#44 Obesity Medication Overview from AACE 2017

June 19, 2017 | By Matthew Watto, MD

Master safe and effective use of obesity medications with Endocrinologist, Dr. Karl Nadolsky (co-author of 2016 AACE Obesity guidelines), Director of the Diabetes, Obesity & Metabolic Institute at Walter Reed National Military Medical Center. We get under the hood of each FDA approved obesity medication along with some of our normal hijinks. Check out episode #23 for a more general overview of obesity.

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Case: 45 yo M with Type 2 diabetes, BMI 39 presents asking for bariatric surgery referral. Has initially lost weight on multiple diets, but always regains the weight.

Clinical Pearls:

1. Obesity is a chronic DISEASE. It may require lifelong medical therapy like diabetes, hypertension (HTN) because once wt loss meds are stopped wt returns to pretreatment baseline : (
2. Obesity related complications: prediabetes, metabolic syndrome, DM2, dyslipidemia, HTN, cardiovascular disease, fatty liver, polycystic ovary syndrome, female infertility, male hypogonadism, obstructive sleep apnea, asthma/reactive airway disease, osteoarthritis, urinary stress incontinence, gastroesophageal reflux, depression
3. Indication for use of obesity medications: BMI > 30 or BMI >27 with obesity related complication (e.g. sleep apnea, DM2)
4. Stages of obesity: Stage 0: No complications; Stage 1: Mild to moderate complications. Treat with moderate weight loss, and consider pharmacotherapy; Stage 2: One or more severe complications. Aggressive weight loss therapy (add pharmacotherapy and consider bariatric surgery).
5. History: Start w/taking a detailed history of lifestyle (e.g. weight history, dietary baseline, activity level). Use Dr. Colburn’s questionnaire
6. All obesity medications have about 0.6% reduction in a1c. Liraglutide has 1% a1c reduction!
7. All FDA approved obesity medications are contraindicated in pregnancy.
8. Orlistat (Alli, Xenical): Reversible inhibitor of gastric and pancreatic lipases. Blocks 30% of fat absorption. Brands = Alli 60 mg tab, or Xenical 120 mg tab taken 3 times daily with fat containing meal. Side effects: steatorrhea (oil stools), flatulence with discharge, abdominal pain. Average of 4% weight loss.
9. Liraglutide (Saxenda): GLP-1 agonist (incretin). Works on GLP-1 receptors in brain to inhibit appetite. Also slows gastric emptying and improves beta cell function in pancreas. Start at 0.6 mg injected subQ daily and titrate up weekly (or as tolerated) to 3mg subQ once daily. Need at least 4% weight loss by 12 weeks to continue. Contraindicated if family history MEN2, or medullary thyroid cancer. Data on pancreatitis risk is still uncertain. Adverse effects: tachycardia, headache, hypoglycemia, GI upset, diarrhea. Discontinue at 16 weeks if at least 4% wt loss not achieved. (Ref: Lexicomp)
10. Phentermine/topiramate (Qsymia): Central appetite suppressant. About 8-9% weight loss on average. Side effects: Dry mouth, upper respiratory infection (pharyngitis), paresthesias, insomnia, palpitations, headaches, kidney stones, non-gap acidosis. Start phentermine/topiramate 3.75/23 mg capsule once daily. After 2 weeks increase to 7.5/46 mg once daily. At 12 weeks assess for at least 3% weight loss. Max dose 15/92 mg daily (max 7.5/46 mg if CrCl <50ml/min). Check Cr and electrolytes after 1 month (Ref: Lexicomp)
11. Naloxone/bupropion (Contrave): Central appetite suppressant. Contraindicated in uncontrolled HTN, anorexia/bulimia, seizure disorder, patient on linezolid. Side effects: nausea, vomiting, constipation, headache, “sleep disorder”. Comes in 8/90 mg tablets. Start 1 tab once daily for 1 week then 1 tab twice daily for 1 week, then titrate up by 1 tab weekly to max 2 tabs twice daily. Discontinue at 12 weeks if at least 5% wt loss has not been achieved.
12. Lorcaserin: believed to activate serotonin 5-HT2C receptors → stimulates proopiomelanocortin (POMC) neurons in arcuate nucleus of hypothalamus → satiety and decreased food intake. Dose = Immediate release 10 mg twice daily or extended release 20 mg once daily. Discontinue at week 12 assess if at least 5% weight loss not achieved. Fewer patients respond, but those who do often have 10% weight loss. Side effects: headache, hypoglycemia, abnormal lymphocyte count (low), upper respiratory infection (pharyngitis).

Physiology Reviewed

1. Pathophysiology: Appetite and metabolism are controlled by the hypothalamus. Receives input of hormones from fat cells (leptin, adiponectin, adipokines), intestines (GLP1, PYY, CCK), and stomach (ghrelin).
2. Leptin: Hormone produced by stomach. Binds receptors in central nervous system (CNS), including the hypothalamus and brainstem →  activates neural pathways that decrease appetite and increase sympathetic nervous system activity and energy expenditure (J Biol Chem 2010)
3. Ghrelin: Hormone produced by stomach. CNS action in hypothalamus stimulates appetite, enhances use of carbs and reduces fat utilization, increases gastric motility and acid secretion (Clin Chem 2004).
4. GLP-1 (glucagon-like peptide-1): hormone produced in the intestinal L cells; acts via circulation on satiety in the brain, gut motility, and insulin and glucagon secretion in the pancreatic islet (Diabetes Care 2013).

Goal: Listeners will safely and effectively use the FDA approved medications in the chronic management of obesity.

Learning objectives:
By the end of this podcast listeners will:

1. Explain the basic pathophysiology of obesity to patients
2. Utilize the FDA approved medications for weight loss therapy
3. Counsel patients on the risks and benefits of weight loss medications
4. Recall contraindications for approved weight loss medications
5. Counsel patients on common side effects of approved weight loss medications
6. Evaluate for efficacy of weight loss medications
7. Recall that obesity is a chronic disease that may require chronic medical therapy

Disclosures:
Dr. Karl Nadolsky reports no relevant financial disclosures.

Time Stamps
00:00 Intro
03:12 Picks of the week
08:44 Rapid fire questions
13:00 Counsel patients about obesity
14:40 Pathophysiology of obesity
18:00 Case
22:46 Phentermine/topiramate (Qsymia)
26:20 Bupropion/naltrexone (Contrave)
29:18 Liraglutide (Saxenda)
34:32 Orlistat (Alli, Xenical)
37:35 Cost issues
40:18 Lifelong medical therapy for obesity
42:44 Dr. Nadolsky’s take home points
44:45 The Curbsiders recap and discuss their experience with obesity medications
52:28 Outro

Links from the show:

1. Judge John Hodgman (podcast) on iTunes
2. Ragnarok (Netflix Special) by John Hodgman
3. Pilgrim at Tinker Creek (book) by Annie Dillard
4. The PreMed Playbook: Guide to the Medical School Interview (book) by Ryan Gray
5. http://Docswholift.com
6. Dr. Nadolsky on Facebook and Twitter
7. New patient lifestyle questionnaire. Courtesy Dr. Colburn’s Endocrinology practice
8. Tomlinson, S et al. Mechanisms, Pathophysiology, and Management of Obesity. NEJM 2016; 376(3)
9. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. NEJM 2016
10. Torgerson, JS et al. XENical (orlistat) in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004 Jan;27(1):155-61.
11. Treat and Reduce Obesity Act (article) on Obesity.org
12. AACE 2016 Obesity Guidelines:  https://www.aace.com/files/final-appendix.pdf
13. AACE Obesity Treatment Algorithm (highly recommended):  https://www.aace.com/files/guidelines/ObesityAlgorithm.pdf