When Lifestyle Modification Therapy is Not Enough: Pharmacotherapy for Severe/Complicated Pediatric Obesity

Transcription

1 When Lifestyle Modification Therapy is Not Enough: Pharmacotherapy for Severe/Complicated Pediatric Obesity Claudia Fox, MD MPH Diplomate, American Board of Obesity Medicine Medical Director, Pediatric Weight Management Clinics

2 Disclosures I have no financial relationships to disclose I will be discussing off-label use of: Metformin Topiramate Exenatide Phentermine

3 Learning Objectives Describe severe pediatric obesity Identify biological underpinnings of obesity Detail rationale for using pharmacotherapy for pediatric obesity Review current state of pediatric obesity pharmacotherapy

4 Why Consider Medications for Severe Pediatric Obesity?

5 Why Consider Medications for Severe Pediatric Obesity? Severe obesity is a progressive, chronic, debilitating disease

6 Why Consider Medications for Severe Pediatric Obesity? Severe obesity is a progressive, chronic, debilitating disease Lifestyle modification therapy is often insufficient for reducing adiposity

7 Why Consider Medications for Severe Pediatric Obesity? Severe obesity is a progressive, chronic, debilitating disease Lifestyle modification therapy is often insufficient for reducing adiposity Obesity has significant biological underpinnings

8 Why Consider Medications for Severe Pediatric Obesity? Severe obesity is a progressive, chronic, debilitating disease Lifestyle modification therapy is often insufficient for reducing adiposity Obesity has significant biological underpinnings (Bariatric surgery is not always available or desired)

9 Why Consider Medications for Severe Childhood Obesity? Severe obesity is a progressive, chronic, debilitating disease

10 Obesity-Related Co-morbidities in Childhood Carotid artery ITM thickening Dyslipidemia Hypertension Impaired glucose tolerance Metabolic syndrome Sleep apnea Non-alcoholic fatty liver disease Depression Poor quality of life Urinary incontinence Musculoskeletal problems

11 BMI Tracks into Adulthood Children with severe obesity become adults with severe obesity: Bogalusa Heart Study: 100% developed adult BMI 30 kg/m 2 88% developed adult BMI 35 kg/m 2 65% developed adult BMI 40 kg/m 2!!! Freedman DS et al. J Pediatr, 2007

12 Patient A 16 yo boy BMI 59 kg/m 2 Multiple attempts at weight loss; Never lost a pound Diet: snacks all day; 32 oz/d choc milk Eating: Feels hungry all the time Eats to cope with negative emotions Binge eats with loss of control Eats large amounts when not hungry Eats alone (in bedroom) Eats until uncomfortable Feels bad after overeating PMH Recently dx d with insulin resistance OSA; on CPAP since age 10 Chronic headaches Constipation I m good at nothing Meds Metformin 500 mg BID Labs HbA1c 5.8 ALT 52 TC 138, TG 106, HDL 38, LDL 79

13 Patient A 2000 kcal/d meal plan No eating in bedroom Eliminate all liquid calories Start topiramate 100 mg QD Increase metformin to 1000 mg BID Start miralax Physical therapy

14 Timing of Intervention A Window of Opportunity Adults who were obese as children, but no longer obese in adulthood, are equally as healthy as adult peers who were never obese It is reasonable to conclude that long-term, cumulative exposure to obesity (and its comorbidities) will lead to poor outcomes Obesity without the presence of co-morbidities may be precisely the scenario in which to intervene Juonala M et al. NEJM, 2011

15 Patient B 16 yo girl BMI 44 kg/m 2 Heavy most of life Tried multiple diets and protein shakes Diet: breakfast sandwich, skips lunch, pork chop and salad for dinner, minimal SSB Eating: Eats when bored Binge eats on weekends and after school PMH?Hypothyroidism Chronic headaches Meds: amitriptyline PHQ9-5, GAD7-2 PE acanthosis nigricans Labs ALT 40, HbA1c 5.1, normal lipid panel except HDL 39

16 Patient B * ** 1600 kcal meal replacement plan Wean off amitriptyline Start topiramate 75 mg QD* Add phentermine 15 mg QD**

17 Why Consider Medications for Severe Childhood Obesity? Severe obesity is a progressive, chronic, debilitating disease Lifestyle modification therapy is often insufficient for reducing adiposity

18 Lifestyle Modification Therapy Primary components: Dietary counseling Physical activity counseling Behavioral modification counseling Essential part of weight management intervention!

19 Lifestyle Modification Therapy Danielsson P et al. Arch Pediatr Adolesc Med, 2012

20 Just recently started to get heavy Diet: skips breakfast, school lunch, gold fish and animal crackers for snack, family dinners, juice, no SSB Eating: Often hungry Eats large portions Watches TV while snacking No food sneaking or hoarding No food insecurity Activity: minimal Patient C 7 yo boy BMI 28 kg/m 2 PMH: elevated LFTs ROS: snoring, fatigue, leg pain SH: adopted from Guatemala, does well in school PE: acanthosis nigricans Labs: HbA1c 5.5 ALT 134, AST 59 TC 206, TG 356

21 Patient C ** Evaluation: U/S: steatosis with enlarged spleen Liver bx: grade 3 steatosis with focal bridging fibrosis PSG: mild OSA Treatment: LSMT RD: progressed to 1000 kcal/d meal replacement plan** Topiramate 75 mg qd**

22 Why Consider Medications for Severe Childhood Obesity? Severe obesity is a progressive, chronic, debilitating disease Lifestyle modification therapy is often insufficient for reducing adiposity Obesity has significant biological underpinnings

23 Homeostatic Mechanisms of Obesity Elmquist JK & Scherer PE. JAMA, 2012

24 Homeostatic Mechanisms of Obesity Vetter ML et al. Nat Rev Endocrinol, 2010

25 Bupropion-Naltrexone for Obesity Billes SK et al. Pharmacol Res, 2014

26 Non-homeostatic Mechanisms of Obesity Shin AC & Berthoud HR. Trends Endocr Met, 2013

27 Why Consider Medications for Severe Childhood Obesity? Severe obesity is a progressive, chronic, debilitating disease Lifestyle modification therapy is often insufficient for reducing adiposity Obesity has significant biological underpinnings (Bariatric surgery is not always available or desired)

28 Limited Access to Bariatric Surgery Insurance coverage is spotty 48% of pediatricians would not ever refer their adolescent patients with obesity to bariatric surgery Inge TH et al. Obesity, 2014 Woolford SJ et al. Obes Surg, 2010

29 Indications for Pharmacotherapy for Pediatric Obesity Significant weight related health risks Failed structured diet and lifestyle modifications Understand the limitations of available pharmacotherapy, including the need for concomitant lifestyle changes and uncertain durability of medications Referred to a tertiary care center for evaluation and treatment Medication should be used only as part of a multimodal weight loss therapy that includes diet, physical activity, and behavior modification Spear BA et al. Pediatrics, 2007

30 Choice of Pharmacotherapy Made on an individual basis Take into account: patient s weight related health risks mechanism of action adverse side effects patient/family preferences cause of obesity, if known Spear BA et al. Pediatrics, 2007

31 FDA-Approved Medications for Pediatric Obesity Orlistat (Phentermine)

32 FDA-Approved Medications for Adult Obesity Orlistat Phentermine Topiramate/phentermine Lorcaserin Bupropion/naltrexone Liraglutide

33 Orlistat Gastrointestinal lipase inhibitor Decreases intestinal fat absorption by 30% FDA-approved for children 12 yo No systemic action Side effects: defecation urgency, steatorrhea, abdominal discomfort

34 RCT: Orlistat vs Placebo Chanoine J et al. JAMA Peds, 2005

35 Phentermine Stimulates hypothalamus release of NE Promotes appetite suppression FDA approved >16 yo (1959) No studies in adolescents > 1 month duration Avg weight loss in adults: 3.6 kg over 24 weeks Side effects: abuse potential, increased BP and HR, GI symptoms Li Z et al. Ann Int Med, 2005

36 Non-FDA Approved Medications for Metformin Exenatide Topiramate Pediatric Obesity For review see: R Sherafat-Kazemzadeh, SZ Yanovski, and JA Yanovski, Int J Ob (2013) 37, 1 15; doi: /ijo

37 Change in BMI with Metformin McDonagh MS et al. JAMA Pedtr, 2014

38 Exenatide Glucagon-like peptide-1 receptor agonist Used in adults to treat T2DM Proposed mechanisms of weight loss slows gut motility heightens satiety via GLP-1 receptors in brain

39 RCT: Exenatide vs Placebo for Severe Adolescent Obesity Kelly AS et al. JAMA Pediatr, 2013

40 Chart Review: Topiramate for Severe Adolescent Obesity Fox CK et al. Clinical Pediatr, 2014

41 RCT: Meal Replacements followed by Topiramate for Severe Adolescent Obesity Fox CK et al, unpublished

42 Pediatric Obesity Pharmacotherapy Special Considerations Chronic treatment Predictors of response Ideal agents will have weight lossindependent pleiotropic effects Combination therapy Need for accelerated pediatric development

43 Effective and durable treatment of severe pediatric obesity will require multi-faceted, chronic, and intensive approaches