OBESITY…GUIDELINES, DRUGS AND TIKTOK!

Author: Wendy Mobley-Bukstein, PharmD, BCACP, CDCES, CHWC, FAPhA; Associate Professor of Pharmacy Practice, Drake University; Ambulatory Care Pharmacist, Primary Health Care East Side Clinic

In 2013, obesity was classified as a chronic medical condition by the American Medical Association. 2021 National Health and Nutrition Examination Survey (NHANES) data tells us that 41.9% of Americans are obese.1 Obesity complicates comorbid chronic conditions such as heart disease, type 2 diabetes, stroke and certain types of cancer.1 Studies have shown that obesity also disproportionately affects certain ethnic/racial groups.2 There has been a correlation with lower socioeconomic status and lower education level too.3 Adults, children and adolescents experience similar social determinants of health and health inequities. In order to create more equitable accessibility to education, information and treatment, it is imperative that we as accessible healthcare providers be up-to-date on the guidelines and the best way to help the people in our communities.

Adult Obesity Guidelines

In 2013, the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society published the guideline for the Management of Overweight and Obesity in Adults. These guidelines were published prior to pharmacologic therapies that are available today, except for orlistat. These recommendations focused on five critical questions that guide providers in the evaluation and treatment of obesity. They focus on the benefits of weight loss, comprehensive lifestyle interventions, weight loss maintenance, and risk versus benefit of bariatric surgery.4

In 2016, the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) published evidence-based clinical practice guidelines that incorporated both body mass index (BMI) and weight-related complications. These guidelines also focused on nine critical questions with 123 recommendations that have specific statements associated with them. These evidence-based recommendations allow for screening, diagnosis, evaluation, selection of therapy, treatment goals and individualized care. These guidelines included the use of pharmacotherapy. The guidelines evaluated five products and their respective key clinical trials: orlistat, lorcaserin (removed from the market in 2019), phentermine/topiramate ER, naltrexone ER/bupropion ER, and liraglutide 3mg.(Table 10) The guideline took it a step further and outlined preferred medications for comorbid medical conditions.5 (Table 11)

In both guidelines, bariatric surgery is recommended for individuals where benefits outweigh risks and the BMI is >40 kg/m2 without comorbid conditions or BMI >35 kg/m2 if comorbid conditions exist.

ADOLESCENT & PEDIATRIC OBESITY GUIDELINES

The Centers for Disease Control and Prevention (CDC) states that obesity is affecting 14.4 million kids in the U.S. To address this critical health urgency, on January 9, 2023, the American Academy of Pediatrics (AAP) released their clinical practice guidelines for the Evaluation and Treatment of Children and Adolescents with Obesity.6 The guidelines have key action statements and consensus recommendations for pediatricians and other primary care providers who see children. These recommendations include an algorithm for screening, diagnosis, evaluation, and treatment of children and adolescents with obesity. Comprehensive therapy is based on four areas of treatment: motivational interviewing, intensive health behavior and lifestyle treatment, weight loss pharmacotherapy for individuals with obesity >12 years of age, and bariatric surgery for individuals with obesity over the age of 12.6 (Appendix 1)

The recommendation in the guideline outlines the following medications that can be used in pediatric obesity:* orlistat (12 years and older); liraglutide (12 years and older); metformin (if the child has type 2 diabetes, polycystic ovary syndrome or prediabetes, 10 years and older); phentermine (for short-term use of 3 months, 16 years or older), topiramate (headache prophylaxis and seizure control), phentermine/ topiramate (off-label use in 12-17 year-olds) or lisdexamfetamine (if the child has ADHD, off-label use).6

Bariatric surgery is recommended for BMI >35 kg/m2 with clinically significant disease such as metabolic diseases or cardiovascular disease or BMI >40 kg/m2 without comorbid conditions.

Conclusion

The current drug shortages being seen in the U.S. are numerous. We are seeing shortages of semaglutide for both obesity and diabetes indications (Wegovy and Ozempic). With guidelines and such positive weight loss results, these drugs are being used by EVERYONE looking to shed a few pounds, not just those individuals who meet the obesity criteria. These drugs are considered the new “quick fix” to weight loss and are part of a Hollywood weight loss craze after going viral on the social media platform, TikTok. It is our responsibility to educate on the benefits and risks of using these medications.

The prescribing of Ozempic to patients who need Wegovy for weight loss is causing a downstream supply issue with other products like Trulicity and Mounjaro. These have become mainstays of treatment for patients with type 2 diabetes. Due to the drug shortage, we have many patients who are waiting for their medication to be available. Most will have to begin the medication titration over because they have been out of drug, and they will have negative adverse effects if they go back to the dose they were taking prior to the shortage.

Obesity is a medical condition that has long term effects on health. It knows no boundaries. There are guidelines and clinical literature available to help us navigate the best way to help the people in our communities with obesity. We can advocate for our patients and recommend the best pharmacotherapy for each individual patient, if that is what is best for them. Be the resource in your community.

Current Approved Pharmacotherapy Options Available for Adults 18 Years and Older

Weeks 1-4: 0.25mg weekly

Weeks 5-8: 0.5mg weekly

Semaglutide (subcutaneous injection) Wegovy

Increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, slows gastric emptying, acts in the areas of the brain involved in regulation of appetite and caloric intake

Liraglutide (subcutaneous injection) Saxenda

Weeks 9-12: 1mg weekly

Weeks 13-16: 1.7mg weekly

Weeks 17 and maintenance: 2.4 mg weekly

Week 1: 0.6 mg daily

Week 2: 1.2mg daily

Week 3: 1.8mg daily

Week 4: 2.4mg daily

Week 5 and maintenance: 3 mg daily

Severe Adverse Effects: Acute kidney injury, pancreatitis, diabetic retinopathy

Common Adverse Effects: Nausea, vomiting, diarrhea/ constipation, injection site reaction, headache

Contraindications: Pancreatitis, medullary thyroid cancer

Phentermine: reduces appetite secondary to CNS effects, including stimulation of the hypothalamus to release norepinephrine

Phentermine/ Topiramate (tablet) Qsymia

Topiramate: weight management may be due to effects on appetite suppression and satiety enhancement based on the following potential mechanisms: blocks neuronal voltage dependent sodium channels, enhances GABA(A) activity, antagonizes AMPA/kainite glutamate receptors, and weakly inhibits carbonic anhydrase

Orlistat (capsule) Xenical, Alli (OTC)

Reversible inhibitor of gastric and pancreatic lipases; inhibits absorption of dietary fats by 30%

3.75mg/23mg daily for 14 days; increase as tolerated to 7.5mg phentermine/46mg topiramate daily for 12 weeks. If >3% baseline body weight has not been lost then switch to every other day dosing and discontinue after 1 week taper. For those individuals getting results, the dose can be tapered up every 14 days to a max dose of 15mg phentermine/92mg topiramate taken once daily. Evaluate weight loss after 12 weeks of therapy at max dose. If >5% of baseline weight has not been lost then gradually taper off over at least 1 week prior to discontinuation.

Xenical: 120mg TID with each main meal; can start with 60mg to improve GI tolerability;

Consider discontinuation after 3 months if weight loss is less than 4-5% of baseline weight

Alli: 60mg TID with each main meal containing fat; max dose OTC is 180mg/day

Increased heart rate, constipation, dry mouth, headache, sleep disorder (insomnia), decreased bone mineral density, increased SCr, decreased serum sodium bicarbonate

Suicidal Ideation

Contraindications: Hyperthyroidism, glaucoma, MAOIs therapy within 14 days, pregnancy, psychiatric disturbances

Fat soluble vitamin deficiency (A,D,E,K), steatorrhea, oily stools, oily rectal leakage, bowel urgency, flatulence with discharge, frequent bowel movements, abdominal pain and distress, headache, back and lower extremity pain

Warnings: Hepatotoxicity, increased urinary oxalate

Naltrexone: pure opioid antagonist

Bupropion: Weak inhibitor of neuronal uptake of dopamine and norepinephrine

Naltrexone/ buproprion (tablet) Contrave

Exact mechanism of combination is unknown; thought to be due to effects on areas of the brain involved in regulation of food intake: the hypothalamus and mesolimbic dopamine circuit

Week 1: naltrexone 8mg/bupropion 90mg (1 tablet) daily

Week 2: 1 tablet twice daily

Week 3: 2 tablets in the morning, 1 tablet in the evening

Week 4: 2 tablets twice daily

Max dose is naltrexone 32mg/ bupropion 360mg daily (4 tablets/day); Consider discontinuation after 3 months if weight loss is less than 4-5% of baseline weight

Drug Interactions!

Headache, sleep disorders, nausea, constipation, vomiting

Suicidal ideation/behavior has been reported

Contraindications: Concomitant use of MAOIs, uncontrolled hypertension, seizure disorder

Limited supply and in some areas on backorder

No current limitations on drug distribution

No current limitations on drug distribution

No current limitations on drug distribution

No current limitations on drug distribution

References:

1. https://www.cdc.gov/obesity/data/adult.html. Accessed 2.21.2023.

2. https://stacks.cdc.gov/view/cdc/106273. Accessed 2.21.2023.

3. https://www.cdc.gov/mmwr/volumes/66/wr/mm6650a1.htm?s_cid=mm6650a1_w. Accessed 2.21.2023.

4. https://www.ahajournals.org/doi/full/10.1161/01.cir.0000437739.71477.ee#T4. Accessed 2.21.2023.

5. https://www.endocrinepractice.org/article/S1530-891X(20)44630-0/fulltext. Accessed 2.21.2023.

*Please contact IPA for full pediatric drug table and dosing information.

6. https://publications.aap.org/pediatrics/article/151/2/e2022060640/190443/Clinical-Practice-Guideline-for-the-Evaluation-and?autologincheck=redirected. Accessed 2.21.2023.