Professional Documents
Culture Documents
DISCLOSURE SUMMARY
Dr. Wyatt has served as an advisor for Orexigen Pharmaceuticals, Arena Pharmaceuticals, Wellspring Camps, Retrofit Inc. and Eisai Inc.
She receives royalties from Up to Date and has received grant funding from the NIH, Orexigen, Norvo Nordisk and GI Dynamics. She has ownership interests in Active Planet LLC and has co-ownership on a patent for a weight loss maintenance strategy.
GAME PLAN
Current Treatment Guidelines Advances in Diet Advances in PA
New Medications
Surgery
+ +
27-29.9
30-34.9
Pharmacotherapy
Treatment Risk HIGH
+ with a comorbidity
Surgery
TREATMENT GAP
WHAT IS THE BEST APPROACH FOR WEIGHT LOSS AND WEIGHT LOSS MAINTENANCE?
Importance to Success
Over Time
Slide Source: James Hill and Holly Wyatt
Wadden TA, Webb VL, Moran CH, Bailer BA 2012 Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation 125:1157-1170
COMPARISON OF WEIGHT LOSS DIETS WITH DIFFERENT COMPOSITIONS OF CARBOHYDRATE/ PROTEIN/ FAT (N=811)
IT IS NOT WHAT YOU EAT BUT HOW LONG YOU CAN EAT IT
As well as a recent prospective analysis in the Nurses Health Study published in 2010
Donnelly JE et al. 2009. Medicine and science in sports and exercise 41:459-471 Mekary RA et al. 2010. Obesity 18:167-174
WE DO KNOW A LOT ABOUT WHAT WILL WORK ! BUT HOW DO WE GET OUR PEOPLE TO DO IT ?
MOST EXCITING RECENT ADVANCES IN OBESITY TREATMENT IN 2013 ARE IN DRUG THERAPY
Cost
$
Restlessness Insomnia ? Increase in pulse ? Increase in blood pressure
$$
GI symptoms including oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, and others less frequently Increase in urinary oxalate
Phentermine/ Topiramate
Qsymia
Drug:5-11% Placebo:1-2%
Depression Cognitive Issues Cardiovascular Risk from increased heart rate Birth Defects
Bupropion SR/Naltrexone SR
Contrave
Dopamine and Sustained release 360 norepinephrine mg/ 32mg reuptake inhibitor and po q day opioid receptor antagonist
Drug:5-6% Placebo:1-2%
LORCASERIN
Selective serotonin 2C receptor agonist that works by decreasing food intake. Mechanism of action is similar to fenfluramine and dexfenfluramine except it is specific for the 2C serotonin receptor that is not found on the heart or heart valves.
The result is a compound with a desirable increased satiety effect and no heart valve damage. Echo studies showed no increased incidence of FDA-defined cardiac valvulopathy. There is some concern the studies were not powered adequately for complete confidence because of a lower than expected event rate. The FDA advisory panel voted in favor of approval 18-4 in May 2012 and locaserin was officially approved by the FDA in June 2012. It should be available in 2013.
47.5%
20.3%
22.6% 7.7%
Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, Bays H, Shanahan WR 2010 Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med 363:245-256
Headache Back pain Nasopharyngitis Nausea Urinary tract infection Cough Symptomatic hypoglycemia Fatigue Gastroenteritis, viral Dizziness Influenza Procedural pain Hypertension Gastroenteritis Depression ONeil PM, et al. Obesity. 2012;20:1426-1436.
37 (14.5) 30 (11.7) 29 (11.3) 24 (9.4) 23 (9.0) 21 (8.2) 19 (7.4) 19 (7.4) 18 (7.0) 18 (7.0) 15 (5.9) 13 (5.1) 13 (5.1) 8 (3.1) 6 (2.3)
16 (16.8) 8 (8.4) 22 (23.2) 8 (8.4) 9 (9.5) 5 (5.3) 10 (10.5) 5 (5.3) 5 (5.3) 11 (11.16) 8 (8.4) 0 6 (6.3) 5 (5.3) 5 (5.3)
18 (7.1) 20 (7.9) 25 (9.9) 20 (7.9) 15 (6.0) 11 (4.4) 16 (6.3) 10 (4.0) 11 (4.4) 16 (6.3) 13 (5.2) 5 (2.0) 8 (3.2) 5 (2.0) 5 (2.0)
For this drug, it is important for clinicians to realize that certain individuals may respond more (have a significantly greater weight loss) than other individuals.
This drug may be one that eventually will be helpful in a smaller subset of obese responders Locaserins reduction in HbA1c levels appears more substantial than the weight loss reduction in the BLOOM-DM study and therefore diabetics may also prove to be a subset that may have greater benefit
Locaserin has not been studied in combination with other drugs such as phentermine. While combining the two drugs (phentermine and locaserin) may increase weight loss, the safety of the combination has not been evaluated
Nasopharyngitis
Dysgeusia Insomnia Headache Dizziness Sinusitis Back pain Nausea Fatigue Diarrhoea Blurred vision UTI Arthralgia Bronchitis
9
1 5 9 3 7 5 4 5 5 4 4 5 4
11
7 6 7 7 7 6 4 4 6 4 5 5 4
0.2204
<0.0001 0.3832 0.1983 0.0005 1.0000 0.6199 0.6754 0.7010 0.2229 0.7729 0.1753 0.5373 1.0000
10
10 10 10 10 9 7 7 7 6 6 5 4 5
0.3947
<0.0001 <0.0001 0.4467 <0.0001 0.1511 0.0386 0.0139 0.1270 0.3690 0.0157 0.0855 0.3025 0.4004
GADDE KM, ET AL. LANCET . 2011;377:1341-1352. INFECTION; UTI, URINARY TRACT INFECTION
EMERGING PHARMACOTHERAPY
Agent Naltrexone/BupSR1 Liraglutide2,3
Approval Status
Mechanism
Follow-up Duration
56 weeks
Nausea Headache Constipation Dizziness Vomiting Dry mouth
56 weeks
Common AEs
Greenway FL, et al. Lancet. 2010;376:595-605. et al. Lancet. 2009;374:1606-1616. 3 Lean ME, et al. Obesity. 2010;18(suppl 2) Abst# 484-P:S153.
2 Astrup A,
The FDA advisory panel voted in favor of approval (13-7) of this combination in December of 2010 however the FDA declined to approve the drug in early 2011 going against the advisory panel recommendation
A study of this size and scope will take tremendous resources and time to complete. The earliest this drug could be approved is late 2014 or early 2015.-
WEIGHT LOSS WITH NALTREXONE SR/BUPROPION SR COMBINATION THERAPY AS AN ADJUNCT TO BEHAVIOR MODIFICATION: THE COR-BMOD TRIAL
ENDO BARRIER
Morning exercise