INS and diabetes mellitus: Treatment of manifest diabetes in patients treated with clozapine should closely follow current guidelines including the use of insulin when indicated.355,356 Adequate antidiabetic treatment substantially reduces cardiovascular risk and the risk for ketoacidosis or hyperosmolar coma.274 Importantly, pre-existing diabetes mellitus in patients with TRS does not constitute a contraindication for clozapine treatment,357 but rather requires intensified antidiabetic treatment.