Extended release metformin for metabolic control assistance during prolonged clozapine administration: a 14 week, double-blind, parallel group, placebo-controlled study.
BACKGROUND
Clozapine is the most effective agent in treatment-resistant schizophrenia. However, it is frequently associated with excessive body weight (BW) gain, type 2 diabetes mellitus and hyperlipidemia. The antidiabetic metformin (MET) has proved effective to assist in BW control during olanzapine administration. Therefore, we aimed to test whether MET may improve the metabolic profile in patients under prolonged clozapine administration.


METHODS
In a double-blind, parallel group protocol, 61 patients (94.4% with schizophrenia) receiving clozapine (196.8+/-132 mg daily, range: 25-500) for more than 3 consecutive months (86.5+/-40.6 months, range: 4-168) were randomly allocated to extended release MET (n=31; 500 to 1000 mg daily) or placebo (n=30) group for 14 weeks. The BW, the body mass index, waist circumference, serum glucose, insulin, lipids, glycated hemoglobin (HBA1c), leptin and cortisol, and the HOMA-IR index were assessed at baseline, and weeks 7 and 14.


RESULTS
MET was well tolerated and the mental state was not impaired during the study. The protocol was completed by all the placebo subjects and by 24 MET-treated patients. In a complete analysis at week 14, without including data of the 7 dropouts, the MET group lost -1.87+/-2.9 kg, whereas the placebo group had a stable BW: 0.16+/-2.9 kg, p=0.01 for the between group comparisons (effect size: 0.70). Leptin levels also tended to decrease after MET (p=0.08). Insulin and the triglyceride-HDL-C ratio significantly decreased (p<0.05, effect size 0.59 and 1.99 respectively) and the HDL-C significantly increased (p=0.001, effect size 0.95) after MET.


CONCLUSIONS
MET improves metabolic control during prolonged clozapine administration.
Carrizo
Edgardo
E
Institute of Clinical Research Dr. Américo Negrette, Zulia University Medical School, Maracaibo, Venezuela.
Fernández
Virginia
V
Connell
Lisette
L
Sandia
Ignacio
I
Prieto
Dexy
D
Mogollón
Johana
J
Valbuena
Dennys
D
Fernández
Iliana
I
de Baptista
Enma Araujo
EA
Baptista
Trino
T
D000328:Adult; D000886:Anthropometry / Q000379:methods; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D003024:Clozapine / Q000008:administration & dosage* / Q000494:pharmacology; D004311:Double-Blind Method; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D055105:Waist Circumference / Q000187:drug effects
D014150:Antipsychotic Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D008687:Metformin; D003024:Clozapine; D006854:Hydrocortisone