Orlistat (Xenical) vs Sibutramine (Meridia)

Mode of action

Generally diet pills work by suppressing appetite. Their working involves suppression of appetite by acting on nervous system and the brain to make the stomach believe that it is full.

Xenical acts in another way. Unlike other anti-obesity medications, Xenical through its fat-blocking mode of action works non-systemically in the gastrointestinal tract, not requiring entry into the bloodstream or brain. It prevents the absorption of dietary fat by inhibiting the key enzymes needed for converting dietary fat to its absorbable form.

Gastrointestinal symptoms are the most commonly observed side effects associated with the use of Xenical and are primarily a manifestation of its mechanism of action.

These effects are generally mild and transient and may include oily spotting, flatulence with discharge, fecal urgency, fatty or oily stool, oily evacuation, increased defecation and fecal incontinence.

Xenical also improves some obesity-related disease risk factors including high cholesterol, high blood pressure and diabetes.

Xenical vs Meridia

Orlistat and Sibutramine work by very different mechanisms of action - orlistat prevents fat absorption whereas sibutramine enhances satiety.

Weight loss efficacy

Orlistat may be slightly less effective than sibutramine in reducing body weight5. Although orlistat and sibutramine undoubtedly produce weight loss, the effect is modest. Neither orlistat, nor sibutramine is able to induce large weight reduction in a majority of obese people2.

Extra health benefits

Orlistat may be more powerful in improving blood glucose control.

Orlistat promotes a significant reduction of total cholesterol levels6.

Orlistat therapy is associated to a mild reduction in blood pressure1. Weight loss >/=5% of initial body-weight during orlistat therapy is associated with reductions in blood pressure in obese patients with or without hypertension.

Sibutramine can increase blood pressure and heart rate4 In obese patients with hypertension, sibutramine appears to increase blood pressure only if patients do not reduce caloric intake.

Side effects

Two drugs have disparate tolerability profiles. Sibutramine is generically better tolerated than orlistat1. However, sibutramine is contraindicated in people with coronary artery disease, congestive heart failure, arrhythmias, stroke, or inadequately controlled hypertension or those receiving psychiatric drugs.

The most common side effects with orlistat are oily stools, flatus and fecal urgency. And with sibutramine side effetcs are headache, dry mouth and anorexia. Sibutramine can also increase blood pressure and heart rate.

Feature Orlistat (Xenical) Sibutramine (Meridia)
Drug class Gastric and pancreatic lipase inhibitor Noradrenaline (norepinephrine) and serotonin reuptake inhibitor (via active metabolites M1 and M2)
Mechanism of action Locally: prevents absorption of approximately 30% of dietary fat Centrally: enhances satiety (decreases food intake)
Target population Initial BMI of >/=30 kg/m2, or >/=27 kg/m2 (US) or >/=28 kg/m2 (UK) with risk factors (hypertension, diabetes mellitus, dyslipidaemia) Initial BMI of >/=30 kg/m2, or >/=27 kg/m2 with risk factors (hypertension, diabetes mellitus, dyslipidaemia.)
Usual dosage 120mg orally 3 times daily with each main meal 10-15mg orally once daily with or without food
Special instructions Patients must take a multivitamin supplement (2h before a dose). No dose should be taken if a meal is missed or contains no fat Blood pressure monitoring is required before and during therapy
Contraindications Chronic malabsorption syndrome, cholestasis, pregnant/nursing women, hypersensitivity CAD, CHF, arrhythmias, stroke, severe renal or hepatic impairment, poorly controlled or uncontrolled hypertension, anorexia nervosa, patients taking MAOIsc or other serotonergic drugs
Use with caution History of hyperoxaluria or calcium oxalate nephrolithiasis History of hypertension, seizures, narrow angle glaucoma
Use in children Safety and efficacy have not been established Safety and efficacy in pediatric patients (<16 years of age) have not been established
Abuse potential As with any weight-loss agent, the potential exists for misuse in inappropriate patient populations (e.g. with anorexia nervosa or bulimia) Physicians should evaluate patients for history of abuse and observe closely for signs of misuse or abuse
Most common side effects Gastrointestinal (oily spotting or stool, flatus, increased fecal urgency) Headache, dry mouth, anorexia, insomnia, constipation
Cardiovascular side effects None Increased blood pressure and heart rate
Potential drug interactions Decreased absorption of fat-soluble vitamins May potentiate action of MAOIs and drugs that increase BP or HR; metabolism may be inhibited by CYP3A1 inhibitors
"Differential features: Comparison of various features of the antiobesity drugs orlistat and sibutramine"
from http://www.medscape.com/content/2000/00/40/64/406413/406413_tab.html3

What to Choose?

Both sibutramine (Meridia) and orlistat (Xenical) promote and maintain weight loss. Orlistat does not cause cardiovascular side effects and may be particularly useful for obese people with pre-existing cardiovascular disease.

On the other hand, the time frame for deciding if drug therapy is effective is 12 weeks for orlistat but only 4 weeks for sibutramine. This shorter time frame for evaluation with sibutramine allows more rapid treatment reconsideration.

The possibility of oily stools and discharge, the need for vitamin supplementation and a 3 times daily dosage schedule with orlistat can be bothersome or inconvenient. The once-daily dosage regimen with sibutramine is attractive but the potential for drug interactions or increased blood pressure, and contraindicatins in patients with cardiovascular disease and renal impairment, excludes a number of people from treatment.

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Further reading

References
  • 1. Hvizdos KM, Markham A. Orlistat: a review of its use in the management of obesity. Drugs 1999 Oct; 58 (4): 743-760
  • 2. Scheen AJ, Ernest P. New antiobesity agents in type 2 diabetes: overview of clinical trials with sibutramine and orlistat. Diabetes Metab. 2002 Dec;28(6 Pt 1):437-45. PubMed
  • 3. Better Than Slim Chances for Orlistat and Sibutramine to Promote Weight Loss. Drugs & Therapy Perspectives. 2000;15(12):1-6
  • 4. McNeely W, Goa KL. Sibutramine: a review of its contribution to the management of obesity. 1998 Dec: 56 (6): 1093-1124
  • 5. Gursoy A, Erdogan MF, Cin MO, Cesur M, Baskal N. Comparison of orlistat and sibutramine in an obesity management program: efficacy, compliance, and weight regain after noncompliance. Eat Weight Disord. 2006 Dec;11(4):e127-32. PubMed
  • 6. Mannucci E, Dicembrini I, Rotella F, Rotella CM. Orlistat and sibutramine beyond weight loss. Nutr Metab Cardiovasc Dis. 2008 Jun;18(5):342-8. PubMed

Published: March 31, 2008
Last updated: March 28, 2016

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