The AACE/ACE guidelines recommend that weight loss medications be initiated as an adjunct to lifestyle therapy when a patient has failed or regained weighton lifestyle therapy or in the presence of weight-related complications. The algorithm categorizes the five US Food and Drug Administration-approved weight-loss medications for chronic weight management as “preferreddrug,” “use with caution,” or “avoid” to help clinicians individualize treatment based on a patient’s clinical characteristics or coexisting disease. A total of19 are included, from diabetes prevention to hepatic impairment to opioid use to post-bariatric surgery.1 

These five weight-loss medications—orlistat, lorcaserin, phentermine/topiramate ER, naltrexone/bupropion, and liraglutide—and where they rank as “preferred agents” based on comorbidity or patientcharacteristics are highlighted in the Table. The FDA indication for all medications is BMI ≥30 kg/m2 or BMI ≥27 kg/m2 withsignificant comorbidity.1

The American Heart Association/American College of Cardiology, The Obesity Society and The Endocrine Society guidelines also endorse consideration ofantiobesity medications.4 However, a recent study found few received this option: of more than 2 million eligible patients, only 1% were written aprescription, and their use of these medications was not continuous.2 Cited barriers to successful use of weight-loss medications include lack ofphysician training, lack of reimbursement for office visits, and poor insurance coverage.


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These are all areas that need improvement in order to better treat obesity as a chronic disease.

Anti-obesity agents in the pipeline are the injectable beloranib, whichreduces appetite and stimulates use of stored fat; low-dose phentermine; and combination therapies.

References

1.       American Association of Clinical Endocrinologists/American College of Endocrinology. AACE/ACE Algorithm for theMedical Care of Patients with Obesity. Available at: https://www.aace.com/files/guidelines/ObesityAlgorithm.pdf

2.   Bessesen DH, McCormick E, Saxon, DR, et al. Patterns of prescribing weight loss medications in a large cohort of adults. Paper Presentation at ENDO2016, Boston, MA, April 3, 2016. Available at: https://endo.confex.com/endo/2016endo/webprogram/Paper28282.html

3.   Garvey WT, Mechanick JI, Brett EM, et al., and Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of ClinicalEndocrinologists and American College of Endocrinology. Clinical Practice Guidelines for Comprehensive Medical care of Patients with Obesity – ExecutiveSummary. Endocr Pract. 2016; DOI:10.4158/EP161365.GL. Available at: https://www.aace.com/files/guidelines/ObesityExecutiveSummary.pdf

4.   Saunders KH, Kumar RB, Igel LI, Aronne LJ. Pharmacologic approaches to weight management: recent gains and shortfalls in combating obesity. CurrAtheroscler Rep. 2016;18:36.

U.S. Food and Drug Administration-Approved Agents for Long-term Treatment of Obesity

Agent Trade Name FDA Approval MOA Preferred Agent for the Following Coexisting Disease/Patient Characteristic Possible Adverse Events

Orlistat (capsule)

Xenical Alli

1999

Lipase inhibitor

Age ≥65 years (limited data)

Alcoholism/addiction

Anxiety

Binge eating disorder

Cardiovascular disease (CAD, arrhythmia)

Chronic kidney disease (mild or moderate)

Depression

Diabetes prevention (metabolic syndrome, prediabetes)

Glaucoma

Hypertension

Opioid Use

Pancreatitis (monitor for symptoms)

Seizure disorder

Type 2 diabetes

Women of reproductive potential (discontinue with pregnancy)

Oily spotting

Flatus with discharge

Fecal urgency

Fatty/oily stool

Oily evacuation

Increased defecation

Fecal incontinence

Lorcaserin (tablet)

Belviq

2012

Serotonin (5HT2c) receptor antagonist; promotes appetite suppression, increases satiety

Anxiety

Cardiovascular disease (CAD, arrhythmia [monitor for bradycardia])

Chronic kidney disease (mild or moderate)

Glaucoma

Hypertension

Nephrolithiasis

Opioid Use

Pancreatitis

Seizure disorder

Type 2 diabetes

Women of reproductive potential (discontinue with pregnancy)

Non-diabetic patients:

Headache

Dizziness

Fatigue

Nausea

Dry mouth

Constipation

Diabetic patients:

Hypoglycemia

Headache

Back pain

Cough

Fatigue

Phentermine/ topiramate ER (capsule)

Qsymia

2012

Phentermine: NE-releasing agent; promotes weight loss via sympathetic nervous system activation

Topiramate: GABA receptor modulation; suppresses appetite, enhances satiety

Age ≥65 years (limited data)

Anxiety (avoid maximum dose)

Chronic kidney disease (mild or moderate; for moderate, do not exceed recommended dose)

Depression (avoid maximum dose)

Diabetes prevention (metabolic syndrome, prediabetes)

Hypertension (monitor heart rate)

Opioid use

Pancreatitis

Post-bariatric surgery (limited data)

Seizure disorder (if discontinued at maximum dose, taper slowly)

Type 2 diabetes mellitus

Women of reproductive potential (discontinue with pregnancy; check monthly to identify early)

Paresthesia

Dizziness

Dysgeusia

Insomnia

Constipation

Dry mouth

Naltrexone/bupropion (extended-release tablets)

Contrave

2014

Naltrexone: Opioid antagonist

Bupropion: Reuptake inhibitors of DA and NE

Synergistic action in the CNS reward pathways reduces food intake

Anxiety

Chronic kidney disease (mild or moderate; for moderate, do not exceed Week 2 dose)

Nephrolithiasis

Pancreatitis

Type 2 diabetes mellitus

Women of reproductive potential (discontinue with pregnancy)

Nausea

Constipation

Headache

Vomiting

Dizziness

Insomnia

Dry mouth

Diarrhea

Liraglutide (SC injection)

Saxenda

2014

Glucagon-like peptide-1 (GLP-1) receptor agonist; improves glycemic control, decreases appetite, enhances satiety

Age ≥65 years (limited data)

Alcoholism/addiction

Anxiety

Chronic kidney disease (mild and moderate)

Depression

Diabetes prevention (metabolic syndrome, prediabetes)

Glaucoma

Hypertension (monitor heart rate)

Nephrolithiasis

Opioid use

Pancreatitis (monitor for symptoms; avoid if prior or current disease)

Post-bariatric surgery (data available for 1.8–3.0mg/day)

Seizure disorder

Type 2 diabetes mellitus

Women of reproductive potential (discontinue with pregnancy)

Hypoglycemia

Nausea

Diarrhea

Constipation

Vomiting

Headache

Decreased appetite

Dyspepsia

Fatigue

Dizziness

Abdominal pain

Increased lipase