Die Kombinationstherapie Insulin/Sulfonylharnstoff in der Langzeittherapie des Typ-II-Diabetes nach „Sekundärversagen“

Summary

In type 2 diabetes with “secondary failure of sulfonylurea therapy” good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia.

16 type 2 diabetics with “secondary failure” were treated either with insulin alone (group A;n=8) or with 3.5 mg b.i.d glibenclamide plus small amounts of intermediate insulin (group B;n=8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years.

Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14±2 IU$(\bar x \pm SEM)$ after one month and 19±2 IU after two years in group B. In contrast 30±3 IU and 43±5 IU respectively were needed in group A (p<0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6±3.7 vs. 18.6±1.6 mcU/ml;p<0.01). Endogenous C-peptide response was suppressed in group A compared to group B after inpatient period and after one month (0.12±0.01 vs. 0.49±0.15 and 0.09±0.04 vs. 0.13±0.08 pmol/ml;p<0.05). The combined therapy of insulin and sulfonylureas demonstrates the benefit of a prolonged sulfonylurea administration in the treatment of type 2 diabetes with “secondary failure”.

As compared to common insulin therapy a small amount of exogenous insulin by one daily injection additionally to glibenclamide shows similar improvement in metabolic control. Hyperinsulinemia as a risk factor of macroangiopathy is markedly reduced in patients treated with combined therapy compared to those with insulin alone.