Faculty/Presenter Disclosure

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1 Weight loss & Obesity WHAT S NEW & EXCITING? Tina Korownyk Dept of Family Medicine, UofA Faculty/Presenter Disclosure Faculty/Presenter: Tina Korownyk Relationships with commercial interests: None 1

2 Drowning in obesity Literature April 2016 October 2016 Difference Obesity Obesity RCTs Obesity Systematic Reviews Obesity Studies / Year Pubmed 2

3 Obesity Studies / Year Pubmed Obesity & Genetics 3

4 FTO ALlele Fat mass and Obesity Associated Gene FTO gene = the strongest known association with obesity. 1? loss of control eating Those homozygous for the FTO allele 2 Weigh ~3 kg more 1.7- fold odds of being obese. 2 1) Nature Feb 12;518(7538): ) Science May 11;316(5826):

5 FTO ALlele Fat mass and Obesity Associated Gene Genome wide association studies: multiple loci associated with BMI loci (so far) Average 0.1 BMI units per BMI-increasing allele (~ g) ~ kg diff in those carrying the most BMI-increasing alleles and those carrying the mean number ~ kg difference between individuals carrying the least BMI-increasing alleles and those carrying the mean number. 1) Nature Feb 12;518(7538): FTO ALlele Fat mass and Obesity Associated Gene Cool Science Does it change our approach in primary care? 5

6 Does Knowledge of Genetic Risk Change Behavior? RCT, 1279 pts, 874 had AA or AT genotype, 405 had non-risk TT genotype 1 Patients randomly assigned to one of 4 interventions. One group made aware of FTO genotype No difference in Physical Activity between groups at baseline Knowledge of FTO had no impact on PA at 6 months Attrition was higher in non-risk participants for whom genotype was disclosed (P=.01) 20% vs 11% NNH = 11 1) J Med Internet Res Feb 5;18(2):e30. 2) BMJ Mar 15;352:i

7 FTO 2 Recent Systematic Reviews 1) 10 studies, 6951 pts: if homozygous for FTO allele 1 greater weight loss (0.44kg) with diet/lifestyle interventions 2) 8 RCTs, 9563 pts: 2 No difference between FTO genotypes in changes in BMI in response to weight loss intervention 1) Am J Clin Nutr Apr;103(4): ) BMJ Sep 20;354:i4707. Gadgets, Gizmos and Cash 2 systematic reviews of financial incentives for behavior change 1,2 : Majority demonstrate benefit in the short term (ie < 6 mo) Reversion to baseline weight and lack of effect once incentives removed 2 recent RCTs on activity trackers 4,5 24 mo: those WITHOUT activity tracker had more weight loss 4 2.4kg (5.9kg vs 3.5kg) No difference in fitness levels in either group 1) J Acad Nutr Diet Jul;114(7): ) Am J Prev Med Nov;45(5): ) BMC Sports Sci Med Rehabil Jun 4;8:15.. 4) JAMA Sep 20;316(11): ) Effectiveness of activity trackers with and without incentives to increase physical activity (TRIPPA): a randomised controlled trial 7

8 Is this where we step In? Primary Care Interventions Behavioral weight loss interventions, 15 RCTs, 4539 pts 1 Mean weight loss at 12 mo: 1.36kg Most successful RCT: 4.3kg weight loss at 12 mo Private coaches with 57 contacts over 2 yrs Motivational Interviewing, Sys Review, 24 RCTs 2 Versus usual care: 12 studies: no difference vs control 9 studies: up to 4.9 kg loss, + limitations 1)Fam Pract Dec;31(6): ) Obes Rev April ; 16(4): ) Int J Obes (Lond) Jan;37(1): ) 8

9 Real World Interventions kg kg kg (-1.34 to 0.43) Obes Rev Nov;15(11):

10 US Guideline For Obesity Management Bottom LIne Interventions emphasizing both diet & physical activity can result in 6-month weight loss of 8% to 10% 1 Challenges remain to sustaining weight loss long-term 1 1) Circulation. 2014;129(25)(suppl 2):S102-S138. 2) American Psychologist 2016:71(7): Guidelines CTFPHC Endocrine Society Medications For adults who are overweight or obese (BMI ), we recommend that practitioners not routinely offer pharmacologic interventions aimed at weight loss In order to promote long term weight maintenance we recommend weight loss medication to ameliorate comorbidities and amplify adherence to behavioural changes in those with BMI 30 or 27 + co-morbitiies 1) CMAJ Feb 17;187(3): ) J Clin Endocrinol Metab, February 2015, 100(2):

11 Interventions for obesity Systematic review and meta-analysis, 66 RCTs 68 studies, 49 in meta-analysis, median 12 mo 94% high/unclear risk of bias Overall weight loss: 3.02kg ( ) No difference behavioral (3.13) vs behavioral + pharmacological (2.89) Diet = largest weight loss: 4.71kg Exercise alone not significant 5% body weight NNT = 5* 10% body weight NNT = 9 Prevention of DM NNT = 17 CMAJ Open Oct 1;2(4):E Drug Weight Loss kg Time wks Mechanism of Action Side Effects Phentermine Sympathomimetic Elevated BP, pulse Cost/ mus 2 Diethylpropion Sympathomimetic Elevated BP, pulse Orlistat Lorcaserin (Belviq) Naltrexone/b uproprion (Contrave) 52 Lipase Inhibitor Fecal incontinence $ HT2c Receptor serotonin synd, h/a, dizziness, tumors, psychiatric d/o, valvulopathy Opioid antagonist, dopamine/norepi reuptake inhibitor N/V Constipation Rejected by FDA x1 due to CV concerns $263 $239 Liraglutide GPL-1 agonist N/V $128 2 Phentermine/ topiramate (Qsymia) GABA receptor modulation + 1) Endocrine Society Clinical Practice Guideline 2) ADA standards of care 2016 Teratogenicity, tingling hands/feet, dizziness $239 11

12 Drug Weight Loss kg Time wks Mechanism of Action Side Effects Phentermine Sympathomimetic Elevated BP, pulse Cost/ mus 2 Diethylpropion Sympathomimetic Elevated BP, pulse Orlistat Lorcaserin (Belviq) Naltrexone/b uproprion (Contrave) 52 Lipase Inhibitor Fecal incontinence $ HT2c Receptor serotonin synd, h/a, dizziness, tumors, psychiatric d/o, valvulopathy Opioid antagonist, dopamine/norepi reuptake inhibitor N/V Constipation Rejected by FDA x1 due to CV concerns $263 $239 Liraglutide GPL-1 agonist N/V $128 2 Phentermine/ topiramate (Qsymia) GABA receptor modulation + 1) Endocrine Society Clinical Practice Guideline 2) ADA standards of care 2016 Teratogenicity, tingling hands/feet, dizziness $239 Drug Weight Loss kg Time wks Mechanism of Action Side Effects Phentermine Sympathomimetic Elevated BP, pulse Cost/ mus 2 Diethylpropion Sympathomimetic Elevated BP, pulse Orlistat Lorcaserin (Belviq) Naltrexone/b uproprion (Contrave) 52 Lipase Inhibitor Fecal incontinence $ HT2c Receptor serotonin synd, h/a, dizziness, tumors, psychiatric d/o, valvulopathy Opioid antagonist, dopamine/norepi reuptake inhibitor N/V Constipation Rejected by FDA x1 due to CV concerns $263 $239 Liraglutide GPL-1 agonist N/V $128 2 Phentermine/ topiramate (Qsymia) GABA receptor modulation + 1) Endocrine Society Clinical Practice Guideline 2) ADA standards of care 2016 Teratogenicity, tingling hands/feet, dizziness $239 12

13 Drug Weight Loss kg Time wks Mechanism of Action Side Effects Phentermine Sympathomimetic Elevated BP, pulse Cost/m US 2 Diethylpropion Sympathomimetic Elevated BP, pulse Orlistat Lorcaserin (Belviq) Naltrexone/b uproprion (Contrave) Liraglutide 3mg Saxenda Lipase Inhibitor Fecal incontinence $ HT2c Receptor serotonin synd, h/a, dizziness, tumors, psychiatric d/o, valvulopathy Opioid antagonist, dopamine/norepi reuptake inhibitor N/V Constipation Rejected by FDA x1 due to CV concerns $263 $ GLP-1 agonist N/V $1282 ($400) Phentermine/ GABA receptor Teratogenicity, 1) topiramate Endocrine Society Clinical Practice Guideline modulation 2) ADA standards + of care tingling 2016 hands/feet, $239 Liraglutide NEJM, 3731 pts, mean 45 yrs & 106 kg, 56 weeks Wt loss 8.4 vs 2.8kg ( 5.6kg) Intention to treat analysis ~ 5kg 63% vs 27% lost 5% body weight NNT = 3 33% vs 11% lost 10% body weight NNT = 5 Adverse Events: nausea (NNH ~4) & vomiting (NNH ~9) In high risk diabetics (mean BMI 32, hx CVD, A1C 8.7) liraglutide 1.8mg = 13% RR in CV events (NNT 53) over ~4 years. 12 N Engl J Med Jul 2;373(1):

14 Liraglutide Bariatric Surgery Long Term Benefit? Swedish Obesity Subjects study: prospective matched cohort, 4047 obese subjects. 16 yr Mortality: 6.3% control vs 5.0% surgery. ~24% Relative Reduction Other studies, surgery: DM, WT, BP, CVD 1 RCT, 150 pts (BMI 36), DM2 (A1C 9.3), medical tx +/- surgery 2 At 3 yrs: surgery = significant A1C (9.3 to ~ 6.9), medications (~5 to ~2), weight (23%), albumin-to-cr ratio, & improved QOL scores RCT 61 pts (BMI 36), DM2 (A1C 7.8) 3 DM2 remission achieved by 40% bypass, 29% banding, 0% lifestyle 1) N Engl J Med. 2016;374(2): ) N Engl J Med. 2014;370(21): ) JAMA Surg. 2015;150(10):

15 Sugar Sweetened Beverages Sys Rev, 30 RCTs, 38 cohorts 1 : intake of dietary sugars associated with weight (0.80 kg, p<0.001) RCT 641 avg wt children 2 250ml/day sugar vs artificially sweetened beverage Results: Sugar group gained additional 1.02kg at 18 months RCT 224 obese adolescents, sugar beverage drinkers 3 Intervention: bottled water/ diet beverages delivered q 2 weeks Results: Year 1: Intervention group gained 1.9kg less Year 2: No significant difference 1) BMJ Jan 15;346:e7492 2) N Engl J Med Oct 11;367(15): ) N Engl J Med2012;367:

16 Sugar Sweetened Beverages policy Modeling studies: 20% sugar drink tax may obesity in UK by 1.3% 1 ( people) Sugary drink tax in Mexico (~10%, Jan 2014) 2 Mean 6% reduction in SSBs (12ml/person/day) Berkeley CA, (0.01 /oz, Mar 2015) 3 consumption of SSBs 21% (1.25/d to 0.97/d) 4% in comparison cities (P =.046). Water consumption (+63%) compared to comparison cities (+19%; P <.01) 1) BMJ Oct 31;347:f61892) BMJ Jan 6;352:h6704 3) Am J Public Health Oct;106(10):

17 Bottom Line FTO allele exists, doesn t change management Incentivizing behavior = short term benefit Intensive interventions weight by ~3-5 kg over 1 year. primary care alone less effective Liraglutide 3mg qd weight loss ~5kg at 1 year. CV benefit in DM for lower dose Pts regain weight once stopped Bariatric Surgery long term mortality and QOL benefit Major systemic changes required Questions? 17