Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin

Aims To assess the effects and safety of increasing sulphonylurea dosages o r adding metformin in poorly controlled elderly Type 2 diabetic patients. Methods A 18-month multicentre clinical study was performed on sulphonylure a-treated diabetic patients over 70 years of age with well-preserved renal function, steady fasting blood glucose greater than or equal to 200 mg/dl a nd HbA(1c) greater than or equal to 9%. Patients were randomly assigned to sulphonylurea increased up to its maximum dosage (1st group) or to addition of metformin (2nd group). Glycaemic control, lipid pattern, haemostatic st atus and safety were monitored during run-in, at baseline and at scheduled intervals for 18 months. Results refer to 85 patients in the 1st group and 89 patients in the 2nd with complete data. Results Similar improvements in glycaemic levels were observed with both tr eatments within the first month and a similar decrease in HbA(1c) within th e third month. No further changes occurred in glycaemic control. In the 1st group, fasting glucose (mmol/l, mean +/- SE) decreased from 14.21 +/- 0.49 to 9.88 +/- 0.21, average day-long glucose from 14.87 +/- 0.27 to 10.69 +/ - 0.19 and HbA(1c) (%) from 10.32 +/- 0.13 to 8.66 +/- 0.13. In the 2nd tre atment group fasting glucose decreased from 14.59 +/- 0.61 to 9.05 +/- 37.2 8, average day-long glucose from 15.09 +/- 0.29 to 10.32 +/- 0.21 and HbA(1 c) from 10.33 +/- 0.13 to 8.77 +/- 0.12 (for all P < 0.0005). In this 2nd g roup, a decrease in LDL-cholesterol (P < 0.05) and an increase in HDL-chole sterol levels (P < 0.02) were also observed. In the 1st group, anthrombin I II activity increased significantly (P < 0.01). In the 2nd group, significa nt reductions in markers of platelet function (FP4 and beta TG, P < 0.01), thrombin generation (FPA, F1 + 2 and D-D, P < 0.01), and fibrinolysis inhib ition (PAI-1 activity, PAI-1 antigen, P < 0.001) were observed. Increases i n some fibrinolytic activation markers (t-PA activity, and AT-III activity, P < 0.01) occurred. Fasting lactate concentrations were unchanged in the m etformin-treated group. No serious adverse effects were observed in either group. Conclusions These results suggest that either high sulphonylurea dosages or a therapy combining lower sulphonylurea dosages with metformin are effecti ve and safe in an aged but healthy population. Metformin provides additiona l benefits counteracting several cardiovascular risk factors but must be ad ministered with caution, bearing in mind the general contra-indications for the drug but not age alone.