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Comparative effectiveness of incretin-based therapies and the risk of death and cardiovascular events in 38,233 metformin monotherapy users.
Medicine (Baltimore). 2016 Jun; 95(26):e3995.M

Abstract

There is limited comparative effectiveness evidence to guide approaches to managing diabetes in individuals failing metformin monotherapy. Our aim was to compare the incidence of all-cause mortality and major adverse cardiovascular events (MACEs) among new metformin monotherapy users initiating a dipeptidyl-peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP-1RA), sulfonylurea (SU), thiazolidinedione, or insulin.We conducted a cohort study using the UK-based Clinical Practice Research Datalink. Participants included a cohort of 38,233 new users of metformin monotherapy who initiated a 2nd antidiabetic agent between January 1, 2007 and December 31, 2012 with follow-up until death, disenrollment, therapy discontinuation, or study end-date. A subcohort of 21,848 patients with linked hospital episode statistics (HES) and Office of National Statistics (ONS) data were studied to include MACE and cardiovascular-related death. The primary exposure contrasts, defined a priori, were initiation of a DPP4i versus an SU and initiation of a GLP-1RA versus an SU following metformin monotherapy. Cox proportional hazards models were used to assess the relative differences in time to mortality and MACE between exposure contrasts, adjusting for important baseline patient factors and comedications used during follow-up.The main study cohort consisted of 6213 (16%) patients who initiated a DPP4i, 25,916 initiated an SU (68%), 4437 (12%) initiated a TZD, 487 (1%) initiated a GLP-1RA, 804 (2%) initiated insulin, and 376 (1%) initiated a miscellaneous agent as their 2nd antidiabetic agent. Mean age was 62 years, 59% were male, and mean glycated hemoglobin was 8.8% (92.6 mmol/mol). Median follow-up was 2.7 years (interquartile range 1.3-4.2). Mortality rates were 8.2 deaths/1000 person-years for DPP4i and 19.1 deaths/1000 person-years for SU initiators. Adjusted hazards ratio (aHR) for mortality in DPP4i versus SU initiators = 0.58, 95% CI 0.46 to 0.73, P < 0.001. MACE rates were 19.1/1000 person-years for DPP4i initiators, 15.9/1000 person-years for GLP1-RA initiators versus 33.1/1000 person-years for SU initiators (aHR: DPP4i vs SU initiators = 0.64, 95%CI 0.52-0.80; GLP1RA vs SU initiators = 0.73, 95% CI 0.34-1.55).In this cohort of metformin monotherapy users, 2nd-line DPP4i use was associated with a 42% relative reduction in all-cause mortality and 36% reduction in MACE versus SUs, the most common 2nd-line therapy in our study. GLP-1RAs were not associated with adverse events in this cohort.

Authors+Show Affiliations

aSchool of Pharmacy bFaculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, A1B 3V6 cDivision of General Internal Medicine, Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2B7, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27368005

Citation

Gamble, John-Michael, et al. "Comparative Effectiveness of Incretin-based Therapies and the Risk of Death and Cardiovascular Events in 38,233 Metformin Monotherapy Users." Medicine, vol. 95, no. 26, 2016, pp. e3995.
Gamble JM, Thomas JM, Twells LK, et al. Comparative effectiveness of incretin-based therapies and the risk of death and cardiovascular events in 38,233 metformin monotherapy users. Medicine (Baltimore). 2016;95(26):e3995.
Gamble, J. M., Thomas, J. M., Twells, L. K., Midodzi, W. K., & Majumdar, S. R. (2016). Comparative effectiveness of incretin-based therapies and the risk of death and cardiovascular events in 38,233 metformin monotherapy users. Medicine, 95(26), e3995. https://doi.org/10.1097/MD.0000000000003995
Gamble JM, et al. Comparative Effectiveness of Incretin-based Therapies and the Risk of Death and Cardiovascular Events in 38,233 Metformin Monotherapy Users. Medicine (Baltimore). 2016;95(26):e3995. PubMed PMID: 27368005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effectiveness of incretin-based therapies and the risk of death and cardiovascular events in 38,233 metformin monotherapy users. AU - Gamble,John-Michael, AU - Thomas,Jamie M, AU - Twells,Laurie K, AU - Midodzi,William K, AU - Majumdar,Sumit R, PY - 2016/7/2/entrez PY - 2016/7/2/pubmed PY - 2017/2/23/medline SP - e3995 EP - e3995 JF - Medicine JO - Medicine (Baltimore) VL - 95 IS - 26 N2 - There is limited comparative effectiveness evidence to guide approaches to managing diabetes in individuals failing metformin monotherapy. Our aim was to compare the incidence of all-cause mortality and major adverse cardiovascular events (MACEs) among new metformin monotherapy users initiating a dipeptidyl-peptidase-4 inhibitor (DPP4i), glucagon-like peptide-1 receptor agonist (GLP-1RA), sulfonylurea (SU), thiazolidinedione, or insulin.We conducted a cohort study using the UK-based Clinical Practice Research Datalink. Participants included a cohort of 38,233 new users of metformin monotherapy who initiated a 2nd antidiabetic agent between January 1, 2007 and December 31, 2012 with follow-up until death, disenrollment, therapy discontinuation, or study end-date. A subcohort of 21,848 patients with linked hospital episode statistics (HES) and Office of National Statistics (ONS) data were studied to include MACE and cardiovascular-related death. The primary exposure contrasts, defined a priori, were initiation of a DPP4i versus an SU and initiation of a GLP-1RA versus an SU following metformin monotherapy. Cox proportional hazards models were used to assess the relative differences in time to mortality and MACE between exposure contrasts, adjusting for important baseline patient factors and comedications used during follow-up.The main study cohort consisted of 6213 (16%) patients who initiated a DPP4i, 25,916 initiated an SU (68%), 4437 (12%) initiated a TZD, 487 (1%) initiated a GLP-1RA, 804 (2%) initiated insulin, and 376 (1%) initiated a miscellaneous agent as their 2nd antidiabetic agent. Mean age was 62 years, 59% were male, and mean glycated hemoglobin was 8.8% (92.6 mmol/mol). Median follow-up was 2.7 years (interquartile range 1.3-4.2). Mortality rates were 8.2 deaths/1000 person-years for DPP4i and 19.1 deaths/1000 person-years for SU initiators. Adjusted hazards ratio (aHR) for mortality in DPP4i versus SU initiators = 0.58, 95% CI 0.46 to 0.73, P < 0.001. MACE rates were 19.1/1000 person-years for DPP4i initiators, 15.9/1000 person-years for GLP1-RA initiators versus 33.1/1000 person-years for SU initiators (aHR: DPP4i vs SU initiators = 0.64, 95%CI 0.52-0.80; GLP1RA vs SU initiators = 0.73, 95% CI 0.34-1.55).In this cohort of metformin monotherapy users, 2nd-line DPP4i use was associated with a 42% relative reduction in all-cause mortality and 36% reduction in MACE versus SUs, the most common 2nd-line therapy in our study. GLP-1RAs were not associated with adverse events in this cohort. SN - 1536-5964 UR - https://www.unboundmedicine.com/medline/citation/27368005/Comparative_effectiveness_of_incretin_based_therapies_and_the_risk_of_death_and_cardiovascular_events_in_38233_metformin_monotherapy_users_ L2 - https://doi.org/10.1097/MD.0000000000003995 DB - PRIME DP - Unbound Medicine ER -