Beyond Dieting: New Weight Loss Medications & Treatments on the Horizon

Daniel Bessesen, MD

Currently Available Options

• Accept weight where it is

• Diet/Exercise: 3-10% weight loss

• Drugs: 5-12% weight loss

• Medically Supervised/Combination

of Diet + Drug: 10-15% weight loss

• Surgery: 15-30% weight loss

Low

High

Effectiveness

Currently Available Options

• Accept weight where it is

• Diet/Exercise: 3-10% weight loss

• Drugs: 5-12% weight loss

• Medically Supervised/Combination

of Diet + Drug: 10-15% weight loss

• Surgery: 15-30% weight loss

Low

High

Risks/Time/Money

A Guide to Selecting Treatment

Treatment

Body Mass Index category

25-26.9 27-29.9 30-34.9 35-39.9 40

Diet, physical activity, and behavior therapy

Pharmacotherapy

Surgery

Withco-morbidity

Withco-morbidity

Withco-morbidity

+ + + +

+

+

+ +

NIH The Practical Guide. 2000 http://www.nhlbi.nih.gov/guidelines/obesity/ob_gdlns.htm2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesityin Adults: http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee.citation

Obesity Treatment Pyramid

SurgerySurgery

PharmacotherapyPharmacotherapy

Lifestyle ModificationLifestyle Modification

DietDiet Physical ActivityPhysical Activity

PharmacologicalTreatment of Obesity

• Current medications 5-12% wt loss• Benefits only last as long as patient takes the

medication. Chronic treatment likely needed.• Drugs probably not paid for by insurance so

cost is a big issue for patients.• Issues of FDA approval, long term safety, and

efficacy. • Are medications an appropriate treatment

modality for obesity?

New and Emerging Medications

• FDA approved– Lorcasarin (Belviq)– Phentermine/topiramate ER (Qsymia)

• May be approved in near future– Liraglutide – Bupropion/naltrexone

Lorcasarin (Belviq)

• Serotonin 2C receptor agonist• Previous serotonin agonists fenfluramine

and dexfenfluramine caused cardiac valve disease, removed from market

• 2C receptor only in the brain not in heart• Studies in 1-2,000 people for up to 2

years do not show evidence if valvulopathy with lorcasarin.

Lorcasarin (Belviq)

• Weight loss: 3-5% no better than phentermine or orlistat

• Side effects: headache, dizziness and nausea

• Cost: $220/month• Unclear if physicians will prescribe off

label with phentermine (no data on safety or efficacy)

Lorcasarin: Weight Effects

N Engl J Med. 2010 Jul 15;363(3):245-56

Phentermine/Topiramate

• Combination gives greater effectiveness with fewer side effects

• Cost: $150.00/month• Side effects: dry mouth, numbness,

tingling, insomnia, dizziness, anxiety, irritability and disturbance in attention

Lancet. 2011 Apr 16;377(9774):1341-52

Topiramate/Phentermine (Qsymia) Effects on Weight

Phentermine/Topiramate

• Risk of birth defects: women need – pregnancy test on starting and monthly while using.

• Reduces blood pressure, glucose, insulin, triglycerides and raises HDL

• Unclear if physicians will prescribe off label using generic phentermine and topiramate.

• Most effective medication available 10-12% weight loss.

Gastric BypassLap Band

Effectiveness

Risk

Low High

Comparison of Operations• Lap band: 20% weight loss, very low

mortality, 1% serious or 2.4% any complication

• Sleeve gastrectomy: 25% weight loss, 0.1% mortality, 2.4% serious or 6.3% any complication

• Gastric bypass: 30% weight loss, 0.2% mortality, 2.5% serious or 10% any complication

Ann Surg 2013;257: 791–797; Flum DR, N Engl J Med. 2009 Jul 30;361(5):445-54

Benefits of Weight Loss Surgery the Swedish Obese Subjects Trial

Bariatric Surgery vs. Usual Care

• Nonrandomized prospective controlled study

• 2010 pts. had surgery compared to 2037 contemporaneously matched controls

• Began 1987

• Median follow up 14.7 years

Weight loss in the SOS

JAMA. 2012;307(1):56-65

Bariatric Surgery is Associated with aReduced Mortality: the SOS Study

Sjostrom L NEJM 2007: 357-741-752

30% lower riskOf dying

MI: 25 in controlGroup 13 in theSurgery group

Cancer: 47 inThe control group29 in the surgerygroup

Benefits of Bariatric Surgery for T2DM

N Engl J Med 2012;366:1567-76

• 150 patients randomized to intensive medical therapy, gastric bypass or sleeve gastrectomy for management of type 2 diabetes

• Average baseline A1C was 9.2% (diabetes >6.5, goal <7%)

• Followed for 12 months

Stampede Trial: Benefits of Surgery for Type 2 Diabetes

Parameter Medical Therapy (n=41)

Bypass(n=50)

Sleeve(n=49)

P Value

HbA1c<6 12% 42% 37% 0.008

HbA1C<6 without DM med

0% 42% 27% 0.003

% change in Tg -14% -44% -42% 0.08

% change in HDL 11% 28% 28% 0.001

N Engl J Med 2012;366:1567-76

Who is a Good Candidate?

• BMI>35 with co-morbidities or >40 without

• Age 20-60

• Co-morbidities: Diabetes, sleep apnea, reflux > Hypertension, DJD

• Failed other forms of therapy

• No serious, active cardiac, pulmonary, or psychiatric disease

Thank you