['The therapeutic efficacy of oral hypoglycaemic drugs varies between individuals, and pharmacogenetic factors contribute to this variability. The Gly972Arg polymorphism in the insulin receptor substrate-1 (IRS-1) has been shown to play a role in insulin signal transduction and therapeutic failure to sulphonylurea drugs.', 'We studied the association between the IRS-1 polymorphism and the haemoglobin A1c (HbA1c) level in diabetic patients treated with insulinotropic versus non-insulinotropic hypoglycaemic drugs as a marker for the efficacy of an antidiabetic treatment. Genotyping of the IRS-1 Arg(972) variant was performed in type 2 diabetes patients treated with either sulphonylurea drugs, glinides or insulin or with metformin, acarbose or glitazones using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.', 'Significantly higher HbA1c levels were observed in carriers of the Arg(972) variant after treatment with insulinotropic drugs compared to wild-type carriers (8.3 vs. 7.6%, p = 0.005, independent t-test). Furthermore, patients with secondary failure to insulinotropic hypoglycaemic drugs switching finally to insulin showed even higher HbA1c levels in carriers of Arg(972) compared to wild-type (8.7 vs. 7.6%, p = 0.005, independent t-test).'] Are genetic variants of the insulin receptor substrate-1 influencing the therapeutic efficacy of oral antidiabetics?