Presentation on theme: "The Skinny on Old and New Weight Loss Medications"— Presentation transcript:
1 The Skinny on Old and New Weight Loss Medications Steven R Smith, MS, RPh, BCACPTASHPSeptember 27, 2012
2 Objectives1. State the rules that control the prescribing of weight loss medicines in Ohio,2. Given patient characteristics, select the best weight loss medication,3. Educate a patient on the expected success / known risks of weight loss medications
3 Weight Loss MedicinesDietary supplements (herbal)OTCPrescription
4 Dietary supplements Dr. Oz Uncontrolled claims on TV, in magazines, and on the webClaims fall under FDA and FTCNot removed from the market until substantial harm is provedEndless list of ingredients / Proprietary blends
5 Dietary supplements Supplement How it works Conjugated linoleic acid (CLA)Feeling of fullnessChromiumTrace element needed for insulin actionGreen tea extractsDecreased appetite, fat burnerGuar gumDietary fiberSennaLaxativeEphedra (ma huang)Stimulant (off the market in US)Hydroxycitric acid (Garcinia combogia extract)Promotes fat oxidation by inhibiting ATP-citrate lyaseGymnemia sylvestreDecrease blood sugar
6 Dietary supplements Supplement How it works Ginger root Reduce nausea Raspberry ketonesFat burnerGinsengAdaptogenicCoconut oilMCT not stored in adipose tissue but high in calories / fatApple cider vinegarDrink before eating to decrease appetiteBitter orangeContains stimulants (synephrine, octopamine)Caffeine (guarana)Short acting stimulant, diureticLipovarinContains synephrine
7 Dietary supplements Supplement How it works Hoodia Appetite suppressant (P57), FDA warnings for false claimsGlucomannan (LipozeneR)Dietary fiber to increase “fullness”ChitosanSugar from the hard outer layers of lobsters, crabs, shrimps. Blocks absorption of fatLicorice rootAdaptogenicCayenne powderFat burnerMagnolia bark extractCortisol blocker(CortiSlim –FTC-false claims)
8 Other weight loss ideas Sensa, Aroma Patch, SlimScents:Alter taste / appetite by sense of smellEar Stapling:Principles of accupuncture
9 OTC Historical: Phenylpropanolamine 75mg once daily Increased strokes and other CV events11/2000 – FDA advises to not make itOfficially off the market in 2005 due to concern over its use to make amphetaminesstrokes / year in yo users
10 OTCOrlistat (AlliR) 60mg up to three times daily with meals became available in 2007Blocks 25% of dietary fat absorptionThe “Antabuse” of dietingNo more than 15gm of fat with the mealExpected weight loss: 3 to 5 pounds / year
11 PrescriptionOrlistat (XenicalR) 120mg up to 3 times a day with meals approved in 1999Blocks at least 25% of dietary fat absorptionExpected weight loss: 5 to 7 pounds / yearDrug interactions: cyclosporine, warfarin, T4Take a multivitamin daily at bedtime
12 OrlistatA meta-analysis of 29 studies where enrolled patients had an average BMI of 36.7Average weight loss compared to placebo2.89kg (-3.51 to -2.27)RR for diarrhea: 3.4, for flatulence: 3.1, for bloating-abdominal pain-dyspepsia: 1.48In a second year extension study:1/3 on orlistat regained weight lost in 1st year2/3 on placebo regained weight lost in 1st year
13 Orlistat Patient Education Take it 60 minutes prior or with a meal or up to 60 minutes after.Reduce the fat in your diet for 3 days prior to starting orlistat.Teach symptoms of liver disease: itching, yellow eyes or skin, loss of appetiteGo to myalli.com for lots of good information about fat in the diet and other tips to be successful.
14 Prescription Historical: Amphetamine, dextroamphetamine, methamphetamine, phenmetrazine were C-II drugs no longer indicated for weight lossFenfluramine (PondominR), dexfenfluramine (ReduxR) worked through serotonin and were taken off the market in 1997 due to pulmonary hypertension and heart valve disease.
15 Prescription Historical: Sibutramine (MeridiaR) works on serotonin at lower doses, norepinephrine at higher dose. Questionable efficacy / increased risk of CV event so the FDA pressured Abbott to remove it from the market in Oct, 2010Rimonobant, a cannabinoid CB1 antagonist was on the market in 56 other countries. FDA said it was approvable in 2006, an advisory committee said not to approve in 2007, Europe took it off the market in Sanofi-Aventis dropped pursuing it.
16 PrescriptionBenzphetamine (DidrexR) – CIII is converted to methamphetamine and amphetamine. Dose is 25 to 50mg up to 3 times daily.Phendimetrazine (BontrilR) – CIII is a prodrug to phenmetrazine (PreludinR – CII). Phenmetrazine gained notoriety when the Beatles were found to favor it. Phendimetrazine dose is 105mg sustained release capsule daily or 17.5 to 35mg tablets 2 or 3 times daily one hour AC.
17 What do we have today Orlistat – previously discussed Diethylpropion PhentermineLorcaserinPhentermine / Topiramate
18 Diethylproprion C-IV 25mg immediate release 2 or 3 times a day 75mg sustained release once dailyMeta-analysis of 13 studies, 6 to 52 weeks, fromWeight loss compared to placebo3kg (-1.6 to 11.5kg)Side effects as expected from a stimulant
19 Phentermine C-IV Sustained release resin (ionamin): 15, 30, 37.5mg Tablet: 37.5mg; Oral disintegrating: 15, 30mgMeta-analysis of 9 studies, 2 to 24 weeks, fromDoses of 15 to 30mg dailyWeight loss compared to placebo: 3.6kg (0.6 to 6kg)Side effects as expected from a stimulant
20 FluoxetineMeta-analysis of 9 studies using 60mg/day in patients with baseline BMI of 35.56 month results: 0.9 to 9.1kg weight loss12 month results: -0.4 to 14.5 kgSide effects:Nervous, sweating, tremor: RR 6.37Nausea & vomiting: RR 2.68Insomnia: RR 2.06
21 Other Antidepressants Sertraline: only one study with negative resultsBupropion:3 studies, avg baseline weight: 94.3kgmg/day2.77 (1.1 to 4.5) kg weight lossSide effect: dry mouth RR 2.99
22 So what’s new? Two new drugs recently approved Lorcaserin (BelviqR): a 5HT-2c agonistPhentermine / Topiramate (QsymiaR)Results now presented as (%) of body weight lost with proportion losing 5% and losing 10%Studies tending to be longer durationBelviqR studies evaluated echocardiographic signs of valvulopathyQsymiaR studies evaluated depression/suicides
23 Lorcaserin BLOSSOM Study design: 52 weeks on 10mg daily (1/5) vs. 10mg twice daily(2/5) vs. placebo (2/5)18 to 65 year oldsBMI =>30 or BMI =>27 with HTN, dyslipidemia, CV disease, glucose intolerance, sleep apneaExcluded if on on SSRI, recent use of other weight loss medications, unable to participate in moderate-intensity exercise, recent CV event, major surgery, recent low calorie diet, 5kg change in weight, bariatric surgery
24 Lorcaserin: BLOSSOM Follow-up at 2 and 4 weeks then monthly Reduce daily caloric intake to 600 kcal below WHO equations for estimating daily energy requirements using 1.3 for the activity factor (1.4 if patient already exercised => 1 hour/day)Encouraged to exercise moderately for 30 minutes dailyAlso Beck Depression Inventory-II, echocardiograms, DEXA, and other testing
25 Lorcaserin: BLOSSOM Primary endpoints: Proportion achieving 5% weight lossMean weight change from baselineProportion achieving 10% weight lossAssumed 15% of placebo would lose 5%, 40% dropout at week 52: need 720 patients per groupPrimary echocardiographic endpoint at week 52 using FDA criteria of aortic or mitral regurgitation
26 Lorcaserin: BLOSSOM End point L 10mg BID 1561 pts L 10mg /day 771 pts Placebo1541 ptsDays on drug2572652425% weight loss737 (47.2%)Sig vs placeboSig vs L10/day310 (42%)385 (25%)10% weight loss353 (22.6%)134 (17.4%)150 (9.7%)Base weight100.3 kg100.1 kg100.8 kgChange in wt-5.8 kg-4.7 kg-2.9 kgBase BMI36.135.936Change in BMI-2.1-1.7-1
27 Lorcaserin: BLOSSOM No effect on: LDL cholesterolTotal cholesterol (sig diff, not clinically diff)Triglycerides (sig diff, not clinically diff)HgbA1cBlood pressureHeart rateEchocardiographic valvulopathyDifferent: Slight increase in HDL, Quality of Life
28 Lorcaserin: BLOOM Same inclusion and exclusion as BLOSSOM L: 10mg twice daily vs placeboPrimary endpoints same as BLOSSOM2nd year extension study for those who achieved 5% or more body weight reductionStay on placebo if on it year oneIf on L: randomized to continue L or get placebo
29 Lorcaserin: BLOOM End points -1st L 10mg BID 1538 pts Placebo 1499 pts 5% weight loss47.5%P < 0.00120.3%10% weight loss22.6%7.7%Weight change-5.8 kg-2.2 kgWithdrawal due toHeadacheDizziness2%0.8%0.1%
30 Lorcaserin: BLOOM Secondary endpoints – year 1: Total and LDL cholesterol (sig diff, not clinically)Triglycerides reduced approximately 6%Fasting glucose and insulin (sig diff, not clinically)HgbA1c (sig diff, not clinically)Quality of Life (sig diff, questionable clinical sig)Beck Depression Inventory-II (not diff)FDA-defined valvulopathy: no difference over the two years
31 Lorcarserin: BLOOM Year 2 continuation 67.9% of locaserin patients vs 50.3% of placebo patients maintained their weight loss.(p<0.001)
32 Lorcaserin: BLOOM-DMThis trial was the first to enroll patients diagnosed with diabetes mellitus type 2.The design was the same as BLOSSOM.37.5% of lorcaserin patients lost 5% or more of their body weight compared to 16.1% of placebo patients.HgbA1c was reduced 0.9% in lorcaserin patients compared to 0.4% in placebo patients.
33 Lorcaserin SummaryModest weight loss. In fact, if the 5% mark is not achieved by 12 weeks, stop the drug.Daily exercise and 600 less kcal /dayCost of a “venti latte” or $3.57If per day, then $107 per monthIf per tablet, then $214 per monthSide effects: headache, dizziness, fatigue, dry mouth, and all the usual GI side effectsPregnancy: X / C-IV
34 Lorcaserin Summary Low abuse potential Unknown what to expect if on SSRI’s also.Inhibits CYP-2D6 but specifics are unexplored.May take with or without food.If DM patient with good control, watch for hypoglycemia, adjust doses of DM meds.
35 Phentermine / Topiramate QsymiaR (kyoo sim ee’ uh) is a combination of immediate release phentermine HCl and extended release topiramatePhentermine, a stimulant and appetite suppressantTopiramate augments the activity of gamma- amiobutyrate, modulates voltage-gated ion channels, inhibits AMPA/kainite excitatory glutamate receptors, inhibits carbonic anhydrase
36 P + T: CONQUER Patients 18 to 70 years for 56 weeks BMI 27 to 45 Two or more comorbidities (HTN, hypertriglyceridemia, diabetes) and waist circumference (=>102cm for men, =>88cm for women)Excluded uncontrolled HTN, uncontrolled hypertriglyceridemia, DM-1, use of DM medications other than metformin, hx of nephrolithiasis, recurrent major depression / suicidal behavior, TCA’s, MAOI’s
37 P + T: CONQUER Assigned in 2:1:2 ratio PlaceboP 7.5mg + T 46mgP 15mg + T 92mgTitration starting at P 3.75mg + T 23mg with weekly increases in the 3.75 / 23 increments until the assigned dose was achieved
38 P + T: CONQUER All patients given: A LEARN manual by Kelly D. Brownell, PhDLifestyle, Exercise, Attitude, Relationships, NutritionAdvised to implement lifestyle changesInstructed to reduce calories by 500 kcal/dayMonthly visits
40 P + T: CONQUERWaist circumference: reduced 5.1 to 6.8 cm more than placeboSystolic but not diastolic BP reduced by 2 to 3 mm HgTotal cholesterol reduced 1.6 to 3%, Triglycerides reduced 12 to 15%, HDL raised 4 to 5%HgbA1c reduced (sig diff, but not clinically)Side effects: dry mouth, dysgeusia, paraesthesia, insomnia, dizziness, anxiety, irritability, disturbance in attention, tachycardia.
41 P + T: EQUIP Assigned in 2:1:2 ratio PlaceboP 3.75mg + T 23mgP 15mg + T 92mgTitration starting at P 3.75mg + T 23mg with weekly increases in the 3.75 / 23 increments until the assigned dose was achieved
42 P + T: EQUIPEnrolled 18 to 70 year olds with BMI =>35 and controlled hypertriglyceridemia, controlled hypertension, and fasting blood sugar =<110.Same titration as CONQUER studyStudy design same as CONQUER study
44 P + T: SEQUELPatients who finished the CONQUER trial were eligible to participate in an additional 52 week continuation trial.866 eligible / 676 participatedResults are calculated from baseline of the CONQUER trial to 108 weeks
45 P + T: SEQUEL End point Placebo 227 pts P7.5/T46 154 pts P15/T92 % weight loss1.8%9.3%10.5%5% weight loss30%75.2%79.3%10% weight loss11.5%50.3%53.9%15% weight loss6.6%24.2%31.9%20% weight loss2.2%9.2%15.3%
46 Qsymia titration Take daily in the morning. P 3.75mg / T 23mg for 14 days, thenP 7.5mg / T 46mg daily.If do not lose 3% of body weight on this dose at 12 weeks, discontinue or escalate doseTo escalate: P 11.25mg / T 69mg daily for 14 days, thenP 15mg / T 92mg for 12 weeks then re-evaluate.
47 QsymiaR Available via certified mail order pharmacies: CVSWalgreensPrescriptions faxedfor patient guides, provider guides, etc
48 Ohio Regulations Ohio Medical Board Rule Schedule II controlled stimulantsMay not use these for weight loss / management
49 Ohio RegulationsRule Controlled substances for weight reductionMay only use a C-III or C-IV for weight reduction if it is FDA approved for that usePatient must have made a good faith effort to lose weight via other meansPhysician does good examBMI =>30 or =>27 with comorbiditiesMeets with the patient every 30 days face-to-face to assess success
50 Ohio RegulationsRule Controlled substances for weight reductionDuration of use matches how it was FDA approved, ie “a few weeks” = 12 weeksMay use for maintenance of weight loss if FDA approved for that manner of useMust discontinue the medication if the patient is not losing weight over a 30 day period.
51 Patient EducationSide effects / adverse effects specific to the prescribed medication.Treatment agreement on monthly appointments and 30 day prescriptionsImportance of exercise / calorie restriction / life- style modification for both short term and long term success.If diabetes, knowledge of symptoms of hypoglycemia and how to respond to them.
52 35 yo, wt 110kg, BMI 44. 4, Read about the new diet pills 35 yo, wt 110kg, BMI 44.4, Read about the new diet pills. Old pills didn’t work.Phentermine / TopiramateLocaserinOrlistatLife-style
53 Phentermine / topiramate Locaserin Orlistat None are safe for her 55 yo, wt 150kg, BMI 55, Read about the new diet pills. Old pills didn’t work. DM-2 (A1c=9.8%) on metformin and sitagliptin. Controlled HTN on metoprolol, Lipids ok on simvastain.Phentermine / topiramateLocaserinOrlistatNone are safe for her
54 42yo, lost his job, BMI=28. 5, girlfriend says lose some weight 42yo, lost his job, BMI=28.5, girlfriend says lose some weight. Serious exercises 4 days/week, still not losing weight. Ex-wife suing for custody of 2 kids. Nothing is going right in life. On citalopram 40mg daily. BP good on lisinopril / amlodipine.Phentermine / topiramateLocaserinOrlistatGet a new girlfriend
55 ConclusionMedications for weight loss, both old and new, produce modest benefit.Life-style change, exercise, calorie restriction are required.How much are we willing to spend to lose 5 to 15 kg and what are the other health benefits (mortality, strokes, MI’s, etc) ?