Wed Nov 13

New study suggests weight loss drugs like Ozempic could help with knee pain. Here’s why there may be a link

Written by Giovanni E. Ferreira, NHMRC Emerging Leader Research Fellow, Institute of Musculoskeletal Health, University of Sydney

The drug semaglutide, commonly known by the brand names Ozempic or Wegovy, was originally developed ^[1] to help people with type 2 diabetes manage their blood sugar levels.

However, researchers have discovered it may help with other health issues, too. Clinical trials show semaglutide can be effective for weight loss ^[2], and hundreds of thousands of people around the world are using it for this purpose ^[3].

Evidence has also shown the drug can help manage heart failure ^[4] and chronic kidney disease ^[5] in people with obesity and type 2 diabetes.

Now, a study published in the New England Journal of Medicine ^[6] has suggested semaglutide can improve knee pain in people with obesity and osteoarthritis. So what did this study find, and how could semaglutide and osteoarthritis pain be linked?

Osteoarthritis and obesity

Osteoarthritis is a common joint disease, affecting 2.1 million Australians ^[7]. Most people with osteoarthritis have pain ^[8] and find it difficult to perform common daily activities such as walking. The knee is the joint most commonly affected ^[9] by osteoarthritis.

Being overweight or obese is a major risk factor ^[10] for osteoarthritis in the knee. The link between the two conditions is complex ^[11]. It involves a combination of increased load on the knee, metabolic factors ^[12] such as high cholesterol and high blood sugar, and inflammation.

For example, elevated blood sugar levels increase the production of inflammatory molecules in the body, which can damage the cartilage in the knee, and lead to the development of osteoarthritis ^[13].

Weight loss is strongly recommended to reduce the pain of knee osteoarthritis in people who are overweight or obese. International ^[14] and Australian guidelines ^[15] suggest losing as little as 5% of body weight can help.

But losing weight with just diet and exercise can be difficult for many people. One study ^[16] from the United Kingdom found the annual probability of people with obesity losing 5% or more of their body weight was less than one in ten.

Semaglutide has recently entered the market as a potential alternative route to weight loss. It comes from a class of drugs known as GLP-1 receptor agonists and works by increasing a person’s sense of fullness.

Semaglutide for osteoarthritis?

The rationale for the recent study ^[17] was that while we know weight loss alleviates symptoms of knee osteoarthritis, the effect of GLP-1 receptor agonists was yet to be explored. So the researchers set out to understand what effect semaglutide might have on knee osteoarthritis pain, alongside body weight.

They randomly allocated 407 people with obesity and moderate osteoarthritis into one of two groups. One group received semaglutide once a week, while the other group received a placebo. Both groups were treated for 68 weeks and received counselling on diet and physical activity. At the end of the treatment phase, researchers measured changes in knee pain, function, and body weight.

As expected, those taking semaglutide lost more weight than those in the placebo group. People on semaglutide lost around 13% of their body weight on average, while those taking the placebo lost around 3% on average. More than 70% of people in the semaglutide group lost at least 10% of their body weight compared to just over 9% of people in the placebo group.

Osteoarthritis of the knee is the most common type of osteoarthritis. SKT Studio/Shutterstock ^[18]

The study found semaglutide reduced knee pain significantly more than the placebo. Participants who took semaglutide reported an additional 14-point reduction in pain on a 0–100 scale compared to the placebo group.

This is much greater than the pain reduction in another recent study ^[19] among people with obesity and knee osteoarthritis. This study investigated the effects of a diet and exercise program compared to an attention control (where participants are provided with information about nutrition and physical activity). The results here saw only a 3-point difference between the intervention group and the control group on the same scale.

The amount of pain relief reported in the semaglutide trial is also larger than that reported with commonly used pain medicines such as anti-inflammatories ^[20], opioids ^[21] and antidepressants ^[22].

Semaglutide also improved knee function compared to the placebo. For example, people who took semaglutide could walk about 42 meters further than those on the placebo in a six-minute walking test.

How could semaglutide reduce knee pain?

It’s not fully clear how semaglutide helps with knee pain from osteoarthritis. One explanation may be that when a person loses weight, there’s less stress on the joints, which reduces pain.

But recent studies have also suggested semaglutide and other GLP-1 receptor agonists might have anti-inflammatory ^[23] properties, and could even protect against cartilage wear and tear ^[24].

While the results of this new study are promising, it’s too soon to regard semaglutide as a “miracle drug” for knee osteoarthritis. And as this study was funded by the drug company that makes semaglutide, it will be important to have independent studies in the future, to confirm the findings, or not.

The study also had strict criteria, excluding some groups, such as those taking opioids for knee pain. One in seven Australians seeing a GP for their knee osteoarthritis are prescribed opioids ^[25]. Most participants in the trial were white (61%) and women (82%). This means the study may not fully represent the average person with knee osteoarthritis and obesity.

It’s also important to consider semaglutide can have a range of side effects ^[26], including gastrointestinal symptoms and fatigue.

There are some concerns that semaglutide could reduce muscle mass ^[27] and bone density ^[28], though we’re still learning more about this.

Further, it can be difficult to access.

I have knee osteoarthritis, what should I do?

Osteoarthritis is a disease caused by multiple factors, and it’s important to take a multifaceted approach ^[29] to managing it. Weight loss is an important component for those who are overweight or obese, but so are other aspects of self-management ^[30]. This might include physical activity, pacing strategies, and other positive lifestyle changes such as improving sleep, healthy eating, and so on.