Obesity Drug Shows Promise in Easing Knee Osteoarthritis Pain

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pastafan

Interventional Pain Physician
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NYT article, not what I've observed:​

Obesity Drug Shows Promise in Easing Knee Osteoarthritis Pain​

A large trial showed that semaglutide, sold as Ozempic for diabetes and as Wegovy for obesity, was better than any current medications in alleviating symptoms.


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A person holds a Wegovy injection pen in their hands.

A study of 407 people with obesity and knee osteoarthritis found those who got semaglutide had an average reduction of 41.7 points on a 100-point scale while those who got the placebo had a reduction of 27.5 points.Credit...M. Scott Brauer for The New York Times
Gina Kolata
By Gina Kolata
Oct. 30, 2024, 5:00 p.m. ET
The blockbuster drug semaglutide, sold as Ozempic for diabetes and as Wegovy for weight loss, now has a new proven benefit: It markedly soothed knee pain in people who are obese and have moderate to severe osteoarthritis, according to a large study.
The effect was so pronounced that some arthritis experts not involved with the clinical trial were taken aback.
“The magnitude of the improvement is of a scope we haven’t seen before with a drug,” said Dr. Bob Carter, deputy director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. “They had an almost 50 percent reduction in their knee pain. That’s huge.”
Dr. David T. Felson, an arthritis expert and professor of medicine at Boston University School of Medicine, said the study “changes the landscape,” adding that the pain reduction is greater than anything that can be achieved short of knee replacement surgery.

The results were published Wednesday in the New England Journal of Medicine.
Knee osteoarthritis affects nearly one in five Americans over the age of 45. Those with obesity are especially likely to develop it because their weight puts more stress on the knee and because obesity is associated with inflammation, which contributes to deterioration of cartilage.
There are no good medical treatments. Doctors can suggest patients take over-the-counter pain relievers like acetaminophen or ibuprofen. But long-term use of those medications can damagevital organs.
When the pain gets bad enough, many turn to knee replacement surgery.
“The good news is that surgery works for most people,” Dr. Carter said. “The bad news is that it is hugely expensive,” draining money from Medicare.

“We desperately need an effective way to treat knee pain,” he added.
In the 68-week study by Novo Nordisk, the maker of semaglutide, 407 people with obesity and knee osteoarthritis were randomly assigned to receive semaglutide in the form of Wegovy or a placebo. All patients also received exercise counseling and a reduced calorie diet.
The participants were mostly women. They had an average age of 56 and an average body mass index of 40.3, placing them firmly in the obesity category. They had to have knee pain and meet additional criteria for knee osteoarthritis like stiffness in the morning or knees that creaked or clicked when they walked. Their average pain on a 100-point scale was 70.9 at the start of the study.

“They were really in pain,” said Dr. Henning Bliddal, the principal investigator for the study and a rheumatologist at Copenhagen University Hospital. “They can’t exercise. You are trapped with knees like this.”
As expected, those who received semaglutide lost a significant amount of weight — an average of 13.7 percent of their starting weight — while those who got the placebo lost 3.2 percent of their starting weight.
The study’s primary outcome was a change in a standard measure called WOMAC, which assesses pain, physical functioning and stiffness on a 100-point scale. Those who got semaglutide had an average reduction of 41.7 points, while those who got the placebo had a reduction of 27.5 points.
Dr. Carter said that placebo participants often reported some degree of pain relief in studies. But, he added, the 41.7 point drop in the pain score of semaglutide participants “is huge.”
“To be frank, this is what we had hoped for,” Dr. Bliddal said. “But it even exceeded our expectations.”

Semaglutide controls blood sugar, curbs food cravings and reduces appetite. But it also has other effects — it reduces the risk of having a heart attack, stroke or cardiovascular death in people with heart disease, and it reduces the risk of kidney complications,heart issues and death in people with kidney disease.
Doctors and many patients have high hopes that the drugs can do much more, and they cite observational studies leading to clinical trials now underway testing the drugs for treating addiction, Parkinson’s disease, Alzheimer’s disease, depression and schizophrenia.
One potential reason for some of these effects — and a possible reason semaglutide helped people with knee osteoarthritis — is that the drug seems to quell inflammation, a central factor in a variety of diseases, including obesity and osteoarthritis.
Until fairly recently, investigators thought knee osteoarthritis was a mechanical problem. Cartilage wears down. The natural cushioning around the knee joint erodes. And heavier people are more at risk because their greater weight puts more strain on their joints.
But the more they studied arthritis, the more researchers discovered that mechanical damage may not be the only factor.

“The pain seemed out of proportion” to the damage actually observed in patients, said Dr. Felson, who wrote an editorialaccompanying the study.
And the pain is not just because cartilage that lies over the bone gets worn down, Dr. Carter added.
In arthritis, the lining of a thin rim of cartilage that lies over the bone becomes inflamed and sends pain signals to the spinal cord.
The bone itself also contributes to the pain. With arthritis the knee bone changes, Dr. Carter said. Pores open in the bones that didn’t use to be there, and nerves from the bone grow into the base of the cartilage.
Now, with the new study, it looks as if there is a way to treat both the mechanical problem caused by excess weight and the other factors with just one very expensive drug.

But Dr. Carter is hopeful. If it could be learned what exactly semaglutide is doing inside the joint, perhaps researchers could develop drugs that do the same thing and cost less.
“We never really understood where the pain was coming from,” he said. Now, perhaps, there is a handle to figure it out.

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I find the statement interesting that they found the pain out of proportion to the damage when we know of so many pain syndromes with severe pain and not much or indeed no damage meaning that proportionality to damage is not really a thing when it comes to pain..
 
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a kind of obvious study with potential ramifications regarding public perception.

the study's conclusions were appropriate.

the conclusions of articles pertaining the study are debatable.



we all know that weight loss improves knee pain.

patients on Wegovy lose more weight than those on placebo.

is it any surprise that people who get Wegovy and subsequently lose weight have less knee pain?



good study in terms of randomized, blinded, placebo controlled.

i would not be surprised that the main proponents of this study are the drug companies who will push to get these agents FDA approved for knee pain.
 
a kind of obvious study with potential ramifications regarding public perception.

the study's conclusions were appropriate.

the conclusions of articles pertaining the study are debatable.



we all know that weight loss improves knee pain.

patients on Wegovy lose more weight than those on placebo.

is it any surprise that people who get Wegovy and subsequently lose weight have less knee pain?



good study in terms of randomized, blinded, placebo controlled.

i would not be surprised that the main proponents of this study are the drug companies who will push to get these agents FDA approved for knee pain.

There's an independent disease-modifying effect of the GLP-1's beyond just biomechanical reduction of forces.

J Arthroplasty. 2023 Nov;38(11):2311-2315.e1.
doi: 10.1016/j.arth.2023.05.071. Epub 2023 Jun 4.

Does Semaglutide Use Decrease Complications and Costs Following Total Knee Arthroplasty?​

Matthew L Magruder 1, Vincent J H Yao 2, Ariel N Rodriguez 1, Mitchell K Ng 1, Victor Sasson 1, Orry Erez 1
Affiliations Expand

Abstract​

Background: Diabetes mellitus (DM) and obesity are associated with total knee arthroplasty (TKA) complications. Semaglutide, a medication for DM and weight loss, can potentially affect TKA outcomes. This study investigated whether semaglutide use during TKA demonstrates fewer: (1) medical complications; (2) implant-related complications; (3) readmissions; and (4) costs.
Methods: A retrospective query was performed using a National database to 2021. Patients undergoing TKA for osteoarthritis with DM and semaglutide use were successfully propensity score-matched to controls semaglutide = 7,051; control = 34,524. Outcomes included 90-day postoperative medical complications, 2-year implant-related complications, 90-day readmissions, in-hospital lengths of stay, and costs. Multivariate logistical regressions calculated odds ratios (ORs), 95% confidence intervals, and P values (P < .003 as significance threshold after Bonferroni correction).
Results: Semaglutide cohorts had higher incidence and odds of myocardial infarction (1.0 versus 0.7%; OR 1.49; P = .003), acute kidney injury (4.9 versus 3.9%; OR 1.28; P < .001), pneumonia (2.8 versus 1.7%; OR 1.67; P < .001), and hypoglycemic events (1.9 versus 1.2%; OR 1.55; P < .001), but lower odds of sepsis (0 versus 0.4%; OR 0.23; P < .001). Semaglutide cohorts also had lower odds of prosthetic joint infections (2.1 versus 3.0%; OR 0.70; P < .001) and readmission (7.0 versus 9.4%; OR 0.71; P < .001), and trended toward lower odds of revisions (4.0 versus 4.5%; OR 0.86; P = .02) and 90-day costs ($15,291.66 versus $16,798.46; P = .012).
Conclusion: Semaglutide use during TKA decreased risk for sepsis, prosthetic joint infections, and readmissions, but also increased risk for myocardial infarction, acute kidney injury, pneumonia, and hypoglycemic events.
Keywords: complications; diabetes mellitus; prosthetic joint infections; semaglutide; sepsis; total knee arthroplasty.


Effects of semaglutide on gut microbiota, cognitive function and inflammation in obese mice​

Jing Feng 1 2, Zhenjie Teng 3 4, Yu Yang 1, Jingzhen Liu 2, Shuchun Chen 1 2
Affiliations Expand

Abstract​

Objective: This study aims to investigate the effects of semaglutide on gut microbiota, cognitive function, and inflammation in obese mice.
Method: Twenty-four C57BL/6J male mice were randomly assigned to three groups: a normal-chow diet group (NCD, n = 8), high-fat diet group (HFD, n = 8), and HFD+semaglutide group (Sema, n = 8). The mice were fed a HFD to establish an animal model of obesity and then administered with semaglutide or saline for 12 weeks. Cognitive function was assessed using the Morris water maze test. Serum pro-inflammatory cytokines were measured. 16S rRNA gene sequencing technology was used to explore gut microbiota characteristics in obese mice.
Result: Obese mice showed significant cognitive impairment and inflammation. Semaglutide improved cognitive function and attenuated inflammation induced by a HFD diet. The abundance of gut microbiota was significantly changed in the HFD group, including decreased Akkermansia, Muribaculaceae, Coriobacteriaceae_UCG_002, Clostridia_UCG_014 and increased Romboutsia, Dubosiella, Enterorhabdus. Whereas semaglutide could dramatically reverse the relative abundance of these gut microbiota. Correlation analysis suggested that cognitive function was positively correlated with Muribaculaceae and Clostridia_UCG_014, and negatively associated with Romboutsia and Dubosiella. Romboutsia was positively correlated with TNFα, IL-6 and IL-1β. While Clostridia_UCG_014 was negatively related to TNFα, IL-6 and IL-1β.
Conclusions: For the first time semaglutide displayed different regulatory effects on HFD-induced gut microbiota dysbiosis. Semaglutide could regulate the structure and composition of gut microbiota associated with cognitive function and inflammation. Thus, affecting gut microbiota might be a potential mechanism of semaglutide in attenuating cognitive function and inflammation.
Keywords: Cognitive function; Glucagon-like peptide-1 receptor agonist; Gut microbiota; Obesity; Semaglutide.
 
so you are saying the people on semaglutide who had TKA had lower odds of sepsis and infection if they survived the MI or renal failure or pneumonia?


got it.


the second article is about mice and their poop.



neither specifically address the issue you are trying to raise - does semaglutide help independently with knee pain?
 
My team was having a very academic discussion about it, and I was surprised that it was considered ground breaking and generated so much discussion among physicians.

Increased weight on painful tissue = increased pressure = increased pain.
Decreased weight on painful tissue = decreased pressure = decreased pain.

Now we have an article to use as a tool to educate patients on how their weight impacts their pain, so the article is still a net positive.
 
In their defense, when someone is taking GLP-1 agonists, weight loss is pretty much inevitable
correct. If they aren't losing weight, it is a dosage/compliance issue 95% of the time.

"What is your dosage?"
-- 3

"3?"

--yeah, 3.

"3... 3 what? 3 isn't a typical dosage. 3 units would be way too little. 3mls way too much. 3mg way too much. What do you mean 3??"

--hmmm, I dunno. It isn't working though.
 
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