Pharmacotherapy Of Obesity:

Past, Present and Future

Control of energy intake mainly through modification of appetite. Control of energy expenditure

essentially through increase of thermogenesis.

Control of availability of substrates to cells mainly through hormonal and other metabolic factors available at the energy substrate Control of fat reserves through modulation of Lipogenesis

OBESITY:DRUG TREATMENT

Dr.R.N.MISHRA
PG.DEPT. OF PHARMACOLOGY Hi-Tech MEDICAL COLLEGE

CORPULENCY,

WHEN

IN

AN

EXTRA ORDINARY DEGREE, MAY BE

RECKONED A DISEASE, AS IT IN SOME MEASURE

OBSTRUCTS THE

FREE EXERCISE OF ANIMAL FUNCTIONS; AND HATH

A TENDENCY TO SHORTEN LIFE, BY PAVING THE WAY TO DANGEROUS

DISTEMPERS

A SHORT HISTORY
1.
2. 1893-THYROID EXTRACT. 1933-DNF.NEUROPATHY,CATARACT

3.
4.

1937-AMPHEAMINE.ADDICTION
1967-AMPHETAMINE+DIGITALIS+DIURETIC SEVERAL DEATHS

5.
6. 7. 8.

1971-AMINOREX,AN APETITE SUPPRESANT

OUTBREAK OF PPH IN EUROPE 1978-VERY LOW CALORIE DIET WITH COLLAGEN AS THE PRINCIPLE SOURCE OF PROTEIN. 17 DEATHS. 1991-PROBLEMS WITH DIET CLINICS. FINAL PROBLEM-VALVULAR HEART DISEASE

 PREFERENCE TO TREAT COMPLICATIONS

IGNORANCE LACK OF RECOGNITION

LACK OF HARD EVIDENCE OF EFFICACY

OF THE DRUGS

CAUCASIANS-BMI:25-29-OVERWEIGHT BMI:30 OR MORE-OBESE SOUTH ASIANS-BMI:23-24.9-OVERWEIGHT BMI:=>25-OBESE (NORMAL:18-22.9) WAISTLINE MEN:CAUCASIANS-102 cm. SOUTH ASIANS-90cm. WOMEN:CAUCASIANS-88cm. SOUTH ASIANS-80cm.

WHY TREAT OBESITY

OBESITY RELATED TO DEVELOPMENT OR POOR CONTROL OF: INSULIN RESISTANCE T2DM HTN CORONARY ARTER DISEASE STROKES DYSLIPIDEMIA OSA PULMONARY HTN OA SOME CANCERS ETC.

WHY TREAT OBESITY

ENORMOUS POTENTIAL 10 Kg WEIGHT LOSS:REDUCTION OFA. SYSTOLIC BP BY 10 mm B. CHOLESTEROL BY 10% C. LDL BY 15% D. TG BY 30%

E. FBS BY 50%

INCREASE IN HDL:8%

BASIC RULES:
1. 2. NEVER FOR COSMETIC PURPOSES ALWAYS COMBINE WITH HEALTHY EATING AND PHYSICAL EXERCISE SUBJECT SHOULD HAVE TRIED WEIGHT LOSS THRU DIET AND PHYSICAL ACTIVIES

3.

 1.BMI:>30

APROVAL:

2.BMI:>27-WHEN 2 OR MORE RELATED

COMPLICATIONS LIKE HTN, T2DM, OSA,HEART DISEASE,DYSLIPIDEMIA ETC.

INDIAN GUIDELINE:CONSIDER WHEN

BMI:=>27 WITHOUT ANY CO-MORBIDITY

BMI:=>25 WITH COMORBIDITY

FDA APPROVED DRUGS:

APETITE SUPPRESANTS:

1. 2. 3. 4.

SIBUTRAMINE PHENTERMINE PHENDIMETRAZINE DIETHYLPROPION

LIPASE INHIBITOR: ORLISTAT(1997-FOR OTC SALE TO PERSONS >18 YRS.)

NOT APPROVED BUT MAY BE USED OFF-LABEL:

A .ANTI-DEPRESSANTS: 1. BUPROPION 2. SERTRALINE 3. VENLAFAXINE 4. FLUOXETINE ETC. B. ANTI-CONVUSANTS: 1. TOPIRAMATE 2. ZONISAMIDE C. METFORMIN

EUROPEAN MARKET:AVAILABLE DRUGS 1.SIBUTRAMINE, 2.ORLISTAT AND 3.REMONABANT

COMBINATIONS:
FLUOXETINE+PHENTERMINE

ORLISTAT+SIBUTRAMINE
PHENDIMETRAZINE+PHENTERMINE HERBALS
SAFETY UNKNOWN

NAME

FDA APPROVAL
YES.UP TO ONE YR. ADULTS

TYPE

SIDE EFFECTS
BP, PR INCREASE

1. SIBUTRAMINE

APETITE SUPPRESANT

2. PHENTERMINE

YES.UP TO 12 WKS ADULTS

-DO-

-DO. DECREASED SLEEP,ANXIETY -DO. DECREASED SLEEP,ANXIETY DIZZINESS, HEADACHE, DECREASED

3. PHENDIMETRAZINE

YES.UP TO 12 WKS. ADULTS

-DO-

4. DIEYES.UP TO 12 WKS. THYLPROPION ADULTS

-DO-

NAME

FDA APPROVAL

TYPE

SIDE EFFECT S
GI ISSUES

5. ORLISTAT

YES.UP TO 1 YR. LIPASE INHIBITOR

NO ANTIDEPRESSANT ANTISEIZURE

6. BUPROPION

DRY MOUTH, INSOMNIA TASTE CHANGE, NUMBNESS DRY MOUTH, DROWSINESS, DIZZINESS,HEA DACHE,NAUSEA

7. TOPIRAMATE

NO

8. ZONISAMIDE

NO

DO

HOW LONG:
1. EFFICACY

2.

SIDE EFFECTS

ONE RECENT STUDY:1 MONTH ON AND 1 MONTH OFF SHOWED EFFICACY OF SIBUTRAMINE TO LOSE AND MAINTAIN WT. FOR >2 YEARS

STORM STUDY:GOOD EVIDENCE OF LONG-TERM EFFECTIVENESS OF SIBUTRAMINE

EFFICACY-RECENT EVIDENCES
A.FIVE LONG-TERM STUDIES WITH SIBUTRAMINEMEAN WT. REDUCTION: 4.45Kgs FOR SIBUTRAMINE vs. PLACEBO DECREASE IN WAIST CIRCUMFERENCE DECREASE IN TG,URIC ACID INCREASE IN HDL IMPROVED GLYCATED Hb. IN DIABETICS BP-CNNFLICTING RESULTS.MINIMAL TO MODEST INCREASE IN DIFFERENT STUDIES INCREASE IN PULSE RATE
B.ORLISTAT:META-ANALYSIS OF 22 STUDIES ALL LASTING FOR >12 MONTHS(MEAN BMI:36.7) WITH ORLIST+DIET/BEHAVIOUR THERAPY: 1. AVERAGE WT. LOSS:2.89 Kgs 2. SIGNIFICANT DECREASE IN WAISTLINE,BP,TC, LDL-C 3. NO EFFECT ON HDL,TG 4. SIGNIFICANT IMPROVEMENT IN IGT IN DIABETICS

CONTD. RIO STUDY:n=6600 OVERWEIGHT OR OBESE INDIVIDUALS EFFECT OF RIMONABANT OVER AND BEYOND 600 Kcal RESTRICTION FOUR DOUBLE BLIND TRIALS(RIO-NORTH AMERICA,RIOEUROPE,RIO-LIPIDS,RIO-DIABETES) DECREASE IN WT. BY 5.3 Kgs DECREASE IN WAIST-LINE,TG INCREASE IN HDL NO SIGNIFICANT DECREASE IN LDL RIO-LIPIDS-DECREASE IN SMALL DENSE LDL RIO-DIABETES:HbA1c IMPROVED BY .7% CONCLUSION:3 AVAILABLE DRUGS IN EUROPE ASSOCIATED WITH IMPROVEMENT OF CARDIOMETABOLIC RISK FACTORS

SOME SPECIAL AGENTS

NEUROPEPTIDE Y ANTAGONIST RECOMBINANT LEPTIN Fc-LEPTIN ANTI-OBESITY VACCINE

ALL IN EXPERIMENTAL STAGES

OBESITY HAS REACHED AN EPIDEMIC PROPORTION MANAGEMENT-A CHALLENGE AS RAPID EVOLUTION OF UNFAVOURABLE LIFE-STYLE
CURRENTLY NO EFFECTIVE Rx. FOR MAJORITY POTENTIAL OF BENEFIT IS ENORMOUS

CONCLUSION: