Obesity Medicine Sacramento

Transcription

1 Dr Ed Hendricks Obesity Medicine Sacramento 11:00-11:55 WS #31: The Role of Duromine in Obesity Management - The US experience 12:05-13:00 WS #39: The Role of Duromine in Obesity Management - The US experience (Repeated)

2 GP CME, 2016 Rotorua, New Zealand American Experience: Phentermine Ed J. Hendricks, MD Fellow, Obesity Medicine Association Diplomate, American Board Obesity Medicine

3

4

5 Successful Medical Management of Excess Adiposity Frequent Office Visits Diet Low Carbohydrate, Ketogenic Behavior change Eating behaviors Exercise behaviors Pharmacotherapy Duromine New Drugs?

6 Phenethylamine

7 Substituted Phenethylamines

8 Phentermine Formulations Phentermine base as an ion-exchange resin; C 10 H 15 N; MW = Duromine, Ionamin, others Phentermine-HCl; C 10 H 16 ClN; MW = ; generic phentermine, Adipex, others..

9 Dose Correspondence Duromine Phentermine-HCl 15 mg mg 30 mg 37.5 mg 40 mg* 50 mg * Not available in New Zealand

10 Phentermine-HCl Pharmacokinetics Addy, J Clin Pharmacol 2009;49:

11

12 History FDA Approvals 1943 Amphetamine for depression, narcolepsy Amphetamine for obesity Amphetamine in use for obesity 1959 Phentermine approved for obesity 1960s P most widely used Rx for obesity 1963 FD&C Act amended to include efficacy 1970s New trials 1973 FDA reapproves P, for short-term use Colman, Ann Intern Med 2005;143:

13 Phentermine Treatment Start with Duromine 15 mg or 30 mg. Most adults tolerate 30 mg/day. Evaluate for adverse effects. Evaluate for effectiveness Weight loss Eating behavior

14 Side Effects Common Dry mouth - usually tolerable Insomnia typically fades quickly Increased energy, mood elevation Mild anti-cholenergic effects e.g. constipation Less Common Impotence, decreased sex drive Irritability Slowing of micturation

15 Phentermine Effectiveness Effects: eating behavior change, weight loss Clinical trials have generally been wks. Average weight loss across the trials ~ 7% No phentermine long-term RCTs reported Report: Frank Obes Res 2004;12: We conducted a retrospective observational study of 300 patients (Hendricks Obesity 2011; 19: )

16 Study Selection Criteria 1) Continuing patient, started with VLCKD 2) Exams at 0, 1, 2, 3, 4, 8, & 12 weeks 3) Data for 26, 40 weeks and then yearly 4) Pts with hiatus in Rx < 1 yr. included 5) Completers only, drop out rate not determined Hendricks, Obesity 2011;19:

17 Demographics Total P Rx No P Rx Age BMI Wt, lbs Wt, Kg Hendricks, Obesity 2011;19:

18 Demographics Total P Rx No P Rx Number Male/female 46/254 38/231 8/23 male/female 15/85 % 14/86 % 26/74 % Ethnicity (W/B/H/A) 284/1/12/3 256/1/10/2 28/0/2/1 Hendricks, Obesity 2011;19:

19 % Weight Loss Phentermine Treated v No Rx Rx Rx No Rx No Rx Weeks N % Loss N % Loss Hendricks, Obesity 2011;19:

20 Wt Loss, P Rx, 52 Wk, N % 0.0% -5.0% -10.0% -15.0% -20.0% -25.0% -30.0% -35.0% -40.0% -45.0% Mean: 17.3 Kg, 17.6% 5% Weight Loss 97% 10% Loss 83% 20% Loss - 32% Hendricks, Obesity 2011;19:

21 5 All Phentermine Treated Weeks/Years Hendricks, Obesity 2011;19: % Wt Loss Delta SBP Delta DBP Delta HR

22 Average % Wt Loss by Year 0% % -10% -15% -20% Phen Rx No Phen Hendricks Obesity 2011; 19:

23 JNC 7 BP Categories Normal < 120/80 Prehypertension /80-89 Hypertension 140/90

24 Blood Pressure JNC 7 Count Percent Optimum 42 14% PreHTN % HTN 96 32% TOTAL % Hendricks, Obesity 2011;19:

25 PreHTN vs BMI (NHANES)

26 PreHTN Progression to HTN Framingham* 37.3% In 4 years Strong Heart Study* 38% In 4 years Taiwan* 31.3% In 5 years Expected Progression Rate ~ 6 9 %/year *Total population, not stratified for BMI

27 Categorical BP Shifts NBP PreHTN: Expected no data Observed: 3 cases in 22 patients NBP HTN: Expected: 3 % per year (general population) Observed: None PreHTN HTN: Expected: 6-9%/ year Observed: 1 case in 93 at 1 yr. or 1% Hendricks, Obesity 2011;19:

28 5 All Phentermine Treated Weeks/Years Hendricks, Obesity 2011;19: % Wt Loss Delta SBP Delta DBP Delta HR

29 Qsymia vs Phentermine No Q Rx All Q HTN Q No P Rx All P HTN P Data at One Year SBP DBP Wt Loss

30 Study Conclusions Long-term phentermine Rx can be effective for weight loss and for wt. loss maintenance. Phentermine-induced elevation of BP or HR if this indeed does occur, is rare. Phentermine-treated overweight patients with HTN and prehtn typically have significant decreases in BP and sustained CV benefit. Hendricks, Obesity 2011;19:

31 Cardiovascular Benefits 1 Long-term P Rx, by improving maintenance, may help retard the natural progression from NBP to PreHTN to HTN in the obese. 2 Wt Loss, sustained by P Rx, may substantially reduce CVD mortality in prehypertensive and hypertensive obese patients. Hendricks, Obesity 2011;19:

32 Adverse Cardiovascular Effects due to Phentermine Pulmonary Hypertension no evidence Cardiac Valvulopathy no evidence Arrhythmias - no evidence Blood pressure elevation no evidence Hypertension, CVD contraindication no Sudden Cardiac Death no evidence Palpitations do occur, rate is low, often PVCs evidence

33 Phentermine & Atrial Fibrillation Atrial Fibrillation most common arrhythmia No association between AF & phentermine Known Risk Factors for AF: Obesity, incidence correlates with BMI Diabetes, hypertension, hyperlipidemia, low HDL Advancing age, female sex, family history Weight loss lowers risk of AF Phentermine administration assists weight loss - lowering risk of AF

34 Recommendations New patient with BP > 140/90 Hold phentermine until BP < 140/90 Start diet - Low Carb Ketogenic Diet induces lower BP Consider Rx for HTN Start phentermine once BP < 140/90 If BP > 140/90 on subsequent exam, hold phentermine until BP in control

35 ADDICTION?

36 Phentermine status 1959 No evidence of human addiction potential, but Phentermine induced increased loco motor activity in rats thus a stimulant. All stimulants were then considered addictive. Phentermine differs from amphetamine by one methyl group. FDA phentermine presumed addicting. A presumption no evidence in humans.

37 Phentermine after 50 years (2010) No evidence of human addiction. No reports of phentermine addiction. No investigations of addiction potential. Clinical observations no addiction. Abuse (e.g. non-prescribed uses) Polydrug users Long-haul truck drivers

38 Phentermine status 2016 Hendricks et al, Am J Thera 2011; 18: No amphetamine-like withdrawal, no cravings. Hendricks et al, Int J Obes 2014; 38: Clinical Trial results: No cravings, no withdrawal, no symptom of addiction in 269 patients phentermine-treated as long as 21 years, some on doses higher than maximum recommended. Phentermine Rx does not induce addiction.

39 DUROMINE BENEFITS OTHER THAN WEIGHT LOSS

40 Beneficial Effects Improvement in obesity-related diseases e.g. T2DM, Sleep apnea, HTN, CHF, PCOS, arthritis, NASH, metabolic syndrome, etc. Successful maintenance of weight loss Counteract drug-induced weight gain Arrest or slow progressive weight gain Improvement in compliance with diet Improvements in harmful eating behaviors

41 Duromine A Behavioral Drug Beneficial eating behavior changes Better control of eating & compliance with diet Less emotional and stress eating Diminished eating due to cravings Improved eating restraint Beneficial exercise behavior changes More energy Exercise more often and with intensity

42 Changes in Eating Behavior When asked What is the effect of the drug? obese patients treated with phentermine offer a wide variety of answers such as: I don t eat as much. I can stop eating. I don t graze all day and night. I m not hungry as soon as I stop eating. I m normal (in respect to eating).

43 Eating Behavior Questionnaire Design Questions taken from patient descriptions of treatment effects. Questions phrased in simple sentences. Visual Analog Scale; parametric data. Patients answer questions by marking a 100 millimeter line under each question. Scored by measuring mm from left end. Question 8, reverse; measured from right end.

44

45 EBQ Questions 1. Are you preoccupied with thoughts of food or eating? 2. Do you eat to comfort yourself? 3. Do you crave any specific foods? 4. Once you start eating, do you find it hard to stop? 5. Do you find it difficult to stick to an eating plan?

46 EBQ Questions 6. Do you eat rapidly, more rapidly than those around you? 7. Do you graze or eat continually during any part of a 24- hour day? 8. Are you in control of your eating? (Reverse) 9. Do you eat more when under stress? 10. Do you eat more during highly emotional times?

47 Number of Patients Treated N = 197 Mean (SD) 36.9 (15.7) Distribution of EBQ Scores Untreated N = 217 Mean (SD) 62.0 (13.6)

48 TREATMENT RECOMMENDATIONS

49 Summation & Recommmendations Treat Early focus on co-morbidities Treatment components Behavioral - what to eat Behavioral - exercise/activity Behavioral manage harmful eating behaviors Low carbohydrate, ketogenic diet Pharmacotherapy Lifelong treatment duration include Duromine

50 THANK YOU