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Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality.
Diabetes Obes Metab. 2014 Oct; 16(10):977-83.DO

Abstract

AIMS

To compare the risk of major adverse cardiovascular events (MACE) and mortality for combination therapies with metformin and either sulphonylurea (SU) or dipeptidyl peptidase-4 inhibitor (DPP-4i).

METHODS

Data were from the UK Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with combination therapies comprising metformin plus SU or DPP-4i 2007-2012. The co-primary endpoints were all-cause mortality and MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score.

RESULTS

A total of 33 983 patients were prescribed SU and 7864 DPP-4i, and 5447 patients in each cohort could be matched directly and 6901 by propensity score. In the main analysis, there were 716 MACE events and 1217 deaths. Crude event rates for MACE were 11.3 events per 1000 person-years (pkpy) for SU, versus 5.3 pkpy for DPP-4i. For all-cause mortality, rates were 16.9 versus 7.3 pkpy, respectively. Following adjustment, there was a significant increase in the adjusted hazard ratio (aHR) for all-cause mortality in those exposed to SU across all analytical models: aHR = 1.357 (95% CI 1.076-1.710) for all subjects, 1.850 (1.245-2.749) directly matched and 1.497 (1.092-2.052) propensity-matched. For MACE, aHR was 1.710 (1.280-2.285) for all subjects, 1.323 (0.832-2.105) directly matched and 1.547 (1.076-2.225) propensity-matched.

CONCLUSIONS

There was a reduction in all-cause mortality for patients treated with metformin combined with DPP-4i versus metformin plus SU, and a similar trend for MACE.

Authors+Show Affiliations

Global Epidemiology, Pharmatelligence, Cardiff, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24762119

Citation

Morgan, C Ll, et al. "Combination Therapy With Metformin Plus Sulphonylureas Versus Metformin Plus DPP-4 Inhibitors: Association With Major Adverse Cardiovascular Events and All-cause Mortality." Diabetes, Obesity & Metabolism, vol. 16, no. 10, 2014, pp. 977-83.
Morgan CL, Mukherjee J, Jenkins-Jones S, et al. Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. Diabetes Obes Metab. 2014;16(10):977-83.
Morgan, C. L., Mukherjee, J., Jenkins-Jones, S., Holden, S. E., & Currie, C. J. (2014). Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. Diabetes, Obesity & Metabolism, 16(10), 977-83. https://doi.org/10.1111/dom.12306
Morgan CL, et al. Combination Therapy With Metformin Plus Sulphonylureas Versus Metformin Plus DPP-4 Inhibitors: Association With Major Adverse Cardiovascular Events and All-cause Mortality. Diabetes Obes Metab. 2014;16(10):977-83. PubMed PMID: 24762119.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. AU - Morgan,C Ll, AU - Mukherjee,J, AU - Jenkins-Jones,S, AU - Holden,S E, AU - Currie,C J, Y1 - 2014/05/22/ PY - 2014/02/10/received PY - 2014/04/02/revised PY - 2014/04/18/accepted PY - 2014/4/26/entrez PY - 2014/4/26/pubmed PY - 2015/5/15/medline KW - MACE KW - dipeptidyl peptidase-4 inhibitors KW - metformin KW - mortality KW - myocardial infarction KW - stroke KW - sulphonylurea SP - 977 EP - 83 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 16 IS - 10 N2 - AIMS: To compare the risk of major adverse cardiovascular events (MACE) and mortality for combination therapies with metformin and either sulphonylurea (SU) or dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: Data were from the UK Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with combination therapies comprising metformin plus SU or DPP-4i 2007-2012. The co-primary endpoints were all-cause mortality and MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score. RESULTS: A total of 33 983 patients were prescribed SU and 7864 DPP-4i, and 5447 patients in each cohort could be matched directly and 6901 by propensity score. In the main analysis, there were 716 MACE events and 1217 deaths. Crude event rates for MACE were 11.3 events per 1000 person-years (pkpy) for SU, versus 5.3 pkpy for DPP-4i. For all-cause mortality, rates were 16.9 versus 7.3 pkpy, respectively. Following adjustment, there was a significant increase in the adjusted hazard ratio (aHR) for all-cause mortality in those exposed to SU across all analytical models: aHR = 1.357 (95% CI 1.076-1.710) for all subjects, 1.850 (1.245-2.749) directly matched and 1.497 (1.092-2.052) propensity-matched. For MACE, aHR was 1.710 (1.280-2.285) for all subjects, 1.323 (0.832-2.105) directly matched and 1.547 (1.076-2.225) propensity-matched. CONCLUSIONS: There was a reduction in all-cause mortality for patients treated with metformin combined with DPP-4i versus metformin plus SU, and a similar trend for MACE. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/24762119/Combination_therapy_with_metformin_plus_sulphonylureas_versus_metformin_plus_DPP_4_inhibitors:_association_with_major_adverse_cardiovascular_events_and_all_cause_mortality_ L2 - https://doi.org/10.1111/dom.12306 DB - PRIME DP - Unbound Medicine ER -