Mortality risk falls in patients with osteoarthritis who gradually lose weight
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Key takeaways:
- Slow-to-moderate weight loss via anti-obesity drugs was associated with lower all-cause mortality in patients with knee or hip osteoarthritis.
- A fast rate of weight loss showed no difference from stable weight or weight gain.
The risk for all-cause mortality decreases among patients with knee or hip osteoarthritis who achieve slow-to-moderate, but not fast, weight loss via anti-obesity medications, according to data published in Arthritis & Rheumatology.
“Overweight and obesity is an important risk factor for OA,” Jie Wei, PhD, of Xiangya Hospital and the Xiangya School of Public Health, Central South University, in Changsha, China, and colleagues wrote. “Previous studies have found a significant dose-response relationship between the percentage of weight loss and improvement of pain and function in patients with knee OA. There is consensus among international guidelines that weight loss is one of the core treatments for patients with knee and/or hip OA who are overweight or obese.
“To date, there is a paucity of data on all-cause mortality according to the rate of weight loss among patients with overweight or obesity and knee or hip OA,” they added.
To analyze how the rate of weight loss induced by anti-obesity drugs impacts all-cause mortality in overweight or obese patients with knee or hip OA, Wei and colleagues studied electronic health record data from the U.K.-based IQVIA Medical Research Database. The researchers emulated a targeted, randomized controlled trial using a cloning, censoring and weighting approach. Their analysis included 6,524 patients with hip or knee OA aged between 40 and 90 years. All included patients were either overweight or had obesity, and had experienced at least 1 year of continuous enrollment with general practitioners.
During the study, 5,916 included patients began taking orlistat, 488 initiated sibutramine (Merida, Abbott) and 120 initiated rimonabant (Acomplia, Sanofi-Aventis). The researchers compared patients’ baseline weight to their weight after 1 year of medication and categorized the rate of each patient’s weight loss as fast (greater than 10%), slow-to-moderate (between 2% and 10%), or stable/gaining weight.
According to the researchers, the all-cause mortality rates among patients with stable/weight gain, slow-to-moderate weight loss, and fast weight loss were 5.3%, 4%, and 5.4%, respectively. Compared with patients in the stable/weight gain group, HRs for all-cause mortality were 0.72 (95% CI, 0.56-0.92) for those who achieved slow-to-moderate weight loss, and 0.99 (95% CI, 0.67-1.44) for those who logged rapid weight loss. In addition, the researchers reported dose-response protective effects of weight loss on incident hypertension, type 2 diabetes and venous thromboembolism.
“Our results provide empirical evidence that a slow to moderate rate of weight loss induced by anti-obesity medications within 1 year lowers all-cause mortality,” Wei and colleagues wrote. “The rate of weight loss is consistent with the guidelines worldwide that gradual weight loss should be recommended for the treatment of obesity.
“Orlistat, accounting for the majority of anti-obesity medications in the current study, has been available for treating obesity for two decades and has a good safety profile,” they added. “Our finding that gradual weight loss by anti-obesity medications lowers all-cause mortality, if confirmed by future studies, could guide policymaking and improve the wellbeing of patients with overweight or obesity and knee or hip OA.”
Perspective
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Patricia Happel, DO
Weight loss medications that promote slow or moderate weight loss, such as Qsymia (phentermine/topiramate, Vivus) and Contrave (naltrexone/bupropion, Currax), have titration dose requirements based on the percentage of weight loss. For example, for the initial dose of Qsymia, if weight loss is less than 3% after 12 weeks, we can ascertain the quantity dose and re-evaluate after 12 weeks. Qsymia must be discontinued if weight loss is less than 5% on the maximum dose.
Most GLP-1 receptor agonist-based therapies are initiated at a low dose and then slowly advanced to avoid adverse gastrointestinal side effects, such as nausea, vomiting and/or GERD, which are likely secondary to delayed gastric emptying.
Loss of lean muscle mass is one major side effect of rapid weight loss. Losing weight is not always the same as losing fat. Although weight loss medications may delay gastric emptying, this can result in the patient ingesting a very low-calorie diet (less than 800 calories a day). This may help you lose weight fast, but a lot of the weight you lose may come from muscle and water.
Losing weight too fast may also slow down your metabolism. Your metabolism determines how many calories you burn each day. A slower metabolism means you burn fewer calories per day. Two reasons why the metabolism drops with a very low-calorie diet are a loss of muscle and a reduction in hormones that regulate your metabolism, such as thyroid hormone. If you are not eating enough calories regularly, you may be at risk for a nutritional deficiency. Some examples include fatigue, hair loss, poor immune function, and weak or brittle bones.
Two of the medications in this study, sibutramine (Merida, Abbott) and rimonabant (Acomplia, Sanofi-Aventis), have been withdrawn from the market in the United States due to adverse effects. In the sibutramine cardiovascular outcomes trial, an increase in major adverse cardiovascular events prompted its withdrawal in Europe and the United States. Rimonabant is an endocannabinoid receptor antagonist that reduces body weight and ameliorates some cardiovascular risk factors. However, adverse psychiatric side effects led to its withdrawal as well. Therefore, we need additional studies using the newer anti-obesity medications.
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