Weight Reduction Programs and Devices

Number: 0039

Policy

Note: Many Aetna plan benefit descriptions specifically exclude services and supplies for or related to treatment of obesity or for diet and weight control. Under these plans, claims for weight reduction medications and for physician supervision of weight reduction programs will be denied based on that exclusion. Please check benefit plan descriptions for details.

Clinician Supervised Weight Reduction Programs

Aetna considers up to a combined limit of 26 individual or group visits by any recognized provider per 12-month period as medically necessary for weight reduction counseling in adults who are obese (as defined by BMI greater than or equal to 30 kg/m²Footnotes**). The number of medically necessary visits for obese children are left to the discretion of the member's physician.

Medical Evaluation

Aetna considers the following services as medically necessary for the evaluation of overweight or obese individuals:

• Complete blood count
• Comprehensive history and physical examination
• Dexamethasone suppression test and 24-hour urinary free cortisol measures if symptoms suggest Cushing's syndrome.
• Electrocardiogram (EKG) – adult
• Glucose tolerance test (GTT)
• Hand x-ray for bone age – child
• Lipid profile (total cholesterol, HDL-C, LDL-C, triglycerides)
• Metabolic and chemistry profile (serum chemistries, liver tests, uric acid) (SMA 20)
• Thyroid function tests (T3, T4, TSH)
• Urinalysis.

Very Low Calorie Diets (VLCD)

For obese members who have been prescribed a very low calorie diet (VLCD) (less than 799 Kcal/day) (e.g., Optifast, Medifast), the following services are considered medically necessary for up to 16 weeks after initiation of the VLCD:

• EKG after 50 lbs of weight loss; and
• Lipid profile at the beginning and end of the VLCD program; and
• Serum chemistries and liver function tests (SMA 20) weekly during the rapid weight loss phase of the VLCD, then every 2 weeks thereafter up to 16 weeks.

Note: VLCDs extending beyond 16 weeks are subject to medical review to determine if additional services are medically necessary.

Notes: Prepackaged food supplements or substitutes and grocery items are generally excluded from coverage under most benefit plans.  Diagnostic tests required by, for or as a result of non-covered weight loss programs (e.g., those not requiring physician supervision) are not covered.  Please check benefit plan descriptions for details.

Weight Reduction Devices

Aetna considers the FDA-cleared weight reduction device, Plenity (Gelesis, Inc.), as medically necessary to aid in weight management in overweight and obese adults with a Body Mass Index (BMI) of 25-40 kg/m², when used in conjunction with diet and exercise. 

Weight Reduction Medications

Note: Many Aetna benefit plans specifically exclude coverage of weight reduction medications under the pharmacy benefit and/or under the health benefits plan. The medical necessity criteria set forth below do not apply to health plans that specifically exclude services and supplies for or related to treatment of obesity or for diet or weight control. Under these plans, claims for weight loss drugs will be denied based on this exclusion. 

For weight reduction medications and associated criteria, see Aetna Pharmacy CPB on Antiobesity Agents: Antiobesity Agents PA Policy.

For Aetna’s clinical policy on surgical management of obesity, see CPB 0157 - Obesity Surgery.

Excluded Services

Aetna considers the following interventions/procedures as experimental and investigational for weight reduction:

• Acupuncture for weight loss
• Body plethysmography (diagnostic study)
• Low-level laser therapy
• Dual-energy X-ray (DEXA) body composition (diagnostic study)
• Fat mass and obesity-associated (FTO) genotyping
• FTO genotyping
• Gastric electrical stimulation (see CPB 0678 - Gastric Pacing / Electrical Stimulation and Gastric Per Oral Endoscopic Myotomy)
• Human chorionic gonadotropin (HCG) or vitamin injections for weight loss
• Indirect calorimetry (also known as oxygen uptake analysis; diagnostic study)
• Normobaric hypoxic conditioning.

Whole body calorimetry and composition and whole body bioimpedance analysis are considered experimental and investigational for weight reduction and other indications.

Hospital confinement is considered not medically necessary for a weight reduction program.

Note: Under most benefit plans, the following services and supplies for weight reduction are specifically excluded from coverage (please check benefit plan descriptions for details)

• Exercise programs or use of exercise equipment
• Rice diet or other special diet supplements (e.g., amino acid supplements, Optifast liquid protein meals, NutriSystem pre-packaged foods, Medifast foods, or phytotherapy), see CPB 0061 - Nutritional Support 
• Weight Watchers, Jenny Craig, Diet Center, Zone diet, or similar programs.

Background

Weight Reduction Medication and Supplements

Weight reduction medications should be used as an adjunct to caloric restriction, exercise, and behavioral modification, when these measures alone have not resulted in adequate weight loss. Factors influencing successful weight loss are weight loss during dieting alone, adherence to diet, eating habits, motivation and personality.

Weight loss due to weight reduction medication use is generally temporary. In addition, the potential for development of physical dependence and addiction is high. Because of this, their use to aid in weight loss is not regarded as therapeutic, but rather involves a risk/benefit ratio, which makes it medically inappropriate in most cases.

Individuals who cannot maintain weight loss through behavioral weight loss therapy and are at risk of medical complications of obesity are an exception to this; for these persons, the risk of physical dependence or other adverse effects may present less of a risk than continued obesity. For such individuals, use of weight reduction medication may need to be chronic.

Tests with weight loss drugs have shown that initial responders tend to continue to respond, while initial non-responders are less likely to respond even with an increase in dosage. If a person does not lose 2 kg (4.4 lb) in the first four weeks after initiating therapy, the likelihood of long-term response is very low. If weight is lost in the initial 6 months of therapy or is maintained after the initial weight loss phase, this should be considered a success and the drug may be continued.

The following medications have been approved by the FDA for weight reduction:

• Benzphetamine (Didrex),
• Diethylpropion (Tenuate),
• Liraglutide (Saxenda),
• Naltrexone and bupropion (Contrave)
• Orlistat (Xenical, Alli),
• Phendimetrazine tartrate  
• Phentermine (Adipex-P), and
• Phentermine and topiramate (Qsymia).

Didrex tablets contain the anorectic agent benzphetamine hydrochloride. Didrex is indicated in the management of exogenous obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction in patients with an initial body mass index (BMI) of 30 kg/m2 or higher who have not responded to appropriate weight reducing regimen (diet and/or exercise) alone. Didrex is contraindicated in patients with advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to sympathomimetic amines, and glaucoma. Benzphetamine should not be given to patients who are in an agitated state or who have a history of drug abuse. Hypertensive crises have resulted when sympathomimetic amines have been used concomitantly or within 14 days following use of monoamine oxidase inhibitors. Didrex should not be used concomitantly with other CNS stimulants. Didrex may cause fetal harm when administered to a pregnant woman. Didrex is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Didrex hould not be used in combination with other anorectic agents, including prescribed drugs, over-the-counter preparations and herbal products. Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine has been reported. Possible contributing factors include use for extended periods of time, higher than recommended dose, and/or use in combination with other anorectic drugs. However, no cases of this valvulopathy have been reported when benzphetamine has been used alone (Pfizer, 2020).

Contrave is a combination of naltrexone, an opioid antagonist, and bupropion, an aminoketone antidepressant, indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia). Warnings include suicidal thoughts and behaviors (Nalpropion, 2019).

Orlistat is a reversible inhibitor of gastric and pancreatic lipases. Binding of orlistat to these enzymes forms inactive intermediates in the gut. This non‐systemic action does not allow fat to be broken down and absorbed. Rather, an oil phase that includes triglycerides and cholesterol is excreted in feces. This effect may lead to weight loss. Xenical (orlistat) is indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced‐calorie diet. It is also indicated to reduce the risk for weight regain after prior weight loss. Orlistat is available as Xenical in 120mg capsules and as Alli in 60mg capsules. Alli is available over‐the‐counter. Recommended dosage of Xenical is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal). Supplementation with fat‐soluble vitamins (A, D, E, K) and beta carotene is recommended in some patients as these may not be adequately absorbed when given orlistat therapy. Comorbidities associated with obesity appear to be improved through weight loss in orlistat treated patients. However, studies are limited in time span and comparison with other pharmacologic agents is needed to determine place in therapy. Dosage reductions of hypoglycemic agents may be necessary when glycemic control is improved with weight loss. Risk of cholelithiasis increases with substantial weight loss. Pharmacologic treatment of exogenous obesity should be adjunctive to caloric restriction, increased physical activity, and behavioral modification.

Other than orlistat (Xenical), which is approved for use in adolescents aged 12 years or older, weight reduction medications have not been proven to be safe and effective for treatment of obesity in children and adolescents.  Orlistat (Xenical) is contraindicated in persons with chronic malabsorption syndromes and cholestasis. Qsymia (phentermine and topiramate) is contraindicated in pregnancy, glaucoma, hyperthyroidism, hypersensitivity to sympathomimetic amines, and within 14 days of taking monoamine oxidase inhibitors. Belviq (lorcaserin) is contraindicated in pregnancy. Other drugs listed in this policy are contraindicated in the following conditions: hypertension, atherosclerosis, coronary artery disease, and stroke.

Qsymia is a combination of phentermine, a sympathomimetic amine anorectic, and topiramate extended-release, an antiepileptic drug, indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of: 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia. Limitations of use includes the effect of Qsymia on cardiovascular morbidity and mortality, which has not been established. The safety and effectiveness of Qsymia in combination with other products intended for weight loss, including prescription and over-the-counter drugs, and herbal preparations, also has not been established (Vivus, 2018).

Ioannides-Demos et al (2006) stated that there is limited safety and effectiveness data for amfepramone (diethylpropion) and phentermine and their approvals for the management of obesity are limited to short-term use.  The authors stated that, although the benefit-risk profiles of sibutramine and orlistat appear positive, sibutramine continues to be monitored because of long-term safety concerns.  The safety and effectiveness of currently approved drug therapies have not been evaluated in children and elderly patient populations.

On October 8, 2010, Abbott Laboratories announced that that it was withdrawing its diet drug Meridia (sibutramine) from the United States, Australian and Canadian markets as a consequence of heightened concerns that the medication can trigger heart attack or stroke, especially in patients with underlying cardiovascular disease.

Balázs (2010) stated that the rapidly increasing prevalence of over-weight and diabetes mellitus is a serious global threat to healthcare. Nowadays, medicinal plants and natural treatments are becoming more and more popular. Diabetes has historically been treated with plants or plant-derived formulations in different cultures, mainly in China, Asia and India. Different mechanisms for the anti-diabetic effect of plants have been proposed: increased release of insulin, reduction of intestinal glucose absorption, as well as enhancement of glycogen synthesis. The scientific evidences for most of these plants are still incomplete. The large market for plant remedies has resulted in an array of unauthorized products or marketed as dietary supplements and, at the same time, no reliable pharmaceutical-grade products are registered for this purpose.

Belviq was approved in June 2012 by the FDA as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related co-morbid condition, and was launched in the United States in June 2013. However, in 2020, Eisai Inc. announced that it will voluntarily withdraw from the market and discontinue sales of Belviq (lorcaserin HCl) CIV and Belviq XR (lorcaserin HCl) CIV in the U.S. This action is due to a request from the U.S. Food and Drug Administration (FDA), based on the Agency’s completed analysis of data from the CAMELLIA-TIMI 61 trial. CAMELLIA-TIMI 61 was a randomized, double-blind, placebo-controlled clinical trial to study approximately 12,000 men and women over five years with established cardiovascular disease or at high risk for cardiovascular disease. This study was conducted at over 400 sites in eight countries including the U.S. The study aimed at evaluating long-term cardiovascular and metabolic safety and efficacy of lorcaserin as part of a post-marketing requirement by the FDA. Although in this trial lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo, the FDA reviewed that data and concluded that the potential risks of lorcaserin outweight its benefits. More specifically, the FDA noted there was a numberical imbalance in the number of patients with malignancies. FDA's analysis of the study found that during the course of the trial, 462 (7.7 percent) patients treated with lorcaserin were diagnosed with cancers compared to the placebo group, in which 423 (7.1 percent) patients were diagnosed with cancers (Eisai, 2020). In addition, there were more reports of severe hypoglycemia among patients taking lorcaserin than placebo (0.4 percent vs 0.1 percent) (Echouffo Tcheugui and Ahima, 2019). The FDA’s February 13, 2020 Drug Safety Communication advised patients to stop taking Belviq and Belviq XR and talk to their health care professional about alternative weight-loss medications and weight management programs (Eisai, 2020). Although the investigators of the CAMELLIA-TIMI 61 study did not find the same cancer data in its own analysis as that of the FDA, the manufacturer decided to withdraw the medication after the FDA issued a warning that Belviq might be associated with increased cancer risk.

Garvey et al (2012) conducted a placebo-controlled, double-blind, 52-week extension study to evaluate the long-term efficacy and safety of controlled-release phentermine/topiramate (PHEN/TPM CR) in overweight and obese subjects with cardiometabolic disease.  Subjects were randomly assigned to placebo, 7.5 mg phentermine/46 mg controlled-release topiramete, or 15 mg phentermine/92 mg controlled-release topiramate.   Of the 676 extension study participants, 84% completed the study.  At week 108 PHEN/TPM-CR was associated with significant, sustained weight loss.  Significantly more PHEN/TPM CR-treated subjects at each dose achieved ≥ 5%, ≥ 10%, ≥ 15%, and ≥ 20% weight loss compared with placebo (P < 0.001).  The authors therefore concluded that PHEN/TPM CR, in conjunction with lifestyle modification, may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease.

Whiting et al (2014) stated that capsaicinoids are a group of chemicals naturally occurring in chilli peppers with bioactive properties that may help to support weight management.  These investigators conducted a meta-analysis investigating the potential effects of capsaicinoids on energy intake, clarified previous observations and formed evidence-based conclusions about possible weight management roles.  Medical databases (Medline, Web of Knowledge and Scopus) were systematically searched for papers.  Search terms were: 'capsaicin(*)' or 'red pepper' or 'chilli(*)' or 'chili(*)' with 'satiety' or 'energy intake'.  Of the 74 clinical trials identified, 10 were included, 8 of which provided results suitable to be combined in analysis (191 participants).  From the studies, 19 effect sizes were extracted and analyzed using MIX meta-analysis software.  Data analysis showed that capsaicinoid ingestion prior to a meal reduced ad libitum energy intake by 309.9kJ (74.0kcal) during the meal (p < 0.001). However, results should be viewed with some caution as heterogeneity was high (I(2) = 75.7 %).  Study findings suggested a minimum dose of 2 mg of capsaicinoids is needed to contribute to reductions in ad libitum energy intake, which appears to be attributed to an altered preference for carbohydrate-rich foods over foods with a higher fat content.  The authors concluded that meta-analysis findings suggested that daily consumption of capsaicinoids may contribute to weight management through reductions in energy intake.  Subsequently, there may be potential for capsaicinoids to be used as long-term, natural weight-loss aids.  They stated that further long-term randomized trials are now needed to investigate these effects. 

In a systematic review, Onakpoya et al (2014a) evaluated the evidence for or against the effectiveness of glucomannan, a soluble fiber, in body weight reduction.  Electronic searches were conducted in Medline, Embase, Amed, and The Cochrane Library.  Hand searches of bibliography were also conducted.  Outcomes of interest were body weight and BMI.  Studies involving only over-weight and/or obese participants were included.  Two reviewers independently determined the eligibility of studies and assessed the reporting quality of included randomized controlled trials (RCTs), using the CONSORT and PRISMA guidelines.  A total of 18 trials were identified, and 9 were included.  There was a variation in the reporting quality of the included RCTs.  A meta-analysis (random effect model) of 8 RCTs revealed a non-statistically significant difference in weight loss between glucomannan and placebo (mean difference [MD]: -0.22 kg; 95 % confidence interval [CI]: -0.62, 0.19; I(2) = 65 %).  Adverse events included abdominal discomfort, diarrhea, and constipation.  The authors concluded that the evidence from available RCTs does not show that glucomannan intake generates statistically significant weight loss.  They stated that future trials should be more rigorous and better reported. 

Onakpoya et al (2014b) noted that several slimming aids being sold as food supplements are widely available.  One of them is pyruvate.  Its effectiveness in causing weight reduction in humans has not been fully established.  The objective of this systematic review was to examine the effectiveness of pyruvate in reducing body weight.  Electronic and non-electronic searches were conducted to identify all relevant human RCTs.  The bibliographies of all located articles were also searched.  No restrictions in language or time were applied.  Two independent reviewers extracted the data according to predefined criteria.  A fixed-effect model was used to calculate MD and 95 % CI.  A total of 9 trials were identified and 6 were included.  All had methodological weaknesses.  The meta-analysis revealed a statistically significant difference in body weight with pyruvate compared to placebo (MD: -0.72 kg; 95 % CI: -1.24 to -0.20).  The magnitude of the effect is small, and its clinical relevance is uncertain.  Adverse events included gas, bloating, diarrhea, and increase in low-density lipoprotein (LDL) cholesterol.  The authors concluded that the evidence from RCTs does not convincingly show that pyruvate is effective in reducing body weight; limited evidence exists about the safety of pyruvate.  They stated that future trials involving the use of this supplement should be more rigorous and better reported.

The FDA approved liraglutide [rDNA origin] injection (Saxenda), a once-daily injection of a glucagon-like peptide-1 (GLP-1) receptor agonist, for chronic weight management (Novo Nordisk, 2014). Liraglutide is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI ≥30 kg/m2) or who are overweight (BMI ≥27 kg/m2) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia) (FDA, 2014).

The FDA approval of liraglutide was based upon the SCALE (Satiety and Clinical Adiposity−Liraglutide Evidence in Non-diabetic and Diabetic adults) phase 3 clinical trial program, which included study participants who have obesity (BMI ≥30 kg/m2) or who are overweight (BMI ≥27 kg/m2) with comorbidities (Novo Nordisk, 2014). Trial data showed that liraglutide, in combination with a reduced-calorie diet and increased physical activity, resulted in significantly greater weight loss than diet and physical activity alone. 

The SCALE phase 3 clinical trial program of the safety and effectiveness of liraglutide for chronic weight management included three clinical trials that included approximately 4,800 obese and overweight patients with and without significant weight-related conditions (FDA, 2014). All patients received counseling regarding lifestyle modifications that consisted of a reduced-calorie diet and regular physical activity. 

Results from a clinical trial that enrolled patients without diabetes showed that patients had an average weight loss of 4.5 percent from baseline compared to treatment with a placebo at one year (FDA, 2014). In this trial, 62 percent of patients treated with liraglutide lost at least 5 percent of their body weight compared with 34 percent of patients treated with placebo. Results from another clinical trial that enrolled patients with type 2 diabetes showed that patients had an average weight loss of 3.7 percent from baseline compared to treatment with placebo at one year. In this trial, 49 percent of patients treated with liraglutide lost at least 5 percent of their body weight compared with 16 percent of patients treated with placebo. 

The FDA approved labeling states that patients using liraglutide should be evaluated after 16 weeks to determine if the treatment is working (Novo Nordisk, 2020). If a patient has not lost at least 4 percent of baseline body weight, liraglutide should be discontinued, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment. 

Saxenda is a glucagon-like peptide-1 (GLP-1) receptor agonist and should not be used in combination with any other drug belonging to this class, including Victoza, a treatment for type 2 diabetes. Saxenda and Victoza contain the same active ingredient (liraglutide) at different doses (3 mg and 1.8 mg, respectively). However, Saxenda is not indicated for the treatment of type 2 diabetes, as the safety and efficacy of Saxenda for the treatment of diabetes has not been established (Novo Nordisk, 2020). 

Saxenda has a boxed warning stating that liraglutide causes thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Saxenda is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and the symptoms of thyroid tumors (Novo Nordisk, 2020).

In clinical trials, the most common adverse reactions of liraglutide, reporting in ≥5%, included nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, and increased lipase (Novo Nordisk, 2020). 

Warnings and precautions for Saxenda (liraglutide) includes acute pancreatitis, acute gallbladder disease, serious hypoglycemia when used with an insulin secretagogue or insulin, increased heart rate, renal impairment, hypersensitivity reactions, and suicidal behavior and ideation (Novo Nordisk, 2020).

The labeling states that nursing mothers should either discontinue liraglutide for chronic weight management or discontinue nursing. Furthermore, the safety and effectiveness of liraglutide has not been established in pediatric patients and, thus, not recommended for use (Novo Nordisk, 2020). 

Dual-energy X-ray (DEXA)

Dual-energy X-ray (DEXA) was developed for the diagnosis of osteoporosis and was employed originally to clinically significant locations of the forearm, femoral neck, and lumbar spine.  With body composition measurements by means of DEXA, a controlled x-ray beam scans the entire body to ascertain bone mineral content, body fat and lean tissue mass.  The comprehensive view of body composition provided by DEXA is thought to be the method of choice for evaluating body composition by its advocates because of its speed, ease of application as well as relatively low-dose of ionizing radiation.  Its purported uses entail determining appropriate nutritional support during disease progression and monitoring response to therapeutic interventions.

Available evidence does not support the use of whole body DEXA for managing obesity. There is a lack of reliable evidence demonstrating that whole body DEXA measurement improves the management of persons with obesity over simpler methods of measuring body composition (including BMI and anthropomorphic measures), such that clinical outcomes are significantly improved. Published data have focused on the level of agreement between whole body DEXA and various other methods of measuring body composition, and on the use of DEXA as an endpoint in research studies. Well-designed studies are needed to assess the clinical value of whole body DEXA scanning (Ball and Altena, 2004; Williams et al, 2006; Ritz et al, 2007; Pineau et al, 2007; Pineau et al, 2009).

de Miguel-Etayo et al (2013) noted that nutrition, physical activity and behavior-modifying techniques are widely applied components of interventions treating obesity.  These investigators reviewed available information on the short- and long-term effects of intervention treatment on body fat composition of overweight and obese children and adolescents and, to obtain a further understanding on how different body composition techniques detect longitudinal changes.  A total of 13 papers were included; 7 included a multi-disciplinary intervention component, 5 applied a combined dietary and physical activity intervention and 1 a physical activity intervention.  Body composition techniques used included anthropometric indices, BIA, and dual energy X-ray absorptiometry.  Percentage of fat mass change was calculated in when possible.  Findings suggested, no changes were observed in fat free mass after 16 weeks of nutritional intervention and the lowest decrease on fat mass percentage was obtained.  However, the highest fat mass percentage with parallel increase in fat free mass, both assessed by DXA was observed in a multi-component intervention applied for 20 weeks.  The authors concluded that more studies are needed to determine the best field body composition method to monitor changes during overweight treatment in children and adolescents.

Whole Body Calorimetry and Composition and Whole Body Bioimpedance

There is currently no established role for whole body bioimpedance for weight reduction or other indications. Current ACC/AHA guidelines on obesity mention no role for bioimpedance analysis (Jensen, et al., 2013). Current NICE obesity guidance (NICE, 2014) states: "Do not use bioimpedance as a substitute for BMI as a measure of general adiposity." 

Lingwood (2013) stated that there is a critical need for improved technologies to monitor fluid balance and body composition in neonates, particularly those receiving intensive care.  Bioelectrical impedance analysis (BIA) meets many of the criteria required in this environment and appears to be effective for monitoring physiological trends.  These researchers reviewed the literature regarding the use of bioelectrical impedance in neonates.  It was found that prediction equations for total body water, extracellular water and fat-free mass have been developed, but many require further testing and validation in larger cohorts.  Alternative approaches based on Hanai mixture theory or vector analysis are in the early stages of investigation in neonates.  The authors concluded that further research is needed into electrode positioning, bioimpedance spectroscopy and Cole analysis in order to realize the full potential of this technology.

Lifestyle Modification Program

Borel et al (2012) conducted a prospective intervention study in 104 viscerally obese men classified according to their glucose tolerance status.  They were followed for one year while participating in a healthy eating-physician activity/exercise lifestyle modification program while their insulin sensitivity was tracked.  The goals of the study were to evaluate glucose tolerance as well as to evaluate the respective contribution so fo changes in body fat distribution versus changes in cardiorespiratory fitness (CRF) to the improvements in indices of plasma glucose/insulin homeostasis.  The results showed insulin sensitivity improved in assocication with decreases in both visceral (VAT) and subcutaneous adiposity (SAT) as well as improvement in CRF, regardless of baseline glucose tolerance.  The results of this study also showed that reduction in VAT was associated with an improvement in homeostasis model assessment of insulin resistance, whereas reduction in SAT was rather associated with improvement of the insulin sensitivity index of Matsuda.  The authors concluded that a one year lifestyle intervention improved plasma glucose/insulin homeostasis in viscerally obese men, including those with normal glucose tolerance status at baseline. 

Very Low Energy Diets and Very Low Calorie Diets (VLCD)

Mulholland et al (2012) stated that evidence from the literature supports the safe use of very-low-energy diets (VLED) for up to 3 months in supervised conditions for patients who fail to meet a target weight loss using a standard low-fat, reduced-energy approach.  There is, however, a need for longer-term outcomes on obesity and associated morbidities following a VLED.  These researchers investigated longer-term outcomes from studies using VLED, with a minimum duration of 12 months, published between January 2000 and December 2010.  Studies conducted in both children and adults, with a mean/median BMI of greater than or equal to 28 kg/m2 were included.  PubMed, Medline, Web of Science and Science Direct were searched.  Reference lists of studies and reviews were manually searched.  Weight loss or prevention of weight gain and morbidities were the main outcomes assessed.  A total of 32 out of 894 articles met the inclusion criteria.  The duration of the studies ranged from 12 months to 5 years.  Periods of VLED ranged from 25 d to 9 months.  Several studies incorporated aspects of behavior therapy, exercise, low-fat diets, low-carbohydrate diets or medication.  Current evidence demonstrated significant weight loss and improvements in blood pressure, waist circumference and lipid profile in the longer term following a VLED.  Interpretation of the results, however, was restricted and conclusions with which to guide best practice were limited due to heterogeneity between the studies.  The authors concluded that the present review clearly identified the need for more evidence and standardized studies to assess the longer-term benefits from weight loss achieved using VLED.

Indirect Calorimetry

Indirect calorimetry is designed to measure an individual’s oxygen consumption.  Using this measurement, the device calculates a person’s resting energy expenditure (REE), also known as resting metabolic rate (RMR).  Clinicians supposedly can screen for abnormally low metabolic rates, teach energy balance, and identify the precise caloric intake needed for weight loss.  Clinical applications of indirect calorimetry include obesity treatment, as well as treating obesity related diseases such as diabetes, dysmetabolic syndrome X, hypothyroidism, hyperthyroidism, hypertension, cardiovascular disease, as well as sleep apnea.  Under strict laboratory protocol, indirect calorimetry can also be used to measure basal metabolic rate.

Published studies of indirect calorimetry in weight management have focused on its accuracy (Frankenfeld, et al., 2010; Henes, et al., 2015; Wilms, et al., 2010). There is a lack of reliable evidence that indirect calorimetry measurements result in improved clinical outcomes in obesity management.

McDoniel, et al., (2008) evaluated the efficacy of a weight management program using indirect calorimetry to set energy goals. Fifty-four overweight, active duty adult employees of the US Air Force (age 18-46 years, BMI 25.2–35.6 kg/m2) participated in this quasi-experimental control design study. All participants were enrolled in a four-session US Air Force ‘Sensible Weigh’ group weight control program. Treatment participants received a personalized nutrition energy goal message developed using measured resting metabolic rate (RMR) from a hand-held indirect calorimeter (MedGem®). Usual care participants received a nutritional message using a standard care equation (25 kcal/day × body weight) to set energy intake goals. Investigators reported that treatment participants lost significantly more weight than usual care participants (p ≤ 0.05). Ten of the 54 subjects dropped from the study before completion. Difference in weight loss between the treatment and usual care group were –4.3 kg ± 3.3 vs. –1.8 kg ± 3.2, respectively. The investigators reported that were no significant differences in reported food intake or energy expenditure between groups. The investigators posited that a possible reason why experimental individuals experienced greater weight loss from measured resting metabolic rate may be that the individualized nutrition message influenced psychobehavioral constructs (i.e. motivation, self-efficacy, etc.) for weight loss change. The investigators noted that study limitations include small sample size, short duration, and small treatment effect. An additional issue is the generalizability of the findings, given that, at the time of the study, the Air Force had regulations that all personnel maintain a desired body weight and body fat percentage, or these individuals could be discharged from service. The investigators stated that future research is needed to determine the long-term efficacy of using indirect calorimetry as part of a comprehensive weight control program.

An UpToDate review on "Palliative care: Assessment and management of anorexia and cachexia" (Bruera and Dev, 2013) states that "Handheld indirect calorimetry, which is more accurate than equations at estimating basal energy needs but less precise than traditional devices used in the research setting, may be useful in the outpatient setting.  Close to one-half of cancer patients being evaluated in an outpatient cachexia clinic are noted to be hypermetabolic by indirect calorimetry.  These assessments are appropriate in the research setting, but have little if any utility in the clinic".

Bioelectrical Impedance Analysis

Talma et al (2013) stated that bioelectrical impedance analysis (BIA) is a practical method to estimate percentage body fat (% BF).  In this systematic review, these researchers evaluated validity, responsiveness, reliability and measurement error of BIA methods in estimating % BF in children and adolescents.  They searched for relevant studies in PubMed, Embase and Cochrane through November 2012.  Two reviewers independently screened titles and abstracts for inclusion, extracted data and rated methodological quality of the included studies.  These investigators performed a best evidence synthesis to synthesize the results, thereby excluding studies of poor quality.  They included 50 published studies.  Mean differences between BIA and reference methods (gold standard [criterion validity] and convergent measures of body composition [convergent validity]) were considerable and ranged from negative to positive values, resulting in conflicting evidence for criterion validity.  These investigators found strong evidence for a good reliability, i.e., (intra-class) correlations greater than or equal to 0.82.  However, test-retest mean differences ranged from 7.5 % to 13.4 % of total % BF in the included study samples, indicating considerable measurement error.   The authors concluded that the findings of this systematic review suggested that BIA is a practical method to estimate % BF in children and adolescents.  However, they stated that validity and measurement error were not satisfactory.

Goldberg et al (2014) stated that the sensory and gastro-intestinal changes that occur with aging affect older adults' food and liquid intake.  Any decreased liquid intake increases the risk for dehydration.  This increased dehydration risk is compounded in older adults with dysphagia.  The availability of a non-invasive and easily administered way to document hydration levels in older adults is critical, particularly for adults in residential care.  This pilot study investigated the contribution of BIA to measure hydration in 19 older women in residential care: 13 who viewed themselves as healthy and 6 with dysphagia.  Mann-Whitney U analyses documented no significant between-group differences for total body water (TBW), fat free mass (FFM), Fat Mass (FM), and % BF.  However, when compared to previously published data for age-matched women, the TBW and FFM values of the 2 participant groups were notably less, and FM and % BF values were notably greater than expected.  The authors concluded that if results are confirmed through continued investigation, such findings may suggest that long-term care facilities are unique environments in which all older residents can be considered at-risk for dehydration and support the use of BIA as a non-invasive tool to assess and monitor their hydration status.

Buffa et al (2014) defined the effectiveness of bioelectrical impedance vector analysis (BIVA) for assessing 2-compartment body composition.  These researchers performed a systematic literature review using MEDLINE database up to February 12, 2014.  The list of papers citing the first description of BIVA, obtained from SCOPUS, and the reference lists of included studies were also searched.  Selection criteria included studies comparing the results of BIVA with those of other techniques, and studies analyzing bioelectrical vectors of obese, athletic, cachectic and lean individuals.  A total of 30 articles met the inclusion criteria.  The ability of classic BIVA for assessing 2-compartment body composition has been mainly evaluated by means of indirect techniques, such as anthropometry and BIA.  Classic BIVA showed a high agreement with body mass index, which can be interpreted in relation to the greater body mass of obese and athletic individuals, whereas the comparison with BIA showed less consistent results, especially in diseased individuals.  When a reference method was used, classic BIVA failed to accurately recognize FM % variations, whereas specific BIVA furnished good results.  The authors concluded that specific BIVA is a promising alternative to classic BIVA for assessing 2-compartment body composition, with potential application in nutritional, sport and geriatric medicine.

Haverkort et al (2015) noted that BIA is a commonly used method for the evaluation of body composition.  However, BIA estimations are subject to uncertainties. These researchers explored the variability of empirical prediction equations used in BIA estimations and evaluated the validity of BIA estimations in adult surgical and oncological patients.  Studies developing new empirical prediction equations and studies evaluating the validity of BIA estimations compared with a reference method were included.  Only studies using BIA devices measuring the entire body were included.  Studies that included patients with altered body composition or a disturbed fluid balance and studies written in languages other than English were excluded.  To illustrate variability between equations, fixed normal reference values of resistance values were entered into the existing empirical prediction equations of the included studies and the results were plotted in figures.  The validity was expressed by the difference in means between BIA estimates and the reference method, and relative difference in %.  Substantial variability between equations for groups (including men and women) was found for TBW and FFM.  The gender-specific existing general equations assume less variability for TBW and FFM.  BIA mainly under-estimated TBW (range relative difference -18.8 % to +7.2 %) and FFM (range relative differences -15.2 % to +3.8 %).  Estimates of the FM demonstrated large variability (range relative difference -15.7 % to +43.1 %).  The authors concluded that application of equations validated in healthy subjects to predict body composition performs less well in oncologic and surgical patients.  They suggested that BIA estimations, irrespective of the device, can only be useful when performed longitudinally and under the same standard conditions.

FTO Genotyping

Xiang and colleagues (2016) noted that studies have suggested that the fat mass and obesity-associated (FTO) genotype is associated with individual variability in weight loss in response to diet/lifestyle interventions, but results are inconsistent.  These investigators provided a summary of the literature evaluating the relation between the FTO genotype and weight loss in response to diet/lifestyle interventions.  They performed a search of English-language articles in the PubMed and Embase databases (through April 30, 2015).  Eligible studies were diet/lifestyle weight-loss intervention studies conducted in adults that reported changes in body weight or BMI by the FTO variant rs9939609 (or its proxy).  Differences in weight loss between FTO genotypes across studies were pooled with the use of fixed-effect models.  A meta-analysis of 10 studies (comprising 6,951 participants) that reported the results of additive genetic models showed that individuals with the FTO TA genotype and AA genotype (those with the obesity-predisposing A allele) had 0.18-kg (95 % CI: -0.09 to 0.45-kg; p= 0.19; NS) and 0.44-kg (95 % CI: 0.09- to 0.79-kg; p = 0.015) greater weight loss, respectively, than those with the TT genotype.  A meta-analysis of 14 studies (comprising 7,700 participants) that reported the results of dominant genetic models indicated a 0.20-kg (-0.43- to 0.04-kg) greater weight loss in the TA/AA genotype than in the TT genotype (p = 0.10).  In addition, differences in weight loss between the AA genotype and TT genotype were significant in studies with a diet intervention only, adjustment for baseline BMI or body weight, and several other subgroups.  However, the relatively small number of studies limited these stratified analyses, and there was no statistically significant difference between subgroups.  The authors concluded that the findings of this meta-analysis suggested that individuals carrying the homozygous FTO obesity-predisposing allele may lose more weight through diet/lifestyle interventions than non-carriers; and clinical applications of these findings need further investigations.  They stated that these findings provided some support for considering genetic variability in response to diet/lifestyle interventions in the development of more effective strategies for weight loss; nevertheless, more studies are needed to explore which types of diet/lifestyle interventions most powerfully facilitate the FTO genetic effect on weight loss. 

Ketogenic Diets for Weight Loss

Gibson et al (2015) stated that VLEDs and ketogenic low-carbohydrate diets (KLCDs) are 2 dietary strategies that have been associated with a suppression of appetite.  However, the results of clinical trials investigating the effect of ketogenic diets on appetite are inconsistent.  To evaluate quantitatively the effect of ketogenic diets on subjective appetite ratings, these researchers conducted a systematic literature search and meta-analysis of studies that assessed appetite with visual analog scales (VAS) before (in energy balance) and during (while in ketosis) adherence to VLED or KLCD.  Individuals were less hungry and exhibited greater fullness/satiety while adhering to VLED, and individuals adhering to KLCD were less hungry and had a reduced desire to eat.  Although these absolute changes in appetite were small, they occurred within the context of energy restriction, which is known to increase appetite in obese people.  Thus, the clinical benefit of a ketogenic diet is in preventing an increase in appetite, despite weight loss, although individuals may indeed feel slightly less hungry (or more full or satisfied).  Ketosis appears to provide a plausible explanation for this suppression of appetite.  The authors concluded that future studies should investigate the minimum level of ketosis required to achieve appetite suppression during ketogenic weight loss diets, as this could enable inclusion of a greater variety of healthy carbohydrate-containing foods into the diet.

Medium-Chain Triglycerides for Weight Loss

Bueno and colleagues (2015) examined the effect of replacing dietary long-chain triacylglycerols (LCTs) with medium-chain triacylglycerols (MCTs) on body composition in adults.  These researchers conducted a meta-analysis of RCTs, to examine if individuals assigned to replace at least 5 g of dietary LCTs with MCTs for a minimum of 4 weeks show positive modifications on body composition.  They systematically searched, through July 2013, the CENTRAL, EMBASE, LILACS, and MEDLINE databases for RCTs that investigated the effects of MCT intake on body composition in adults.  Two authors independently extracted data and assessed risk of bias.  Weighted mean differences (WMDs) were calculated for net changes in the outcomes.  These investigators assessed heterogeneity by the Cochran Q test and I(2) statistic and publication bias with the Egger's test.  Pre-specified sensitivity analyses were performed.  A total of 11 trials were included, from which 5 presented low risk of bias.  In the overall analysis, including all studies, individuals who replaced dietary LCT with MCT showed significantly reduced body weight (WMD, -0.69 kg; 95 % CI: -1.1 to -0.28; p = 0.001); body fat (-0.89 kg; 95 % CI: -1.27 to -0.51; p < 0.001), and WC (-1.78 cm; 95 % CI: -2.4 to -1.1; p < 0.001).  The overall quality of the evidence was low-to-moderate.  Trials with a cross-over design were responsible for the heterogeneity.  The authors concluded that despite statistically significant results, the recommendation to replace dietary LCTs with MCTs must be cautiously taken, because the available evidence is not of the highest quality.

Mumme and Stonehouse (2015) conducted a systematic review and meta-analysis of RCTs comparing the effects of MCTs, specifically C8:0 and C10:0, to long-chain triglycerides (LCTs) on weight loss and body composition in adults.  Changes in blood lipid levels were secondary outcomes.  Randomized controlled trials of greater than 3 weeks' duration conducted in healthy adults were identified searching Web of Knowledge, Discover, PubMed, Scopus, New Zealand Science, and Cochrane CENTRAL until March 2014 with no language restriction.  Identified trials were assessed for bias.  Mean differences were pooled and analyzed using inverse variance models with fixed effects.  Heterogeneity between studies was calculated using I(2) statistic.  An I(2) > 50 % or p < 0.10 indicated heterogeneity.  A total of 13 trials (n = 749) were identified.  Compared with LCTs, MCTs decreased body weight (-0.51 kg [95 % CI: -0.80 to -0.23 kg]; p < 0.001; I(2) = 35 %); waist circumference (-1.46 cm [95 % CI: -2.04 to -0.87 cm]; p < 0.001; I(2) = 0%), hip circumference (-0.79 cm [95 % CI: -1.27 to -0.30 cm]; p = 0.002; I(2) = 0 %), total body fat (standard mean difference -0.39 [95 % CI: -0.57 to -0.22]; p < 0.001; I(2) = 0%), total subcutaneous fat (standard mean difference -0.46 [95 % CI: -0.64 to -0.27]; p < 0.001; I(2) = 20 %), and visceral fat (standard mean difference -0.55 [95 % CI: -0.75 to -0.34]; p < 0.001; I(2) = 0 %).  No differences were seen in blood lipid levels.  Many trials lacked sufficient information for a complete quality assessment, and commercial bias was detected.  Although heterogeneity was absent, study designs varied with regard to duration, dose, and control of energy intake.  The authors concluded that replacement of LCTs with MCTs in the diet could potentially induce modest reductions in body weight and composition without adversely affecting lipid profiles.  However, they stated that further research is needed by independent research groups using large, well-designed studies to confirm the effectiveness of MCT and to determine the dosage needed for the management of a healthy body weight and composition.

Normobaric Hypoxic Conditioning

Hobbins and colleagues (2017) stated that normobaric hypoxic conditioning (HC) is defined as exposure to systemic and/or local hypoxia at rest (passive) or combined with exercise training (active).  Hypoxic conditioning has been previously used by healthy and athletic populations to enhance their physical capacity and improve performance in the lead up to competition.  Recently, HC has also been applied acutely (single exposure) and chronically (repeated exposure over several weeks) to over-weight and obese populations with the intention of managing and potentially increasing cardio-metabolic health and weight loss.  At present, it is unclear what the cardio-metabolic health and weight loss responses of obese populations are in response to passive and active HC.  Exploration of potential benefits of exposure to both passive and active HC may provide pivotal findings for improving health and well-being in these individuals.  These researchers carried out a systematic literature search for articles published between 2000 and 2017.  Studies investigating the effects of normobaric HC as a novel therapeutic approach to elicit improvements in the cardio-metabolic health and weight loss of obese populations were included.  Studies investigated passive (n = 7; 5 animals, 2 humans), active (n = 4; all humans) and a combination of passive and active (n = 4; 3 animals, 1 human) HC to an inspired oxygen fraction between 4.8 and 15.0 %, ranging between a single session and daily sessions per week, lasting from 5 days up to 8 months.  Passive HC led to reduced insulin concentrations (-37 to -22 %) in obese animals and increased energy expenditure (+12 to +16 %) in obese humans, whereas active HC led to reductions in body weight (-4 to -2 %) in obese animals and humans, and blood pressure (BP; -8 to -3 %) in obese humans compared with a matched workload in normoxic conditions.  Inconclusive findings, however, exist in determining the impact of acute and chronic HC on markers such as triglycerides, cholesterol levels, and fitness capacity.  More importantly, most of the studies that included animal models involved exposure to severe levels of hypoxia (= 5.0 %; simulated altitude greater than 10,000 m) that are not suitable for human populations.  The authors concluded that normobaric HC demonstrated observable positive findings in relation to insulin and energy expenditure (passive), and body weight and BP (active), which may improve the cardio-metabolic health and body weight management of obese populations.  However, they stated that further evidence on responses of circulating biomarkers to both passive and active HC in humans is needed.

Weight Reduction Devices

In April 2019, the U.S. FDA cleared Plenity (Gelesis, Inc.), through the De Novo pathway, as a medical device to aid in weight management in overweight and obese adults with a BMI of 25–40 kg/m², when used in conjunction with diet and exercise. Plenity is an oral capsule that promotes fullness and may help to increase satiety to assist patients manage their weight. Per the manufacturer, "Plenity is nonsystemic and works directly in the gastrointestinal (GI) tract. Plenity is made from two natural ingredients, cellulose and citric acid, that form a three-dimensional matrix designed to occupy volume in the stomach and small intestine, to create a sensation of fullness. Each Plenity capsule contains thousands of superabsorbent hydrogel particles (0.75 grams [g] per capsule), and each particle is approximately the size of a grain of salt. Patients consume three (3) capsules (2.25 g/dose) with water before both lunch and dinner. The capsules disintegrate in the stomach and release the Plenity particles, which can hydrate up to 100 times their original weight. When fully hydrated, the individual nonclustering Plenity particles occupy about a quarter of average stomach volume. The gel particles mix with ingested foods, creating a larger volume with higher elasticity and viscosity in the stomach and small intestine, promoting satiety and fullness. Plenity passes through the digestive system, maintaining its three-dimensional structure in the stomach and small intestine before breaking down in the colon. The water is then released and reabsorbed by the body. Plenity particles are eliminated through normal bowel movements (not absorbed)" (Gelesis, 2019a, 2021).

FDA-clearance was based on the safety and efficacy results from the GLOW trial (NCT02307279). The GLOW trial was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study which evaluated 2.25g of Plenity (n=223) versus placebo (n=213) on body weight over 24 weeks in 436 overweight and obese subjects (with and without type 2 diabetes). All subjects were prescribed reduced caloric intake and exercise. Enrollment included patients aged 22-65 years with BMI 27-40 kg/m². Those with BMI less than 30 kg/m² needed to have at least one of the following comorbidities: type 2 diabetes (untreated or metformin-treated), dyslipidemia, or hypertension. Fasting glucose was required to be between ≥90 mg/dL and ≤145 mg/dL. Patients were excluded if pregnant, had known type 1 diabetes, or a known history of gastrointestinal or endocrine disease. A total of 324 subjects completed the study, or 172 / 223 in the treatment group and 152 / 213 in the placebo group. Ninety-five subjects withdrew during the study, with personal reasons being cited as most common. Seventeen subjects, or 4% of all treated subjects were lost to follow-up during the study treatment phase. 

The co-primary effectiveness endpoints in the GLOW trial were an intent-to-treat, multiple imputation (ITT-MI) analysis of total body weight loss, defined as the percent change from baseline to Day 171 with a super-superiority margin of 3%; and body weight responders, defined as 5% or more total body weight loss from baseline to Day 171, with at least 35% of subjects in the active arm achieving 5% or more weight loss (categorical endpoint). The study met and exceeded the predefined categorical endpoint, with 59% of adults in the treatment group achieving weight loss of 5% or greater. The co-primary endpoint of percent change in total body weight demonstrated greater weight loss at six months in subjects assigned to Plenity (p=0.0007). Though the Plenity group achieved statistically superior weight loss compared to placebo, it did not meet the predefined super-superiority margin of 3% to successfully meet this co-primary endpoint. No weight loss plateau was observed during the 6-month GLOW study, and weight loss was sustained during a 24-week follow-up period. Plenity-treated individuals had twice the odds of achieving at least 5% weight loss vs. placebo (p=0.0008). In addition, 26% of the adults who completed the treatment with Plenity were “super-responders,” defined as achieving at least 10% weight loss. These super-responders achieved an average of about 14% weight loss or approximately 30 pounds. 

The overall incidence of adverse events (AEs) in the Plenity treatment group was no different than placebo (71% in both groups). The most common treatment related adverse events (TRAEs) were gastrointestinal disorders (158 TRAEs in 84 [38%] subjects in the Plenity arm, compared to 105 events in 58 [28%] subjects receiving placebo), infections and infestations (2 events in 2 [1%] subjects with Plenity and 1 events in 1 [1%] subjects with placebo), and musculoskeletal and connective tissue disorders (3 events in 2 [1%] subjects with Plenity and 0 in 0 [0%] subjects with placebo). There were no serious adverse events (SAE) in the Plenity group, whereas there was one (1) SAE in the placebo group. Plenity was therefore found to be well tolerated with no significant safety concerns compared to placebo. 

The GLOW-EX Study (NCT03021291) was an open-label extension trial to study the safety of long-term exposure to Plenity and the effectiveness of Plenity in maintaining weight loss achieved after 6 months (combined with lifestyle modification). At that time, less than 20% (73 subjects) of the original cohort remained in the GLOW study. Of the remaining subjects, 52 had completed Visit 13 (Day 171) and had lost 3% or more body weight in either the treatment or control arm, which was required to be considered for GLOW-EX. Subjects who were assigned to placebo during GLOW crossed over to the Plenity arm (n=18), while the subjects who were assigned to Plenity during GLOW continued on Plenity for an additional 24 weeks (n=21). The duration of the open-label treatment with Plenity 2.25 g was 165 days in the GLOW-EX Study. The objectives are intended to evaluate 1) safety of one year exposure to Plenity, and 2) efficacy of Plenity to maintain weight loss achieved after 6 months of Plenity combined with diet and exercise. At the time of enrollment in GLOW-EX, the subjects treated with Plenity during GLOW had already reached a mean (SD) weight loss of 7% ± 3% weight loss in 24 weeks. The additional six months of exposure to Plenity provided an additional 0.8% ± 3% weight loss and demonstrated maintenance of the weight loss effect. The 18 subjects assigned to placebo in GLOW had lost 7% ± 4% during the GLOW study before starting on Plenity for 24 weeks. At the time when weight regain is expected, the subjects who successfully lost with lifestyle modification were able to lose an additional 3% ± 4% over the subsequent 24 weeks with the addition of Plenity treatment. The primary endpoint of weight maintenance was demonstrated as the unadjusted 95% confidence intervals at Day 171 (end of GLOW, 95% CI [-8.37 to -5.78]) and 339 (end of GLOW-EX, 95% CI [-10.54 to -5.22]) overlap. At the end of one year of therapy with Plenity, 67% of subjects achieved at least 5% weight loss. The results also demonstrated that the safety profile for the extension phase of the study were consistent with the initial 6-month phase. There were no new AEs identified and the overall rates of each type of AE were similar to those seen during the blinded treatment phase of the study.

Plenity is contraindicated for use in pregnancy and history of allergic reaction to cellulose, citric acid, sodium stearyl fumarate, gelatin, or titanium oxide. Precautions include the following:

• Patients should contact a healthcare provider (HCP) immediately if a severe or continued adverse event occurs. If a severe allergic reaction, severe abdominal pain, or severe diarrhea occurs, patients should discontinue the product until speaking with an HCP. 
• Patients with symptoms of dysphagia that may affect ability to swallow capsules are likely to have difficulty swallowing the capsule.
• Patients should not consume Plenity if the package is damaged.
• If any capsules are broken, crushed, or damaged, they should be discarded.
• Use with caution in patients with active gastrointestinal conditions such as gastro-esophageal reflux disease (GERD), ulcers, or heartburn.
• Avoid using in patients with the following conditions:
  
  
  • Esophageal anatomic anomalies, including webs, diverticuli, and rings.
  • Suspected strictures (such as patients with Crohn’s disease).
  • Complications from prior gastrointestinal surgery that could affect GI transit
    and motility.
    
    
• Plenity is not a food substitute. It is not absorbed by the body and therefore has no nutritional or caloric value.
• Plenity should be taken under the direction of an HCP as part of a structured weight loss program. Failure to adhere to prescribed dietary and exercise instructions may result in failure to lose weight.

Wearable Devices (e.g., Fitbit or Health Apps on Mobiles)

Jo and colleagues (2019) noted that wearable devices have become a standard health care intervention with emerging health care technologies.  These devices are designed to promote healthy behaviors and decrease risk for chronic disease like cardiovascular disease and diabetes.  These researchers provided evidence of the benefit of wearable devices in chronic disease outcomes among adults.  They carried out a systematic search of PubMed, Web of Science, World Health Organization (WHO) international clinical trials registry platform, BMC ISRCTN registry, and the Institute of Electrical and Electronics Engineers based upon the PRISMA guideline.  Included articles were randomized controlled trials (RCTs) or quasi-experimental studies with health outcomes published in English up to October 2018.  Studies focusing on adults were selected; 3 investigators reviewed the selected publications and made agreement on final selection.  Of a total of 550 publications extracted, 6 studies met the final criteria.  There was little indication that wearable devices provided a benefit for health outcomes.  Of the 6 studies examined, only 1 study showed a significant reduction for weight loss among subjects who used wearable devices.  No significant reduction was discovered in cholesterol or blood pressure.  Among the 6 studies, only 1 study examined hemoglobin A1c, and it showed a significant reduction in older patients with type 2 diabetes mellitus.  The authors concluded that available evidence evaluating wearable devices showed little benefit of the devices on chronic disease health outcomes.  These researchers stated that wearable devices play a role as a facilitator in motivating and accelerating physical activity; however, current data do not suggest other consistent health benefits.

Appendix

Ideal Body Weight and BMI Calculator

To calculate ideal body weight (Devine formula) and adjusted body weight, see MD+Calc Ideal Body Weight and Adjusted Body Weight.

To calculate adult BMI, see CDC.gov Adult BMI Calculator.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
97802	Medical nutrition therapy; initial assessment and intervention, individual, face-to-face with the patient, each 15 minutes
97803	re-assessment and intervention, individual, face-to-face with the patient, each 15 minutes
97804	group (2 or more individual(s)), each 30 minutes
CPT codes not covered for indications listed in the CPB:
Fat mass and obesity-associated (FTO) genotyping, normobaric hypoxic conditioning – no specific code:
0358T	Bioelectrical impedance analysis whole body composition assessment, with interpretation and report
94690	Oxygen uptake, expired gas analysis; Rest, indirect (separate procedure) [Indirect calorimetry]
94726	Plethysmography for determination of lung volumes and, when performed, airway resistance
97810	Acupuncture, one or more needles without electrical stimulation; initial 15 minutes of personal one-on-one contact with patient
+ 97811	without electrical stimulation, each additional 15 minutes of personal one-on-one contact with the patient, with re-insertion of needle(s) (List separately in addition to code for primary procedure)
97813	Acupuncture, one or more needles with electrical stimulation; initial 15 minutes of personal one-on-one contact with the patient
+ 97814	each additional 15 minutes of personal one-on-one contact with the patient, with re-insertion of needle(s) (List separately in addition to code for primary procedure)
Other CPT codes related to the CPB:
77072	Bone age studies
80048	Basic metabolic panel (Calcium, total)
80053	Comprehensive metabolic panel
80076	Hepatic function panel
80418	Combined rapid anterior pituitary evaluation panel
80420	Dexamethasone suppression panel, 48 hour
81000	Urinalysis, by dipstick or tablet reagent for bilirubin, glucose, hemoglobin, ketones, leukocytes, nitrite, pH, protein, specific gravity, urinobilogen, any number of these constituents; non-automated, with microscopy
81001	automated, with microscopy
81050	Volume measurement for timed collection, each
82465	Cholesterol, serum or whole blood, total
82530	Cortisol, free
82533	total
82951	Glucose; tolerance test (GTT), three specimens (includes glucose)
82952	tolerance test, each additional beyond 3 specimens (list separately in addition to code for primary procedure)
83718	Lipoprotein, direct measurement; high density cholesterol (HDL cholesterol)
83719	direct measurement, VLDL cholesterol
83721	direct measurement; LDL cholesterol
84443	Thyroid stimulating hormone (TSH)
84478	Triglycerides
84479	Thyroid hormone (T3 or T4) uptake or thyroid hormone binding ratio (THBR)
84550	Uric acid; blood
84560	other source
85025	Blood count; complete (CBC), automated (Hgb, Hct, RBC, WBC and platelet count) and automated differential WBC count
85027	complete (CBC), automated (Hgb, Hct, RBC, WBC and platelet count) and automated differential WBC count
93000 - 93010	Electrocardiogram, routine ECG with at least 12 leads
HCPCS codes covered if selection criteria are met:
G0270	Medical nutrition therapy; reassessment and subsequent intervention(s) following second referral in same year for change in diagnosis, medical condition or treatment regimen (including additional hours needed for renal disease), individual, face to face with patient, each 15 minutes
G0271	Medical nutrition therapy; reassessment and subsequent intervention(s) following second referral in same year for change in diagnosis, medical condition or treatment regimen (including additional hours needed for renal disease), group, (2 or more individuals), each 30 minutes
HCPCS codes not covered for indications listed in the CPB:
J0725	Injection, chorionic gonadotropin, per 1,000 USP units
J7336	Capsaicin 8% patch, per sq cm
S8948	Application of a modality (requiring constant provider attendance) to one or more areas; low-level laser; each 15 minutes
S9449	Weight management classes, non-physician provider, per session
Other HCPCS Codes related to the CPB:
S9451	Exercise classes, non-physician provider, per session
S9452	Nutrition classes, non-physician provider, per session
ICD-10 codes covered if selection criteria are met:
E66.01 - E66.9	Overweight and obesity
Z68.27 - Z68.45	Body mass index (BMI) 27.0 - 40+, adult
Plenity (Gelesis, Inc.):
HCPCS codes covered if selection criteria are met:
Plenity (Gelesis, Inc.) - no specific code
Other HCPCS Codes related to the CPB:
S9449	Weight management classes, non-physician provider, per session
S9451	Exercise classes, non-physician provider, per session
S9452	Nutrition classes, non-physician provider, per session
ICD-10 codes covered if selection criteria are met:
E66.01 – E66.9	Overweight and obesity
Z68.25 – Z68.45	Body mass index (BMI) 25.0 – 40+, adult

The above policy is based on the following references: