Orlistat – What Is Our Take On It?

Prescription drugs for causing weight loss have been a miserable failure. Orlistat is one drug that is most-often recommended for causing fat loss. Only moderately effective in causing fat loss, use of orlistat is associated with adverse effects – some potentially severe. Despite this, orlistat still remains the most readily available and prescribed drug for treating obesity. Let us have a look if it is indeed worth using.

Orlistat XenicalLifestyle modification, drugs and bariatric surgery are some physician prescribed treatments for obesity (Stern, Peerson, Mishra, Mathukumalli, & Konda, 2013).

Pharmacotherapy of obesity include using drugs like sibutramine and orlistat. These prescription drugs for weight loss, however, have been a miserable failure. Dr Emil L. Sigurdsson, in the editorial of Scandinavian Journal of Primary Health Care expresses his opinion about pharmacotherapy of obesity – “it is unlikely that the obesity epidemic can be solved with pills” (Sigurdsson, 2013). Furthermore, although mildly effective, drugs used for causing weight loss are associated with adverse effects (Kang & Park, 2012).

Orlistat (marketed in the US as Xenical; Roche) is the most prescribed drug for treating obesity.

It was approved as a prescription drug by the European commission in 1998 (Douglas, Langham, Bhaskaran, Brauer, & Smeeth, 2013) and by the FDA in 1999 (Sun & Chen, 2012). Orlistat is now available as an OTC drug in most countries including the UK (Douglas, Langham, Bhaskaran, Brauer, & Smeeth, 2013).

Currently, orlistat is the only approved drug that can be legally used for long-term treatment (up to a year) of obesity both in the US and Europe (Williams, 2010; Araujo & Martel, 2012; Hauptman, Jeunet, & Hartmann, 1992). Since the ban on Sibutramine (because of cardiovascular adverse effects) came into effect in 2010, orlistat remains the only choice for testing the hypothesis that weight loss reduces the risk of developing cardiovascular diseases (Araujo & Martel, 2012).

How Does Orlistat Cause Weight-Loss?

Chemically, orlistat is tetrahydrolipstatin (Tom & Martin, 2013).

Pharmacologically, it is a non-selective inhibitor of enzymes called lipases. Now, these enzymes are responsible for breaking down fat present in diet making their absorption easier. The suppression of gastric and pancreatic lipases, therefore, leads to suppression in fat absorption. (Guerciolini, 1997; Tom & Martin, 2013; Hadvary, Sidler, Meister, Vetter, & Wolfer, 1991).

According to an estimate, orlistat reduces absorption fat calories by 25% to 30% (Apovian & Gokce, 2012). However, this doesn’t translate into too much loss of body weight – eventual weight loss can at best be described as mild, especially when compared to fat-loss agents cause appetite suppression (Torgerson, Hauptman, Boldrin, & Sjostrom, 2004). A meta-analysis published in 2007 reported that orlistat may cause an average loss of body weight of only 6.4 pounds a year (Rucker, Padwal, Li, Curioni, & Lau, 2007).

How Do I Use Orlistat?

Orlistat is usually available as 120mg pills. The recommended dosage is 120mg orally, three times a day taken with a meal.

Reduction in calories is also recommended to aid weight loss.

A word of caution here: if you suffer from chronic malabsorption syndrome or cholestasis, you would be well advised to avoid using orlistat. Also, there is not data available regarding dose adjustment in liver or kidney disease.

Are There Any ill-effects Using Orlistat?

Adverse effects associated with the use of orlistat are usually mild and self-limiting (Douglas et al., 2013). However, these occur frequently – almost 10% of patients treated with orlistat suffer from these adverse effects (Sun & Chen, 2012).Some of the reported ill-effects are (Kang & Park, 2012; Sun & Chen, 2012):

  • Abdominal pain,
  • Flatulence (gases),
  • Oily spotting,
  • Indigestion and diarrhoea, and
  • Deficiency of fat-soluble vitamins

Since orlistat reduces the absorption of dietary fat, there is a likelihood that it seriously affects the absorption of fat-soluble vitamins and carotene as well. The symptoms of deficiencies that ensue may become apparent especially on long-term use. Concurrently using a multivitamin can help overcome this problem.

However, there are some – including the FDA – who have expressed concerns about the graver adverse effects of orlistat – use of orlistat may predispose you to liver injury (FDA, 2009; FDA, 2010).

Scientific Evidence for Orlistat

As stated earlier, although orlistat is proven to cause weight-loss, the results, at best, can only be described as mild or modest. Rucker et al., in their updated meta-analysis conclude that orlistat may cause weight-loss of an average of only 6.4 pounds a year (Rucker et al., 2007).

Regarding the adverse effects – especially severe ones – associated with orlistat use, opinion seems to be divided.
As mentioned earlier, the FDA reports increase in risk of liver injury with orlistat. However, some researchers beg to differ.

  • A large meta-analytical study (of about 10,000 patients treated with orlistat) concluded that orlistat may not, after all, be associated with causing deranged liver functions (Morris, Lane, Lee, & Parks, 2012).
  • The European Medicines Agency also reported similar results in their study to investigate possible links between orlistat and liver injury (EMA, 2012).
  • Douglas et al., in a recent paper published in the British Medical Journal, conclude that there seems to be no causal link between orlistat and liver injury. And that, the presence of underlying acute liver conditions due to obesity and its ill-effects are more likely to be responsible (Douglas et al., 2013).

However, notwithstanding the safety exhibited by orlistat in clinical trial, no large-scale, population-based studies proving the safety of orlistat have ever been conducted (up until April 2013). As such, ‘results from clinical trials do not always reflect the effects of drugs when used in general population’ (Douglas et al., 2013).

Our Verdict on Orlistat

Although opinion regarding adverse effects of use of Orlistat for reducing weight remains divided, there is no denying that Orlistat remains the only approved drug in the world (available over-the-counter in most countries). However, in view of its feeble effect in causing weight loss and pending further research on the safety of its use, we do not recommend its use for causing weight loss.

Useful References

  • Apovian, C. M. & Gokce, N. (2012). Obesity and cardiovascular disease. Circulation, 125, 1178-1182. Online Resource
  • Araujo, J. R. & Martel, F. (2012). Sibutramine effects on central mechanisms regulating energy homeostasis. Curr.Neuropharmacol., 10, 49-52. Online Resource
  • Douglas, I. J., Langham, J., Bhaskaran, K., Brauer, R., & Smeeth, L. (2013). Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink. BMJ, 346, f1936. Online Resource
  • EMA. (2012). European Medicines Agency confirms positive benefit-risk balance of orlistat-containing medicines.
    EMA report
  • FDA. (2009). Orlistat (marketed as Alli and Xenical): Early Communication about an Ongoing Safety Review.
    FDA report
  • FDA. (2010). FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury. FDA safety report
  • Guerciolini, R. (1997). Mode of action of orlistat. Int J Obes Relat Metab Disord, 21 Suppl 3, S12-S23.
  • Hadvary, P., Sidler, W., Meister, W., Vetter, W., & Wolfer, H. (1991). The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase. J Biol.Chem., 266, 2021-2027. Online Resource
  • Hauptman, J. B., Jeunet, F. S., & Hartmann, D. (1992). Initial studies in humans with the novel gastrointestinal lipase inhibitor Ro 18-0647 (tetrahydrolipstatin). Am J Clin Nutr., 55, 309S-313S. Online Resource
  • Kang, J. G. & Park, C. Y. (2012). Anti-Obesity Drugs: A Review about Their Effects and Safety. Diabetes Metab J, 36, 13-25.
  • Morris, M., Lane, P., Lee, K., & Parks, D. (2012). An integrated analysis of liver safety data from orlistat clinical trials. Obes Facts., 5, 485-494. Online Resource
  • Rucker, D., Padwal, R., Li, S. K., Curioni, C., & Lau, D. C. (2007). Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ, 335, 1194-1199. Online Resource
  • Sigurdsson, E. L. (2013). Up and running: an underutilized prescription in primary care. Scand.J Prim.Health Care, 31, 1-2.
  • Stern, J. S., Peerson, J., Mishra, A. T., Mathukumalli, V. S., & Konda, P. R. (2013). Efficacy and tolerability of an herbal formulation for weight management. J Med Food, 16, 529-537. Online Resource
  • Sun, Y. & Chen, J. D. (2012). Rimonabant, gastrointestinal motility and obesity. Curr.Neuropharmacol., 10, 212-218. Online Resource
  • Tom, C. T. & Martin, B. R. (2013). Fat chance! Getting a grip on a slippery modification. ACS Chem.Biol., 8, 46-57. Online Resource
  • Torgerson, J. S., Hauptman, J., Boldrin, M. N., & Sjostrom, L. (2004). XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care, 27, 155-161. Online Resource
  • Williams, G. (2010). Withdrawal of sibutramine in Europe. BMJ, 340, c824. Online Resource

Disclaimer: Our reviews and investigations are based on extensive research from the information publicly available to us and consumers at the time of first publishing the post. Information is based on our personal opinion and whilst we endeavour to ensure information is up-to-date, manufacturers do from time to time change their products and future research may disagree with our findings. If you feel any of the information is inaccurate, please contact us and we will review the information provided.

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1 comment on 'Orlistat – What Is Our Take On It?'

  1. I can say from personal experience that Xenical works very well. I lost around 4 stones a few years ago at a rate of around 2lbs per week. I ate as much food as I wanted, which was quite a lot, and reduced my fat intake whilst taking Xenical. I still ate meals high in fat on occasions and still with very good weight loss.