Sulfonylurea in combination with insulin is associated with increased mortality compared with a combination of insulin and metformin in a retrospective Danish nationwide study

TY - JOUR

T1 - Sulfonylurea in combination with insulin is associated with increased mortality compared with a combination of insulin and metformin in a retrospective Danish nationwide study

AU - Mogensen, Ulrik M

AU - Andersson, Charlotte

AU - Fosbøl, Emil L

AU - Schramm, Tina K

AU - Vaag, Allan

AU - Scheller, Nikolai M

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar

AU - Køber, Lars

PY - 2015/1

Y1 - 2015/1

N2 - AIMS/HYPOTHESIS: Individual sulfonylureas (SUs) and metformin have, in some studies, been associated with unequal hypoglycaemic, cardiovascular and mortality risks when used as monotherapy in type 2 diabetes. We investigated the outcomes in patients treated with different combinations of SUs and insulin vs a combination of metformin and insulin in a retrospective nationwide study.METHODS: All Danish individuals using dual therapy with SU + insulin or metformin + insulin without prior myocardial infarction (MI) or stroke were followed from 1 January 1997 to 31 December 2009 in nationwide registries. Risks of all-cause mortality, cardiovascular death, hypoglycaemia and a composite endpoint of MI, stroke and cardiovascular death were compared. Rate ratios (RR) [95% CIs] were calculated using time-dependent multivariable Poisson regression analysis.RESULTS: A total of 11,081 patients used SU + insulin and 16,910 used metformin + insulin. Patients receiving metformin + insulin were younger and had less comorbidity and a longer history of glucose-lowering treatment. SU + insulin was associated with higher mortality rates compared with metformin + insulin (76-126 vs 23 per 1,000 person-years). In adjusted analyses, SU + insulin was associated with increased all-cause mortality (RR 1.81 [1.63, 2.01]), cardiovascular death (RR 1.35 [1.14, 1.60]) and the composite endpoint (RR 1.25 [1.09, 1.42]) compared with metformin + insulin. Hypoglycaemia was more frequent with SU + insulin than with metformin + insulin (17-23 vs six events per 1,000 person-years) and was associated with increased mortality (RR 2.13 [1.97, 2.37]). There were no significant differences in risk between individual SUs in combination with insulin.CONCLUSIONS/INTERPRETATION: In combination with insulin, the use of SUs was associated with increased mortality compared with metformin. There were no significant risk differences between SUs.

AB - AIMS/HYPOTHESIS: Individual sulfonylureas (SUs) and metformin have, in some studies, been associated with unequal hypoglycaemic, cardiovascular and mortality risks when used as monotherapy in type 2 diabetes. We investigated the outcomes in patients treated with different combinations of SUs and insulin vs a combination of metformin and insulin in a retrospective nationwide study.METHODS: All Danish individuals using dual therapy with SU + insulin or metformin + insulin without prior myocardial infarction (MI) or stroke were followed from 1 January 1997 to 31 December 2009 in nationwide registries. Risks of all-cause mortality, cardiovascular death, hypoglycaemia and a composite endpoint of MI, stroke and cardiovascular death were compared. Rate ratios (RR) [95% CIs] were calculated using time-dependent multivariable Poisson regression analysis.RESULTS: A total of 11,081 patients used SU + insulin and 16,910 used metformin + insulin. Patients receiving metformin + insulin were younger and had less comorbidity and a longer history of glucose-lowering treatment. SU + insulin was associated with higher mortality rates compared with metformin + insulin (76-126 vs 23 per 1,000 person-years). In adjusted analyses, SU + insulin was associated with increased all-cause mortality (RR 1.81 [1.63, 2.01]), cardiovascular death (RR 1.35 [1.14, 1.60]) and the composite endpoint (RR 1.25 [1.09, 1.42]) compared with metformin + insulin. Hypoglycaemia was more frequent with SU + insulin than with metformin + insulin (17-23 vs six events per 1,000 person-years) and was associated with increased mortality (RR 2.13 [1.97, 2.37]). There were no significant differences in risk between individual SUs in combination with insulin.CONCLUSIONS/INTERPRETATION: In combination with insulin, the use of SUs was associated with increased mortality compared with metformin. There were no significant risk differences between SUs.

U2 - 10.1007/s00125-014-3372-z

DO - 10.1007/s00125-014-3372-z

M3 - Journal article

C2 - 25205223

SN - 0012-186X

VL - 58

SP - 50

EP - 58

JO - Diabetologia

JF - Diabetologia

IS - 1

ER -