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Orl6.0
Orlistat Research
Mostly mechanism / observational
12 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Orlistat studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 1998–2017 with a typical study size of 688 participants.
Based on 12 studies · 3 meta-analyses · 4 RCTs · 5,293 total participants
Confidence
High confidence
By outcome
Weight managementAbout 2.6–2.9 kg more weight loss than placebo at one year; 44% of users reach ≥5% body-weight loss vs 23% on placebo · 4-12 weeks
Mostly mechanism / observational9 studies
Cholesterol & lipids
Mostly mechanism / observational4 studies
Safety profile
Mostly mechanism / observational4 studies
Glucose & metabolicIn obese type 2 diabetes on sulfonylureas, significant HbA1c and fasting-glucose reduction with sulfonylurea dose reductions · 3-6 months · Lower total and LDL cholesterol, lower fasting insulin, and a 37.3% relative reduction in new type 2 diabetes over 4 years — but only in those with impaired glucose tolerance at baseline, not across obese adults generally · 6-12 months
Mostly mechanism / observational3 studies
Heart & blood pressure
Too few graded studies2 studies
Therapeutic & clinical
Too few graded studies2 studies
Kidney & renal health
Too few graded studies2 studies
Recovery
Too few graded studies1 study
1 more outcome with fewer studies not shown.
Older research base
Newest study from 2017 · Latest meta-analysis: 2016
199820072017
1RCTn=3,305 · very large study2004
In plain English: After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032).
Torgerson, Hauptman, Boldrin, Sjöström · Diabetes Care (2004)
4-year double-blind trial randomising 3,305 obese patients (BMI ≥30) to lifestyle changes plus orlistat 120 mg or placebo three times daily
Cumulative 4-year diabetes incidence 6.2% with orlistat vs 9.0% with placebo — a 37.3% relative risk reduction (P = 0.0032)
Mean 4-year weight loss 5.8 kg with orlistat vs 3.0 kg with placebo (P < 0.001); with baseline-carried-forward for dropouts, 3.6 vs 1.4 kg (P < 0.001)
In plain English: From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p<0.001] from randomisation to the end of year 1).
743 obese patients (BMI 28–47) entered a 4-week placebo lead-in at 15 European centres; 688 were randomised double-blind to orlistat 120 mg three times a day or placebo for 1 year on a 600 kcal/day-deficit diet, then reassigned for a second 52-week weight-maintenance period
Year 1: 10.2% (10.3 kg) body-weight loss with orlistat vs 6.1% (6.1 kg) with placebo; least-squares-mean difference 3.9 kg from randomisation (p<0.001)
Year 2: patients continuing orlistat regained on average half as much weight as those switched to placebo (p<0.001); those switched from placebo to orlistat lost a further 0.9 kg vs a mean 2.5 kg regain on continued placebo (p<0.001)
In plain English: During the first year orlistat-treated subjects lost more weight (mean ± SEM, 8.76±0.37 kg) than placebo-treated subjects (5.81±0.67 kg) (P<.001).
2-year randomised, double-blind, placebo-controlled trial at 18 US research centres; 1,187 obese adults (BMI 30–43) entered and 892 were randomised, with 223 placebo- and 657 orlistat-treated subjects in the intent-to-treat analysis
Year 1: 8.76 ± 0.37 kg weight loss with orlistat 120 mg three times daily vs 5.81 ± 0.67 kg with placebo (P<.001)
Year 2 regain: 3.2 kg (35.2% regain) on orlistat 120 mg tid vs 4.26 kg (51.3%) on 60 mg tid vs 5.63 kg (63.4%) on placebo (P<.001) — the dose comparison behind the 120 mg Rx vs 60 mg OTC strengths
In plain English: Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg).
Rucker, Padwal, Li, Curioni, Lau · BMJ (2007)
Updated meta-analysis of double-blind randomised placebo-controlled trials of approved anti-obesity drugs lasting one year or longer; 30 trials met inclusion, of which 16 were orlistat trials (n=10,631 participants)
Orlistat reduced weight by 2.9 kg vs placebo (95% CI 2.5 to 3.2 kg) — smaller than sibutramine (4.2 kg) and rimonabant (4.7 kg) in the same analysis
Patients on active drug were significantly more likely to achieve 5% and 10% weight-loss thresholds
In plain English: A median 23% of placebo participants had at least 5% weight loss vs ... 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22).
Bayesian network meta-analysis of 28 randomised trials in 29,018 overweight or obese adults comparing the five FDA-approved long-term weight-loss agents
Orlistat: 44% of patients achieved ≥5% weight loss vs a 23% placebo median (OR 2.70, 95% CrI 2.34–3.09), with the lowest SUCRA ranking (0.22) of the five agents
Excess weight loss with orlistat was 2.6 kg vs placebo (95% CrI −3.04 to −2.16), compared with 8.8 kg for phentermine-topiramate and 5.3 kg for liraglutide
In plain English: After 1 year of treatment, the orlistat group lost 6.2 ± 0.45% (mean ± SEM) of initial body weight vs. 4.3 ± 0.49% in the placebo group (P < 0.001).
Multicentre 57-week randomised double-blind placebo-controlled trial of orlistat 120 mg three times daily in 391 obese adults with type 2 diabetes stable on oral sulfonylureas
Weight loss 6.2 ± 0.45% vs 4.3 ± 0.49% of initial body weight (P < 0.001); twice as many orlistat patients lost ≥5% of body weight (49% vs 23%, P < 0.001)
Significant improvement in glycaemic control — decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) — with dosage reductions of oral sulfonylurea (P < 0.01)
In plain English: Orlistat interferes with the absorption of many drugs (such as warfarin, amiodarone, ciclosporin and thyroxine as well as fat-soluble vitamins), affecting their bioavailability and effectiveness.
Filippatos, Derdemezis, Gazi, Nakou, Mikhailidis, Elisaf · Drug Safety (2008)
Critical review of orlistat's adverse effects and drug interactions, written in light of the FDA approval of over-the-counter orlistat 60 mg three times daily
Gastrointestinal adverse effects are mild-to-moderate but frequent: oily stools, diarrhoea, abdominal pain and faecal spotting
Documented absorption interactions with warfarin, amiodarone, ciclosporin and thyroxine, as well as with fat-soluble vitamins
In plain English: While idiosyncratic liver injury following exposure to orlistat cannot be excluded, it is likely to be extremely rare.
Morris, Lane, Lee, Parks · Obesity Facts (2012)
Integrated analysis of liver function data from randomised orlistat trials in over 10,000 subjects, using summary-level meta-analysis, time-to-event analysis and an FDA eDISH-derived method, prompted by post-marketing reports of possible drug-induced liver injury that led to product-information changes
Pooled odds ratio for treatment-emergent ALT abnormality was 1.09 (95% CI 0.93–1.28); for total bilirubin 1.24 (95% CI 1.03–1.49), partly attributable to longer average exposure to orlistat than placebo
Patient-level display adjusting for regression to the mean and Kaplan-Meier analysis of ALT and bilirubin changes showed no significant difference between orlistat and placebo
In plain English: Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation.
Prospective open-label pilot study of 17 adolescents with BMI above the 95th percentile and at least one obesity-related comorbidity, given orlistat 120 mg three times daily plus a daily multivitamin (vitamin A 5000 IU, D 400 IU, E 300 IU, K 25 µg)
Acute absorption of alpha-tocopherol (vitamin E) was significantly reduced compared with baseline (p<0.001); acute retinol (vitamin A) absorption was not significantly altered
Mean vitamin D levels were significantly reduced versus baseline after 1 month (p<0.02) despite the multivitamin
In plain English: Two patients developed kidney failure due to oxalate deposition in the kidney while taking orlistat.
Solomon, Nixon, Ogden, Nair · BMJ Case Reports (2017)
Two patients developed kidney failure from calcium-oxalate deposition in the kidney while taking orlistat
Cessation of orlistat was followed by partial recovery of kidney function in both
They suggest that all patients taking orlistat are at risk of this condition, which may develop insidiously and is easily overlooked, and that monitoring of kidney function is warranted
In plain English: An increased INR was reported after the introduction of orlistat; there had been no other recent changes to medication or medical conditions. According to the Naranjo probability scale, this reaction was probable.
MacWalter, Fraser, Armstrong · Annals of Pharmacotherapy (2003)
Case report of a 66-year-old man with chronic atrial fibrillation on a stable warfarin dose who developed an increased INR after starting orlistat for weight reduction
No other recent changes to medication or medical conditions; the reaction was rated 'probable' on the Naranjo probability scale
Warfarin was withheld and the dose reduced to re-establish INR control
In plain English: A 29-year-old woman had subtherapeutic plasma levels of cyclosporine after orlistat treatment (360 mg/day) was initiated.
Barbaro, Orsini, Pallini, Piazza, Pasquini · Endocrine Practice (2002)
Case report of a 29-year-old woman after renal transplantation who developed subtherapeutic plasma cyclosporine levels after starting orlistat 360 mg/day
The subtherapeutic levels persisted despite administering orlistat the recommended 2 hours before cyclosporine and despite reducing orlistat to 240 mg/day
Six prior cases of reduced therapeutic plasma cyclosporine levels on orlistat had been reported in the literature