1. Pediatric obesity Can medications help? Dr mahtab ordooei

2. Dramatic rise of pediatric obesity

3. Early recognition and treatment of pediatric obesity reduce a
lifetime of morbidity and mortality

4. What can we do?
At EVERY visit for EVERY patient, record a BMI : get a table or BMI calculator
Properly label the problem :
Underweight < 18.5
Normal weight
Overweight >25 to < 30
Obese 30 to < 40
Morbidly Obese 40 or more

5. BMI in Kids BMI //apps.nccd.cdc.gov/dnpabmi/calculator.aspx
Labels are based on BMI percentiles, not weight %-iles :
BMI //apps.nccd.cdc.gov/dnpabmi/calculator.aspx
> 75th to 84th Caution and close observe
85th to 94th Overweight
95th & more Obese

6. Plotted BMI-for-Age Age= 4 y, 4 wks Height=106.4 cm (41.9 in)
Measurements:
BMI
BMI
Girls: 2 to 20 years
Age= 4 y, 4 wks
Height=106.4 cm (41.9 in)
Weight=15.7 kg (34.5 lb)
BMI=13.9
BMI-for-age= th percentile Normal
BMI
BMI

7. Sinha et al NEJM 2003

8. Obesity comorbidities
Cardiovascular: hypertension, coronary artery disease, angina pectoris, congestive heart failure
Cerebrovascular: stroke
Hyperlipidemia
Metabolic syndrome/type 2 DM
Cholelithiasis
Gout, uric acid nephrolithiasis
Osteoarthritis
Obstructive sleep apnea, hypoventilation
Hyperandrogenism, hirsutism, irregular menses, complications of pregnancy, stress incontinence
Malignancies: breast, endometrium, colon, prostate
Increased surgical risk
Psychological disorders

10. Pediatric weight management
A challenge for patients, their families, physicians
Family-based lifestyle intervention is the core treatment modality

11. Obesity Treatment Pyramid
Diet
Physical Activity
Lifestyle Modification
Pharmacotherapy
Surgery
Obesity treatment pyramid
The clinical approach to obesity can be viewed as a pyramid consisting of several levels of therapeutic options. All patients should be involved in an effort to change their lifestyle behaviors to decrease energy intake and increase physical activity. Lifestyle modification also should be a component of all other levels of therapy. Pharmacotherapy can be a useful adjunctive measure for properly selected patients. Bariatric surgery is an option for patients with severe obesity, who have not responded to less-intensive interventions. The number of obese patients who require a specific level of treatment decreases as one moves up the pyramid.

12. Body weight reductions of more than5% require
Numerous clinical visits
Access to health-promoting food
Physical activity environments
Motivation

13. Pharmacotherapy
May be considered in obese children if a formal program of intensive lifestyle modification has failed to limit weight gain

14. Anti Obesity Drugs
The decision to initiate drug therapy should be made only after a careful evaluation of risks and benefits

15. Anti Obesity Drugs May be a helpful But along with Diet Exercise
Behavior modification.
Most patients regain their weight when their weight-loss drugs are stopped.

16. When to start treatment?
BMI greater than 30 kg/m2
BMI ≥95th percentile for age and sex in children
BMI between the 85th and 95th with significant and severe co morbidities
BMI ≥99th percentile for age and sex
pediatrics 2007
Rev Endocr Metab Disord 2009

17. When the treatment is successful?
Success measured by
Degree of weight loss
Improvement in associated risk factors.

18. When the treatment is successful?
Weight loss should exceed 2 kg during the first month of drug therapy
Fall more than 5 percent below baseline by three to six months
Weight remain at this level to be considered effective

19. What happens after weight loss ?
A weight loss of 5 to 10 percent reduce the risk for diabetes  and CVD in high risk patients
weight loss of 10 to 15 percent is considered a very good response
weight loss exceeding 15 percent is considered an excellent response.

20. Can they cure obesity? Drug therapy does not cure obesity.
Obese subjects given drugs should be advised that when the maximal therapeutic effect is achieved, weight loss ceases.
When drug therapy is discontinued, weight is regained.

21. Classification of anti obesity drug
Current anti obesity drug can be classified
into three categories
Agents that suppress appetite
peripherally acting agents that impair absorption
Agents that affect energy expenditure

22. Sympathomimetic Drugs
Sibutramine
Block Reuptake norepinephrine ,serotonin, dopamine
increased risk of heart attack and stroke, MI
was removed from 2010

23. Sympathomimetic Drugs
Bupropion
Norepinephrine and dopamine reuptake
inhibitor that is used as an atypical antidepressant
Several adult trials have documented weight loss

24. Antidepressants Fluoxetine and sertraline
Serotonin reuptake inhibitors
May facilitate weight loss in the short run.

25. FDA non approved drugs Fenfluramine
Because of associated cardiac valve &pulmonary hypertension
Raising concerns about the long-term use of other serotoninergic preparations (eg, fluoxetine) in children
Removal of ephedra and phenylpropanolamine because of cardiovascular concerns
Pediatric 2007

26. Sympathomimetic Drugs
Tolerance is achieved within 2 weeks.
Contraindications
Angina
Atherosclerotic disease,
Cardiac arrhythmia
Hyperthyroidism
Concomitant use of MAOI

27. .

28. Drugs That Alter Fat Digestion
Orlistat (Xenical ,venustat)
FDA approved
Orlistat in obese adolescents
Aged 12 to 16 years
use in significant obesity comorbidities

29. Orlistat Recommended dose 60- 120 mg three times daily
Vitamin A 5000 IU
Vitamin D 400IU
Vitamin E 300 IU
Vitamin K 25mg
food intake >2 h apart from orlistat

30. Mode of action inhibit a gastric and pancreatic lipases
Hydrolyze dietary fat to free fatty acids and glycerol
Systemic absorption is minimal
Fecal fat excretion is increased.
Curr Opin Endocrinol Diabetes Obes 2015

31. Orlistat
Reduces fatty acid absorption by ∼30% (16 g/day) in persons consuming a 30% fat diet
It has a modest effects on triglycerides and HDL-cholesterol

32. Orlistat 2–3 kg/m2 loss in BMI 0.5 to 4 kg/m2
Curr Opin Endocrinol Diabetes Obes 2015
Ann Pharmacother 2015

33. Orlistat Current effect of orlistat along with behaviour
therapy may not be more effective than behaviour therapy alone >12 years
Curr Opin Endocrinol Diabetes Obes 2015

34. Side Effects Of Orlistat
Fecal incontinence, oily spotting, and flatus with discharge, steatorrhea,
Gallstones,, nausea, bloating, liquid stools, fecal urgency and abdominal cramping

35. Contraindication of Orlistat
Malabsorption syndrome
Cholestasis
Advanced liver disease
Failure to decrease dietary fat
Frequent meals at restaurant

36. Future anti-obesity drugs
Exenatide is GLP-1 receptor agonist
Recommended for adults with T2DM
increases insulin secretion while decreasing glucagon secretion.
increasing satiety and decreasing appetite.
Reduced BMI by 1.1 to 1.7 kg/m2
Ann Pharmacother 2015

37. Case study 11 children aged 8–19 years. 5ug twice a day given SC
3-month, open-labelled study BMI> 95th
11 children aged 8–19 years.
5ug twice a day given SC
BMI reduction of 1.7 kg/m2
Improvements in insulin and glucose markers
Curr Opin Endocrinol Diabetes Obes 2015

38. a randomized, double blind, case–control study with lifestyle changes
The effect of glucagon-like peptide-1 receptor agonist therapy on body mass index in adolescents with severe obesity
a randomized, double blind, case–control study with lifestyle changes
children aged 12–19 years
10ug twice a day
The most common adverse events
Nausea, vomiting, diarrhea, headaches.

39. Glucagon-like peptide-1 receptor
 Exenatide elicited a greater reduction in percent change in BMI compared with placebo
JAMA Pediatr 2013

41. Diabetic Drugs Metformin Stimulation of glucose uptake by the muscle
Activate of AMP-activated protein kinase which results in
Stimulation of glucose uptake by the muscle
Inhibits hepatic gluconeogenesis
Diminishes insulin resistance and hyperinsulinemia,
Decrease lipogenesis in adipose tissues.
Small reduction in total cholesterol level (∼0.26 SD).
Ann Pharmacother 2015

42. Metformin& weight loss
BMI reductions of 0.17 to 1.8 kg/m2
Ann Pharmacother 2015

43. Metformin Recommended for those aged 10 years and older who have T2DM
is not FDA approved for the obese children
It is useful for insulin resistance, or PCOS
Doses :500mg-2500mg PO twice a day .

44. Metformin
Effective in children aged 6–12 years with insulin resistance
A supplement of vitamin and calcium is
recommended to improve B12 absorption during metformin treatment

45. Metformin Side effects
Abdominal discomfort, which improves when the medication is taken with food. flatulence, bloating,nausea ,diarrhea ,Lactic acidosis
Vitamin B12 deficiency; therefore, a multivitamin is recommended.
lactic acidosis, which has been observed in adults but not seen in pediatric patients.

46. Metformin Contraindication
Heart, kidney, and liver disease,
Severe illness
Decreased perfusion
Stop for surgical and radiological procedure
Patients with liver function tests less than three times the upper limit of normal are considered appropriate to take the medication.

47. Leptin Leptin gene defect Is a cause of severe early-onset obesity.
Children have severe hyperphagia and obesity
Daily subcutaneous injections effects on fat mass, hyperinsulinemia ,hyperlipidemia
is not approved by FDA

48. At low physiological doses Starting at 0.02-0.04 ug/kg/day
Effects of Recombinant Leptin Therapy in a Child with Congenital Leptin Deficiency
At low physiological doses
Starting at ug/kg/day
Given subcutaneously at 6 pm.
Might benefit from leptin therapy.
Arq Bras Endocrinol Metab. 2010

49. Growth hormone
is FDA-approved in Prader-Willi syndrome only for the increasing height velocity
is not FDA approved for the treatment of obesity.

51. Conclusion If patients do not lose at least 5% of their
weight loss medications demonstrate only
modest efficacy %3–9 within the first 6 months
Concerns of weight rebound with the discontinuation
If patients do not lose at least 5% of their
baseline weight within 3 months
unlikely to benefit from that treatment

52. THANK YOU FOR YOUR ATTENTION