We compared the effects of twice-daily insulin injections (n = 22) with combined insulin-glibenclamide therapy (n = 25) on glucose and lipid metabolism in 47 type II diabetic patients (age 69 (SD 9) years, BMI 25.5 (4.8) kg/m2, diabetes duration 9 (range 1-34) years) with secondary failure to sulphonylurea. After 6 months, weight gain averaged 4.2 kg (p less than 0.05), fasting blood glucose had decreased from 14.6 to 8.5 mmol/l (p less than 0.001), HbA1c from 10.9% to 8.1% (p less than 0.001). Twenty-one patients reached HbA1c levels less than 8.0%. Patients on insulin alone injected more insulin (42 vs 26 U daily, p less than 0.01). The decrease of fasting blood glucose and HbA1c was comparable in both groups (p less than 0.001). HDL-cholesterol increased (insulin: 1.10 to 1.24 mmol/l, combined therapy: 1.03 to 1.14 mmol/l, both p less than 0.01), while plasma triglycerides and NEFA decreased (p less than 0.01). Only in patients on insulin alone did total cholesterol decrease from 7.1 to 6.3 mmol/l (p less than 0.001), and LDL-cholesterol from 4.7 to 4.1 mmol/l (p less than 0.05). Apolipoproteins AI, AII and B did not show significant changes. Almost all patients reported improved wellbeing; no severe hypoglycaemias were observed.