, while Glipizide stimulates the pancreas to produce more insulin. Researchers are excited about this treatment because it could balance blood sugar levels more effectively by addressing two different aspects of diabetes at once. Additionally, the short-course nature of Metformin in this study may offer faster insights into its effects, potentially leading to quicker adjustments in diabetes management strategies.

What evidence suggests that metformin and glipizide could be effective treatments for diabetes?

This trial will evaluate the combination of glipizide and metformin for managing type 2 diabetes. Studies have shown that using these medications together can significantly improve blood sugar control in people with type 2 diabetes. This combination helps lower HbA1c levels, a measure of blood sugar over time. Some research has even found it to be four times more effective at helping patients reach their target HbA1c levels compared to other treatments. Specifically, one study showed that adding glipizide to metformin improved blood sugar control. These findings suggest that the combination of glipizide and metformin can be a powerful tool for managing type 2 diabetes. ^{1 4 6 7 8}

Who Is on the Research Team?

Jose C Florez, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 who may be at risk of type 2 diabetes or are already managing it with diet alone. This includes those with elevated glucose levels, PCOS, metabolic syndrome, obesity, or a history of gestational diabetes. People with related risks like hypertension or dyslipidemia can also join if they're healthy overall and willing to consent to genetic research.

Inclusion Criteria

Otherwise healthy subjects may also be candidates for the study

I am willing to consent to genetic testing.

The first tier of risk will be illustrated by one of the following variables (e.g. established type 2 diabetes on diet therapy alone, elevated random glucose in electronic medical record, PCOS, metabolic syndrome, obesity, history of gestational diabetes, etc.)

Exclusion Criteria

Known severe allergic reactions to sulfonamides

Enrolled in any other interventional study at time of screening through completion of study protocol

My family has a history of diabetes starting before age 25 across three generations.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single oral dose of glipizide on Day 1 and a short-course metformin treatment from Days 6-8, followed by an Oral Glucose Tolerance Test on Day 8

8 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with measurements of glucose, insulin, and other markers

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Glipizide
• Metformin

Trial Overview

The study is examining how gene variants affect responses to metformin and glipizide—two drugs used for treating type 2 diabetes. It involves an oral glucose tolerance test to understand the action mechanism of these medications in relation to specific genetic profiles.

How Is the Trial Designed?

Group I: Glipizide and Metformin Experimental Treatment 3 Interventions

On day 1, subjects will receive a single oral dose of glipizide 5 mg, and will have blood drawn at various time points for up to 240 minutes. During study days 2-7, the participants will fill out a dietary intake food record, including 3 weekdays and one weekend day. During days 6-8, the subject will receive a short-course metformin treatment of four 500-mg doses. On the morning of study day 8, 60 minutes after taking the fourth metformin dose, the subject will do a 75g Oral Glucose Tolerance Test. Blood draws will again be taken at time points for 120 minutes.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Joslin Diabetes Center

Collaborator

Trials

98

Recruited

26,500+

Broad Institute

Collaborator

Trials

21

Recruited

16,300+

Broad Institute of MIT and Harvard

Collaborator

Trials

21

Recruited

16,300+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

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]

Janumet, a combination of sitagliptin and metformin, effectively addresses multiple abnormalities in type 2 diabetes by enhancing insulin secretion and reducing glucose production, improving glucose control without causing hypoglycemia or weight gain.

The treatment is generally well-tolerated, though it may cause digestive side effects and has contraindications related to renal insufficiency, making it suitable for patients who have not achieved adequate control with metformin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication of the month. Sitagliptin-metformin fixed combination (Janumet)]. Scheen, AJ.[2015]

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]

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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Effect of Combination Glipizide GITS/Metformin on Fibrinolytic ...

RESULTS—Glycemic control was markedly impaired at baseline (mean HbA1c 10.4 ± 0.2% glipizide GITS; 10.0 ± 0.2% metformin) but improved ...

6.

mayoclinic.org

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Glipizide and metformin (oral route) - Side effects & dosage

Glipizide and metformin combination can cause low blood sugar. However, it also can occur if you delay or miss a meal or snack, drink alcohol, ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3631843/

Effects of Metformin Versus Glipizide on Cardiovascular ...

Treatment with metformin for 3 years substantially reduced major cardiovascular events in a median follow-up of 5.0 years compared with glipizide. Our results ...

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mdpi.com

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Short-Term Treatment of Metformin and Glipizide on ...

The results suggest that metformin more effectively controls blood glucose levels in diabetic rats than glipizide. The combination of both drugs showed ...