Pharmacological Strategies for Pediatric Obesity

Abstract

Pharmacological options for the treatment of obesity in the pediatric population are growing rapidly. This chapter will review indications for the use of anti-obesity medications (AOMs) in children and adolescents, as well as detail the mechanisms of action, outcomes, side effects, patient selection, and suggested protocols for use for the following: incretins (liraglutide, semaglutide, tirzepatide), metformin, sympathomimetics (phentermine, phentermine/topiramate, lisdexamfetamine), topiramate, naltrexone/bupropion, orlistat, and setmelanotide. This chapter closes with notes from the field and case examples.

Appendices

Case 1: Patient A Is an 11-Year-old Female with a BMI of 41.3 kg/m²

HPI: Patient presents to the weight management clinic with her mother for assessment and management of high BMI. Mom notes that the Patient has been heavy since about age 2 years and has always been very hungry. Pregnancy was uncomplicated. Weight gain has been very rapid and they report a 15-lb weight gain in the past 2 months alone. She has been getting counseling from an eating disorders program for a diagnosis of binge eating disorder during this time. The patient and mom do not think it has been helpful.

PMH: Patient’s past medical history is notable for pre-diabetes, for which she has been taking metformin for about 1 year. She has had no hospitalizations or surgeries. She has no prior diagnoses of depression, anxiety, learning disabilities, or ADHD.

FH: Patient’s family history is notable for obesity in mother, who had a sleeve gastrectomy 5 years ago, and mother’s family. Father has pre-diabetes and mother has obstructive sleep apnea.

SH: Patient is an average student in sixth grade. She lives with both parents and four siblings in a blended family. Both parents are employed.

Medications: Her current medications include metformin XR 1000 mg QD.

ROS: Patient snores and has daytime fatigue. Menarche was last week.

Diet: Patient eats a well-balanced diet including meat, fish, whole grains, fruits, and vegetables. She also has chips and cookies sometimes but snacks tend to be leftovers (like spaghetti) or sandwiches (1–2). She rarely eats out and does not drink liquid calories.

Eating behaviors: Patient is always hungry, even after a meal she is looking for more to eat. She eats large portions of food and goes to the nurse’s office at 1:00 pm to get a snack so she will not overeat after school. She endorses eating in her bedroom and sometimes eats when bored or sad. She describes loss of control of eating a couple of times per week, which has not changed since starting treatment at the eating disorder program. She eats past fullness and sometimes feels bad after overeating.

Physical activity: Patient has gym class twice per week.

PE:	Weight: 228 lbs. (103.6 kg), >99th percentile
	Height: 5′ 2.32″ (1.583 m), 91%
	BMI: 41.34 kg/m2, 1.67 x 95th percentile
	BP: 120/56, P: 58
	Acanthosis nigricans at posterior neck
	Otherwise normal

Labs:	ALT 31 U/L, AST 20 U/L
	TC 143 mg/dL, TG 86 mg/dL, HDL 43 mg/dL, LDL 83 mg/dL
	HbA1c 5.8%, glucose 87 mg/dL

Assessment and Plan: Patient is an 11-year-old female with no significant past medical history who presents with early onset class 3 obesity complicated by pre-diabetes and symptoms of OSA. She endorses poor satiation (needs a lot of food to feel full), poor satiety (often hungry), and some features of binge eating disorder. Given the severe nature of her obesity disease, aggressive management is warranted. We discuss various treatment options including metabolic and bariatric surgery (MBS) and anti-obesity medications (AOMs). Although she meets the eligibility criteria for MBS, neither mom nor patient is ready to entertain this option presently. In terms of AOM, she is already taking metformin XR 1000 mg daily without much effect on her BMI, though HbA1c has been stable. While a GLP1RA may be the best choice for the Patient because of her pre-diabetes, it is not available at the time of her presentation to clinic. We opt to start topiramate as it has been shown to reduce weight and binge eating in adult clinical trials. Many patients also report “feeling full faster” when taking topiramate. Because of the early onset of her weight gain (i.e., severe obesity onset before 5 years of age), we discuss monogenic obesity as a potential etiology of her weight gain and plan for genetic testing. Finally, she is referred to sleep medicine with the knowledge that healthy sleep is critical for successful weight management.

• 1. Meet with RD today to start planning for portion size reduction.

• 2. Start topiramate 25 mg tablets: take 1 tablet (25 mg) PO QD x 1 week, then 2 tablets (50 mg) PO QD x 1 week, then 3 tablets (75 mg) PO QD until next visit. Obtain a basic metabolic panel for baseline bicarbonate to monitor for metabolic acidosis.

• 3. Continue metformin XR 1000 mg PO QD.

• 4. Sleep medicine referral.

• 5. Prevention Genetics monogenic obesity panel.

Treatment Course

PSG: AHI 2.3 events/hour; montelukast and intranasal fluticasone are recommended.

At week 6, weight remains stable with lifestyle therapy, metformin XR 1000 mg QD and topiramate 100 mg QD (family decided to increase from 75 to 100 mg on their own). Mom thinks metformin is more helpful than topiramate. Patient is still hungry. We increase metformin XR to 1000 mg BID, continue topiramate (though she did not have weight loss, weight gain has slowed), and added phentermine 8 mg QAM.

At month 2, weight is down 14 lbs. and binge eating behavior has improved with metformin XR 1000 mg BID, topiramate 100 mg QD, and phentermine 8 mg QAM. She is tolerating medications well (no side effects, normal BP, and HR) so we increase phentermine to 15 mg QAM and continue the others.

At month 8, weight continues to decrease but mom notes some sneaking of food after school and Patient endorses some binge eating with LOC eating. We add topiramate 50 mg after school.

At month 11, weight is stable and because they do not think the after-school topiramate is helping, we switch it to phentermine 8 mg, with caution to monitor sleep closely. At this time her AOM regimen is:

• Metformin XR 1000 mg BID.

• Topiramate 100 mg QAM.

• Phentermine 15 mg QAM + phentermine 8 mg Q afternoon.

Then, the COVID-19 pandemic started. We continue to meet, now virtually, every 2–3 months, alternating visits between the RD and MD. Her BMI continues to decrease despite the pandemic and being home for almost a year. She is walking regularly with her mom who continues to be very supportive.

In-person school resumes and the Patient is now in ninth grade. Her weight has been stable for many months (low 190 lbs) and she has to work very hard to keep it here. She is exercising a lot and is very mindful of her eating. She is open to starting a GLP1RA and fortunately, her insurance covers Ozempic (semaglutide) for pre-diabetes. She starts Ozempic 0.25 mg SQ weekly x 4, then increases to 0.5 mg weekly x 4, then 1 mg weekly. We continue topiramate 100 mg QAM and phentermine 15 mg QAM + 8 mg Q afternoon and stop metformin.

Her genetic panel revealed: variant of uncertain significance in ALMS.

Lessons Learned

• Obesity is a chronic health condition that requires long-term care. During that time, providers should expect to have to make medication adjustments, whether trying new options or changing doses.

• It is common for patients, particularly those with class 3 severe obesity, to require the use of multiple AOMs to achieve clinically significant weight reduction and maintain that progress.

Case 2: Patient B Is a 5-Year Old Boy with a BMI of 32.9 kg/m²

HPI: Patient presents to the weight management clinic with his mother for assessment and management of high BMI. Patient is an otherwise healthy boy with severe obesity. Mom reports that his birth weight was 8 pounds and 9 ounces. Pregnancy was uncomplicated including no history of hypertension or smoking. Mom gained approximately 40 pounds during her gestation. Patient’s neonatal course was uncomplicated. Mom reports that Patient’s weight started to increase more rapidly in this past year. From his growth chart, it appears that his weight was far above the 95th percentile as young as 2.5 years of age.

PMH: None. No concerns regarding development.

FH: Patient’s family history is notable for obesity in both parents and maternal grandparents, who also have diabetes. No gestational diabetes in mom.

SH: Patient lives with both parents but parents are separated. He attends pre-school two ½-days per week. When not at school, he is either at his maternal grandmother’s home or with mom at her boyfriend’s house. Mom works part-time as a nurse assistant in a clinic.

Medications: None.

ROS: Behavior can be challenging, especially when trying to enforce limits. This applies to food, but also to screens and sleep. Sleep is adequate and he does not snore. 10 point ROS is otherwise negative.

Diet: Patient’s diet is comprised primarily of simple carbohydrates and processed foods. He eats sugared cereal, pizza, ham sandwiches, and occasionally has whole fruit. He does not drink liquid calories except for 1% milk. He eats fast food 1–2 times per week.

Eating behaviors: Patient feels hungry all the time. Mom states that he is constantly asking for food and can eat very large amounts of food if allowed. For example, mom reports that his dad let him have 4 pieces of pizza followed by a sandwich, which was a snack. He gets upset when his food is limited. He does not access food on his own. He does not sneak or hide food. He does not experience abdominal pain or vomiting after eating too much.

Physical activity: Daily outdoor play.

PE:	Weight: 42.1 kg (92 lb. 13 oz), >99%
	Height: 1.13 m (3′ 8.5″), 73%
	BMI: 32.95 kg/m2, 1.83 x 95th percentile
	BP: 94/58, P: 78
	Poor coordination and lower extremity strength, otherwise normal

Labs:	ALT 28 U/L, AST 20 U/L
	TC 174 mg/dL, TG 85 mg/dL, HDL 68 mg/dL, LDL 91 mg/dL
	HbA1c 5.2%, glucose 84 mg/dL

Assessment and Plan: Patient is a 5-year-old boy with otherwise normal development and no significant past medical history who presents with class 3 severe obesity complicated by challenging behaviors. The primary contributors to Patient’s weight status include familial predisposition with poor satiation and satiety resulting in frequent consumption of very large amounts of food. Approximately 7% of children with early onset severe obesity with hyperphagia have a genetic variant that accounts for their size. This may be the case for this Patient. A syndrome is unlikely given his normal cognitive development. We plan to start lifestyle therapy alone and discuss that mom may benefit from meeting with a counselor for supportive parenting strategies given Patient’s history of resistance to limits. He will also see physical therapy (PT) to address his gross motor difficulties.

• 1. Meet with RD today to start planning for portion size reduction.

• 2. PT referral.

• 3. Genetics referral.

• 4. Mom wants to hold off on meeting with our psychologist for now.

Treatment Course

At 2 months: Weight remains stable. Mom offers that he is now drinking sugar-free soda and she is measuring his macaroni and cheese. Patient is not sneaking/hiding food and is not resistant to dietary changes. He is meeting with PT every 2 weeks.

At 6 months: Weight continues to remain stable. Patient continues to be very compliant with dietary changes. He has finished his course of PT and started kindergarten. Insurance will not pay for genetic testing.

At 8 months: BMI is down 6% from baseline with lifestyle therapy. Indeed, this is progress, but family is getting weary of their need for constant vigilance about healthy eating. Further, his BMI is still well within the range of class 3 obesity. We start Vyvanse 10 mg to see if this can quiet his hunger feelings.

At 10 months: BMI is decreasing faster. Patient and mom are now living with their grandmother. Grandmother observes a definite decrease in Patient’s eating since starting Vyvanse. This is especially obvious on days they accidentally miss doses. We increase Vyvanse dose from 10 mg to 20 mg as he is tolerating it well.

At 12 months: BMI is stable. Patient is very hungry, especially in evenings and mom does not think Vyvanse is working anymore. Patient is attending weekly karate classes and school is ending in summer. Knowing that most patients with severe obesity require more than one AOM which targets different neuropathways, we add topiramate 50 mg every afternoon to Vyvanse 20 mg QAM.

At 20 months: BMI has decreased with lifestyle therapy supported by topiramate 50 mg and Vyvanse 20 mg. But he is now beginning to sneak food and complain of being hungry again. We increase topiramate to 75 mg. Then, the COVID-19 pandemic starts. We continue to meet virtually and increase Vyvanse to 30 mg.

At 29 months: Patient is sneaking food and when at dad’s house, eating is unlimited and medication dispensing is irregular. We increase topiramate to 100 mg. Although divided doses of topiramate may be better, dosing is kept at once daily due to concerns with adherence. The patient was sent back to PT to re-establish care.

At 40 months: Patient is now 8 years old. Over the past 7 months, he gained 40 lbs. Family had been without health insurance and Patient was not taking any AOM. He is very hungry, sneaking and hiding food, and eating in the middle of the night. He also has symptoms of OSA. Physical activity is good (football season started). He also wants to resume PT. We discuss the very serious nature of Patient’s high BMI and that bariatric surgery is indicated for patients who have a BMI >1.4 times 95th percentile (Patient’s BMI is 1.95 × 95th percentile). We restart Vyvanse 30 mg and topiramate starting at 25 mg QD and ramping up to 100 mg QD.

Lessons Learned

• Patients less than 12 years of age, particularly those with severe obesity, benefit from the use of AOMs.

• Engagement in regular physical activity is strongly recommended for many health-related benefits, however, increased activity alone is very unlikely to yield a significant BMI reduction for children with severe obesity.

• When starting AOMs, the expectation is that this will be a long-term medication to treat a chronic biologic condition. Stopping of AOMs often leads to weight regain.

Case 3: Patient C Is a 15-Year-Old Adolescent Male with a BMI of 57.4 kg/m²

HPI: The Patient is a 15-year-old male who presents to the weight management clinic with a long-standing history of severe obesity, weighing approximately 90 pounds at 4 years, 150 pounds at 8 years, and nearly 200 pounds at 9 years of age. He had been seen in a weight management clinic between ages 8 and 10 years, during which time he was treated with lifestyle therapy and topiramate. However, he did not tolerate topiramate because it made him “weepy.” He was then lost to follow-up until now. He is presently interested in bariatric surgery.

PMH: Patient has depression and anxiety, with a history of passive suicidal ideation, but no suicide attempts. He started treatment with an SSRI several months ago. He meets weekly with a therapist. He had a broken arm 4 years ago.

FH: Patient is adopted but family knows that both biological parents had obesity.

SH: Patient lives with both adoptive parents. He is in ninth grade and gets average grades. He plays percussion.

Medications: Prozac 20 mg QD.

ROS: 10 point ROS is negative except for snoring and napping during the day.

Diet: Patient’s diet consists of very large portions of whole foods mostly. For example, breakfast consists of 4 eggs +4 pieces of toast. Lunch is 3–4 sloppy Joe sandwiches + extra meat. He used to drink a lot of liquid calories but this is now much reduced. Very little snacking between meals. He eats out twice per week.

Eating behaviors: Patient denies feeling hungry all the time. He eats during the night about once per week and eats when bored at times. He denies emotional eating and symptoms of binge eating disorder.

Physical activity: Sedentary.

PE:	Weight: 207.2 kg (456 lb. 12.7 oz), >99%
	Height: 1.9 m (6′ 2.8″), >99%
	BMI: 57.4 kg/m2, 2.22 × 95th percentile
	BP: 128/72, P: 78
	Acanthosis nigricans at posterior neck

Labs:	ALT 31 U/L, AST 28 U/L
	TC 153 mg/dL, TG 91 mg/dL, HDL 44 mg/dL, LDL 94 mg/dL
	HbA1c 4.3%, glucose 82 mg/dL

Assessment and Plan: Patient is a 15-year old adopted male who presents with class 3 severe obesity complicated by depression and anxiety, which is well-managed with Prozac, and symptoms of OSA. He was seen in a weight management clinic when he was 8–10 years of age and was treated with lifestyle therapy alone. Now, he and his parents are interested in bariatric surgery. We agree that this is an appropriate intervention given the severity of his obesity and begin the pre-surgery program, which at this center includes at least 6 monthly visits with a pediatric obesity medicine specialist, registered dietician, and psychologist.

Treatment Course

At month 3: Patient is losing weight with lifestyle therapy. He is keeping a meticulous food log.

At month 4: Patient is still losing weight but he is having passive suicidal ideation. We increase Prozac from 20 to 30 mg QD. Family and patient want to wait until summer to have surgery.

At month 7: Weight is starting to increase. Mood is unchanged. Still has chronic passive suicidal ideation and still taking Prozac 30 mg and meeting with a therapist weekly. We start phentermine 15 mg AQM and a few weeks later topiramate 75 mg QAM. We review the potential impact of topiramate on mood and risk of suicide as noted in the package insert. The Patient has very open communication with his parents and has a safety plan with the therapist. His weight starts decreasing again, albeit slowly. He continues to meet regularly with the multidisciplinary team and his mood stabilizes and passive suicidal ideation resolves. Also during this time, he has a PSG which shows mild OSA.

At month 12: He undergoes an uncomplicated laparoscopic sleeve gastrectomy (LSG) and BMI decreases from 55.4 to 46.9 kg/m² (15%) over the first 7 months.

At month 24 (10 mos s/p LSG): We are in the midst of COVID pandemic. Access to food is increased and he is feeling hungrier. Mood continues to be good with Prozac 30 mg and therapy. Patient is open to restarting AOM and prefers topiramate 75 mg QD as it had helped him with food cravings in the past.

At month 28 (14 mos s/p LSG): Weight is up 25 lbs. over past 4 months with topiramate 75 mg. We restart phentermine 15 mg QAM.

At 4.5 years (3.5 years s/p LSG): BMI is down 25% from time of LSG; down 30% from peak (initial consultation). He continues to take phentermine 15 mg + topiramate 75 mg QAM. Mood is stable. He is pleased with his progress.

Lessons Learned

• Children with severe obesity should not be observed with “watchful waiting.” Intervention is indicated, even at a young age, particularly in children with class 3 severe obesity.

• Topiramate is not contraindicated with suicidal ideation but close monitoring is necessary.

• Bariatric surgery should be considered in pediatric patients with class 3 severe obesity, regardless of the presence of weight-related complications.

• AOMs are important adjunct treatments for patients who are experiencing weight regain following bariatric surgery.

Case 4: Patient D Is a 9-Year-Old Girl with a BMI of 33.2 kg/m²

HPI: The Patient is a 9-year-old girl whose parents report that their daughter’s weight started to increase when she was approximately 4 years of age. Around this time she broke one of her arms and the following summer she broke the other arm. This resulted in diminished physical activity. Two years ago, she was diagnosed with nonalcoholic fatty liver disease (NAFLD) and mom indicates that they were instructed to cut out 100 cal/day from Patient’s diet. They did so and indeed she experienced some weight reduction. However, because of persistently high BMI she was referred to the weight management clinic for further treatment.

PMH: Patient has a history of frequent croup which has been treated about annually with prednisone. She also has nocturnal enuresis treated with DDAVP. She had a tonsillectomy at 6 years of age.

FH: Both parents have obesity and maternal aunt had MBS. Dad and paternal grandparents have T2DM, HTN, and hypercholesterolemia. No gestational DM in mom.

SH: Patient lives with both parents and her 16-year-old sister. She is in fourth grade and does well academically. No food insecurity.

Medications: DDAVP, budesonide-formoterol inhaler.

ROS: Ten point ROS is negative except for nocturnal enuresis. She is pre-menarchal.

Diet: Patient’s diet consists of many simple carbohydrates (sugared cereal, peanut butter, and jelly sandwich) but also good sources of protein like roast beef. She eats some fruits and vegetables. Limited liquid calories. She eats fast food once per month.

Eating behaviors: Patient eats when bored and eats large portions of food, especially when it is food that she likes. She really enjoys eating in general. She sometimes eats in her bedroom or on the couch. She denies emotional eating or loss of control eating. No sneaking or hiding food.

Physical activity: Tae kwon do twice per week; gym class at school 4 times per week.

PE:	Weight: 73.4 kg (161 lb. 13.1 oz), >99%
	Height: 1.486 m (4′ 10.5″), >99%
	BMI: 33.24 kg/m2, 1.5 x 95th percentile
	BP: 96/62, P: 97
	Normal PE, Tanner 1

Labs:	ALT 51 U/L, AST 31 U/L
	TC 117 mg/dL, TG 121 mg/dL, HDL 61 mg/dL, LDL 32 mg/dL
	HbA1c 5.4%, glucose 86 mg/dL
	BMP normal, including bicarbonate

Assessment and Plan: Patient is 9-year-old girl with otherwise normal development and PMH of nocturnal enuresis who presents with class 3 severe obesity complicated by NAFLD. Some of the main contributors to her obesity include her strong FH of obesity and tendency toward hedonic eating; that is, she eats more because it tastes good rather than because she is especially hungry. We review that the foundation of treatment is behavioral modification to improve dietary and physical activity patterns. In certain circumstances, more intensive interventions, such as pharmacotherapy and/or metabolic and bariatric surgery, are needed. Patient has already made some progress with lifestyle modification therapy. However, this has been insufficient for reducing her BMI to a significant degree. Because of this and because of the seriousness of her weight status, we opt to start anti-obesity pharmacotherapy. In particular, we start with a trial of topiramate, which seems to decrease the craving for food.

• 1. Meet with RD to review age-appropriate portions as a start.

• 2. Start topiramate 25 mg tablets: Take 1 tablet (25 mg) daily for week 1, then take 2 tablets (50 mg) daily for week 2, then take 3 tablets (75 mg) daily thereafter.

Treatment Course

At week 6: Weight is down 4 lbs. Patient notes decreased food cravings and appetite. Plan to continue lifestyle therapy supported by topiramate 75 mg QD. Soon after this appointment, COVID pandemic started.

At month 7: Patient had gained 8 lbs. over past 1.5 months. This was despite ongoing lifestyle therapy and use of topiramate, phentermine 8 mg QD.

At month 13: Patient continues to do well with lifestyle therapy supported by topiramate 75 mg + phentermine 8 mg QD. BMI is down 18% from baseline.

At month 21: BMI is now down about 25%. Because she is doing so well with weight management and to avoid the development of tolerance to phentermine, we decide to decrease phentermine from 8 mg to 4 mg QAM. Mom also notes that Patient has been somewhat irritable. We continue topiramate 75 mg QD.

At month 26: Patient is tired of taking medications and family wants to see how she does without them. We agree to decrease topiramate from 75 to 50 mg QD and continue phentermine 4 mg QD.

At month 32: Patient regained 20 lbs. She stopped taking all of her AOMs. Parents were tired of fighting with her to keep taking them. Patient agrees to restart topiramate because this, she says, is the most helpful for her. We restart topiramate 50 mg QD.

At month 36: Her weight continues to increase. She does not want to restart phentermine and is open to trying a GLP1RA. We send a prior authorization and wait.

Lessons Learned

• When starting AOMs, the expectation is that this will be a long-term medication to treat a chronic biologic condition. Stopping AOMs often leads to weight regain.

• Patients less than 12 years of age, particularly those with severe obesity, benefit from the use of AOMs.

• AOMs can be effective at managing weight-related health complications.