Metformin for High Blood Sugar After Joint Replacement

Overseen By Ryland Kagan

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Oregon Health and Science University

Must be taking: Metformin

Disqualifiers: Advanced renal insufficiency, Liver cirrhosis, Congestive heart failure, Alcohol abuse, 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: Unknown

Duration: 3 months

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It seems you can continue your current medication regimen, including metformin, if applicable.

What data supports the effectiveness of the drug Metformin for high blood sugar after joint replacement?

Research suggests that Metformin, commonly used for type 2 diabetes, may reduce complications after knee replacement surgery and lower the risk of hip replacement in patients with diabetes and osteoarthritis. This indicates potential benefits for managing high blood sugar after joint replacement. ^{1 2 3 4 5}

How does the drug Metformin differ from other treatments for high blood sugar after joint replacement?

Metformin is unique because it is an oral medication that effectively lowers blood sugar without causing hypoglycemia (dangerously low blood sugar), unlike some other diabetes drugs. It is also the first-line treatment for type 2 diabetes, making it a well-established option for managing high blood sugar. ^{6 7 8 9 10}

What is the purpose of this trial?

The goal of this pilot, randomized, single-blind, placebo-controlled trial is to evaluate the feasibility of and provide preliminary information for a multi-center randomized controlled trial that will assess the effects of metformin on blood sugar control in patients after total hip or total knee replacement surgery. The primary objective of this study is to assess the feasibility of conducting a large, randomized trial with regards to timely recruitment, study drug administration, protocol adherence, and overall retention in patients undergoing total joint arthroplasty. Secondarily, the investigators aim to obtain preliminary estimates of group-specific outcome means and variances for primary and secondary outcomes of a larger future trial.

Research Team

Ryland Kagan

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for individuals with high blood sugar who are undergoing total hip or knee replacement surgery. It's a pilot study to see if it's possible to do a larger trial on how well metformin controls blood sugar after these surgeries.

Inclusion Criteria

I am having a hip or knee replacement surgery.

I can take pills and will follow the metformin plan, regardless of my diabetes status.

Exclusion Criteria

I have Type 1 diabetes.

Vulnerable populations: Children, pregnant women, neonates, decisionally impaired adults, prisoners

I have not abused alcohol in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oral metformin hydrochloride or placebo for blood sugar control in the perioperative period of total joint replacement surgery

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of surgical site and periprosthetic joint infections

3 months

Treatment Details

Interventions

• Metformin

Trial Overview The study is testing the drug metformin against a placebo (a pill without any medicine) in patients having joint replacement surgery. The goal is to gather initial data on whether metformin helps control blood sugar levels post-surgery.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Oral metformin hydrochloride

Group II: Placebo Placebo Group 1 Intervention

Placebo tablet

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?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Findings from Research

In a study of 40,694 patients with type 2 diabetes, those using metformin had a significantly lower risk of needing total knee or hip replacements, with adjusted hazard ratios indicating a 30% reduction in risk for TKR or THR.

The findings suggest that metformin may help reduce the need for joint replacements in diabetic patients, highlighting the need for further randomized controlled trials to confirm its effectiveness in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study. Zhu, Z., Huang, JY., Ruan, G., et al.[2023]

In a study of 716 elderly patients with hip osteoarthritis and type 2 diabetes, those using metformin had a significantly lower incidence of total hip arthroplasty (THA) compared to non-users (4.9% vs 25.0%) over a maximum follow-up of 10 years.

The analysis showed that metformin users had a much lower risk of needing THA, with a hazard ratio of 0.17, and this protective effect was even stronger with long-term use or higher dosages of metformin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Reduces the Risk of Total Hip Arthroplasty in Elderly Patients with Hip Osteoarthritis and Type 2 Diabetes Mellitus. Li, F.[2023]

In a study of over 41,000 individuals with type 2 diabetes, metformin treatment was associated with a 24% reduced risk of developing osteoarthritis (OA) compared to those treated with sulfonylureas.

While metformin showed a significant reduction in OA risk, there was no significant difference in the risk of joint replacement between the two treatment groups, suggesting that while metformin may help prevent OA, it does not necessarily affect the need for joint replacement surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea. Baker, MC., Sheth, K., Liu, Y., et al.[2023]

A single preoperative dose of 125 mg methylprednisolone (MP) in 134 patients undergoing hip and knee surgeries led to significantly higher plasma glucose levels at 2 and 6 hours post-surgery compared to a control group, indicating a temporary disruption in glycemic control.

The use of MP also resulted in impaired insulin secretion and increased insulin resistance 24 hours after surgery, although these effects normalized by 48 hours, suggesting that while MP may have short-term effects on glucose metabolism, they are not long-lasting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative High-Dose Methylprednisolone and Glycemic Control Early After Total Hip and Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial. Lindberg-Larsen, V., Kehlet, H., Bagger, J., et al.[2019]

In a study of 64,372 patients with type-2 diabetes undergoing total knee arthroplasty (TKA), those using metformin had significantly lower odds of complications such as periprosthetic joint infection and acute kidney injury compared to those not using metformin.

Metformin use was also associated with reduced hospital readmissions and shorter hospital stays, suggesting that it may improve overall outcomes for diabetic patients undergoing TKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Use Is Associated with Fewer Complications in Patients with Type-2 Diabetes Undergoing Total Knee Arthroplasty: A Propensity Score-Matched Analysis. Wilson, JM., Farley, KX., Broida, SE., et al.[2023]

Metformin is the first-line treatment for type 2 diabetes, especially for overweight patients, while glibenclamide is recommended for others; however, combining metformin with sulphonylureas may pose risks of excess mortality according to limited data.

Rosiglitazone and pioglitazone can effectively lower blood glucose levels but are associated with significant side effects, including weight gain and potential heart failure, leading to their recommendation only in controlled clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosiglitazone and pioglitazone: new preparations. Two new oral antidiabetics both poorly assessed. [2022]

In a study of 688 patients with type 2 diabetes, Avandamet® (rosiglitazone/metformin) was found to be more effective than metformin alone in reducing blood sugar levels, achieving significant reductions in HbA1c and fasting plasma glucose over 18 months.

However, while Avandamet® improved glycaemic control, it was associated with a significant decrease in bone mineral density at the lumbar spine and total hip compared to metformin, indicating a potential safety concern regarding bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients. Borges, JL., Bilezikian, JP., Jones-Leone, AR., et al.[2022]

Metformin is the preferred first-line treatment for diabetes due to its effectiveness in reducing mortality rates, while other antihyperglycemic drugs can be used if metformin is not suitable, but they lack evidence for improving long-term health outcomes.

Combining metformin with sulfonylureas increases the risk of hypoglycemia and mortality compared to combining it with thiazolidinediones, which are contraindicated in patients with severe heart failure or liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes update: new drugs to manage type 2 diabetes. Erlich, DR., Slawson, DC., Shaughnessy, A.[2022]

Metformin is an effective oral medication for treating non-insulin-dependent diabetes mellitus (type II diabetes) and does not cause hypoglycemia, which is a common side effect of other diabetes medications like sulfonylureas.

The drug is considered safe when proper precautions are taken, including monitoring liver and kidney function, and it has gained widespread use internationally, recently receiving FDA approval under the brand name Glucophage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. Tanja, JJ., Langlass, TM.[2013]

Metformin remains the first-choice glucose-lowering drug for type 2 diabetes, as other alternatives like sulphonylureas and gliptins have significant adverse effects and lack proven efficacy in preventing diabetes complications.

Many alternative medications, such as sulphonylureas and gliptins, not only lower HbA1c levels modestly but also carry risks of serious side effects, including hypoglycemia, cardiovascular issues, and potential cancer risks, making them less favorable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose-lowering treatment of type 2 diabetes. Part II--Glucose-lowering drugs after metformin: a choice based largely on adverse effects. [2022]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study. [2023]

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

Metformin Reduces the Risk of Total Hip Arthroplasty in Elderly Patients with Hip Osteoarthritis and Type 2 Diabetes Mellitus. [2023]

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

Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea. [2023]

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

Preoperative High-Dose Methylprednisolone and Glycemic Control Early After Total Hip and Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial. [2019]

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

Metformin Use Is Associated with Fewer Complications in Patients with Type-2 Diabetes Undergoing Total Knee Arthroplasty: A Propensity Score-Matched Analysis. [2023]

6. France pubmed.ncbi.nlm.nih.gov

Rosiglitazone and pioglitazone: new preparations. Two new oral antidiabetics both poorly assessed. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients. [2022]

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

Diabetes update: new drugs to manage type 2 diabetes. [2022]

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

Metformin: a biguanide. [2013]

10. France pubmed.ncbi.nlm.nih.gov

Glucose-lowering treatment of type 2 diabetes. Part II--Glucose-lowering drugs after metformin: a choice based largely on adverse effects. [2022]