Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study

U M Mogensen; Charlotte Andersson; E L Fosbøl; T K Schramm; A Vaag; N M Scheller; C Torp-Pedersen; G Gislason; L Køber

doi:10.1111/dom.12314

Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study

U M Mogensen, Charlotte Andersson, E L Fosbøl, T K Schramm, A Vaag, N M Scheller, C Torp-Pedersen, G Gislason, L Køber

Institut for Klinisk Medicin

40 Citationer (Scopus)

Abstract

AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.

METHODS: Danish individuals without prior myocardial infarction or stroke that initiated combinations of metformin with sulphonylurea (SU), DPP-4 inhibitors, GLP-1 agonists or insulin between 9 May 2007 and 31 December 2011 were followed up for the risk of all-cause mortality, cardiovascular (CV) mortality or a combined end point of myocardial infarction, stroke and CV mortality. Rate ratios (RR) were calculated using time-dependent multivariable Poisson regression analysis.

RESULTS: A total of 40 028 patients (59% men, mean age 60 ± 13 years) used metformin with SU (n = 25 092), DPP-4 inhibitor (n = 11 138), GLP-1 agonist (n = 4345) or insulin (n = 6858). Crude incidence rates per 1000 patient years for the combined end point were 18 (SU), 10 (DPP-4 inhibitor), 8 (GLP-1 agonist) and 21 (insulin). In adjusted analyses with metformin + SU as reference, metformin + DPP-4 inhibitor was associated with an RR of 0.65 (0.54-0.80) for mortality, an RR of 0.57 (0.40-0.80) for CV mortality and an RR of 0.70 (0.57-0.85) for the combined end point. For metformin + GLP-1 agonist, the RR for mortality was 0.77 (0.51-1.17), for CV mortality 0.89 (0.47-1.68), and for the combined end point 0.82 (0.55-1.21).

CONCLUSION: Incretin-based drugs combined with metformin were safe compared with conventional combinations of glucose-lowering therapy. Use of incretin-based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important baseline differences.

Originalsprog	Engelsk
Tidsskrift	Diabetes, Obesity and Metabolism
Vol/bind	16
Udgave nummer	10
Sider (fra-til)	1001-1008
Antal sider	8
ISSN	1462-8902
DOI	https://doi.org/10.1111/dom.12314
Status	Udgivet - 2014

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Citationsformater

Mogensen, U. M., Andersson, C., Fosbøl, E. L., Schramm, T. K., Vaag, A., Scheller, N. M., Torp-Pedersen, C., Gislason, G., & Køber, L. (2014). Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study. Diabetes, Obesity and Metabolism, 16(10), 1001-1008. https://doi.org/10.1111/dom.12314

Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study. / Mogensen, U M; Andersson, Charlotte; Fosbøl, E L et al.

I: Diabetes, Obesity and Metabolism, Bind 16, Nr. 10, 2014, s. 1001-1008.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Mogensen, UM, Andersson, C, Fosbøl, EL, Schramm, TK, Vaag, A, Scheller, NM, Torp-Pedersen, C, Gislason, G & Køber, L 2014, 'Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study', Diabetes, Obesity and Metabolism, bind 16, nr. 10, s. 1001-1008. https://doi.org/10.1111/dom.12314

@article{16dc65a312454622b7a86f7b95a12040,

title = "Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study",

abstract = "AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.METHODS: Danish individuals without prior myocardial infarction or stroke that initiated combinations of metformin with sulphonylurea (SU), DPP-4 inhibitors, GLP-1 agonists or insulin between 9 May 2007 and 31 December 2011 were followed up for the risk of all-cause mortality, cardiovascular (CV) mortality or a combined end point of myocardial infarction, stroke and CV mortality. Rate ratios (RR) were calculated using time-dependent multivariable Poisson regression analysis.RESULTS: A total of 40 028 patients (59% men, mean age 60 ± 13 years) used metformin with SU (n = 25 092), DPP-4 inhibitor (n = 11 138), GLP-1 agonist (n = 4345) or insulin (n = 6858). Crude incidence rates per 1000 patient years for the combined end point were 18 (SU), 10 (DPP-4 inhibitor), 8 (GLP-1 agonist) and 21 (insulin). In adjusted analyses with metformin + SU as reference, metformin + DPP-4 inhibitor was associated with an RR of 0.65 (0.54-0.80) for mortality, an RR of 0.57 (0.40-0.80) for CV mortality and an RR of 0.70 (0.57-0.85) for the combined end point. For metformin + GLP-1 agonist, the RR for mortality was 0.77 (0.51-1.17), for CV mortality 0.89 (0.47-1.68), and for the combined end point 0.82 (0.55-1.21).CONCLUSION: Incretin-based drugs combined with metformin were safe compared with conventional combinations of glucose-lowering therapy. Use of incretin-based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important baseline differences.",

keywords = "Blood Glucose, Body Weight, Denmark, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Drug Therapy, Combination, Female, Humans, Hypoglycemic Agents, Incretins, Male, Metformin, Middle Aged, Myocardial Infarction, Retrospective Studies, Stroke, Sulfonylurea Compounds, Treatment Outcome",

author = "Mogensen, {U M} and Charlotte Andersson and Fosb{\o}l, {E L} and Schramm, {T K} and A Vaag and Scheller, {N M} and C Torp-Pedersen and G Gislason and L K{\o}ber",

note = "{\textcopyright} 2014 John Wiley & Sons Ltd.",

year = "2014",

doi = "10.1111/dom.12314",

language = "English",

volume = "16",

pages = "1001--1008",

journal = "Diabetes, Obesity and Metabolism",

issn = "1462-8902",

publisher = "Wiley-Blackwell",

number = "10",

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TY - JOUR

T1 - Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study

AU - Mogensen, U M

AU - Andersson, Charlotte

AU - Fosbøl, E L

AU - Schramm, T K

AU - Vaag, A

AU - Scheller, N M

AU - Torp-Pedersen, C

AU - Gislason, G

AU - Køber, L

PY - 2014

Y1 - 2014

N2 - AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.METHODS: Danish individuals without prior myocardial infarction or stroke that initiated combinations of metformin with sulphonylurea (SU), DPP-4 inhibitors, GLP-1 agonists or insulin between 9 May 2007 and 31 December 2011 were followed up for the risk of all-cause mortality, cardiovascular (CV) mortality or a combined end point of myocardial infarction, stroke and CV mortality. Rate ratios (RR) were calculated using time-dependent multivariable Poisson regression analysis.RESULTS: A total of 40 028 patients (59% men, mean age 60 ± 13 years) used metformin with SU (n = 25 092), DPP-4 inhibitor (n = 11 138), GLP-1 agonist (n = 4345) or insulin (n = 6858). Crude incidence rates per 1000 patient years for the combined end point were 18 (SU), 10 (DPP-4 inhibitor), 8 (GLP-1 agonist) and 21 (insulin). In adjusted analyses with metformin + SU as reference, metformin + DPP-4 inhibitor was associated with an RR of 0.65 (0.54-0.80) for mortality, an RR of 0.57 (0.40-0.80) for CV mortality and an RR of 0.70 (0.57-0.85) for the combined end point. For metformin + GLP-1 agonist, the RR for mortality was 0.77 (0.51-1.17), for CV mortality 0.89 (0.47-1.68), and for the combined end point 0.82 (0.55-1.21).CONCLUSION: Incretin-based drugs combined with metformin were safe compared with conventional combinations of glucose-lowering therapy. Use of incretin-based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important baseline differences.

AB - AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited.METHODS: Danish individuals without prior myocardial infarction or stroke that initiated combinations of metformin with sulphonylurea (SU), DPP-4 inhibitors, GLP-1 agonists or insulin between 9 May 2007 and 31 December 2011 were followed up for the risk of all-cause mortality, cardiovascular (CV) mortality or a combined end point of myocardial infarction, stroke and CV mortality. Rate ratios (RR) were calculated using time-dependent multivariable Poisson regression analysis.RESULTS: A total of 40 028 patients (59% men, mean age 60 ± 13 years) used metformin with SU (n = 25 092), DPP-4 inhibitor (n = 11 138), GLP-1 agonist (n = 4345) or insulin (n = 6858). Crude incidence rates per 1000 patient years for the combined end point were 18 (SU), 10 (DPP-4 inhibitor), 8 (GLP-1 agonist) and 21 (insulin). In adjusted analyses with metformin + SU as reference, metformin + DPP-4 inhibitor was associated with an RR of 0.65 (0.54-0.80) for mortality, an RR of 0.57 (0.40-0.80) for CV mortality and an RR of 0.70 (0.57-0.85) for the combined end point. For metformin + GLP-1 agonist, the RR for mortality was 0.77 (0.51-1.17), for CV mortality 0.89 (0.47-1.68), and for the combined end point 0.82 (0.55-1.21).CONCLUSION: Incretin-based drugs combined with metformin were safe compared with conventional combinations of glucose-lowering therapy. Use of incretin-based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important baseline differences.

KW - Blood Glucose

KW - Body Weight

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - Dipeptidyl-Peptidase IV Inhibitors

KW - Drug Therapy, Combination

KW - Female

KW - Humans

KW - Hypoglycemic Agents

KW - Incretins

KW - Male

KW - Metformin

KW - Middle Aged

KW - Myocardial Infarction

KW - Retrospective Studies

KW - Stroke

KW - Sulfonylurea Compounds

KW - Treatment Outcome

U2 - 10.1111/dom.12314

DO - 10.1111/dom.12314

M3 - Journal article

C2 - 24827939

SN - 1462-8902

VL - 16

SP - 1001

EP - 1008

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 10

ER -