Continuing vs Holding Metformin for Type 2 Diabetes

Overseen By Emily Hanners, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Illinois at Chicago

Must be taking: Metformin

Disqualifiers: Dialysis, Acidosis, Hepatic cirrhosis, 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: Unknown

Duration: During hospitalization

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether people with type 2 diabetes should continue or pause their metformin medication while hospitalized for general medical issues. Researchers aim to understand how this decision affects blood sugar control, stomach problems, hospital stay length, and overall health outcomes. Participants will be divided into two groups: one will continue taking metformin, while the other will stop during their hospital stay. This study suits those admitted to the hospital who have been taking metformin before admission and can still take oral medications. As a Phase 4 trial, this research helps determine how an already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial specifically looks at whether to continue or stop taking metformin during hospital stays, so you may need to stop taking it temporarily. The protocol does not mention other medications, so it's unclear if you need to stop any others.

What is the safety track record for metformin?

Research has shown that metformin is generally safe for people with type 2 diabetes. Studies have found it effective and well-tolerated, even for those at high risk of developing diabetes. Metformin is also considered safe for patients with mild chronic kidney disease (CKD), which was previously a concern. In a large study involving over 51,000 patients, metformin did not cause serious side effects such as lactic acidosis, a condition where too much lactate builds up in the body. Overall, metformin is a safe option for managing type 2 diabetes, offering benefits like heart protection and weight loss. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores whether continuing or holding metformin during hospitalization affects the management of Type 2 Diabetes. Metformin is a standard treatment for this condition, but its use during hospital stays is not always well-defined. By comparing these two approaches, the trial aims to provide clearer guidance on managing diabetes in hospitalized patients, potentially improving outcomes and safety. This could lead to more personalized and effective care for individuals with Type 2 Diabetes during hospital admissions.

What is the effectiveness track record for metformin in managing Type 2 Diabetes?

This trial will compare the effects of continuing versus holding metformin during hospitalization for patients with type 2 diabetes. Research has shown that metformin effectively manages type 2 diabetes by consistently lowering blood sugar levels and improving HbA1c, a measure of long-term blood sugar control. Studies indicate that metformin can reduce the risk of developing type 2 diabetes in high-risk adults by about 23%. Even a low dose of 500 mg can be beneficial. Metformin's effectiveness has been proven over many years, making it a reliable choice for managing diabetes. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Type 2 Diabetes who are already taking Metformin and have been admitted to an internal medicine service. It's not for those with severe acidosis, pregnant women, patients on dialysis, individuals unable to take oral meds or consent, or those with specific heart or liver conditions.

Inclusion Criteria

I was taking Metformin before being admitted.

I am currently admitted under an internal medicine department.

Exclusion Criteria

Current Acidosis (pH < 7.35) including diabetic ketoacidosis

Pregnant women

I am on dialysis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are either continued on or have their metformin regimen held during hospitalization to assess effects on glucose control and other outcomes

During hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment, including mortality and GI effects

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests whether continuing the diabetes medication Metformin during hospital stays is better than stopping it. The focus is on how this affects blood sugar control, risk of acidosis and abdominal issues, length of hospital stay, and survival rates.

How Is the Trial Designed?

Group I: Metformin discontinuation Active Control 1 Intervention

Holding home metformin regimen during hospitalization to an internal medicine service

Group II: Metformin continuation Active Control 1 Intervention

Continuation of home metformin regimen during hospitalization to an internal medicine service

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Emily Hanners

Collaborator

Trials

1

Recruited

300+

Peggy Choye

Collaborator

Trials

1

Recruited

300+

Dulal Bhaumik

Collaborator

Trials

1

Recruited

300+

Julie Jun

Collaborator

Trials

1

Recruited

300+

Avisek Datta

Collaborator

Trials

1

Recruited

300+

Annesti Elmasri

Collaborator

Trials

1

Recruited

300+

Hailey Soni

Collaborator

Trials

1

Recruited

300+

Colin Goodman

Collaborator

Trials

1

Recruited

300+

Published Research Related to This Trial

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 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]

In a study of 453 patients with type 2 diabetes, combination therapy using insulin glargine and exenatide led to significant reductions in A1C levels, indicating improved glycemic control, especially in patients who started with exenatide or both medications together.

The therapy was associated with a low risk of hypoglycemia, as the increase in hypoglycemic events remained minimal across all treatment groups, suggesting that this combination is safe for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with insulin glargine and exenatide: real-world outcomes in patients with type 2 diabetes. Levin, P., Wei, W., Wang, L., et al.[2022]

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 52-week trial involving 582 insulin-naive adults with type 2 diabetes, both insulin detemir and glargine effectively improved glycemic control, with similar reductions in HbA1c levels and low risk of hypoglycemia.

Insulin detemir was associated with less weight gain compared to glargine, particularly in patients using once-daily dosing, suggesting a potential advantage in managing weight alongside blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Rosenstock, J., Davies, M., Home, PD., et al.[2022]

Metformin is the first-line treatment for type 2 diabetes but often has limited efficacy over time, leading to the need for additional medications due to its gastrointestinal side effects and contraindications in certain patients.

Incretin-based therapies, particularly GLP-1 receptor agonists, are emerging as effective add-on treatments that can help achieve glycemic control while potentially offering cardiovascular benefits and improving β-cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological management of type 2 diabetes: the potential of incretin-based therapies. Charbonnel, B., Cariou, B.[2022]

In a study of 256,384 patients with type 2 diabetes, the 1-year persistence rates for initial treatment with metformin, sulphonylureas, and their combination were 47.7%, 45.4%, and 55.8%, respectively, indicating that adherence to these medications is suboptimal.

Persistence was significantly better for metformin at a higher dose (1000 mg - 60 tablets) at 60.4% compared to lower doses, suggesting that medication formulation and patient education are crucial for improving adherence to diabetes treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence of initial oral antidiabetic treatment in patients with type 2 diabetes mellitus. Jermendy, G., Wittmann, I., Nagy, L., et al.[2021]

GLP-1 receptor agonists (GLP-1RAs) have shown long-term efficacy in managing type 2 diabetes, with studies lasting up to 7 years demonstrating sustained reductions in HbA1c levels and weight loss without unexpected adverse events.

Compared to traditional treatments like sulfonylureas and insulin, GLP-1RAs, particularly exenatide, have shown a longer time to treatment failure and greater effectiveness in lowering blood glucose levels and promoting weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists. Courtney, H., Nayar, R., Rajeswaran, C., et al.[2020]

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]

In a study of 12,411 Canadians with Type 2 diabetes, only 47% persisted with a loose-dose combination therapy of a GLP-1 receptor agonist and basal insulin after 12 months, indicating low adherence to this treatment regimen.

The persistence rate was similar (45%) when including all patients, regardless of their previous experience with the therapy, suggesting that improving adherence to this combination treatment is crucial for better management of Type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence of GLP-1 RA in combination with basal insulin among adults with type 2 diabetes in Canada. Abitbol, A., Siemens, R., Nightingale, N., et al.[2022]

Semaglutide, an oral antidiabetic agent approved by the US-FDA, showed the highest efficacy in lowering HbA1c levels in Type 2 Diabetes Mellitus patients, with a significant reduction of 1.6% at a dose of 1.0 mg (p < 0.0001).

The safety profiles of the newer antidiabetic agents were generally similar to placebo, with no fatal adverse events reported; however, gastrointestinal issues and hypoglycemic events were the most common side effects, with alogliptin having the least frequency of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients. Palanisamy, S., Yien, ELH., Shi, LW., et al.[2020]

A study of 405 patients with type 2 diabetes showed that both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are safe to use alongside other glucose-lowering medications over a 12-month period.

The safety evaluation indicated no significant adverse effects on kidney function or liver enzymes, suggesting that these medications can be effectively integrated into standard diabetes treatment regimens without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists in the Standard of Care Treatment of Type 2 Diabetes Mellitus. Salmen, T., Bobirca, FT., Bica, IC., et al.[2023]

In a study of 78 patients with uncontrolled type 2 diabetes, dapagliflozin showed the most significant reduction in HbA1c levels after 24 months, with a mean change of -1.05%, compared to sitagliptin (-0.81%) and lobeglitazone (-1.08%).

Dapagliflozin also improved body composition by decreasing whole body fat percentage and increasing muscle percentage, while sitagliptin and lobeglitazone led to increases in body fat, suggesting dapagliflozin may be a better option for patients looking to improve their body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study. Hong, JH., Moon, JS., Seong, K., et al.[2023]

Patients with type 2 diabetes on dual therapy with metformin and sitagliptin (M-Sita) maintained their treatment for a significantly longer duration (43.2 months) compared to those on metformin and a sulphonylurea (M-SU) (20.2 months), indicating better long-term adherence with M-Sita.

Both treatment groups showed similar reductions in HbA1c levels (-0.6%), but the incidence of hypoglycaemia was notably lower in the M-Sita group (9.7%) compared to the M-SU group (21.0%), suggesting a safer profile for M-Sita.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment maintenance duration of dual therapy with metformin and sitagliptin in type 2 diabetes: The ODYSSEE observational study. Valensi, P., de Pouvourville, G., Benard, N., et al.[2022]

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