Slow vs. fast weight loss: What are the safety concerns?

Overweight or obese people with hip or knee osteoarthritis (OA) may be better off with a slow to moderate rate of weight loss when using anti-obesity medications. That’s because rapid weight loss appears to be associated with a slightly increased of risk of all-cause mortality.Generally, symptomatic OA is known to be associated with an increased risk of all-cause mortality, but weight loss can improve function and pain. Various guidelines recommend weight loss as a key treatment for both hip and knee OA.But while some studies show an association between weight loss and a reduction in mortality, there is a paucity of data pertaining to the effects of how quickly weight loss is achieved, said Jie Wei, a professor of orthopedics at Central South University in Hunan, China. Dr. Wei was coauthor of a study in Arthritis & Rheumatology investigating rate of weight loss and all-cause mortality.Being overweight is a risk factor for developing OA in the first place. When it comes to weight loss some studies suggest there is a dose-response relationship between the amount of weight loss and improvement of pain and function. In short, the more weight loss, the better the symptoms. But does fast versus slow weight loss show any differences?The researchers conducted a population-based cohort study to determine what relationships there may be between the rate of weight loss among OA patients using anti-obesity medications and all-cause mortality over one year. Various secondary outcomes such as hypertension, type 2 diabetes (T2D), cardiovascular disease, and others were taken into account.The approach used in the study was a method that used observational data to emulate a targeted trial, according to Dr. Wei.Researchers used data from the years 2000 through 2022 from an electronic health database in the U.K., which included a range of details including sociodemographics, anthropometric characteristics, lifestyle factors, and details from visits to GPs, prescriptions, specialist referrals, laboratory test results and more. People with cancer or who underwent bariatric surgery were excluded.Patients aged 40 to 90 years with knee or hip OA were the focus of the analyses. The primary outcome sought was all-cause mortality over five-years after patients began anti-obesity medication. A total of 6,525 patients with hip or knee OA were included. They had a mean BMI of 38.1, and a mean weight of 104.5 kg. For the weight loss drugs used at the time, a total of 5,916 had started orlistat, 488 took sibutramine, and 120 used rimonabant. Sibutramine, and rimonabant were used in the earlier years of the study cohort before they were taken off the market.There were patients within each of those medication groups who had differing rates of weight loss. They were divided into one of three groups: a weight gain or stable group; slow-to-moderate rate of weight loss, or fast rate of weight loss.In the orlistat group, the number whose weight loss was stable, slow to moderate or fast were 2,791, 2,510 and 615 respectively. Those rates among the sibutramine users were 189, 235 and 64; and the rimonabant group had 45, 66 and 9, respectively, said Dr. Wei.The results showed that the five-year all-cause mortality rates were 5.3% for the weight gain or stable group; 4.0% for those who underwent slow-to-moderate weight loss, and 5.4% for the fast weight loss.Dose-response protective effects of weight loss were also seen when it came to incidents of hypertension, T2D, and venous thromboembolism. But there was a slightly higher risk of CVD, albeit not statistically significant, among the patients who experienced a fast rate of weight loss arm compared to those who gained weight or whose weight remained stable.The paper did not address how much impact the specific medications used may have affected the risks studied.“The number of patients who have used sibutramine and rimonabant for weight loss is small. As a result, we do not have adequate power to examine the relation of the rate of weight loss from sibutramine and rimonabant to all-cause mortality,” Dr. Wei told the Medical Post.However, the researchers did take a look at the data for the patients who used orlistat since it accounted for most of the anti-obesity medications used. “The results did not change materially” when it came to the relationship between rates of weight loss and the outcomes sought, said Dr. Wei. But there is a chance the medications may have had an impact on some patients.“It is possible because any medication has its treatment effect and potential side effect. However, we believe that among individuals with hip and knee OA plus overweight and obesity, the beneficial effect of anti-obesity medication, such as orlistat, compared with its side effect shall be greater,” Dr. Wei said. The medications included in this retrospective study have notable side effects. In fact, two were taken off the market in many countries part way through the study’s timeline. Sibutramine was withdrawn from both the U.S. and U.K. markets in 2010. It was removed after findings from a large study showed that high-risk overweight patients who had CVD with or without T2D and treated with sibutramine had a 16% increased risk of cardiovascular adverse events compared to placebo.Rimonabant It was never marketed in the U.S., but in Europe had been approved but then removed from the market in 2008. Is a cannabinoid-1 receptor blocker that was intended for use in obesity, smoking cessation, and other conditions. It was found to have dangerous psychological side effects of suicidality and depression.Orlistat is reported to have a better safety profile and is available.

Slow vs. fast weight loss: What are the safety concerns?

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