Orlistat (tetrahydrolipstatin) is a United States Food and Drug Administration (FDA) approved anti-obesity medication. It is a saturated derivative of endogenous lipstatin isolated from Streptomyces toxytricini. FDA approved indications of orlistat include:
The maximum benefit of orlistat occurs when used in conjunction with diet and exercise. The weight starts to decrease within 2 weeks of initiation of orlistat. Statistically, significant weight loss occurs when orlistat use is for greater than 2 months. After 6 months of orlistat use, the mean weight loss is around 5.6 kg compared to 2.4 kg in the placebo group. Orlistat also causes a significant reduction in BMI, waist circumference, total cholesterol, and LDL levels. In the XENDOS trial, orlistat has been found to have a statistically significant impact in reducing the incidence of diabetes in patients with impaired glucose tolerance.
Orlistat acts by reversibly inhibiting the gastric and pancreatic lipases. These lipases have an important role in the digestion of dietary fat. They work by breaking down the triglycerides into absorbable free fatty acids and monoglycerides. Orlistat covalently binds to the serine residues of active sites of lipases and inactivates them. The inactivation of lipases prevents the hydrolysis of triglycerides, and thus free fatty acids are not absorbed. The primary action of orlistat is local lipase inhibition within the gut. Systemic absorption is not necessary for the activity of orlistat. At its recommended dosage, it inhibits dietary fat absorption by approximately 30%.
The recommended orlistat dose is 120 mg capsule orally thrice daily. The administration should be during or within 1 hour after the fat-containing meal. Doses of more than 120 mg have not shown any additional benefit. The recommendation is that the patient adheres to a nutritionally balanced, low-calorie diet with less than 30% calories from fat. If the patient misses the meal, they can omit the dose of orlistat. If the patient misses the dose of orlistat and it has been more than 2 hours past the fat-containing meal, then that dose can be skipped since by that time, most of the fat absorption has already occurred, and the medication would not work effectively. Since orlistat reduces the absorption of fat-soluble vitamins, patients should also take multivitamin supplements once daily, but their administration should be at a gap of more than 2 hours after the orlistat administration.
Also, healthcare professionals need to rule out organic causes of obesity like hypothyroidism or Cushing syndrome before initiating orlistat therapy.
The utility of orlistat in specific patient population groups:
The side effects of orlistat include the following:
Few case reports have illustrated the association of orlistat use with hypertension, diabetic ketoacidosis, depression, cutaneous vasculitis, lichenoid eruptions, and vaginitis. However, a causal relationship between orlistat and these adverse effects remains unproven.
Contraindications to orlistat include the following conditions:
It is necessary to monitor the body weight, body mass index (BMI), waist circumference, and lipid profile in patients taking orlistat. The levels of cyclosporine, antiepileptics, and HIV viral load require monitoring when using orlistat in conjunction with these medications.
There is no specific antidote for orlistat overdose. However, if a significant overdose of orlistat occurs, the patient should immediately come to the emergency department and be observed for 24 hours to provide supportive care.
Obesity and its comorbidities have a significant burden on the healthcare system. Utilizing pharmacotherapy in the form of orlistat can reduce morbidity and mortality from obesity-related complications but should be employed judiciously.
Orlistat is effective in lowering body weight, BMI, cholesterol levels, waist circumference and has also been shown to cause a modest decrease in blood pressure, along with improved glycemic control in patients with diabetes. Gastrointestinal adverse effects are the most common reason for discontinuation of the medication. In the right clinical setting, the drug can be used to achieve weight loss goals and decrease obesity complications.
The clinical nurse is needed to assist the medical team in educating the patient on the expected gastrointestinal effects of the drug. A specialized pharmacist is a key to optimizing therapy with this drug. The pharmacist is needed to assist the medical team in adjusting doses or timing of other medications when starting the patient on orlistat therapy to ensure their efficacy is not reduced. The pharmacist is needed to educate the patient on proper dosing, timing, and frequency of therapy to minimize adverse outcomes. Dieticians should be involved in patient care, ensuring the patient has direction on a nutritionally balanced, low-calorie diet. A coordinated and collaborative interprofessional team can improve the efficacy of orlistat therapy and achieve optimal patient results. [Level 5]
|||Jain SS,Ramanand SJ,Ramanand JB,Akat PB,Patwardhan MH,Joshi SR, Evaluation of efficacy and safety of orlistat in obese patients. Indian journal of endocrinology and metabolism. 2011 Apr; [PubMed PMID: 21731866]|
|||Hollywood A,Ogden J, Taking Orlistat: Predicting Weight Loss over 6 Months. Journal of obesity. 2011; [PubMed PMID: 21113309]|
|||Sjöström L,Rissanen A,Andersen T,Boldrin M,Golay A,Koppeschaar HP,Krempf M, Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet (London, England). 1998 Jul 18; [PubMed PMID: 9683204]|
|||Torgerson JS,Hauptman J,Boldrin MN,Sjöström L, 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. 2004 Jan; [PubMed PMID: 14693982]|
|||Guerciolini R, Mode of action of orlistat. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 1997 Jun; [PubMed PMID: 9225172]|
|||Filippatos TD,Derdemezis CS,Gazi IF,Nakou ES,Mikhailidis DP,Elisaf MS, Orlistat-associated adverse effects and drug interactions: a critical review. Drug safety. 2008; [PubMed PMID: 18095746]|
|||Wang H,Wang L,Cheng Y,Xia Z,Liao Y,Cao J, Efficacy of orlistat in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Biomedical reports. 2018 Jul; [PubMed PMID: 29930810]|
|||McDuffie JR,Calis KA,Booth SL,Uwaifo GI,Yanovski JA, Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy. 2002 Jul; [PubMed PMID: 12126214]|
|||Humayun Y,Ball KC,Lewin JR,Lerant AA,Fülöp T, Acute oxalate nephropathy associated with orlistat. Journal of nephropathology. 2016 Apr; [PubMed PMID: 27152294]|
|||Bigham S,McGuigan C,MacDonald BK, Reduced absorption of lipophilic anti-epileptic medications when used concomitantly with the anti-obesity drug orlistat. Epilepsia. 2006 Dec; [PubMed PMID: 17201727]|
|||Zhi J,Moore R,Kanitra L,Mulligan TE, Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers. Journal of clinical pharmacology. 2003 Apr; [PubMed PMID: 12723464]|
|||Nägele H,Petersen B,Bonacker U,Rödiger W, Effect of orlistat on blood cyclosporin concentration in an obese heart transplant patient. European journal of clinical pharmacology. 1999 Nov; [PubMed PMID: 10638396]|
|||Asberg A, Interactions between cyclosporin and lipid-lowering drugs: implications for organ transplant recipients. Drugs. 2003; [PubMed PMID: 12558459]|
|||Skelin M,Lucijanić T,Amidžić Klarić D,Rešić A,Bakula M,Liberati-Čizmek AM,Gharib H,Rahelić D, Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clinical therapeutics. 2017 Feb; [PubMed PMID: 28153426]|
|||MacWalter RS,Fraser HW,Armstrong KM, Orlistat enhances warfarin effect. The Annals of pharmacotherapy. 2003 Apr; [PubMed PMID: 12659605]|