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

Abstract

BackgroundWe 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.MethodsWe 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.ResultsIn 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s40200-016-0251-9) contains supplementary material, which is available to authorized users.

Associations between multimorbidity, all-cause mortality and glycaemia in people with type 2 diabetes: A systematic review

“…The measure of MM condition count used in the included studies varied considerably. The majority of studies (24/41 (59%)) [19, 21, 27, 28, 30–37, 39–41, 43, 46, 49–53, 55, 57] measured MM in terms of the Charlson Comorbidity Index (CCI) [9]. MM was represented as a simple count of conditions that were available in the study datasets in 15 studies (32%) [17, 18, 22–25, 29, 38, 44, 47, 48, 50, 52, 54, 56].…”

“…9/41 (22%) studies [24, 27, 28, 33, 37, 39, 46, 49, 56] had broad scoping aims of determining factors that were associated with mortality or glycaemia outcomes. More than half, 21/41 (51%) studies [17–19, 21–23, 25, 30–32, 34–36, 40, 41, 44, 45, 48, 51, 53, 55] did not state the investigation of MM as a research objective, but contained MM count as a covariate when exploring the impact of other factors on mortality or glycaemia, including data allowing us to identify the association between MM count and our outcomes of interest. The research aims included describing the effects of a range of factors (e.g.…”

“…Furthermore, MM was treated in analysis either as a continuous or categorical variable in different studies. For studies that showed a significant increase in mortality whilst treating increasing MM as a continuous variable, the HRs from Cox proportional hazard models that explored MM represented by CCI ranged from 1.22 to 1.95 [50, 51, 53, 55]. Whilst the study that represented MM as total illness burden index, the HR was 1.02 [42].…”