OR34-3 The Risk of Overall Mortality and Cardiovascular Events in Patients with Type 2 Diabetes on Dual Drug Therapy Including Metformin: A Large Database Study from Cleveland Clinic

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: OR34-Predictors and Mediators of Cardiovascular Risk: Clinical Research
Clinical/Translational
Monday, June 23, 2014: 11:30 AM-1:00 PM
Presentation Start Time: 12:00 PM
W184 (McCormick Place West Building)
Subramanian Kannan, MD1, Simone Matsuda Torricelli2, Kevin M Pantalone, DO, ECNU, CCD3, Brian J Wells, MD, Ph.D3, Matthew Karafa2 and Robert S Zimmerman, MD3
1Narayana Health City, Bangalore, India, 2Cleveland Clinic, Cleveland OH, Cleveland, OH, 3Cleveland Clinic, Cleveland, OH
Background: Controversy still surrounds the selection of anti-diabetic agents for the treatment of type 2 diabetes mellitus (DM-2) once the first line agent, Metformin, fails.  Recently, the focus in management of DM-2 has shifted to the adverse effects of the anti-diabetic agents, largely the risk of adverse cardiovascular (CV) outcomes and mortality. A prospective trial found an increased risk of hospitalization for congestive heart failure in subjects treated with saxagliptin. A recent re-analysis of the RECORD trial by the US-FDA noted no increase in CV risk with the use of rosiglitazone. Large-scale clinical trials investigating the long-term CV safety of glucagon like peptide-1 agonists (GLP-1a) are ongoing.

Aim: To assess the risk of overall mortality, coronary artery disease, and congestive heart failure in patients with DM-2 treated with dual drug therapy including metformin and an additional anti-diabetic agent. 

Methodology: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13,185 patients with DM-2 who received a prescription for (Metformin (MF) in combination with a Sulfonylurea (SFU) (N=9,419), Thiazolidinedione (TZD) (N=1,846), DPP4-inhibitor (DPP4-I) (N=1,487), or a GLP-1 receptor agonist (N=433), seen in the outpatient clinics, ≥ 18 years of age, and not on insulin or undergoing dialysis at baseline.  The patients were followed for mortality, coronary artery disease, and congestive heart failure by documentation in the EHR and Social Security Death Index.  Cox multiple regression models were used to compare cohorts. Combination therapy with MF+SFU served as the comparator group.

Results: Baseline characteristics for the entire cohort include mean (+ SD) age 60.6 + 12.6 years, 54.6% male and 75.8% Caucasian.  The median follow-up was 4 years.  There were a total of 1,077 deaths, 1,733 CAD events, and 528 CHF events in 55,110.76 person years of follow-up.  No statistically significant difference in the risk of overall mortality or CAD was observed among the different drug combinations. There was a trend towards improved overall survival with users of MF+TZD [HR 0.86 (0.74-1; p=0.05)] and MF+GLP-1a [HR 0.569 (0.30 - 1.07; p=0.08)] users. A higher risk of CHF was observed with MF+DPP4-I use [HR 1.104 (1.04-1.17; p=0.001)] and a trend towards a statistically significant increased risk with other combinations, MF+TZD [HR 1.024 (0.98-1.07)] and MF+GLP-1a [HR 1.1 (0.99-1.22)]. A sub-analysis of the MF+TZD cohort after excluding rosiglitazone demonstrated similar risks of mortality, CAD, and CHF.  

Conclusions: It does not appear that the SU and MF combination confers increased cardiac or mortality risk compared to the other drug combinations. However, an increased risk of CHF was noted with MF+DPP4-I use, as well as a strong statistical trend towards an increased risk with other combinations.

Disclosure: KMP: Consultant, Novo Nordisk, Consultant, Sanofi, Speaker Bureau Member, Bristol-Myers Squibb, Speaker Bureau Member, Eli Lilly & Company. RSZ: Speaker Bureau Member, Novo Nordisk, Speaker, Jansen Pharmaceuticals, Speaker Bureau Member, Bristol-Myers Squibb, Speaker Bureau Member, Merck & Co., Speaker Bureau Member, Santarus. Nothing to Disclose: SK, SMT, BJW, MK

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