Effectiveness of sulphonylureas in the therapy of diabetes mellitus type 2 patients: an observational cohort study.

BACKGROUND: We compared all-cause mortality, major macrovascular events (MACE) and diabetes-related hospitalizations in T2DM-incident patients newly treated with metformin (MET) versus sulphonylureas (SU) monotherapy and in T2DM-prevalent patients newly treated with MET+SU versus MET+DPP4-inhibitor combination therapy.

METHODS: We analysed anonymized data obtained from a German health fund. Patients were included when they had started MET versus SU therapy or MET+SU versus MET+DPP4 therapy between 01/07/2010 and 31/12/2011. Observation started with the first MET/SU prescription or the first prescription of the second agent of a MET+SU/MET+DPP4 combination therapy. Follow-up time lasted until the end of data availability (a minimum of 12 months), death or therapy discontinuation.

RESULTS: In total, 434,291 T2DM-prevalent and 35,661 T2DM-incident patients were identified. Of the identified T2DM-incident patients, 904/7,874 started SU/MET monotherapy, respectively, with a mean age of 70.1/61.4 years (54.6/50.3 % female; Charlson Comorbidity Index (CCI) 1.4/2.2; 933/7,350 observed SU/MET patient years). 4,157/1,793 SU+MET/DPP4+MET therapy starters had a mean age of 68.1/62.2 years (53.4/50.8 % female; CCI 2.8/2.6; 4,556/1,752 observed SU+MET/ DPP4+MET patient years). In a propensity score matched (PSM) comparison, the HRs (95 % CIs) associated with SU monotherapy compared to MET monotherapy exposure were 1.4 (0.9-2.3) for mortality, 1.4 (0.9-2.2) for MACE, 4.1 (1.5-10.9) for T2DM hospitalizations and 1.6 (1.2-2.3) for composite event risk. In a multivariable Cox regression model, SU monotherapy was associated with higher mortality (aHR 2.0; 1.5-2.6), higher MACE (aHR 1.3; 1.0-1.7) and higher T2DM hospitalizations (aHR 2.8; 1.8-4.4), which corresponded with a higher composite event risk (aHR 1.8; 1.5-2.1). No significant differences in event rates were observed in the PSM comparison between DPP4+MET/SU+MET combination therapy starters and in the multivariable Cox regression analysis.

CONCLUSIONS: Our results show that SU monotherapy may be associated with increased mortality, MACE and T2DM hospitalizations, compared to MET monotherapy. When considering SU therapy, the associated cardiovascular risk should also be taken into account.