Metformin + Glipizide for Diabetes

(SUGAR-MGH Trial)

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

1033 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The SUGAR-MGH investigators are studying the influence of inherited gene variants on the response to two commonly prescribed type 2 diabetes medications, metformin and glipizide. They hypothesize that variants in genes that are associated with type 2 diabetes or related traits may impact the effect of anti-diabetic medications. In addition, physiological responses to an insulin secretagogue or an insulin sensitizer may shed light on the mechanism of action of reported genetic associations.

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 the combination of Metformin and Glipizide safe for humans?

Research shows that both Metformin and Glipizide are generally safe for humans. Metformin, including its extended-release form, is well-tolerated and effective for diabetes management, while Glipizide is considered a safe and potent anti-diabetic agent. ^{1 2 3 4 5}

How is the drug Metformin + Glipizide unique for treating diabetes?

The combination of Metformin and Glipizide is unique because it combines Metformin, which helps lower blood sugar by improving insulin sensitivity, with Glipizide, a fast-acting drug that stimulates the pancreas to release more insulin. This combination can be particularly effective for elderly patients due to Glipizide's short action time and lack of excessive insulin production. ^{2 3 6 7 8}

What data supports the effectiveness of the drug combination of Metformin and Glipizide for diabetes?

Research shows that Glipizide is effective in lowering blood sugar levels and is well-tolerated, especially in elderly patients. Additionally, combining Metformin with other drugs like Sitagliptin has been shown to improve blood sugar control without causing weight gain or low blood sugar, suggesting that Metformin combined with Glipizide may also be effective. ^{2 3 6 9 10}

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]

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]

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]

Citations

1. Ireland pubmed.ncbi.nlm.nih.gov

Sitagliptin more effectively achieves a composite endpoint for A1C reduction, lack of hypoglycemia and no body weight gain compared with glipizide. [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. Belgium pubmed.ncbi.nlm.nih.gov

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

4. Poland pubmed.ncbi.nlm.nih.gov

[Glipizide--a short-acting sulphonylurea derivative]. [2013]

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

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

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

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

7. Zambia pubmed.ncbi.nlm.nih.gov

A clinical trial with glipizide - a relative new sulphonylurea. [2013]

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

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

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

Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation. [2015]

10. England pubmed.ncbi.nlm.nih.gov

Combination exenatide-sitagliptin therapy used with glipizide in a patient with type 2 diabetes mellitus. [2022]