OBJECTIVE - To evaluate the long-term efficacy of insulin treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycemic agents. RESEARCH DESIGN AND METHODS- Twenty-one NIDDM patients with secondary failure were studied while they were still on oral agents. Then they were switched to insulin treatment, and after a median of 27 months, a long-term evaluation was conducted. RESULTS - At the long-term evaluation, metabolic control was still markedly improved by insulin treatment, with reduction of HbA(1c) from 8.8 +/- 0.2 (mean +/- SE) to 6.9 +/- 0.3% (P < 0.0001), lowering of very-low-density lipoprotein (VLDL) cholesterol concentration from 0.97 +/- 0.3 to 0.69 +/- 0.1 mM (P < 0.03), and lowering of total triglycerides from 2.8 +/- 0.6 to 1.8 +/- 0.3 mM (P < 0.005), mainly due to reduction of VLDL triglycerides. Body weight increased during the first year, but not thereafter (713 +/- 2.5 kg during oral treatment, 78.9 +/- 2.9 and 79.8 +/- 3.2 kg after 12 and 36 months of insulin treatment, respectively). Blood pressure did not change. Easting and postprandial insulin concentrations increased, and C-peptide concentrations were lowered. CONCLUSIONS - Improvements of glycemic control and lipoprotein concentrations in patients with NIDDM and secondary failure persist also after insulin treatment for 2-3 years in spite of weight gain and hyperinsulinemia.