Schizophrenia, a chronic, severe
and disabling brain disorder affecting approximately 0.5 percent of people
globally, is treated these days with second generation anti-psychotic
medication such as olanzapine, risperidone, quetiapine and other such
antipsychotics. However, one of the major side effects of these medications is
weight gain and changes in the patient's metabolism, thereby increasing the
risk for diabetes and cardiovascular disease. There is evidence that such
patients may lose 25 or more years of life expectancy and may even die of
obesity related cardiovascular disease. Incidentally, current interventions
against drug induced weight gain do not facilitate lasting or significant
weight loss in schizophrenia patients.
In the search for more successful
interventions, Bjorn Ebdrup and his colleagues from the University of
Copenhagen, Denmark, in their debate article published in the BMC journal, have
discussed the potential effects of using GLP-1 analogs to treat schizophrenia
patients with antipsychotic-induced weight gain.
GLP-1 (glucagon-like peptide-1) is a gut hormone and
currently GLP-1 analogs are used in the treatment of diabetes. These analogs
work by mimicking the important functions of GLP-1 in the body, such as causing
the pancreas to secrete insulin when glucose concentrations rise as well as
working in the brain to promote appetite suppression, which ultimately leads to
sustained weight loss.
Although six different GLP-1 analogs are being tested,
only two of them - exenatide and liraglutide - have been approved by the U.S.
Food and the Drug Administration and European Medicines Agency.
A clinical study is already investigating whether
exenatide (a GLP-1 analog) can induce weight loss in overweight patients
treated with olanzapine. Exenatide has already shown evidence of having a role
in neuroprotection, learning and preventing memory impairment in animal models.
According to the researchers, the potential benefits of
GLP-1 analog treatment can be
Significant and lasting weight loss can be obtained in
both diabetic and non-diabetic overweight patients.
An improved glycemic control can be obtained.
Studies have shown that there might be a genetic link
between schizophrenia and overweight /obesity. By exploring the cerebral
effects of GLP-1 analogs in overweight schizophrenia patients and
non-schizophrenia people, the link can be confirmed.
Thus, the researchers opine, that 'If the progressive
brain loss and cognitive decline associated with schizophrenia and
overweight/obesity can indeed be ameliorated by GLP-1 treatment, this will have
major implications for future treatment of schizophrenia, but also for the
treatment of obesity'.
They concluded that 'adjunctive treatment with a GLP-1
analog holds promise as a novel method to treat metabolic and cerebral
deficiencies in schizophrenia patients with antipsychotic-induced weight gain'.
Ebdrup BH, Knop FK, Ishoy PL, Rostrup E, Fagerlund B,
Lublin H, Glenthoj B. Glucagon-like peptide-1 analogues against
antipsychotic-induced weight gain: potential physiological benefits. BMC Med.
2012 Aug 15;10(1):92