Weight Loss Medications: An Adjunct To Lifestyle Interventions?

The primary management of obesity includes diet, physical activity, and behavioral modification. If these therapies alone are not successful in promoting at least a 5% weight reduction, weight loss medications may be considered as a second-line treatment for weight management.1,2  Patients who have a body mass index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 with obesity-related risk factors (e.g., high blood pressure or diabetes) may be eligible for weight loss medications to be utilized alongside primary management therapies.1,2

Currently there are six weight loss medications that are FDA approved for long term use. This means they can be used for as long as it is beneficial for weight reduction or maintenance and is not causing undesirable side effects. We’ve summarized each medication below, covering everything you need to know.

Orlistat (Xenical® or Alli®)3

Indications: Used to manage obesity in combination with a reduced calorie meal plan, as well as reducing risk for weight regain after prior loss.

Mechanism of Action: An intestinal lipase inhibitor that blocks the breakdown of dietary triglycerides into fatty acids and monoglycerides. Because undigested triglycerides are not absorbed, a calorie deficit may occur. Inhibits absorption of dietary fat by 30%.

Contraindications: Cholestasis, chronic fat malabsorption, pregnancy

Adverse Effects: Abdominal discomfort, flatulence, steatorrhea, headache, liver failure, kidney stones

Dosing: 120 mg orally 3 times per day during or within 1 hour of each fat-containing meal. Over-the-counter dose is 60 mg orally 3 times per day during or within 1 hour of each fat-containing meal.

Important Notes: A multivitamin is needed (include fat soluble vitamins A, D, E, K). Take at least 2 hours before/after taking orlistat.

Phentermine/Topiramate Extended Release (Qsymia®)3

Indications: Used to manage obesity as an adjunct to diet and physical activity

Mechanism of Action: Mimics the pharmacologic activity of amphetamines. An anorectic which helps to increase the hypothalamic release of catecholamines, causing decreased appetite and food intake. Topiramate is thought to suppress appetite and increase satiety.

Contraindications: Hyperthyroidism, pregnancy, breastfeeding, glaucoma, concurrent use with monoamine oxidase inhibitors (MAOI) or within 14 days of discontinuing MAOI. Doses higher than maintenance dosing are not recommended for patients with moderate or severe renal impairment or those with moderate hepatic impairment.

Adverse Effects: Paresthesia, dysgeusia, constipation, xerostomia, dizziness, blurred vision, seizures, insomnia, kidney stones, increased heart rate, mental disturbances.

Dosing: The initial dose is phentermine hydrochloride 3.75 mg/topiramate 23 mg orally once per day for 14 days. The maintenance dose is phentermine hydrochloride 7.5 mg/topiramate 46 mg once per day.

Important Notes: If 3% weight loss is not achieved within 12 weeks on 7.5 mg/46 mg dose, discontinue or escalate dosing. Discontinue medication if 5% weight loss is not achieved after 12 weeks on the maximum daily dose of 15 mg/92 mg.

Naltrexone Sustained Release (SR)/Bupropion SR (Contrave®)3

Indications: Used to manage obesity as an adjunct to diet and physical activity.

Mechanism of Action: Naltrexone is an opioid antagonist and bupropion is an aminoketone antidepressant with weak inhibitory effects on neuronal reuptake of dopamine and norepinephrine which helps to regulate food intake, according to nonclinical studies. The exact neurochemical effects that lead to weight loss are not fully understood.

Contraindications: Concomitant use of chronic opiates, opiate agonists, or MAOI; acute opiate withdrawal orabrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs, eating disorders, seizures, pregnancy, breastfeeding, uncontrolled hypertension, or use of other bupropion-containing products.

Adverse Effects: Hypertension, increased heart rate, flushing, rash, abdominal pain, nausea, constipation, vomiting, cholecystitis, diarrhea, xerostomia, headache, dizziness, insomnia, seizure, anxiety, depression, irritability.

Dosing: Initial dose is naltrexone 8 mg/bupropion 90 mg (1 tablet) orally once per day in the morning for week one. Then, 1 tablet two times per day (morning and evening) for week two. Then, 2 tablets in the morning and 1 tablet in the evening for week three. Then, 2 tablets orally two times per day, morning and evening, for a total daily dose of naltrexone 32 mg/bupropion 360 mg for maintenance dosage for week four and beyond.

Important Notes: Discontinue medication if at least 5% weight loss is not achieved after 12 weeks at maintenance dosage.

Liraglutide 3.0 mg (Saxenda®)3

Indications: Used to manage obesity as an adjunct to diet and physical activity.

Mechanism of Action: An acylated human glucagon-like peptide-1 (GLP-1) receptor agonist that increases the release of insulin in the presence of elevated blood glucose levels, decreases glucagon secretion in a glucose-dependent manner, and delays gastric emptying. This helps to decrease the rate that postprandial blood glucose enters circulation. GLP-1 regulates appetite and calorie intake. Weight loss is likely due to decreased energy intake.

Contraindications: Pregnancy, breastfeeding, history of medullary thyroid cancer, history of endocrine neoplasia syndrome type 2

Adverse Effects: Hypertension, increased heart rate, rash, hypoglycemia, indigestion, nausea, headache, abdominal pain, diarrhea, constipation, vomiting, fatigue, dizziness, pancreatitis, cholelithiasis, acute renal failure, sinusitis, angioedema

Dosing: The initial dose is 0.6 mg per day subcutaneous for one week increasing by 0.6 mg/day until maintenance dose of 3 gm per day subcutaneous is reached.

Important Notes: Discontinue medication if 4% weight loss is not achieved by week 16.

Semaglutide (Wegovy®)3

Indications: Used to manage obesity as an adjunct to diet and physical activity.

Mechanism of Action: GLP-1 receptor agonist that binds to and activates the GLP-1 receptor, which is the physiological regulator of appetite.

Contraindications: History of medullary thyroid cancer, multiple endocrine neoplasia syndrome type 2, pregnancy, or intentions of pregnancy within two months.

Adverse Effects: Increased heart rate, depression, nausea, diarrhea, vomiting, constipation, dizziness, flatulence, gastroesophageal reflux disease, headache, pancreatitis, cholelithiasis, hypoglycemia, acute renal impairment, diabetic retinopathy.

Dosing: Initiate at 0.25 mg once a week on the same day for four weeks. Each four weeks following, increase dosing until the maintenance dose of 2.4 mg is reached. Pre-filled, single dose pens are available in 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg.

Important Notes: If patients are unable to tolerate 2.4 mg maintenance dosing, can temporarily decrease to 1.7 mg dose. After 4 weeks, increase dose back to maintenance 2.4 mg. If a patient is unable to tolerate maintenance dosing, discontinue medication.

Setmelanotide (IMCIVREE®)3

Indications: Used to manage obesity in adult and pediatric patients six years of age and older with obesity due to rare genetic conditions such as proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.

Mechanism of Action: Melanocortin 4 (MC4) receptor agonist that restores the impaired MC4 receptor pathway activity. MC4 receptors in the brain are associated with regulation of hunger, satiety, and energy expenditure.

Contraindications: Obesity due to suspected POMC, PCSK1, or LEPR deficiency with POMC, PCSK1, or LEPR variants classified as benign or likely benign, as well as obesity from causes not associated with these rare genetic conditions.

Adverse Effects: Depression, skin hyperpigmentation, nausea, headache, diarrhea, abdominal pain, fatigue, vomiting, spontaneous penile erections, upper respiratory tract infection.

Dosing: In adults and children ages 12 and up, the starting dose is 2 mg (0.2 mL) once a day for two weeks. If tolerated, advance to 3 mg (0.3 mL) once a day. For children ages 6 to 12 years of age, the starting dose is 1 mg (0.1 mL) per day for two weeks; if tolerated may increase to 2 mg (0.2 mL) once daily. If higher dose intolerable, lower doses are provided.

Important Notes: Discontinue medication if a patient has not lost at least 5% of baseline body weight or 5% of baseline BMI (for patients with continued growth potential) within 12 to 16 weeks of use.

Studies demonstrate that weight loss medications generate an approximate 5% reduction in weight at 52 weeks when compared to placebo.4 Individualized diet, increased physical activity, and behavioral modifications remain necessary for optimal weight loss outcomes while utilizing anti-obesity medications, as well as continual monitoring of the safety, efficacy, appropriateness and tolerance of these medications prescribed.

Kimberly Gottesman is a freelance registered dietitian with a strong background in clinical and food service management. Her clinical and research interests include neonatology, critical care, and weight management. Kim Meeuwsen, RDN, CSOWM is a registered dietitian and Certified Specialist in Obesity and Weight Management from West Michigan. Kim has over 10 years of experience providing nutrition care to both inpatients and outpatients in acute care and rehabilitation settings.

Dietitians On Demand is a nationwide staffing and recruiting company for registered dietitians, specializing in short-term, temporary and permanent-hire positions in acute care, long term care and food service positions. We’re dedicated to dietitians and helping them enhance their practice and excel in the workplace. Check out our job openings, request your coverage, or visit our store today! 


References:
Safavi R, Lih A, Kirkpatrick S, Haller S, Bailony MR. Impact of anti‐obesity medication initiation and duration on weight loss in a comprehensive weight loss programme. Obesity Science & Practice. 2019;5(5):468-478. doi:10.1002/osp4.361
Tak YJ, Lee SY. Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review. The World Journal of Men’s Health. 2021;39(2):208. doi:10.5534/wjmh.200010
DRUGS@FDA: FDA-approved drugs. accessdata.fda.gov. https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed July 6, 2022.
Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events. JAMA. 2016;315(22):2424. doi:10.1001/jama.2016.7602

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