Obesity is among the most common chronic diseases affecting adults in the United States. Without treatment, obesity worsens and leads to anatomic, metabolic, and psychological complications that significantly impair health and quality of life and shorten life expectancy.1 Because obesity is at the root of many of the conditions that are routinely seen in clinical practice, it is important for clinicians to recognize obesity as a disease and understand available evidence-based treatment options.
Understanding Obesity as a Disease
More than 42% of adults have obesity and another 33% have preobesity/overweight, which means that more than three-quarters of US adults are at an unhealthy weight.2 Obesity rates are higher for non-Hispanic Black and Hispanic individuals (49.6% and 44.8%, respectively) than for non-Hispanic White and non-Hispanic Asian individuals (42.2% and 17.4%, respectively).2
Obesity is a chronic, progressive, relapsing disease that is multifactorial in nature. It results from a complex interplay between genetics and environmental factors. Genetics and epigenetics influence susceptibility and development of obesity while environmental factors contribute to causation and persistence of obesity.1 Genes influence appetite regulation, energy balance, insulin signaling, glucose and lipid metabolism, adipocyte differentiation, and metabolic disorders.3 Epigenetic factors contribute to obesity in offspring and future generations.
Environmental factors influencing obesity include infections, hypothalamic injury, adverse reactions to medications, access to highly palatable/ultraprocessed foods, reduced physical activity, reduced sleep, untreated sleep apnea, chronic stress, endocrine disruptors, and alterations in the gut microbiome.1
Weight and appetite are tightly regulated by multiple neurohormonal processes that involve adipose tissue, endocrine organs, gastrointestinal tract peptides, and the peripheral nervous system.4,5 The hypothalamus plays an instrumental role in energy metabolism, appetite regulation, and feeding behaviors. 4,6
The health consequences of obesity affect nearly every system in the body. More than 236 adverse health consequences have been attributed to obesity, including 22 types of cancer.7 Obesity leads to serious complications, such as hyperglycemia, hypertension, dyslipidemia, cardiovascular disease, nonalcoholic fatty liver disease, osteoarthritis, female infertility, polycystic ovary syndrome, and obstructive sleep apnea.1 When obesity is left untreated, new complications develop, current complications worsen, and quality of life is negatively affected.
Diagnosis of Obesity
In the adult patient, obesity is defined as a body mass index (BMI) ≥30 and preobesity/overweight is defined as a BMI 25 to <30. These cutoffs are lower for people of Asian or Pacific Islander heritage (≥27 for obesity and 23 to <27 for preobesity/overweight).
Although BMI is a useful value for screening, it is not a true measure of adiposity. Other indicators of excess adiposity are waist circumference and body composition. A waist circumference ≥35 in for women (≥31.5 in for women of Asian or Pacific Islander heritage) or ≥40 in for men (≥35.4 in for men of Asian or Pacific Islander heritage) is an indicator of abdominal obesity. A body fat percentage ≥32% in women or ≥25% in men is also an indicator of obesity.1,8
Evidence-Based Obesity Treatment
Given the causative role that obesity plays in numerous health issues, the most effective strategy for improving health outcomes is to treat obesity first. Treatment should be comprehensive, individualized, patient-centered, and implemented in a stepwise manner. Because obesity is a chronic condition, treatment needs to be continued indefinitely, and the earlier the intervention the better the outcome. Delayed intervention increases the risk for adverse health consequences and negatively affects quality of life. Reduction of 5% to 10% of body weight is clinically meaningful and can confer significant health benefits; greater weight reduction confers greater benefits.9
The goals of obesity treatment are to1,4:
- Stop further weight gain and induce weight reduction
- Prevent complications
- Improve or resolve existing complications
- Improve quality of life
Five comprehensive treatment modalities are available for obesity: nutrition, physical activity, behavioral counseling, pharmacotherapy, and bariatric surgery.1 Although lifestyle therapy is the foundation of obesity treatment, it is often not sufficient when used alone to achieve desired health outcomes. Medication management of obesity and/or bariatric surgery may need to be added to achieve both weight reduction and improved health. Neither bariatric surgery nor medications replace lifestyle therapy; they are used as adjunctive therapies.1
- Nutritional interventions are most effective when they are evidence based, promote patient adherence, consider patient preferences, and specify the quality and quantity of calories.1
- Physical activity has numerous health benefits including improvements in body composition, dyslipidemia, and blood glucose regulation and decreases in blood pressure, insulin resistance, risk for certain cancers, mortality rate, dementia risk, pain, and depression.1
- Behavioral counseling is needed to help patients implement and continue their treatment regimens.1
- Pharmacotherapy encompasses identifying any weight-promoting medications that the patient is currently taking and transitioning to weight-neutral or weight-negative options whenever possible, as well as prescribing medication management for obesity when appropriate.1
- Bariatric surgical procedures include Roux-en-Y gastric bypass, vertical sleeve gastrectomy, laparoscopic adjustable gastric banding, and biliopancreatic diversion with duodenal switch.1
Medication Management for Obesity
Medication management for obesity is prescribed to reduce weight, reduce the likelihood of weight regain, improve adherence to nutritional plans, and counter the effects of metabolic adaptation.9 After weight reduction, the body metabolically adapts by increasing hunger hormones, decreasing satiety hormones, and reducing the metabolic rate, all of which contribute to weight regain.10
Medications can make it easier for patients to follow their nutritional plans by targeting hormonal influences that stimulate hunger and cravings. These agents may be the only therapy that counters the effects of metabolic adaptation that occur after weight reduction. Antiobesity agents may be used prior to bariatric surgery and may also be started or continued after surgery. Data show that people who have undergone bariatric surgery have more weight reduction when medication management for obesity is started at the point when weight plateaus rather than when weight regain occurs.11 Because obesity is a chronic disease, medications will likely need to be continued indefinitely, which is the same approach that is used for other chronic conditions, such as diabetes and hypertension.
The US Food and Drug Administration (FDA) indications for the use of antiobesity medications include patients with obesity (BMI ≥30) and patients with overweight/preobesity (BMI ≥27) with at least 1 weight-related complication.9 These BMI cutoff points do not consider the lower BMI values that are used to diagnose preobesity/overweight and obesity among those of Asian or Pacific Islander heritage. Prescribing for those individuals with lower BMI values who have abdominal obesity, elevated body fat percentage, or other adiposity-based conditions that would improve with weight reduction is considered off-label.9 In these cases, it is important to consider the benefits of intervening before weight increases and complications develop or worsen. The FDA eligibility criteria are based solely on BMI, which may not fully reflect how excess adiposity is affecting the health of an individual.
FDA-Approved Medications
The FDA has approved 5 medications for chronic use in the treatment of obesity: liraglutide 3.0 mg, naltrexone/bupropion, orlistat, phentermine/topiramate, and semaglutide 2.4 mg. Phentermine, diethylpropion, and phendimetrazine have been approved by the FDA for short-term use. The agents work primarily by regulating hormones in the brain, digestive system, and adipose tissue to suppress appetite and cravings, and to promote satiety, with each medication having a unique mechanism of action.11 Reported mean weight reduction from medication is 3% to 15% For individuals who do not respond to treatment, the weight reduction may be minimal to none (Table).9,11
Several investigational agents are in development for the treatment of obesity. A promising new dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist agent, tirzepatide, is in phase 3 clinical trials. The first trial, SURMOUNT-1 (ClinicalTrials.gov Identifier: NCT04184622), weight reduction of up to 25% was reported with 91% to 95% of study participants achieving a weight reduction of greater than >5%.9 On May 13, 2022, tirzepatide received FDA approval for the treatment of type 2 diabetes and is now available for that indication.
Despite its effectiveness, only 1% to 2% of individuals eligible for medication management for obesity receive antiobesity treatments.12 Barriers to prescribing include lack of awareness and education about obesity and antiobesity medications, weight bias, cost/lack of insurance coverage, perception that these medications are not effective, patients not asking for them, and patients not wanting to take them.4,13,14 To overcome these barriers, clinicians must examine their biases, educate themselves and their patients, and familiarize themselves with best prescribing practices.
Medication therapy may be initiated at the beginning of treatment or at any point after lifestyle therapies and/or bariatric surgery have been implemented. Decisions about when to introduce therapy should be made in collaboration with the patient. Agent choice is based on the desired metabolic and feeding effects, as well as contraindications, cost/insurance coverage, and patient preference.4
Patient Education and Treatment Initiation
People with obesity often blame themselves for their condition and see it as their responsibility to manage it. This internalized weight bias may prevent them from considering medication management. Individuals with obesity may have the perception that if they “just try harder,” they can reduce their hunger and cravings, eat more healthfully, and reduce their weight. Helping them understand the biological processes that contribute to their adiposity, hunger, cravings, and reduced satiety can contribute to them seeing obesity as a condition that warrants effective treatment as much as any other chronic condition.
The clinician should present the available options and discuss the desired effects, side effects, cost/insurance coverage, and delivery method of each medication. Two of the agents — liraglutide and semaglutide — are delivered by injection, which may make patients reluctant about these options. Given their enhanced efficacy as compared with oral agents, counseling patients about the small 32-gauge needle and a demonstration of the process may be enough to ease their fears and open them to considering this mode of delivery.
Medication initiation and titration should be performed carefully and strategically. Side effects most often occur during initiation and dose escalation, so frequent monitoring during the early weeks allows the clinician to evaluate and manage side effects, monitor efficacy, and manage patient expectations. Encouraging patients to reach out early if they are experiencing troublesome side effects, such as nausea, vomiting, diarrhea, insomnia, or headaches, can help to mitigate the issues before they become problematic. The titration schedule provided by the manufacturer should be viewed as a suggestion as many patients benefit from a slower titration. It is not advisable to accelerate the titration; it is better to ensure that the patient is tolerating the current dose before escalating to a higher dose. This approach decreases the likelihood of side effects that may lead to treatment discontinuation, thus eliminating a treatment option that may have proven to be effective. Once the patient has reached the full dose and is tolerating the medication, appointment frequency can be decreased.
When starting antiobesity medications, patients may have questions about how long they will need to take the medications or express concerns about taking these agents indefinitely. Patients may not understand the chronic nature of obesity and the need for continued therapy. This provides clinicians with another opportunity to educate patients about the chronic nature of obesity and the need to continue medications in the long term to successfully manage the disease.
Continuation and Discontinuation
For patients with a favorable response to treatment and no safety issues, the antiobesity medication should be continued. If the medication is not providing the expected benefits 12 to 16 weeks after achieving a full dose, the medication should be discontinued and another one started.15 Some antiobesity medication manufacturers recommend discontinuation if weight has not been reduced by 4% to 5% at 12 to 16 weeks after reaching the full dose. It is important to keep in mind that this guidance is not aligned with the fact that obesity is a chronic disease and that treatment goals go beyond weight reduction. Before discontinuing a medication, clinicians must consider the goals of maintaining weight reduction, preventing weight gain, improving and preventing obesity complications, and improving quality of life.
Conclusion
Obesity is a serious chronic disease that causes anatomic, metabolic, and psychological complications that significantly impair health and quality of life and shorten life expectancy.1 Comprehensive, evidence-based treatment should be initiated as early in the disease course as possible as delayed intervention leads to the development and worsening of complications. Medications for the management of obesity are safe and effective and are one of the pillars of comprehensive obesity treatment. When clinicians educate their patients about the chronic nature of obesity and offer them evidence-based treatment, health outcomes and quality of life improve.
Sandra M. Christensen, MSN, ARNP, FNP-BC, FOMA, is an obesity medicine specialist in Seattle, Washington. She founded Integrative Medical Weight Management, where she provides comprehensive evidence-based treatment. She is a trustee of the Obesity Medicine Association and the Washington Obesity Society. She is an associate editor of Obesity Pillars and the author of A Clinician’s Guide to Discussing Obesity with Patients.
References
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