Role of Orlistat in the Treatment of Obese Patients With Type 2 Diabetes: A 1-year randomized double-blind study

Priscilla A Hollander; Steven C Elbein; Irl B Hirsch; David Kelley; Janet McGill; Terry Taylor; Stuart R Weiss; Samuel E Crockett; Roy A Kaplan; John Comstock; Charles P Lucas; Peter A Lodewick; William Canovatchel; Jain Chung; Jonathan Hauptman

doi:10.2337/diacare.21.8.1288

Original Articles

Role of Orlistat in the Treatment of Obese Patients With Type 2 Diabetes: A 1-year randomized double-blind study

Priscilla A Hollander, MD, PHD,
Steven C Elbein, MD,
Irl B Hirsch, MD,
David Kelley, MD,
Janet McGill, MD,
Terry Taylor, MD,
Stuart R Weiss, MD,
Samuel E Crockett, MD,
Roy A Kaplan, MD,
John Comstock, MD,
Charles P Lucas, MD,
Peter A Lodewick, MD,
William Canovatchel, MD,
Jain Chung, MD and
Jonathan Hauptman, MD

Baylor Medical Center Dallas
Veterans Administration Hospital Houston, Texas
University of Utah Salt Lake City, Utah
University of Washington Medical Center Seattle, Washington
University of Pittsburgh Medical School Pittsburgh, Pennsylvania
Washington University Medical School, St. Louis Missouri
Georgetown University Medical School Washington, DC
San Diego Endocrine and Medical Clinic San Diego
East Bay Clinical Trial Center Concord, California
Florida Hospital Diabetic Program Orlando, Florida
William Beaumont Hospital Birmingham, Michigan
Diabetes Care Center Birmingham, Alabama
F. Hoffmann-La Roche Nutley, New Jersey

Address correspondence and reprint requests to Dr. Priscilla A. Hollander, Ruth Collins Diabetes Center, Baylor University Medical Center, 3500 Gaston Ave., Dallas, TX 75246.

Diabetes Care 1998 Aug; 21(8): 1288-1294. https://doi.org/10.2337/diacare.21.8.1288

Abstract

OBJECTIVE Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications.

RESEARCH DESIGN AND METHODS In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28–40 kg/m², and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured.

RESULTS 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). Twice as many patients receiving orlistat (49 vs. 23%) lost ≥ 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA_1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients.

CONCLUSIONS Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.