Type 2 diabetes: Metformin may significantly lower risk of joint replacement

  • Osteoarthritis is a common, chronic disorder causing pain and disability among older adults.
  • Type 2 diabetes mellitus is a well-known risk factor for osteoarthritis regardless of body mass index.
  • Metformin, the current leading type 2 diabetes medication, has shown the potential to improve insulin sensitivity, fight inflammation, and protect joints.
  • Researchers from Taiwan, China, and Australia have found that metformin use may curb osteoarthritis development and reduce the risk of total joint replacements.

Osteoarthritis (OA) is a degenerative joint disease that can cause pain, stiffness, or difficulty with movement. This condition, the most common form of arthritis among older adults, has no known medical prevention or cure.

OA causes the breakdown of cartilage, the tissue covering the ends of bones in the joints. The condition often leads to the need for total joint replacements in people with advanced cases.

By 2030, an estimated 3.5 million Americans will undergo total knee replacements (TKR) yearly. About 572,000 people will have total hip replacements (THR) annually by 2030.

Multiple factors contribute to OA onset, including type 2 diabetes.

Metformin, the most widely used type 2 diabetes medication, is reputed to reduce insulin resistance, counter inflammation, and retard cartilage degradation.

Finding insufficient evidence tying metformin use with lower risk of TKR or THR, an international research team aimed to find a link.

To this end, experts from China, Taiwan, and Australia analyzed data on 40,694 people diagnosed with type 2 diabetes.

Their investigation showed that metformin use in this population was strongly associated with a reduced risk of TKR or THR.

These findings appear in the Canadian Medical Association Journal.

Lead author Prof. Zhaohua Zhu, Ph.D., an associate professor at the Clinical Research Center at Zhujiang Hospital of Southern Medical University, and his colleagues explored data from a subset of Taiwan’s National Health Insurance Research Database (NHIRD).

They focused on patients at least 45 years of age diagnosed with type 2 diabetes between January 2000 and December 2012. Half of the subjects identified were women, and the mean age was 63.

The researchers matched 20,347 metformin users with 20,347 nonusers by age, gender, and time of diabetes diagnosis. They calculated the daily metformin dosages from the first prescription to 12 months and 24 months after the first prescription.

The team also considered diabetes severity, pain medications, insulin, and other diabetes medications such as sulfonylureas and thiazolidinediones.

They accounted for comorbidities, including obesity, hypertension, depression, COPD, rheumatoid arthritis, and osteoporosis.

They also categorized metformin users “as either continuing users (defined as participants who had ever used metformin, including within 9 months before index date), and previous users (defined as participants who had previously used metformin, but not within 9 months before index date) at 12 and 24 months after first prescription of metformin.”

Dr. Zhu and his team found that participants who used metformin had more severe type 2 diabetes than nonusers. These subjects were also more likely to use insulin or other diabetes medications and have hypertension and hyperlipidemia.

Looking at the 14-year follow-up period, they found that metformin use correlates with “a lower cumulative incidence probability of TKR, THR, or either total joint replacement.”

The incidence of knee or hip replacement throughout the study was 3.40 per 10,000 person-months among users, compared to 4.99 per 10,000 person-months among nonusers.

Previous and continuing users had fewer incidences of total joint replacement as well.

Speaking with Medical News Today, Dr. Zhu expressed confidence that his study’s results can extend to Chinese and other Asian populations. He also said that metformin’s protective effect was evident in the Osteoarthritis Initiative study, which included American participants.

However, the professor cautioned: “More studies are needed before we can generalize our findings to other nations [or ethnicities].” The study’s co-authors also call for randomized controlled clinical trials in OA patients to assess metformin’s effectiveness in minimizing the need for joint replacement.

Further, Dr. Zhu told MNT that metformin might be one of several helpful drugs that could improve OA symptoms.

“Some novel anti-hyperglycemic agents, particularly GLP-1 analogues, might produce similar or even better protective effects for people with OA,” he said.

MNT discussed this study with Medhat Mikhael, MD, pain management specialist and medical director of the non-operative program at the Spine Health Center at MemorialCare Orange Coast Medical Center in Fountain Valley, CA. He was not involved in the research.

Dr. Mikhael was impressed and surprised by these findings, as he shared with MNT:

“Although I knew the link between the development of type 2 DM and development of OA, I did not think that the use of metformin in those patients can be effective enough to reduce the risk of the need for joint replacement because of the improvement in the insulin resistance status, and the great anti-inflammatory effect.”

He noted that metformin’s potential to reduce inflammation and preserve cartilage may help relieve OA symptoms. Moreover, he mentioned: “I also believe that the control of diabetes through glucose lowering and improving insulin resistance allows patients to perform proper exercises so they lose weight in addition to the weight loss that metformin offers. All that helps reduce the symptoms and tend to lower the need for joint replacement among diabetic patients.”

Before suggesting metformin as a potential OA treatment, Dr. Mikhael said:

“I would need to know the difference in the use of other medications like anti-inflammatory NSAIDs and painkillers among both groups to find out if the use of metformin in these patients not only reduced their risk for joint replacement but also reduced their needs using pain killers, particularly narcotics.”

The multinational team is exploring metformin’s potential to help people with OA and obesity. Dr. Zhu shared with MNT: “Meanwhile, our team has been conducting a multi-center randomized control trial to examine the effect of metformin on overweight OA patients, which would provide high quality evidence.”

The experts are also utilizing “real-world data” to determine the effectiveness of other medications, including SGLT-2 and Dpp4i. They expect to publish preliminary results in March 2023.

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