Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients.
OBJECTIVE
To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat.


METHODS
Double-blind, parallel, randomized, placebo-controlled, multicentre study.


METHODS
Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline.


RESULTS
After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low.


CONCLUSIONS
Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.
Halpern
A
A
Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Brazil. halpern@netpoint.com.br
Mancini
M C
MC
Suplicy
H
H
Zanella
M T
MT
Repetto
G
G
Gross
J
J
Jadzinsky
M
M
Barranco
J
J
Aschner
P
P
Ramirez
L
L
Matos
A G
AG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000886:Anthropometry; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003131:Combined Modality Therapy; D003920:Diabetes Mellitus / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D004038:Diet, Reducing; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity; D000077403:Orlistat; D012307:Risk Factors; D015431:Weight Loss / Q000187:drug effects
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D007328:Insulin; D007783:Lactones; D008049:Lipase; D008055:Lipids; D000077403:Orlistat