Using Obesity Medication in the Primary Care Setting

Obesity is a chronic medical condition and one of the main public health problems in the United States. Data from the most recent National Health and Nutrition Examination Survey (NHANES) showed that obesity rates from the period of 2015-2016 were 39.6 percent in adults and 18.5 percent in children. These ﬁgures represent the highest percentages ever documented. With the increasing rates of obesity, it is imperative that primary care providers become familiar with the weight- gaining side effects of many common chronic medications and the use of anti-obesity medications.

Medications That May Increase Body Weight

Many medications have the potential to alter body weight. Primary care providers should discuss with patients and other providers to consider ﬁnding pharmacological alternatives with less potential for weight gain.

y Cardiovascular: Some beta-blockers (propranolol, atenolol, metoprolol), dihydropyridines, and calcium channel blockers (amlodipine, nifedipine, felodipine) y Diabetes Mellitus: Most insulins, sulfonylureas, thiazolidinediones, and meglitinides y Hormones: Glucocorticoids, estrogens, injectable or implantable progestins may have the greatest risk for weight gain y Anti-seizure: Carbamazepine, gabapentin, valproate, and pregabalin y Anti-depressants: Some tricyclic antidepressants (tertiary amines) like amitriptyline, doxepin, imipramine; Some selective serotonin re-uptake inhibitors (e.g., paroxetine, citalopram, escitalopram, sertraline, duloxetine); Some selective serotonin and norepinephrine re-uptake inhibitors (e.g., venlafaxine); Some irreversible monoamine oxidase inhibitors (e.g., isocarboxazid, phenelzine); Others like mirtazapine and brexiprazole y Mood Stabilizers: Gabapentin, divalproex, lithium, valproate, vigabatrin, cariprazine, and carbamazepine y Migraine: Amitriptyline, gabapentin, paroxetine, valproic acid, and some beta-blockers y Anti-psychotics: Olanzapine, quetiapine, clozapine, risperidone, zotepine, asenapine, chlorpromazine, Iloperidone, paliperidone, sertindole, lithium, and bexipiprazole y Hypnotics: Diphenhydramine y Human Immunodeficiency Virus (HIV): Some highly active anti-retroviral therapies (HAART) protease inhibitors without HIV lipodystrophy y Chemotherapies and Anti-inflammatory Agents: Tamoxifen, cyclophosphamide, methotrexate, 5-fluorouracil, aromatase inhibitors, and corticosteroids

Written by Doris X. Muñoz- Mantilla, MD, FOMA © Obesity Medicine Association. All rights reserved. Materials may not be reproduced, redistributed, or translated without written permission. Using Obesity Medication in the Primary Care Setting

Medications That May Decrease Body Weight

y Metformin: May help improve adiposopathic disorders (insulin resistance, polycystic ovarian syndrome, fatty liver, and cardiovascular disease, especially when compared to sulfonylurea); May help treat complications of other concurrent drug treatments (antipsychotic-related weight gain and HIV protease inhibitor-associated abnormalities [i.e., HIV lipodystrophy]); May help reduce the overall cancer rate and help improve the treatment of colon, ovary, lung, breast, and prostate cancers; May reduce appetite; May improve leptin sensitivity, reduce neuropeptide Y levels, and increase glucagon- like peptide-1 (GLP-1) activity (i.e., increased GLP-1 levels and receptors) y Other Diabetes Medications: GLP-1 agonists, sodium glucose co-transporter 2 inhibitors, alpha glucosidase inhibitors, and pramlintide y Anti-seizure Medications: Lamotrigine, topiramate, and zonisamide y Anti-depressants: Bupropion and ﬂuoxetine (variable)

As with the treatment of other chronic medical conditions, pharmacotherapy is an important component of a complete obesity treatment plan that also includes nutrition, physical activity, and behavior changes. The beneﬁts of anti-obesity medications include: appetite control, improvement of eating behavior, and slow progression of weight gain and regain. Anti-obesity medications can also improve the metabolic complications of obesity, such as insulin resistance and glucose levels.

Consider using anti-obesity medications in adults with obesity (BMI > 30) or overweight (BMI > 27) with increased complications from adiposity. Before starting a patient on an anti-obesity medication, discuss realistic expectations for weight loss; 5-10 percent weight loss is average with improvements in both metabolic disease and fat disease. After beginning pharmacotherapy for obesity, monitor the patient to determine their progress and periodically reassess their medication regimen. If the patient shows no clinical improvement (e.g., at least 4-5 percent loss of baseline body weight) after 12-16 weeks with one medication, then consider an alternative medication or increasing the dosage (if applicable).

In general, anti-obesity medications are contra-indicated in pregnancy and should not be administered to or taken by women who are pregnant or trying to become pregnant.

Before 2012, there were few anti-obesity medications approved by the U.S. Food and Drug Administration (FDA). The top medications at that time were phentermine and orlistat. Since 2012, the FDA has approved four additional anti-obesity medications for long-term weight management: lorcaserin, phentermine-topiramate, bupropion/naltrexone, and liraglutide.

Currently Available Anti-obesity Medications

y Phentermine: Available in daily doses of 37.5 mg, 30 mg, 15 mg, and 8 mg. FDA-approved for short -term use. Phentermine is an adrenergic agonist that produces appetite suppression. Side effects include: dry mouth, insomnia, dizziness, and irritability. Use caution in patients with hypertension. y Orlistat: Pill that inhibits pancreatic and gastric lipase, decreasing fat absorption in the gastrointestinal tract. Available in doses of 120 mg and 60 mg OTC to be taken with meals. Side effects include: ﬂatulence with fatty discharge and fecal urgency after consumption of high- fat foods and other side effects that lead to medication discontinuation. y Lorcaserin: Selective serotonin 5HT 2c receptor agonist that suppresses appetite. Well-tolerated but has modest weight loss results. Side effects include: headache, nausea, dizziness, euphoria, and impairment of attention-cognition. Lorcaserin is not recommended for patients taking other serotonin-modulating medications or with known cardiac valvular disease. y Phentermine-Topiramate Extended Release: Combines an adrenergic agonist with a neurostabilizer. Daily doses with four strengths start at 3.75/23mg to 15mg/92mg. Good candidates are adults with migraines and obesity. Side effects include: abnormal sensations, dizziness, taste alterations, insomnia, constipation, and dry mouth. Contra-indications include: uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants. If more than 5 percent weight loss is not achieved after 12 weeks of the maximum dose, gradually discontinue.

y Bupropion/Naltrexone: Combines a dopamine/norepinephrine re-uptake inhibitor and an opioid receptor antagonist. Start the patient with a daily dose of 8/90 mg tablet to four tablets a day. Bupropion/Naltrexone controls cravings and addictive behaviors related to food. Side effects include: constipation, headaches, insomnia, and dry mouth. Contra-indications include: uncontrolled hypertension, history of seizures, and opioid use and dependence. y Liraglutide: GLP-1 receptor approved under different names for both type 2 diabetes and weight loss. Doses start at 0.6 mg to 3 mg a day. Liraglutide delays gastric emptying and causes satiety. Good candidates are adults with diabetes and prediabetes. Side effects include: nausea, vomiting, diarrhea, constipation, and abdominal pain. Contra-indicated in patients with personal or family history of medullary thyroid carcinoma.

Like with other chronic medical conditions, the treatment of obesity warrants frequent visits. When initiating pharmacotherapy, the recommended frequency is every 2-4 weeks to monitor medication adherence, side effects, and necessary augmentation of medications. As the patient achieves weight loss, the beneﬁts will extend to other chronic conditions, including diabetes, hypertension, and depression. Monitor other chronic medications, and decrease or adjust doses as necessary. Most anti-obesity medications are safe to use as a long-term therapy and will play an important role in weight maintenance and prevention of weight regain after signiﬁcant weight loss is achieved.

References

1. Bays HE, McCarthy W, Christensen S, Wells S, Long J, Shah NN, Primack C. Obesity Algorithm®, presented by the Obesity Medicine Association. www. obesityalgorithm.org. 2019. 2. Tools for Successful Weight Management in Primary Care. Christy Boling Turer, MD, MHS. Am J Med Sci. Author manuscript; available in PMC 2016 Dec 1. 3. Prescription Medications to Treat Overweight and Obesity, NIH, National Institute of Diabetes and Digestive and Kidney Diseases.

Disclaimer: This article is intended for informational purposes only. It is not intended to serve as or be interpreted as rules, guidelines, and/or directives regarding the prescribing of medications or the medical care of an individual patient. The ﬁnal decision regarding the optimal care of the patient is dependent upon the individual clinical presentation and the judgment of the clinician acting in the best interest of the patient.