Current issues of ACP Journal Club are published in Annals of Internal Medicine


Orlistat with diet was effective and safe for weight loss and coronary risk reduction in obesity


ACP J Club. 2001 Mar-Apr;134:61. doi:10.7326/ACPJC-2001-134-2-061

Source Citation

Lindgärde F, on behalf of the Orlistat Swedish Multimorbidity Study Group. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. J Intern Med. 2000 Sep;248:245-54. [PubMed ID: 10971792]



What is the effectiveness of orlistat for weight loss and coronary artery disease risk factor reduction in persons who are obese and have ≥ 1 coronary risk factor?


Randomized (unclear allocation concealment*), blinded (patients, outcome assessors),* placebo-controlled trial with 1-year follow-up.


33 primary care centers in Sweden.


376 patients between 18 and 75 years of age (mean age 53 y, 64% women) who had a body mass index between 28 and 38 kg/m2. Patients had to have ≥ 1 of the following: fasting serum glucose level ≥ 6.7 mmol/L or type 2 diabetes mellitus treated with sulfonylurea or metformin (not insulin); cholesterol level ≥ 6.5 mmol/L or low-density lipoprotein (LDL) cholesterol level ≥ 4.2 mmol/L on ≥ 2 occasions, or lipid-lowering medication; or diastolic blood pressure level ≥ 90 mm Hg on ≥ 2 occasions or on hypertension treatment. Exclusion criteria were lactation, pregnancy, or not using adequate contraception; recent myocardial infarction; gastrointestinal surgery for weight reduction; gastrointestinal disorders; pancreatic disease; history of postsurgical adhesions; excessive alcohol intake; substance abuse; or use of systemic steroids or weight or lipid-altering drugs.


After a 2-week run-in period, patients were allocated to orlistat, 120 mg (n = 190), or placebo (n = 186) 3 times daily to be taken with main meals. All were encouraged to follow a mildly hypocaloric diet. After 6 months, an additional 300 kcal/d reduction was made to the diet. All patients received dietary counseling and self-help materials and were encouraged to walk every day.

Main outcome measures

Weight loss, waist and hip circumferences, blood pressure, serum lipid levels, fasting glucose levels, hemoglobin (Hb) A1c levels, and adverse events.

Main results

Analysis was by intention to treat. Mean weight loss was greater with orlistat than with placebo (5.9% vs 4.6% of initial body weight, P < 0.05). Orlistat led to greater mean reductions than did placebo in total serum cholesterol levels (0.24 vs 0.09 mmol/L, P < 0.05), LDL cholesterol levels (0.25 vs 0.07 mmol/L, P < 0.05), fasting glucose levels (0.55 vs 0.09 mmol/L, P < 0.01), and HbA1c levels (0.25% vs 0.05%, P < 0.05). Groups did not differ for reductions in waist and hip circumference, blood pressure, or drug-related adverse effects.


Treatment with orlistat combined with a mildly hypocaloric diet was safe and more effective than diet alone for weight loss and coronary heart disease risk factor reduction in persons who are obese and have high coronary risk.

*See Glossary.

Source of funding: Roche AB, Stockholm, Sweden.

For correspondence: Dr. F. Lindgärde, Department of Vascular Disease, Malmö University Hospital, University of Lund, 20502 Malmö, Sweden. FAX 46-4019-4617.


Weight loss is associated with multiple benefits but is difficult to achieve and even more difficult to maintain (1). The effects of orlistat, an intestinal lipase inhibitor, were evaluated by Lindgärde and colleagues in this well-designed, 1-year, multicenter trial of weight loss and cardiovascular risk reduction. The beneficial effects of orlistat were evident but not impressive. Orlistat therapy was safe and was associated with greater weight loss and risk factor reduction than was placebo; however, the difference in mean weight loss between orlistat and placebo groups was small (1.3%, or 1.3 kg, P < 0.05). Although orlistat achieved a greater rate of reaching a ≥ 5% weight loss than did placebo (54% vs 41%, P < 0.001), the likelihood of a ≥ 10% weight loss was not different between groups (19% vs 15% for orlistat vs placebo).

The amount of weight loss with orlistat was slightly less than that observed in previous studies (2), but this finding probably reflects the trial's primary-care approach. Changes in global cardiovascular risk estimates were not reported, and clinical cardiovascular end points were not examined in this study or previous orlistat trials.

Although the average weight loss with orlistat tends to be modest, weight loss of 5% to 10% of body weight appears to produce significant health benefits (1). The reduction in fat absorption caused by orlistat (2) may further improve the lipid profile independent of weight loss. As better cost-effectiveness data for orlistat and other weight-loss and cardiovascular therapies become available, orlistat's role in the clinical management of obesity will be more clearly defined.

Paul D. Levinson, MD
Memorial Hospital of Rhode Island
Pawtucket, Rhode Island, USA


1. Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Arch Intern Med. 1998;158:1855-67.

2. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281:235-42.