LIPASE INHIBITORS



















Orlistat vs Placebo for Weight Loss in Obese Patients, Obesity Research (2000) [PubMed abstract]
  • A trial in Obesity Research enrolled 729 patients with an average BMI of 35
Main inclusion criteria
  • BMI 28 - 43
Main exclusion criteria
  • Lost > 4 kg of body weight in previous 3 months
  • History of weight loss surgery
  • Drug-treated diabetes
  • Uncontrolled hypertension
Baseline characteristics
  • Average age 44 years
  • Average weight - 215 lbs (98 kg)
  • Average BMI - 35
Randomized treatment groups
  • Group 1 (239 patients) - Orlistat 60 mg three times a day
  • Group 2 (242 patients) - Orlistat 120 mg three times a day
  • Group 3 (237 patients) - Placebo
  • There was a 4-week run-in period before randomization where patients had to comply with a 600 calorie deficit/day diet
  • Patients were instructed to continue the diet after randomization. After the first year, the diet was adjusted for patients who lost ≥ 3 kg to 10% calorie deficit/day.
Primary outcome: Weight loss at two years
Results

Duration: 2 years
Outcome Orlistat 60 Orlistat 120 Placebo Comparisons
Primary outcome (% weight loss) 6.8% 7.6% 4.5% 1 vs 3 p=0.005 | 2 vs 3 p<0.001
Primary outcome (weight loss lbs) 14.5 lbs 16.3 lbs 9.5 lbs N/A
Dropout rate 42% 35% 44% N/A
Fatty/oily stools 24% 32% 5% N/A
Fecal urgency 10% 14% 5% N/A
Oily spotting 13% 15% 1% N/A

Findings: Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.












XENDOS trial - Orlistat vs Placebo for the Prevention of Type 2 Diabetes, Diabetes Care (2004) [PubMed abstract]
  • The XENDOS trial enrolled 3305 patients with a BMI ≥ 30 and an average body weight of 242 pounds
Main inclusion criteria
  • 30 - 60 years of age
  • BMI ≥ 30
  • Normal blood sugar or impaired glucose tolerance (FBS of < 120 mg/dl and OGTT of 120 - 180 mg/dl)
Main exclusion criteria
  • Diabetes
  • Cardiovascular disease
  • Gastrointestinal disease
Baseline characteristics
  • Average age 43 years
  • Average weight - 242 pounds (110 kg)
  • Average BMI - 37
  • Average fasting blood sugar - 83 mg/dl
  • Patients with impaired glucose tolerance - 21%
Randomized treatment groups
  • Group 1 (1640 patients) - Orlistat 120 mg three times a day + weight loss counseling
  • Group 2 (1637 patients) - Placebo + weight loss counseling
  • All patients were prescribed a diet with a caloric deficit of 800 calories a day
  • 2-hour OGTT was performed every 6 months
Primary outcome: Time to onset of type 2 diabetes and change in body weight after 4 years
Results

Duration: 4 years
Outcome Orlistat Placebo Comparisons
Primary outcome (diabetes) 6.2% 9% HR 0.63, 95% CI [0.46 - 0.86], p=0.0032
Primary outcome (weight loss) 12.8 lbs 6.6 lbs p<0.001
Dropouts 48% 66% p<0.0001
LDL cholesterol (% decrease from baseline) 12.8% 5.1% p<0.01
GI side effects (during year 1) 91% 65% N/A
GI side effects (during year 4) 36% 23% N/A
  • The orlistat group had significant decreases in vitamin A, K, E, and D when compared to placebo. However, the average level of each vitamin remained within the normal reference range throughout the study.
  • Significant diabetes prevention was only seen in patients with impaired glucose tolerance. The incidence of diabetes was low in normal patients (2.7%) and therefore, the study was underpowered to detect a difference in this group.

Findings: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the impaired glucose tolerance subgroup; weight loss was similar in subjects with impaired glucose tolerance or normal glucose tolerance.




  • Incidence observed with orlistat 120 mg three times a day
  • Reference [10]
Side effect First year of use Second year of use
Oily rectal spotting 26.6% 4.4%
Flatus with Discharge 23.9% 2.1%
Fecal Urgency 22.1% 2.8%
Fatty/Oily stool 17.1% 4.9%
Oily Evacuation 20% 5.5%
Increased defecation 10.8% 2.6%
Fecal Incontinence 7.7% 1.8%