A comprehensive literature review examines the metabolic effects of second-generation (atypical) antipsychotics, including clozapine, olanzapine, risperidone, quetiapine, zotepine, amisulpride, ziprasidone, and aripiprazole. The review investigates the association between these medications and glucose or lipid dysregulation, as well as the role of treatment-induced weight gain in increasing the risk of hyperglycaemia and dyslipidaemia. Substantial evidence indicates that increased adiposity is linked to adverse physiological effects, including decreased insulin sensitivity and changes in plasma glucose and lipid levels. Weight gain varies significantly among the antipsychotics, with clozapine and olanzapine showing the greatest risk of clinically significant weight gain, while ziprasidone and aripiprazole show minimal weight gain and the lowest risk. Published studies show that clozapine and olanzapine are associated with an increased risk of diabetes and dyslipidaemia. Inconsistent results suggest limited risk for risperidone and quetiapine, though less data is available for quetiapine. There is insufficient data for zotepine and amisulpride, though amisulpride appears to have less risk of dyslipidaemia than olanzapine. Ziprasidone and aripiprazole show no evidence of increased risk for diabetes, dyslipidaemia, or other adverse effects on glucose or lipid metabolism. The risk rank order suggests that differing weight gain liability among atypical agents contributes to varying risks of insulin resistance, dyslipidaemia, and hyperglycaemia. This aligns with findings in nonpsychiatric populations, where metabolic risk increases with adiposity. However, case reports suggest that weight gain or obesity may not be a factor in up to one-quarter of new-onset diabetes cases during treatment. Limited controlled studies support the hypothesis that clozapine and olanzapine may directly affect glucose regulation independent of adiposity. These findings are relevant to prevention efforts targeting the factors contributing to type 2 diabetes and cardiovascular disease in populations treated with second-generation antipsychotics. The review raises questions about the increased risk of diabetes and dyslipidaemia associated with second-generation antipsychotics, whether this risk varies between agents, and whether it is related to weight gain or other mechanisms.A comprehensive literature review examines the metabolic effects of second-generation (atypical) antipsychotics, including clozapine, olanzapine, risperidone, quetiapine, zotepine, amisulpride, ziprasidone, and aripiprazole. The review investigates the association between these medications and glucose or lipid dysregulation, as well as the role of treatment-induced weight gain in increasing the risk of hyperglycaemia and dyslipidaemia. Substantial evidence indicates that increased adiposity is linked to adverse physiological effects, including decreased insulin sensitivity and changes in plasma glucose and lipid levels. Weight gain varies significantly among the antipsychotics, with clozapine and olanzapine showing the greatest risk of clinically significant weight gain, while ziprasidone and aripiprazole show minimal weight gain and the lowest risk. Published studies show that clozapine and olanzapine are associated with an increased risk of diabetes and dyslipidaemia. Inconsistent results suggest limited risk for risperidone and quetiapine, though less data is available for quetiapine. There is insufficient data for zotepine and amisulpride, though amisulpride appears to have less risk of dyslipidaemia than olanzapine. Ziprasidone and aripiprazole show no evidence of increased risk for diabetes, dyslipidaemia, or other adverse effects on glucose or lipid metabolism. The risk rank order suggests that differing weight gain liability among atypical agents contributes to varying risks of insulin resistance, dyslipidaemia, and hyperglycaemia. This aligns with findings in nonpsychiatric populations, where metabolic risk increases with adiposity. However, case reports suggest that weight gain or obesity may not be a factor in up to one-quarter of new-onset diabetes cases during treatment. Limited controlled studies support the hypothesis that clozapine and olanzapine may directly affect glucose regulation independent of adiposity. These findings are relevant to prevention efforts targeting the factors contributing to type 2 diabetes and cardiovascular disease in populations treated with second-generation antipsychotics. The review raises questions about the increased risk of diabetes and dyslipidaemia associated with second-generation antipsychotics, whether this risk varies between agents, and whether it is related to weight gain or other mechanisms.