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Fast Facts

A brief refresher with useful tables, figures, and research summaries

Obesity

Obesity has emerged as a primary public health concern in the last century and obesity-related conditions are one of the leading causes of preventable death in the United States. The health effects of obesity are far-reaching and include heart disease, hypertension, type 2 diabetes, obstructive sleep apnea, osteoarthritis, and cancer. In this section, we review management options for obesity.

The Centers for Disease Control and Prevention reports the following obesity statistics derived from the National Health and Nutrition Examination Survey (NHANES):

The prevalence of obesity in the United States between 1999-2000 and 2017-2020 increased from 30.5% to 41.9%. During the same time, the prevalence of severe obesity increased from 4.7% to 9.2%.
Non-Hispanic Black adults had the highest prevalence, followed by Hispanic adults, and non-Hispanic white adults.
Adults aged 40 to 50 years had the highest obesity prevalence, followed by adults older than 60 years, and adults aged 30 to 29 years.

[Image] — **Prevalence of Self-Reported Obesity Among U.S. Adults by State and Territory, 2021**

Classification of Obesity

Although body mass index (BMI) is not a perfect marker of obesity, some organizations use BMI to classify obesity according to the following categories:

Classification of Overweight and Obesity by BMI

Weight	BMI (kg/m²)	BMI (kg/m²) for Asians
Normal weight	18.5-24.9	18.5-22.9
Overweight	25.0-29.9	23-26.9
Obesity class I	30.0-34.9	27-32.4
Obesity class II	35.0-39.9	32.5-37.4
Obesity class III	>40	>37.5

Pathophysiology

The rising prevalence of obesity worldwide is likely multifactorial, and the postulated factors that have influenced its rise in the last few decades include an increasingly sedentary lifestyle, processed and caloric-dense foods, large portion sizes, and obesogenic environments (e.g., food deserts and fast food swamps).

On a microscopic level, adipose tissue deposition occurs over time in subcutaneous and visceral tissue and has several effects including increasing mechanical stress, releasing proinflammatory cytokines, and increasing sympathetic activity. The following figure illustrates the pathophysiology of obesity and its health-related complications.

Some of the health-related effects of obesity are reversible with weight loss. For instance, studies have shown that a 5% weight loss is associated with improvement in pancreatic beta-cell function and insulin sensitivity in liver and skeletal muscle. A 5%-10% weight loss has been associated with clinically meaningful improvements in obesity-related complications, including hypertension and hyperlipidemia.

After the initial period of weight loss, patients tend to regain weight because of factors that include:

decreased adherence to diet
decreased activity
increased endogenous compensatory mechanisms

Treatment

Treatment of obesity is a complex process that depends on the patient’s weight, associated medical conditions, and functional capacity. The main treatment options are lifestyle intervention, pharmacotherapy, and bariatric surgery.

Lifestyle interventions: As the first-line option in weight management, lifestyle interventions involve reduced food intake, increased physical activity, and behavioral motivational training. Studies that provide data to support the efficacy of lifestyle interventions include the Finnish Diabetes Prevention Study, Diabetes Prevention Program, and the Look AHEAD study. The table below summarizes guidelines for both weight loss and subsequent maintenance of weight loss from the 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults.

Counselling patients on weight loss is challenging. The “ABCDEF” approach is one method to consider to guide weight counseling with patients.

Although dietary modification is key to weight loss and maintaining weight loss, no single dietary strategy has been shown to be clearly superior. Current AHA/ACC guidelines recommend a diet high in vegetables, fruits, whole grains, fish, and legumes, with low intake of sugar, sweetened beverages, and red meats.

Medical management: Pharmacotherapy is recommended as an adjunct to dietary modification in patients with a BMI ≥30 or a BMI ≥27 and a weight-related coexisting condition. Several medications have been approved by the U.S. Food and Drug Administration for chronic weight management and several new medications (e.g., retatrutide) are likely to be approved in the next few years. The primary effect of these medications is to decrease appetite and improve dietary adherence. Once started on therapy, patients should be assessed for response to treatment. A target weight loss of 3%-5% should be achieved within 3 months, otherwise the medication should be discontinued. The following table summarizes the most commonly used medications used for long-term weight loss.

Commonly Used FDA-Approved Medications for Long-Term Weight Management

Drug	Main Mechanism of Action	Dose	Study Duration (weeks)	Mean Weight Loss kg (%)	Common Adverse Effects	Contraindications
Orlistat	Pancreatic and gastric lipase inhibitor; resulting fat malabsorption reduces net energy intake	120 mg before meals (three times a day)	52	Drug, 8.8 (8.8); placebo, 5.8 (5.8); PSWL, 2.6	Oily spotting, flatus with discharge, fecal urgency, oily evacuation, increased defecation, fecal incontinence	Pregnancy, chronic malabsorption syndrome, cholestasis
Liraglutide	GLP-1 agonist; delays gastric emptying to reduce food intake	Starting dose, 0.6 mg given subcutaneously once daily; dose increased weekly by 0.6 mg as tolerated to reach 3.0 mg	56	Drug, 8.4 (8.0); placebo, 2.8 (2.6); PSWL, 5.3	Nausea, vomiting, constipation, hypoglycemia, diarrhea, headache, fatigue, dizziness, abdominal pain, increased lipase levels	Pregnancy, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
Semaglutide	GLP-1 agonist; delays gastric emptying to reduce food intake	Starting dose, 0.25 mg given subcutaneously once weekly for first 4 weeks, with the dose increased every 4 weeks to reach the maintenance dose of either 1.7 or 2.4 mg	68	Drug, 15.3 (14.9); placebo, 2.6 (2.4); PSWL, 12.7	Nausea, vomiting, constipation, hypoglycemia, diarrhea, headache, fatigue, dizziness, abdominal pain, increased lipase levels	Pregnancy, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2
Tirzepatide	Dual GLP-1 and GIP agonist, delays gastric emptying to reduce food intake	Starting dose 2.5 mg given subcutaneously once weekly for first 4 weeks, with the dose increased every 4 weeks to reach a maintenance dose of 5, 10 or 15 mg (depending on clinical response)	72	Drug 15 mg dose, 22.1 (20.9); placebo, 3.2 (3.1), PSWL 17.8	Nausea, vomiting, diarrhea, constipation, dyspepsia	Pregnancy, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 Reduces efficacy of combined oral contraceptive pills.
Phentermine- topiramate	Norepinephrine-releasing agent (phentermine), GABA receptor modulation (topiramate); decreases appetite to reduce food intake	Starting dose, 3.75 mg/ 23 mg for 2 wk; recommended dose, 7.5 mg/ 46 mg; maximum dose, 15 mg/92 mg	56	Drug, 8.1 (7.8) at recommended dose, 10.2 (9.8) at maximum dose; placebo, 1.4 (1.2); PSWL, 8.8	Insomnia, dry mouth, constipation, paresthesias, dizziness, dysgeusia	Pregnancy, hyperthyroidism, glaucoma, MAOIs, hypersensitivity to sympathomimetic amines
Naltrexone- bupropion	Opioid antagonist (naltrexone), dopamine and norepinephrine reuptake inhibitor (bupropion); acts on CNS pathways to reduce food intake	1 tablet (8 mg of naltrexone and 90 mg of bupropion) daily for 1 wk; dose subsequently increased each wk by 1 tablet per day until maintenance dose of 2 tablets twice a day at wk 4	56	Drug, 6.2 (6.4); placebo, 1.3 (1.2); PSWL, 5.0	Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea	Uncontrolled hypertension, seizure disorders, anorexia nervosa or bulimia, drug or alcohol withdrawal, use of MAOIs, long-term opioid use, pregnancy

Surgical management: Weight loss through surgery should be considered in patients with BMI ≥40 or a BMI ≥35 and a coexisting condition (e.g., type 2 diabetes, sleep apnea, osteoarthritis). Currently, the following four types of weight-loss surgery are performed most often in the United States:

gastric banding
sleeve gastrectomy
Roux-en-Y gastric bypass
biliopancreatic diversion with duodenal switch

Read about the advantages and disadvantages of these surgical options here.

Research

Landmark clinical trials and other important studies

Research

Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

Jastreboff AM et al. N Engl J Med 2023.

In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight.

Tirzepatide Once Weekly for the Treatment of Obesity

Jastreboff AM et al. N Engl J Med 2022.

In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight.

Read the NEJM Journal Watch Summary

Listen to the Beyond Journal Club Podcast from Core IM

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Wilding JPH et al. N Engl J Med 2021.

In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.

Pharmacotherapy for Adults with Overweight and Obesity: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials

Shi Q et al. The Lancet 2021.

In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists were most effective in reducing weight. Semaglutide appeared to be the most effective of the GLP-1 agonists.

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts

Estruch R et al. N Engl J Med 2018.

In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet.

Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial

Trepanowski et al. JAMA Intern Med 2017.

In a trial comparing standard caloric restriction to intermittent (alternate-day) fasting, there were no differences in adherence, weight loss, weight maintenance, or markers of inflammation.

Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 5 Year Outcomes

Schauer PR et al. N Engl J Med 2017.

Five-year outcome data showed that, among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing, or in some cases resolving, hyperglycemia.

Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes

The LookAHEAD Research Group. N Engl J Med 2013.

An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes.

Effects of 4 Weight-loss Diets Differing in Fat, Protein, and Carbohydrate on Fat Mass, Lean Mass, Visceral Adipose Tissue, and Hepatic Fat: Results from the POUNDS LOST Trial

DeSouza et al. Am J Clin Nutr 2012.

Researchers randomized adults with BMIs of 25−40 to one of four calorie-restricted diets: (1) low fat, average protein; (2) low fat, high protein; (3) high fat, average protein; and (4) high fat, high protein. At 2 years, the mean amount of weight lost was similar with each of the four diets. Although various lipid parameters differed slightly among the four groups, all diets reduced risk factors for cardiovascular disease.