Drug trials involving human test subjects always involve some level of dropout. Dropout refers to how many subjects stopped participating before the planned end date – for any reason. In most instances, the level of dropout has negative connotations because it means that the subjects were either experiencing intolerable side effects or were not sticking to the strict guidelines that are necessary to ensure the validity of results (termed “nonadherence to protocol.”) Thus, the higher the dropout (usually expressed as “discontinued treatment”) level, the less likely is the acceptability of the drug as a financially viable product.
On the flip side, there are also rare instances where a low level of dropout is an indication that the drug being tested has better-than-expected results, and this gives great incentives for the drug to be promoted as a “fast track” solution. One such case was in the early trials of Ozempic (semaglutide) as a treatment for type 2 diabetes. In the SUSTAIN-1 trial, a full double-blind study of nearly 400 subjects, there was hardly any difference in the dropout rates of the subjects receiving a full dose of semaglutide and those receiving the placebo. Ozempic became a major player in the treatment of diabetes and then became a superstar thanks to its unexpected “side effect” of being a treatment for the much larger problem of obesity.
Semglutide has done it again!
A study published at the end of October 2024 detailed the results of a double-blind study over 68 weeks into the effects of semaglutide on obese subjects who also had been diagnosed with moderate pain due to knee osteoarthritis. Patients received either a dose of 2.4 mg of semaglutide weekly or a placebo. All participants were also placed on a reduced-calorie diet and received counseling on physical activity.
The primary measures of success were the percentage change in each subject’s body weight and the change in their pain score. This was measured according to the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), which grades pain on a scale of 0 to 100, with higher scores reflecting worse outcomes.
Over 400 participants were enrolled, with a mean age of 56, an average Body Mass Index (BMI) greater than 40, and a mean WOMAC pain score greater than 70. Just over 80% of the participants were women, which more or less reflects the incidence of osteoarthritis in the general population.
At the end of 68 weeks, the mean decrease in body weight was 13.7% with semaglutide and 3.2% with placebo. This aligns with the results of the many other semaglutide trials as a treatment for obesity. Much more significantly, the mean reduction in the WOMAC pain score was 41.7 points for the participants receiving semaglutide and 27.5 points for the placebo. Participants in the semaglutide group also improved the SF-36 physical-function score more than those in the placebo group. SF-36 measures eight scales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health.
The incidence of serious adverse events was similar in the two groups. Most importantly, semaglutide was so effective in promoting weight loss and lowering pain levels that many participants would no longer have qualified for inclusion in the knee osteoarthritis trial since their BMI and WOMAC pain scores were no longer high enough!
According to Dr. Bob Carter, deputy director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, “The magnitude of the improvement is of a scope we haven’t seen before with a drug. They had an almost 50 percent reduction in their knee pain. That’s huge.”
It’s known that reducing weight can have beneficial effects for people with osteoarthritis in the lower (ankle, knee, and hip) joints. But it’s now possible to attribute at least some of the remarkable benefits to semaglutide’s anti-inflammatory effects. These have already been established as part of semaglutide’s efficiency as a diabetes medication and in its later therapeutic form as a treatment for cardiovascular diseases.
Something special about semaglutide makes it particularly effective for treating knee osteoarthritis and probably for other conditions related to inflammation compared to other weight-loss medications. It’s still too early to know exactly how semaglutide works its magic to reduce knee pain, improve endothelial function, and reduce atherosclerotic plaque formation to protect against cardiovascular events. However, the results of studies establish “what semaglutide does” with great certainty, and in due course, the answer to “how semaglutide works its magic” will surely come along.
FAQs
How does semaglutide reduce cardiovascular risk?
The drug exerts a wide variety of beneficial effects in addition to lowering blood sugar levels and reducing body weight. It lowers blood pressure and blood lipids, such as cholesterol, and it has anti-inflammatory effects, all of which can reduce risk.
Does semaglutide improve kidney function?
Reducing inflammation in renal tissues may slow the progression of diabetic nephropathy. Outcomes of trials with semaglutide have demonstrated that these agents reduce CV risk and slow the rate of kidney function decline.
Does semaglutide reduce fatty liver?
The SLIM LIVER study showed that semaglutide taken for extended periods reduced liver fat by 31%almost one-third. Semaglutide may benefit the liver through its antioxidant and anti-inflammatory actions.
