Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial.
BACKGROUND
Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables.


METHODS
Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment.


RESULTS
The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels.


CONCLUSIONS
Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.
Baptista
Trino
T
Department of Physiology, Los Andes University Medical School, PO Box 93, Mérida, 5101-A, Venezuela. trinbap@yahoo.com
Rangel
Nairy
N
Fernández
Virginia
V
Carrizo
Edgardo
E
El Fakih
Yamily
Y
Uzcátegui
Euderruh
E
Galeazzi
Tatiana
T
Gutiérrez
María A
MA
Servigna
Mercedes
M
Dávila
Adriana
A
Uzcátegui
Marycelvia
M
Serrano
Ana
A
Connell
Lisette
L
Beaulieu
Serge
S
de Baptista
Enma Araujo
EA
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D010054:Brief Psychiatric Rating Scale; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D000077152:Olanzapine; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D013223:Statistics as Topic
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D020738:Leptin; D008055:Lipids; D008687:Metformin; D000077152:Olanzapine