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

Trial Summary

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 data supports the effectiveness of the drug Metformin for type 2 diabetes?

Research shows that Metformin extended-release (ER) provides effective and well-tolerated blood sugar control for people with type 2 diabetes, with once-daily dosing being as effective as twice-daily dosing of the immediate-release version. Clinical trials demonstrated that Metformin ER maintained good blood sugar control for up to 48 weeks, either alone or with another diabetes medication. ^{1 2 3 4 5}

Is metformin generally safe for humans?

Metformin, including its extended-release form, is generally well-tolerated and safe for humans, but it should not be used by people with kidney problems. Common side effects are usually related to the stomach, like nausea or diarrhea. ^{1 6 7 8 9}

How does continuing or holding metformin differ from other diabetes treatments?

Continuing or holding metformin is unique because it focuses on whether to maintain or pause the use of metformin, a common first-line drug for type 2 diabetes, which is known for its effectiveness, weight neutrality, and affordability. Unlike other treatments that may involve adding new medications or switching to injections, this approach evaluates the impact of stopping or continuing an existing medication. ^{10 11 12 13 14}

What is the purpose of this trial?

A randomized study of continuing versus holding metformin during hospitalizations to internal medicine services to determine the effects on glucose control, acidosis, abdominal symptoms, length of stay, and mortality.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Germany 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Combination therapy with insulin glargine and exenatide: real-world outcomes in patients with type 2 diabetes. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Persistence of GLP-1 RA in combination with basal insulin among adults with type 2 diabetes in Canada. [2022]

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

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

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

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

7. Ireland 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. [2023]

8. Switzerland 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. [2020]

9. Switzerland 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. [2023]

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

Long-term management of type 2 diabetes with glucagon-like peptide-1 receptor agonists. [2020]

11. France pubmed.ncbi.nlm.nih.gov

Treatment maintenance duration of dual therapy with metformin and sitagliptin in type 2 diabetes: The ODYSSEE observational study. [2022]

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

Persistence of initial oral antidiabetic treatment in patients with type 2 diabetes mellitus. [2021]

13. England pubmed.ncbi.nlm.nih.gov

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

14. Switzerland pubmed.ncbi.nlm.nih.gov

[Metformin role in the treatment of type 2 diabetes in 2008]. [2013]