Drug-induced Weight Gain

A common side-effect of certain antidiabetic drugs, for example, pioglitazone, is weight gain. This is a serious disadvantage in the clinic, as many diabetic patients are overweight or obese, and further weight gain is undesirable. Animal models can be used to explore the potential of novel antidiabetic drugs to produce weight gain in man. Pioglitazone increases body weight in dietary-induced obese rats.


Drug-induced weight-gain is also a serious side-effect of certain atypical (second generation) antipsychotic drugs such as olanzapine. We therefore developed an animal model of antipsychotic-induced weight gain (neuroleptic-induced weight gain) that can be used to investigate the effects of novel antipsychotic drugs on body weight.


Drug-induced Weight Gain

Results are means (adjusted for differences between the body weights of the different treatment groups at baseline (Day 1) + SEM (calculated from the residuals of the statistical model), n = 9 – 10. Animals were dosed with vehicle (0.5% Natrosol), drug or a combination of drugs as one administration. Multiple comparisons against the vehicle-treated control group or Compound 1/pioglitazone combination were by the multiple t test. Significant differences from the control group are denoted by *p<0.05, **p<0.01 and ***p<0.001. Significant differences from the Compound 1/pioglitazone group are denoted by †p<0.05, ††p<0.01 and †††p<0.001. Values in brackets are differences from vehicle on Day 29.

These animal models can also be used to explore whether novel antiobesity agents can prevent the increase in body weight produced by other drug treatments.

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