Medical Weight Loss in Older Persons with Obesity

Abstract

The prevalence of individuals with obesity or overweight has steadily increased over the past decades both worldwide, and in the United States. This trend is also evident in the older adult population, which has experienced a continuous rise in the number of individuals with overweight or obesity. This is relevant due to the impact of obesity in older adults’ quality of life, physical function, morbidity, and healthcare costs. This review aims to provide practical guidance and currently available approaches for healthcare professionals in managing this population. Both non-pharmacological methods such as intensive behavioral therapy, nutritional interventions, and physical activity, as well as anti-obesity medications, are discussed, with a focus on their potential positive and negative effects in older adults. Additionally, bariatric therapy is evaluated, including current procedures available and the associated results and risks in the older population.

Introduction:

Obesity: a pandemic across the globe and a great challenge to modern medicine

Obesity is a complex chronic disease whose multifactorial nature is characterized by genetic, physiological alterations, socio-cultural, behavioral, and environmental factors, which over time, lead to an imbalance between energy intake and expenditure. This process leads to an accumulation of excess adipose tissue that presents a risk to an individual’s health.¹ In the United States, the older adult population is steadily increasing. This trend also applies to the prevalence of body mass index (BMI) defined obesity among older adults which has increased in the past decade from 30.5% to 41.9%.² What is even more striking is that the rate of severe obesity, defined as a BMI ≥40 kg/m², has risen from 4.7% in 1999–2000, to 9.2% in 2017–2020.² Rates are disproportionately higher in women than men (11.5 vs. 6.9%).² Obesity is major driver of health care costs with the estimated annual medical costs in the United States approaching $173 billion in 2019, with anticipated costs likely to increase in subsequent years. Specifically, the estimated annual direct medical costs for older individuals with obesity will exceed that of an older adult without obesity, irrespective of class of obesity, until age 80.³

Consequences of obesity in older people

Several studies have shown that obesity significantly raises the risk of disability and reduces physical performance.^4,5 With age, there is an observed reduction in metabolic rate, physical activity level, and an increasing duration spent in sedentary activities.⁶ These components are contributing factors that lead to a progressive reduction in mobility, greater risk of developing frailty, and a predisposition to developing sarcopenia, the loss of muscle mass, strength, and physical function.^7,8,9 For instance, studies have shown a higher incidence of falls in older adults with obesity compared to those without obesity.^10,11 A meta-analysis assessing the association between obesity, and falls or multiple falls among older adults, found that older adults with obesity faced an elevated risk of falls compared to those without obesity (n=24 studies, relative risk 1.16 [95% Confidence Interval: 1.07–1.26]), and an increased risk of multiple falls (n=4 studies, relative risk 1.18 [1.08–1.29]).¹² Obesity in older adults has also been associated with a greater risk of disability, premature mortality and nursing home admissions.^8,13,14 A global study demonstrated consistent associations between obesity and an increased risk of all-cause mortality across four continents specifically focusing on the 70–89 age groups, where the hazard ratio increased with higher BMI (>25 kg/m²).¹⁵ This study observed that the risks associated with excess body weight were more pronounced in younger individuals than in older ones, and in men compared to women.¹⁵ Furthermore, both midlife obesity and those who are older adults experience a higher rate of nursing home admissions compared to those without normal BMI of 18.5–24.9kg/m².^16,17

Defining Obesity in Clinical Care

Treatment guidelines exist for persons who are overweight or have obesity from The Obesity Society, the American Association of Clinical Endocrinologists, and the American College of Endocrinology.^18,19 The physical examination relies on an assessment of anthropometric measures that include World Health Organizations and ethnic-specific BMI cutoffs, waist circumference, waist to-hip ratio, and/or waist-to-height ratio.^20,21,22 We caution, though, that BMI was initially used broadly as a population-based screening tool rather than for diagnosing obesity; thus its use in diagnosis should be used with great caution. A new American Diabetes Association standard of care guideline outlined that despite its ease in measurement, BMI is an imperfect measure of adipose tissue mass as it does not measure the distribution or function of adipose tissue nor does it consider the presence of health or health consequences.^23,24 Thus, a clinical diagnosis of obesity without the use of body composition measures should therefore be made using a concurrent overall assessment of adipose tissue mass (e.g., BMI) and its distribution (e.g., waist circumference, waist-hip-ratio) with the presence of consequences associated with health or well-being.²³ The poor diagnostic accuracy of BMI in older adults is highlighted in a study by Batsis et al. using the National Health and Nutrition Examination Survey data.²⁵ These authors compared the diagnostic performance of BMI with dual x-ray absorptiometry (DXA)-defined body fat, which was considered as the referent herein. Diagnostic accuracy of BMI worsened in both sexes with increasing age, and the sensitivity of a BMI ≥30kg/m² for identifying obesity decreased notably to 27% in men and 43% in women in the age group of 70–79 years. Importantly, while its specificity remained high in both sexes (>90%), its negative predictive value decreased with age in both men and women within the 70–79 age group. As a result, use of waist circumference of ≥102 cm for white men and ≥88 cm for white women, has been proposed as an alternative, particularly in persons with either a normal BMI or overweight.²³ Considering accounting for diverse ethnicities and location-specific thresholds in the measurement process may be needed.²⁵ To enhance diagnostic accuracy for adiposity, use of bioelectrical impedance analysis (BIA), DXA, computer tomography or whole-body magnetic resonance imaging can be considered. However, there are marked obstacles in routinely integrating them into clinical practice due to cost and availability. Use of BIA and DXA hold the most promise: BIA can be integrated in routine clinic workflows replacing a scale, and DXA can assess body composition when evaluating other evidence-based preventive measures such as bone mineral density. The strengths and limitations of each of these techniques is reviewed in detail elsewhere.^26,27,28

Evaluation of a Person with Obesity:

At an initial visit, a clinician should aim to evaluate a patient’s medical history and physical examination. As an example, we have outlined in Table 1 our proposed list of targeted clinical questions for use during patient evaluation. The clinician should evaluate the patient’s behavioral sphere to highlight any states of maladaptive eating patterns (binge eating, night eating) and the patient’s physical lifestyle, trying to understand if the individual has a sedentary lifestyle or if they engage in regular physical activity. An often-overlooked aspect in the management of older persons with obesity is the impact of polypharmacy and its propensity for medication-induced weight gain (Table 2). Part of routine management of an older adult should be to try to eliminate polypharmacy and deprescribe medications leading to weight gain. A routine laboratory evaluation should also evaluate for common cardiovascular risk factors and obesity-related conditions such as type 2 diabetes mellitus (T2DM), dyslipidemia, coronary heart disease, and stroke.

Table 1: Expert opinion of targeted clinical questions to consider during the evaluation of the patients.

Expert opinion on the related questions providers should consider asking in comprehensively evaluating a patient with obesity. The listed questions aim to provide a detailed understanding of the multiple factors that influence a patient’s weight and overall health.

Aspect	Questions
Weight History	- What is the patient’s current weight, and how does it compare to historical weights?
	- Can the patient provide a timeline of significant weight changes with dates and events?
	- How many weight loss attempts have been made?
Dietary Patterns	- What are the patient’s typical eating habits and dietary preferences?
	- Have there been significant changes in the patient’s diet over time?
	- In the last 12 months, did you (or other adults in your household) ever cut the size of your meals or skip meals because there wasn’t enough money for food?
	- In the last 12 months, did you ever eat less than you felt you should because there wasn’t enough money to buy food?
	- In the last 12 months, were you ever hungry but didn’t eat because you couldn’t afford enough food?
	- Was the food that [I/we] bought just didn’t last, and [I/we] didn’t have money to get more?
	- Was it never true that “[I/we] couldn’t afford to eat balanced meals?
	- Where does your food come from?
	- Who purchases your food?
Physical Activity	- What is the patient’s level of physical activity, and how has it changed over different periods?
	- Are there specific life events or health conditions affecting the patient’s ability to exercise?
Medical History	- Has the patient experienced any medical conditions or treatments that may influence weight?
	- Have there been recent changes in health status (medical or economic)?
	- Have there been hospitalizations and changes in functional status?
	- How many medications and what types of medications are being taken?
	- Are there medications with potential weight-related side effects?
Psychosocial Factors	- Are there emotional or psychological factors contributing to changes in eating behavior?
	- Have there been stressful life events coinciding with weight fluctuations?
Lifestyle Changes	- Have there been significant lifestyle changes (e.g., work, relationships) correlated with weight changes?
	- How have these changes correlated with weight changes?
Weight Loss or Gain Intentions	- Has the patient intentionally tried to lose or gain weight at any point?
	- What methods or strategies has the patient used for weight management?
Family History	- Is there a family history of weight-related issues or metabolic conditions?
	- How might familial influences have contributed to the patient’s weight history?
Cultural and Environmental Factors	- How has the patient’s cultural background influenced attitudes toward body weight?
	- Is there social support available?
	- What type of income do you have?/Do you receive social security income?
	- Are there environmental factors (e.g., neighborhood characteristics) impacting lifestyle and weight?
Medical Consultations	- Has the patient sought medical advice or interventions for weight management in the past?
	- What were the outcomes of these consultations, and were any recommendations followed?

Table 2: Medication-induced weight gain.

Common classes of medications with specific examples that detail the potential for weight gain and their associated side effects. We present the mean weight gain by class of medication and special attention is given to specific side effects such as increased appetite, fluid retention, and changes in metabolism.

Medication Class	Examples of Medications	Potential Weight Gain Side Effects	Mean weight gain
Antipsychotics	Olanzapine, Clozapine, Quetiapine	Significant weight gain, increased appetite	Ranging from three to nearly six pounds103
Steroid Hormones	Prednisone, Prednisolone, Dexamethasone	Fluid retention, increased appetite, redistribution of body fat	Low-dose prednisone over 2 years leads to a gain of 4% to 8% of their body weight104
Antidepressants	Amitriptyline, Mirtazapine, Paroxetine, Sertraline, Citalopram, Fluoxetina	Weight gain is a common side effect	Up to 10 kg of additional weight gain105,106
Antiepileptic Drugs	Valproic Acid, Carbamazepine, Gabapentin	Weight gain is a potential side effect	Receipt of carbamazepine leads to a mean weight gain of 2.35%, whereas patients receiving monotherapy with valproate experienced a meanweight gain of 7.08%.107
Antihistamines	Cyproheptadine, Diphenhydramine	Increased appetite, sedation, potential weight gain	Up to 10 kg of additional weight gain.108
Hormonal Contraceptives	Some birth control pills, Depo-Provera injection	Fluid retention, increased appetite	Up to 2 kg of additional weight gain.109
Lithium	Lithium carbonate (often used for bipolar disorder)	Weight gain is a common side effect	Mean weight gain of~10 kg in overweight.110
Antidiabetic Medications	Some medications like Pioglitazone, Insulin, Glyburide, Glipizide	Potential for weight gain, Increased appetite, hypoglycemia (with insulin)	Mean weight gain up to 10 kg in six months after initiating treatment.111
Beta-Blockers	Propranolol, Metoprolol, Atenolol, Carvedilol	Potential for weight gain due to altered metabolism and increased appetite	Mean weight gain is ~1.2 kilograms over six or more months.112

The primary laboratory evaluation that should be considered to assess cardiovascular risk includes the following: lipid panel (consisting of triglycerides, total, high- and low-density lipoprotein cholesterol). Other markers can be considered where appropriate, including lipoprotein (a), or when a more specific evaluation of thrombotic and hemorrhagic risk factors is suspected, such as complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (aPTT). Furthermore, consideration should be given to evaluating thyroid-stimulating hormone (TSH) levels and 25-OH Vitamin D levels. In select cases, uric acid can be considered although this is not routinely covered as part of routine testing for persons with obesity in the United States.

Non-Pharmacological Weight Loss Interventions:

The initial treatment strategy for older adults with obesity for intentionally losing weight and improving their physical function are multicomponent lifestyle interventions. These generally consist of intensive behavioral therapy, dietary changes to reduce energy intake, and engagement in physical activity.

Intensive Behavioral Therapy

The behavioral and psychological aspects of obesity can be addressed through cognitive behavioral therapy. This intervention plays an important role in assisting with modifying and sustaining a healthier lifestyle, serving to motivate patients and providing patients an understanding of the benefits of change, enhancing self-efficacy, and improving social support, all to more easily achieve the predetermined specific behavioral goals.²⁹ However, as observed in the LOOK-Ahead study, it is important to note that behavioral therapy alone may often be insufficient and may indeed lead to weight regain after initial weight loss of 5–10% due to diet and exercise behavioral interventions.^30,31 Unfortunately, to our knowledge, there are a paucity of studies regarding the effectiveness of behavioral therapy specifically in the older patient population.³¹ Several studies have evaluated a younger, adult population suggest that behavior-focused weight loss interventions yielded greater weight loss and weight maintenance compared to those without, over a period between 12 and 18 months.³² The establishment of both weight and behavioral goals are deemed to be crucial. Evidence from the Look AHEAD (Action for Health in Diabetes) trial indicates that individuals with larger month-to-month weight losses and sustained weight loss during the first year demonstrated better maintenance of weight loss over four years, independent of characteristics traditionally linked to weight loss success.³¹ Setting behavioral goals, following the SMART criteria (Specific, Measurable, Achievable, Reasonable, Time-bound), are equally important and include aspects such as plate composition and reducing fast-food consumption.³³ Self-monitoring, often involving the use of food diaries, activity records, and self-weighing, are all identified as critical elements in the success of behavioral weight loss programs. A systematic review of 22 studies evaluating the relationship between self-monitoring and weight loss in an adult population consistently showed an association between self-monitoring (of weight, diet, and exercise) and successful weight loss.³⁴ Other important strategies include social support, eating style, and stimulus control. In recent years, the widespread adoption of information and communication technologies (ICT) has extended even to older adults. This avenue has opened up new opportunities in this field. This trend makes the implementation of behavioral and lifestyle change interventions a feasible option.³⁵ Employing personalized digital health tools alongside blended care, which integrates eHealth with in-person interactions, shows promise in enhancing physical activity, exercise, and dietary habits, thereby aiding individuals in their endeavor to adopt healthier lifestyles. These technologies can effectively target the growing demographic of older adults, who are anticipated to progressively embrace internet usage and utilize mobile devices like smartphones and tablets.³⁶

Nutritional Interventions (Dietary changes, Caloric Restriction…)

Current recommendations for weight management emphasize the importance of healthy eating patterns. Advice includes a variety of nutrient-dense foods, limiting portions of high-energy foods, and reducing overall energy density. Generally, weight loss occurs when energy intake is less than energy expenditure (i.e., an energy deficit), resulting in the use of stored fat as an energy source. Following the 2020 US Dietary Guidelines, the specific differences recommended for older adults compared to younger individuals are that the former generally have lower calorie needs than the latter.³⁷ The guidelines also contain the link for the Dietary Reference Intakes (DRI) Calculator for Healthcare Professionals, which healthcare professionals can utilize to estimate an individual’s calorie requirements using factors such as age, gender, height, weight, and activity level. This lower caloric requirement stems from reduced physical activity, changes in metabolism, and/or age-related loss of bone and muscle mass. Generally, calorie needs are lower for females compared to males and for those who are older, smaller, and less physically active.^37,38 An energy deficit can be achieved with various strategies and dietary changes. As an illustration, in accordance with the 2020 US Dietary Guidelines for older adults, nutrient-rich foods and beverages supply essential vitamins, minerals, and other beneficial components for health, while maintaining low levels of added sugars, saturated fats, and sodium.³⁷

Many common diets fall into various categories such as balanced low-calorie diets, low-calorie versions of healthy diets (such as the Mediterranean Diet and Dietary Approaches to Stop Hypertension [DASH] diets), low-fat diets, low-carbohydrate and low glycemic index diets, high-protein diets, and very low-calorie diets.^{39,40,41,42,43,44} The Mediterranean Diet, characterized by a high intake of whole grains, fruits, vegetables, legumes, nuts, and extra virgin olive oil, along with moderate intake of poultry, dairy products, and alcohol, has been extensively studied.^39,45 The Dietary Approaches to Stop Hypertension diet emphasizes fruit, vegetables, and low-fat dairy, with <25% dietary intake from fat.⁴¹ Despite its high fat content of ~40%, the Mediterranean Diet is identified as one of the most effective in preventing diseases related to obesity.⁴⁵ Studies have demonstrated significant improvements in metabolic parameters, weight loss, long-term disability, cardiovascular mortality, and cognitive function among individuals adhering to the Mediterranean Diet. This association is attributed to the Mediterranean Diet ’s low intake of saturated fats and high intake of monounsaturated fats, which contribute to its provision of ample fiber, glutathione, and antioxidants. The Mediterranean Diet has further exhibited protective effects against cognitive functional decline or dementia in older individuals due to the consumption of various foods and nutrients that confer protection, such as fish, monounsaturated fatty acids, vitamin B12, folate, antioxidants, and moderate alcohol consumption.^45,46 It effectively lowers blood pressure, especially when compared to a diet rich in fruits and vegetables alone.⁴⁷ Even without calorie restriction, the Mediterranean Diet has been shown to support weight loss, making it a safer option for older adults to avoid muscle loss or strength, termed sarcopenia.⁴⁶ While dietary changes may be extremely effective in older adults, clinicians must be aware of micronutrient deficiencies that may occur during weight loss efforts. For instance, low-fat diets lead to a higher risk of fat-soluble vitamin deficiencies (A, D, E, K). In older adults, the current obesity guidelines emphasize the significance of vitamin D supplementation, however some recent studies raise questions about its actual usefulness, highlighting the need for further research to understand the effectiveness of vitamin D administration in these patients.^24,37,48 Vitamin D is particularly important for ensuring sufficient intake of vitamin D for the preservation of bone and muscle health and is reviewed elsewhere.^49,50 Moreover, an increasing number of studies emphasize the importance of a higher protein intake in older adults compared to the Recommended Dietary Allowance (RDA) of 0.8 g/kg/day. It has been highlighted that lean body mass (LBM) decreases when protein intake remains at the Recommended Dietary Allowance level, while an increase in protein intake may preserve lean body mass and function. To maximize such benefits, protein intake should be spread out over several meals, aiming for approximately 25 grams at each meal.⁵¹ Protein intake is crucial for older adults because of a phenomenon known as anabolic resistance. This term refers to a decreased responsiveness of muscle protein synthesis to typical anabolic signals in skeletal muscle tissue, which contributes to age-related muscle loss.⁵² Moreover, obesity and sedentary lifestyles can worsen anabolic resistance, partly due to insulin resistance and systemic inflammation.⁵³ This was demonstrated in a meta-analysis where it was found that older men and women, during a period of diet-induced energy restriction, preserve lean mass more effectively while losing body mass when they consume higher protein diets compared to normal protein diets.⁵⁴ Sources of protein include meat, fish, lentils, nuts, or beans. The 2020 US Dietary Guidelines also recommend that older adults increase their water intake and reduce consumption of sugary or alcoholic beverages, while being supported in their dietary choices by selecting foods they enjoy.³⁷

Physical activity:

Dietary interventions alone may have a harmful impact on muscle or bone physiology,⁵⁵ and without exercise, may be less effective in increasing muscle strength and preventing the loss of lean mass.⁵⁶ This is of particular relevance to older adults. Interventions that combine caloric restriction and physical exercise (aerobic and resistance) result in maximum fat loss and a minimal loss of muscle and bone. These interventions allow us to reduce the risks of isolated caloric restriction and improve an individual’s physical function.⁵⁷ Studies conducted by Villareal et al. have shown that weight loss through diet alone or in combination with exercise can improve physical function and reduce the risk of frailty in older adults with obesity.⁵⁸ However, their combination is more efficacious in improving physical function compared to each alone.⁵⁸ Combining aerobic and resistance training can improve cardiovascular fitness and attenuate the loss of lean and bone mass loss. They have also been shown to synergistically improve ectopic fat deposition as well as physical and metabolic function in older adults with obesity.⁵⁹ However, it is important to emphasize that the actual benefit of physical exercise in reducing weight loss-associated bone loss remains uncertain.^60,61 Data on the ability of exercise to mitigate bone loss secondary to caloric restriction are equivocal, and further studies will be necessary to gain a clearer understanding of this topic.^60,61

In clinical practice, we recommend patients adhere to the Physical Activity Guidelines for Americans consisting of aerobic and resistance training for older adults. Specific recommendations include engaging their larger muscle groups in a rhythmic manner for a sustained period, typically for at least 150 minutes per week at moderate intensity or at least 75 minutes at vigorous intensity. Resistance training involves muscle strengthening activities, with at least moderate intensity engaging all major muscle groups at least two days per week.⁶² These recommendations also align with the European Association for the Study of Obesity guidelines. For weight maintenance, it is suggested to engage in at least 200 minutes of moderate-intensity aerobic exercise and resistance training at least at moderate intensity.⁶³ Examples of aerobic workouts include walking, hiking, dancing, swimming, water aerobics, jogging, running, or bicycle riding. Examples of muscle-strengthening activities include exercises using exercise bands, weight machines, or hand-held weights, body-weight exercises such as push-ups, pull-ups, planks, squats, lunges, or activities like digging, lifting, and carrying as part of gardening. Physical activity programs should be personalized for each individual, considering the person’s characteristics physical limitations and preferences and which activity might be easiest for them to follow. Clinicians should also consider the possibility that older adults with obesity may find it challenging to adhere to the quantity and quality of exercise proposed by national guidelines. Several factors, including physical limitations due to aging and obesity, such as decreased muscle strength and balance loss, can hinder exercise adherence, especially among older adults. Moreover, there may be a lack of access to suitable facilities or programs due to the absence of a caregiver to accompany them, or the older adult may lack motivation to engage in an exercise program regularly.

Anti-Obesity Medications:

Emerging and promising therapies represent an exciting treatment modality that is increasingly being considered among older adults to achieve weight loss goals. Despite lifestyle intervention therapies having an ability to promote a 5–10% weight loss with concomitant improvements in comorbidities, major medical societies have endorsed the use of anti-obesity medications (AOMs) in treating obesity.²³ Pharmacotherapy can be used in addition to foundational lifestyle modifications when the latter insufficiently achieves weight loss goals.²³ Guidelines recommend that AOMs be considered for all individuals with a BMI ≥30 kg/m² or if a patient has a BMI ≥27 kg/m² in the presence of one or more comorbidities.^18,19.23,24 The American Association of Clinical Endocrinologists and the American College of Endocrinology guidelines published in 2016, however, explicitly state that there is insufficient evidence to recommend weight-loss medications in older adults; furthermore, more recent guidelines by other societies do not provide information that may be relevant to older adults.^20,23,24 Yet, the emergence of newer incretins begs the need to explore unresolved questions relevant to older adults.

Current selection of AOMs should be based on an individual older adult’s needs, comorbidities, renal and hepatic function and currently prescribed medications. Historically, the Food and Drug Administration has granted approval for several drugs to be used for long-term obesity management, and there are a number of additional Phase II and III medications currently in the pipeline.^64,65 Below, we describe each of the approved classes of medications and their implications to older adults (Table 3).

Table 3: Anti-obesity medications: approval, Dosage and Timing.

Trade names of anti-obesity medicines that are currently available to prescribers, including the year of approval in both the United States and Europe. Each medication details their potential for weight loss and possible side effects, including the dosage and correct timing for the administration of these medications. FDA, Food and Drug Administration; MAO inhibitors, monoamine oxidase inhibitors; MEN 2, multiple endocrine neoplasia 2; MTC, medullary thyroid carcinoma;

Name	Approved (FDA)	Approved (Europe)	Dosage	Timing	Expected weight loss in older adult	Side Effects	Contraindications
Orlistat (Xenical®, Alli®)	1999	1998	60–120mg	With meals or within one hour after meals	Between 5 and 10% after 1 year of treatment63,64,95	Gastrointestinal symptoms such as flatulence, fecal urgency, fatty/oily stool, oily evacuation and increased defecation	Chronic malabsorption syndrome, cholestasis, pregnancy. severe renal impairment and hypersensitivity to Orlistat
Naltrexone/bupropion (Contrave®, Mysimba®)	2014	2015	90mg/8mg	Typically once daily	Between 5 and 10% after 56 weeks of treatment65,66,95	Nausea, constipation, headache, vomiting, dizziness, dry mouth, diarrhea, insomnia and increased blood pressure	Uncontrolled hypertension, seizure disorder or history of seizures, opioid use, bulimia or anorexia nervosa and acute hepatitis or liver failure
Phentermine/topiramate extended-release (Qsymia®)	2012	Not approved	3.75/23mg initially, then 7.5/46mg daily	Typically in the morning	After one year of treatment, patients can lose 10.2%, with high dose65,95	Dry mouth, altered taste, constipation, insomnia, paresthesia, dizziness, increased heart rate, cognitive impairment	Glaucoma, hyperthyroidism, MAO inhibitors or within 14 days, history of cardiovascular disease, pregnant or breastfeeding women and hypersensitivity to any part of the combination drugs
Liraglutide (Saxenda®)	2014	2015	3.0mg	daily	Average of lost of 8% of their body weight after 56 weeks of treatment76,95	Nausea, vomiting, diarrhea, constipation, hypoglycemia, pancreatitis, gallbladder disease, kidney impairment	Personal or family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), hypersensitivity to Liraglutide
Semaglutide(Wegovy®)	2021	2021	2.4mg (once weekly)	once weekly	Mean weight reduction of 14.8% after 68 weeks of treatment77,78,95	Nausea, vomiting,abdominal pain, diarrhea, constipation, decreased appetite, hypoglycemia, pancreatitis and gallbladder disease	Personal or family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), hypersensitivity to Semaglutide
Tirzepatide (Zepbound®)	2023	2023	10mg or 15mg (once weekly)	once weekly	meanweight reduction from week 0 to 88 was 25.3%80	Gastrointestinal symptoms, nausea, vomiting, diarrhea, constipation, abdominal pain, difficulty in breathing, skin itching, rash, decreased appetite, hypoglycemia, pancreatitis, cholelithiasis	Personal or family history of medullary thyroid carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), hypersensitivity to Tirzepatide

Orlistat (Alli^®, Xenical^®):

Its mechanism of action involves inhibiting gastrointestinal lipases, which decreases the absorption of fat from the gastrointestinal tract. This action blocks the absorption of approximately one-third of the dietary fat consumed. Consequently, it reduces calorie absorption without affecting appetite. Clinical trials have consistently supported the efficacy of orlistat for weight loss and weight maintenance when used in conjunction with lifestyle modifications. However, the weight loss achieved with orlistat is typically modest.⁶⁶ A subset of older participants demonstrated that orlistat had similar efficacy between older (aged ≥65 years) and younger adults.⁶⁷ Orlistat has been shown to lower blood pressure, improved insulin sensitivity, and has a favorable impact on lipid profiles as a result of a reduction in the absorption of intestinal fat. Gastrointestinal intolerances were very common with over ~91% of participants experiencing them, and 8% needing to withdraw from the study.⁶⁸ Side effects associated with orlistat include steatorrhea, oily stools, oily spotting, fecal urgency, fecal incontinence, hyper-defecation, flatus with discharge, and deficiencies in fat-soluble vitamins A, D, E, and K. Particular attention must also be paid to comorbidities in older adults as orlistat is contraindicated in case of conditions such as cholestasis, severe renal impairment, or malabsorption disorders.⁶⁸

Naltrexone/bupropion (Contrave^®, Mysimba^®):

Bupropion is a dopamine and norepinephrine reuptake inhibitor that functions to activate central melanocortin pathways and has been used for treating mental health illness. Naltrexone is an opioid receptor antagonist that reduces the auto-inhibitory feedback loop of hypothalamic neurons and is activated by bupropion. These mechanisms lead to sustained weight loss. Several large clinical trials of Naltrexone/Bupropion combined with a diet and exercise program for one year resulted in greater percentage of weight loss than placebo.^69,70,71 However, while a 5% weight loss was observed, an insufficient number of older adults were included in their studies. Thus, conclusions cannot be drawn as to whether similar efficacy exists in older adults to younger adults.⁶⁹ Older adults may also be more sensitive to adverse effects on the central nervous system.⁶⁹ Side effects include nausea which can be attenuated by gradually increasing the dose over a four-week period.⁶⁸ Other common side effects include constipation, vomiting, dizziness, dry mouth, and headache. Contraindications include uncontrolled hypertension, seizure disorders, anorexia or bulimia nervosa, use of certain medications, such as monoamine oxidase inhibitor or opioid agonists. Patients taking this medication should also be monitored for symptoms of depression or suicidal ideation.⁶⁹

Phentermine/topiramate (Qsymia^®):

There is a lack of comprehensive studies examining the combination of phentermine with topiramate, and the mechanism by which they induce weight loss remains unclear.⁷² The current proposed mechanisms of action of the phentermine/topiramate combination include enhanced release of neurotransmitters like dopamine and norepinephrine resulting in decreased appetite, increased heat production, decreased energy efficiency, as well as enhanced glucose uptake and utilization by muscle, fat, and other tissues and finally inhibition of specific ionic receptor subtypes by topiramate.⁷² Results from clinical trials have demonstrated similar efficacy and safety between older and younger participants, few older adults were over the age of 65 years (n=254 [7%]).⁷³ In a meta-analysis, therapy led to an average weight loss of 7.73 kg overall compared to placebo which was dose-dependent.⁷² We advise clinicians considering this medication in older adults, to start with low doses due to the high risk associated with decreased liver, kidney, or heart function. Its main side effects are paresthesia, dizziness, dry mouth, constipation, dysgeusia, insomnia, anxiety and may cause an increase in resting heart rate of more than 20 bpm.⁷⁴ Older adults may be intolerant of this medication as phentermine-topiramate is not recommended for individuals with a significant history of cardiac problems, or in those with conditions such as hyperthyroidism, glaucoma, or those with a recent use of monoamine oxidase (MAO) inhibitors. In those patients who are intolerant or if it is ineffective, it is important to conduct a gradual taper to prevent seizure risk from sudden topiramate withdrawal.⁶⁸

Incretin therapies

Mechanistically, glucagon-like peptide-1 receptor agonists (GLP-1s) and combination GLP-1s with gastric inhibitory polypeptide (GIP) act centrally and peripherally by inhibiting food intake by inducing satiety and diminishing energy intake, hunger perception, all leading to reduced body weight.⁶⁸ Below, we describe both the older generation medication of liraglutide, and the newer medications that include semaglutide and tirzepetide. These medications have been extensively reviewed elsewhere but summarized, in part, below.^75,76,77

Liraglutide (Saxenda^®):

Liraglutide is a short-acting GLP-1s analog. To our knowledge, there are no studies with significant number of older adults enrolled; randomized controlled trials assessing 3mg of liraglutide included 232 (6.9%) patients aged over 65 and 17 (0.5%) patients over the age of 75.¹⁹ No differences in efficacy, safety, and pharmacokinetics have been observed between older and younger adult subgroups.¹⁹ In a subgroup of n=9 older adults (mean age 68 years) with overweight or obesity and T2DM, liraglutide led to a decrease in both fat mass and android fat, while simultaneously resulting in an increase in the skeletal muscle index over a 24-week peroid.⁷⁸ Side effects include nausea (25%), vomiting (12.2%), diarrhea (11.6%) and constipation (11.0%), and dyspepsia (6.4%).⁶⁸ Gradual dose increases have been shown to mitigate the side effects of nausea and vomiting.

Semaglutide (Wegovy^®):

The STEP clinical trial program explored the effectiveness of subcutaneous administration of semaglutide 2.4 mg once weekly for weight management in individuals with obesity or overweight.⁷⁹ A study evaluated the efficacy and safety of semaglutide compared to various treatments in both younger (<65 years) and older (≥65 years) adults with T2DM across the SUSTAIN 1–5 trials.⁸⁰ The effectiveness and safety profile in this combined analysis found a higher proportion experienced a weight loss of ≥5% and improved A1c with semaglutide compared to its comparators this trend was consistent across both age groups. Importantly, this analysis comprised of >850 older adults age ≥65 years).⁸⁰ A post-hoc analysis combining data from the SUSTAIN-6 and PIONEER-6 trials in older adults with obesity and T2DM demonstrated that semaglutide led to a significant decrease in triglyceride levels compared to baseline.⁸¹ Additionally, there was a 24% reduction in the risk of experiencing the first major adverse cardiovascular event (MACE) with semaglutide compared to placebo, regardless of the triglyceride subgroup.⁸¹ Similar proportions of patients in in both younger (<65 years) and older (≥65 years) adults groups experienced adverse events, with most categorized as mild to moderate. However, older adults had more gastrointestinal events leading to premature treatment discontinuations possibly indicating differences in tolerability.⁸⁰

Tirzepatide (Zepbound^®):

A multicenter, randomized, double-blind, parallel-arm study involving participants with T2DM, obesity with a mean age of subjects taking Tirzepatide of 61.1 years, subjects were divided into three groups (tirzepatide, semaglutide, or placebo). Compared with placebo, both semaglutide and tirzepatide led to significant, clinically relevant reductions in weight at 28-weeks, but tirzepatide led to significantly more weight loss than semaglutide (-11.2 kg vs. -6.8 kg).⁸² The adverse effects observed are consistent with those seen with other GLP-1 agonists, with a higher frequency of gastrointestinal issues such as nausea in 24% of participants, diarrhea in 20%, dyspepsia in 7%, and upper abdominal pain in 11%.⁸²

Impact of GLP-1s medication on lifestyle and bariatric surgery

The impact of these medications on lifestyle habits and bariatric surgery outcomes requires further investigation and is incompletely understood.⁸³ In particular, it is still unclear how the use of these drugs may alter dietary habits or affect physical activity.⁸³ These drugs induce a significant and rapid weight loss, primarily through the reduction of appetite and food intake by the patient. This leads to a modification of the lifestyle of the patient; therefore, the physician should carefully explain the mechanism of action of the drug and how it will influence the lifestyle habits of the patient, in addition to closely monitoring their diet. Currently, specific studies on the effect of these drugs on the diet of older adults with overweight or obesity during the weight loss process have not been conducted. Therefore, it is advisable to provide dietary counseling and carefully monitor the patient to ensure that weight loss is not solely due to a reduction in daily food portions, but is accompanied by an overall improvement in diet quality.⁸³ Similarly, it is necessary to assess the physical activity of patients treated with GLP-1, so that weight loss is not solely the result of caloric reduction, but is associated with a more active and healthy lifestyle.⁸³

Furthermore, these medications have been shown to be a safe and effective treatment for post-bariatric surgery, as evaluated in a recent study conducted by Jensen et al. on adult patients.⁸⁴ This study highlighted that the use of GLP-1 medications were safe and effective in achieving a clinically significant weight loss of approximately two-thirds of the weight regained after bariatric surgery.⁸⁴ This is a rapidly emerging area of research that will undoubtedly have additional data published in the coming year.

Comparison between the costs of GLP-1s and other weight loss medications.

The costs of weight loss medications in the United States vary significantly depending on the medication and factors such as insurance coverage and location. For example, Orlistat can range from $300 to $600 for a pack of 90 tablets of 120 mg, and the combination of naltrexone/bupropion, with an average price of a pack of 120 tablets ranging from $600 to $800, tends to be more affordable. In contrast, medications like liraglutide, which can cost between $1200 and $1400 for a pack of 5 injection pens, and semaglutide, with a cost that can exceed $1300 for a month of treatment, are more expensive.

Endoscopic and surgical bariatric therapies:

Bariatric surgery in older adults

In 2022, the American Society of Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) collaborated to issue a joint statement regarding the current scientific understanding of metabolic and bariatric surgery and its appropriate applications.⁸⁵ Bariatric surgery is recommended in individuals with a BMI ≥35 kg/m² “regardless of presence, absence, or severity of obesity-related conditions”, or it be considered for people with a BMI 30–34.9 kg/m² and high-risk comorbidities.⁸⁵ Surgery has been increasingly and successfully been performed in older adults, including those over 70 years of age.^85,86 Sleeve gastrectomy and Roux-en-Y are currently the most commonly performed procedures accounting for approximately 59.4% and 17.8% of all surgeries worldwide in 2019, respectively.^.86 Other procedures include adjustable gastric banding (AGB), biliopancreatic diversion with duodenal switch, and one-anastomosis gastric bypass.⁸⁵ The outcomes in older adults with advancing age have markedly improved. Edwards et al. examined the outcomes of bariatric surgery in 26,000 older adults undergoing either sleeve gastrectomy or Roux-en-Y, they highlighted how surgical interventions in older patients were generally safe with low rates of mortality (0.3%), overall morbidity (7%) and bariatric activity-related morbidity (4.5%).⁸⁷ Studies have also observed higher rates of complications, including leaks, infections, obstructions, and mortality, particularly within 30 days post-surgery, with gastric bypass compared to sleeve gastrectomy.^88,89,90 Moreover, when comparing the two procedures in older adults, gastric bypass was found to be superior in terms of hypertension remission and weight loss outcomes at 1-year follow-up.⁸⁹ Consequently, sleeve gastrectomy appears to be the preferred initial procedure for older adults due to its effectiveness in both weight loss and comorbidity remission.^89,90

In most instances, co-existing medical conditions were more predictive of complications than age alone. Additionally, sleeve gastrectomy was associated with lower odds of complications in older adults.⁸⁵ In a recent retrospective study, clinical characteristics and short-term 30-day outcomes following bariatric surgery, were compared between a group of young adults (aged <65 years) and older adults (aged ≥65 years) undergoing elective bariatric surgery between 2015 and 2019.⁹¹ Of a total of 751,607 patients, 5.3% (n=39,854) were older adults and they exhibited longer operative times and a higher incidence of nearly all 30-day complications, as well as increased mortality rates, compared to their younger counterparts. Pre-operative functional status emerged as a primary independent predictor of both complications and mortality, irrespective of age.⁹¹ Frailty, rather than age alone, is independently associated with higher rates of postoperative complications.⁹²

Minimally invasive surgical techniques, such as laparoscopic or robotic-assisted approaches, are now the preferred methods for such surgical interventions to achieve weight reduction (Table 4). Weight lost has proven to be substantially lasting for years and often greater than 60% percent excess weight loss (64.8% following Roux-en-Y gastric bypass and 53.8% following sleeve gastrectomy), with some differences depending on the type of surgery performed.⁹³ Importantly sleeve gastrectomy involves removing a significant portion of the stomach, this likely leads to reducing the hunger feeling of the patient by decreasing the serum levels of ghrelin, a hormone that stimulates the feeling of hunger, increases fullness, and positively impacts metabolism without anatomical manipulation or alterations.⁹⁴ This is in contrast to Roux-en-Y gastric bypass that creates a small stomach pouch and bypasses a portion of the small intestine, limiting food intake and absorption. Sleeve gastrectomy may be preferable to Roux-en-Y gastric bypass due to its simplicity, effectiveness, and safety. Adjustable gastric banding, once widely used, has declined in use despite its initial safety profile. As part of the preoperative evaluation, we suggest moving past chronological age for older adults. A comprehensive geriatric assessment which evaluates the patient holistically should include a risk/benefit analysis and be considered (Table 5). This includes a thorough assessment of nutritional status. A registered dietitian, specializing in bariatric surgery can comprehensively conduct an evaluation, gather information on weight history, identify any maladaptive eating behaviors, and address micronutrient deficiencies. Both pre- and post-operative nutritional counseling can prepare the patient for dietary changes that are expected after surgery. An assessment should include a mental health evaluation conducted by licensed mental health professionals to assess a patient’s ability to cope with the challenges associated with surgery, including changes in body image and lifestyle adjustments. Additionally, it is essential to identify stressors that may impact long-term outcomes, including financial, housing, and food insecurity, which may be even more important for older adults. These comprehensive evaluations help ensure that patients are adequately prepared for the physical, psychological, and social aspects of metabolic and bariatric surgery.

Table 4: Bariatric Surgery Procedures.

An overview of the current range of bariatric surgery procedures focusing on effectiveness, mean excess weight loss after one year in adults, as well as their respective pros and cons of treatment. Each surgical method undergoes an assessment regarding its efficacy in weight reduction, potential disadvantages, risks of complications, and the level of invasiveness associated. AGB, Adjustable Gastric Banding; BPD-DS, Biliopancreatic Diversion with Duodenal Switch; RYGB, Roux-en-Y Gastric Bypass; SG, Sleeve Gastrectomy; SADI-S, Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy.

Surgery Type	Effectiveness	% mean excess weight loss after one year in adults	Pros	Cons
Roux-en-Y Gastric Bypass (RYGB)	High	Mean excess weight loss after one year in adult 67.3%.113	Significant and long-lasting weight loss, improvement in comorbidities (e.g., diabetes, hypertension), restriction of food intake	Risk of nutritional deficiencies, risk of dumping syndrome, invasive procedure
Sleeve Gastrectomy (SG)	High	Mean excess weight loss after one year in adult 71.2%.113	Significant weight loss, improvement in comorbidities, reduced hunger sensation	Irreversible, potential for acid reflux, may increase risk of nutritional deficiencies
Adjustable Gastric Banding (AGB)	Moderate	Mean excess weight loss after one year in adult 71.2%.113	Less invasive, reversible, adjustable	Lower effectiveness compared to other procedures, risk of band slippage or erosion, frequent adjustments required
Biliopancreatic Diversion with Duodenal Switch (BPD-DS)	High	Up to 80% of excess weight loss after one year in adult.113	Significant weight loss, most effective for type 2 diabetes	Complex procedure, risk of nutritional deficiencies, potential for dumping syndrome
Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S)	High	Up to 95.5% of excess weight loss after one year in adult.114	Effective weight loss, improvement in metabolic health	Limited long-term data, potential for nutritional deficiencies, complex mechanism
Intragastric Balloon	Moderate	mean excess weight loss after one year in adult 46.2%.115	Less invasive, reversible	Temporary weight loss, risk of balloon deflation or migration, requires removal after a few months
Gastric Plication	Moderate	mean excess weight loss after one year in adult 84.4%.116	Less invasive, reversible	Less effective compared to other procedures, risk of complications such as leaks or strictures
Endoscopic Sleeve Gastroplasty	Moderate	achieved a 49.2% excess weight loss at 1 year.117	Less invasive, reversible	Temporary weight loss, risk of complications such as gastric perforation or bleeding

Table 5: Proposed checklist for Assessing Older Patients with Obesity for Bariatric Surgery.

Various steps are outlined to comprehensively evaluate the patient and communicate the proposed intervention and how this may positively or negatively intact their health. This proposed approach includes a thorough evaluation, communication of risks and benefits, nutritional status assessment, counseling for dietary changes, mental health evaluation, and identification of stressors.

1. Comprehensive Geriatric Assessment including a risk/benefit analysis	Evaluate the patient holistically, including a risk/benefit analysis of the intervention, assessing the various comorbidities of the patient and the potential risks they would face if undergoing the procedure.
2. Comprehensive Evaluation	Ensure that patients are adequately prepared for the physical, psychological, and social aspects of metabolic and bariatric surgery through comprehensive evaluationns
3. Explain to the patient the respective risks and benefits of the bariatric procedure	Explain to the patient the type of procedure they will undergo, discussing with him the positive and negative aspects of the intervention
4. Assessment of nutritional status	A registered dietitian specializing in bariatric surgery should conduct a comprehensive evaluation, gather weight history, identify maladaptive eating behaviors, and address micronutrient deficiencies
5. Pre- and Post-operative Nutritional Counseling	Provide both pre- and post-operative nutritional counseling to prepare the patient for dietary changes expected after surgery
6. Mental Health Evaluation	Conduct a mental health evaluation by licensed professionals to assess the patient’s ability to cope with challenges associated with surgery, including changes in body image and lifestyle adjustments.
7. Identification of Stressors	Identify stressors that may impact long-term outcomes, such as financial, housing, and food insecurity, which may be especially important for older adults

Consequences of weight loss in older adults

When an older adult begins to lose weight, the physician must always consider that any weight loss method has side effects that need to be taken into account. An important factor that always needs to be considered is whether weight loss is intentional or unintentional.⁹⁵ Many epidemiological studies base their findings without making this distinction, hence the effects of weight loss in older adults need to be studied more attentively.⁹⁵ Consequently, the data are heterogeneous, showing beneficial effects of weight loss on disability and cardiometabolic health, but also significant risks that might be overlooked by physicians.⁹⁵ Generally, every kilogram of body weight lost comprises approximately 75% fat mass and about 25% muscle mass.⁹⁶ Nevertheless, this leads to an improvement in physical function when older individuals lose weight under supervision. In fact, it is more likely that muscle mass is preserved during intentional weight loss but reduced during unintentional weight loss.⁹⁵

Nutritional interventions have been shown to lead to the significant loss of muscle mass, especially when consuming low-calorie diets. This can potentially weaken muscle strength and function in older adults and exacerbate frailty by accelerating the typical age-related decline in muscle mass.^55,97,98 In addition, rapid weight loss may also increase the risk of bone mineral density loss in the older adult population as has been observed in studies by Villareal et al. and in bariatric surgery studies in younger populations.^55,99

Conversely, if a patient is starting to engage in physical exercise, some of the main risks associated with this include a higher risk of injuries.¹⁰⁰ Older adults with obesity may be more susceptible to both muscular and joint injuries during exercise due to the additional weight they have to bear on their joints and muscle tissues.¹⁰⁰ Another risk, for which it is important for physical therapy to be supervised by healthcare personnel, is the risk of an increase in vasoconstrictor activity, in oxidative stress and in blood pressure and the risk of cardiovascular events due to the cardiovascular stress experienced by older adults with obesity during intense or prolonged exercise.¹⁰¹

Lastly, when evaluating the potential negative effects of anti-obesity medicines, in addition to the adverse effects described in analyzing individual drugs, the physician must consider in general that the utilization of these medications may entail certain consequences such as muscle and bone loss, nutrient deficiencies, and inadvertent and persistent weight loss.⁸³ The data, particularly in those with newer incretin therapies is limited in older adults and additional research is needed.⁸³ While anti-obesity medicines lead to improvements in cardiometabolic variables, clinicians must be cognizant of polypharmacy, drug interactions, and modified pharmacokinetics.¹⁰²

Conclusions:

The number of older persons classified as having obesity is increasing. However, even late in life, it is critically important to seek to prevent or delay the onset of ensuing morbidity and functional decline. The older adult with obesity has considerable multimorbidity and typically has high complexity that requires a comprehensive evaluation. Multifactorial approaches are currently available, each with its advantages and disadvantages. Findings thus far underscore that each individual is unique and requires personalized interventions tailored to individual needs and preferences. Additionally, it highlights the necessity of holistic, patient-centered care in obesity management. Better systems to deploy behavioral interventions are critically needed. Another important need is to obtain efficacy and safety data of anti-obesity medications used in older adults. While previous medications have been withdrawn from the market, we are optimistic that these newer classes hold promise. The use of emerging medications can and should be considered in the appropriate individual, however attention is needed particularly in this high-risk population before initiation, with slower dose escalation with close monitoring side effects. Bariatric surgery is an approved therapy by Medicare, it should be increasingly considered in appropriate candidates.

Abbreviations

BMI

body mass index

DXA

dual-energy X-ray absorptiometry

BIA

bioelectrical impedance analysis

T2DM

type 2 diabetes mellitus

AOMs

anti-obesity medications

GLP1

glucagon-like peptide 1 (GLP-1) agonists