Pharmacoepidemiologic Studies of Diabetes Mellitus - with special reference to - Glucose Control and Prognosis of Type 2 Diabetes

Abstract: The efficacy and safety of antihyperglycaemic drugs have been evaluated in one American and one British randomized clinical trial, which have given contradictory results. The positive results of the latter may be more convincing as it included a greater number of patients and as its duration was longer. However, its conclusions may not be applicable to type 2 diabetes patients in general, as the study population was selected. Therefore, pharmacoepidemiologic studies – i.e. analyses of therapeutic results in unselected populations of type 2 diabetes patients in routine care - are necessary to evaluate the long-term effectiveness and risk of antihyperglycaemic drugs. At the individual level, all type 2 diabetes patients registered at the primary health care centres and the private practicies in two neighbour Swedish municipalities during 11 years were included in a study which compared prescribing, dosage and blood glucose levels. Cause-specific mortality in patients on sulphonylurea and metformin in combination or sulphonylurea alone was estimated in an observational study comprising all type 2 diabetes patients (2,348) in two municipalities during 13 years. Antihyperglycaemic drugs were predominantly prescribed by one specialized diabetes clinician in Tranås municipality, while in Vetlanda municipality prescribing was spread among several different general practitioners and one specialist. In Tranås the mean prescribed daily dose of sulphonylurea was unchanged over time while that of insulin was increased. Conversely, in Vetlanda the mean prescribed daily dose of sulphonylurea was decreased over time while that of insulin was unchanged. The mean fasting blood glucose was lower in Tranås than in Vetlanda both overall, in those without any antihyperglycaemic drugs, in those on sulphonylurea monotherapy and in those on insulin. The adjusted odds ratio for overall mortality was 1.63 (95% CI 1.27-2.09) in patients on sulphonylurea and metformin combination vs.those on sulphonylurea alone. For ischaemic heart disease mortality and stroke mortality the adjusted odds ratios were 1.73 (95% CI 1.17-2.55) and 2.33 (95% CI 1.17-4.63), respectively. In conclusion, in the routine treatment of type 2 diabetes it seems advantageous with specialized care and intense antihyperglycaemic treatment. A plausible explanation of the higher mortality in patients taking sulphonylurea and metformin in combination was that it was secondary to more aggressive diabetes in patients selected for such therapy. However, it should not be entirely excluded that the combination somehow may increase cardiovascular mortality. Therefore, more studies are needed to clarify the benefits and risk of such combination treatment.