ABSTRACT
OBJECTIVE: Treatment with most antipsychotics is associated with an increased risk of weight gain and metabolic disturbances. In a randomized trial, we previously demonstrated that 16 weeks of glucagon-like peptide-1 receptor agonist liraglutide treatment vs. placebo significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. The aim of this study was to investigate whether the beneficial effects of the 16-week intervention were sustained beyond the intervention period. METHOD: One year after completion of the intervention, we investigated changes in body weight, fasting glucose, glycated hemoglobin, C-peptide, and lipids comparing 1-year follow-up levels to end of treatment (week 16) and baseline (week 0) levels. RESULTS: From end of treatment to the 1-year follow-up, body weight had increased in the liraglutide-treated group. However, compared to baseline levels, the placebo-subtracted body weight loss remained significantly reduced (-3.8 kg, 95% CI: -7.3 to -0.2, P = 0.04). Fasting glucose, glycated hemoglobin, C-peptide, and lipids had each returned to baseline levels 1 year after stopping liraglutide. CONCLUSION: The body weight reduction during 16 weeks of liraglutide treatment was partially sustained 1 year after the intervention was completed. However, the improvements in other metabolic parameters returned to baseline levels.
Subject(s)
Hypoglycemic Agents/pharmacology , Liraglutide/pharmacology , Obesity/drug therapy , Overweight/drug therapy , Prediabetic State/drug therapy , Adolescent , Adult , Aged , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Blood Glucose/drug effects , Body Weight/drug effects , C-Peptide/drug effects , Clozapine/adverse effects , Clozapine/therapeutic use , Denmark/epidemiology , Fasting , Female , Follow-Up Studies , Glucagon-Like Peptide-1 Receptor/agonists , Glycated Hemoglobin/drug effects , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Lipid Metabolism/drug effects , Liraglutide/administration & dosage , Liraglutide/therapeutic use , Male , Middle Aged , Obesity/chemically induced , Obesity/epidemiology , Olanzapine/adverse effects , Olanzapine/therapeutic use , Overweight/chemically induced , Overweight/epidemiology , Placebos/administration & dosage , Prediabetic State/chemically induced , Prediabetic State/epidemiology , Schizophrenia/blood , Schizophrenia/diagnosis , Schizophrenia/drug therapy , Young AdultABSTRACT
OBJECTIVE: Therapeutic drug monitoring (TDM) of clozapine is standardized to 12-h postdose samplings. In clinical settings, sampling time often deviates from this time point, although the importance of the deviation is unknown. To this end, serum concentrations (s-) of clozapine and its metabolite N-desmethyl-clozapine (norclozapine) were measured at 12 ± 1 and 2 h postdose. METHOD: Forty-six patients with a diagnosis of schizophrenia, and on stable clozapine treatment, were enrolled for hourly, venous blood sampling at 10-14 h postdose. RESULTS: Minor changes in median percentage values were observed for both s-clozapine (-8.4%) and s-norclozapine (+1.2%) across the 4-h time span. Maximum individual differences were 42.8% for s-clozapine and 38.4% for s-norclozapine. Compared to 12-h values, maximum median differences were 8.4% for s-clozapine and 7.3% for s-norclozapine at deviations of ±2 h. Maximum individual differences were 52.6% for s-clozapine and 105.0% for s-norclozapine. The magnitude of s-clozapine differences was significantly associated with age, body mass index and the presence of chronic basophilia or monocytosis. CONCLUSION: The impact of deviations in clozapine TDM sampling time, within the time span of 10-14 h postdose, seems of minor importance when looking at median percentage differences. However, substantial individual differences were observed, which implies a need to adhere to a fixed sampling time.
