Expert Opinion on Pharmacotherapy | 2021
How do you treat obesity in the elderly pharmacologically?
Abstract
Obesity prevalence is increasing worldwide in both males and females, in different regions, and across the age spectrum. It is usually defined by a body mass index (BMI) of 30 Kg/m or higher, and the proportion of individuals with obesity among adults aged ≥60 years in the U.S. is close to 40% [1]. As life expectancy is increasing worldwide, the aging obese population is also rapidly growing, capturing the attention of many researchers. However, several aspects of the epidemiological association between aging and obesity remain unresolved. Some operational definitions for many important variables in this field are not unanimously accepted. For instance, there is no universally accepted operational definition for ‘elderly’. On the other hand, due to the natural modifications in height and body composition associated with age, the validity of the 30 Kg/m cutoff point for obesity is a controversial matter, especially for patients aged more than 70–75 years [2]. Frailty is another age-related factor that conspires more accurate operationalization of the BMI cutoff value in older adults. However, frailty is difficult to define in operational terms. Obesity is associated with adverse outcomes in older patients with a BMI of 35 Kg/m and above, such as functional decline, increased fall risk, cardiovascular disease, arthropathy, and mortality. However, its impact in individuals with a BMI < 35 Kg/m remains controversial [3]. More consistently, the impact of obesity on quality of life has been identified in several studies, and it remains significant after adjusting for several comorbidities and other covariates [2]. Intentional weight reduction in older patients seems to be associated with some clinical benefit, as demonstrated in calorie restriction studies [4–7]. A meta-analysis of five clinical trials involving behavioral weight loss interventions without any pharmacological or procedural therapies lasting 6 months or longer in subjects aged 60 years and older was published in 2017 [4]. A caloric reduction ranging from 500 to 1000 kcal/ day was associated with weight losses from 0.5 to 10.7 kg in the intervention groups. These interventions resulted in an improvement in physical function and quality of life of the patients; therapies were more effective when associated with physical exercise [4]. Metabolic risk markers also improved. In a secondary analysis of randomized trials, a 600 kcal/day deficit associated with resistance training resulted in a modest weight loss (−5.5%) and a reduction in the frequency of metabolic syndrome components, compared to training alone [5]. Other studies have reported significant reductions in blood glucose and insulin resistance, as well as other markers of cardiovascular risk. In a very consistent manner, caloric restriction plus physical activity seems to reduce cardiovascular risk markers and improve quality of life in patients aged >60 years [5–7]. However, frail and older patients are usually underrepresented in these trials. In addition, the impact of these interventions on hard outcomes, such as cardiovascular events (cardiovascular death, nonfatal myocardial infarction, non-fatal stroke) or overall survival is far from being elucidated in this population [8]. On the contrary, the risk of adverse events potentially associated with weight loss, such as sarcopenia and fractures, remains to be elucidated [8,9]. Sarcopenia is particularly frequent in older patients with obesity, and it can be associated with poor outcomes and impaired quality of life [8]. Sarcopenic obesity is a relatively well-characterized clinical entity [2,4]. Even as the effect of treatment-related weight loss on sarcopenia remains unclear, it is a matter of great concern. Decreased bone quality is also frequent in this population, especially in patients with multiple comorbidities [8,9]. Similarly, the impact of intentional, treatment-induced weight loss on bone fragility is not completely clear, but it may have clinical relevance.