Risk of overall mortality and cardiovascular events in patients with type 2 diabetes on dual drug therapy including metformin: A large database study from the Cleveland Clinic.
BACKGROUND
The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent.


METHODS
A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13,185 adult patients (>18 years) with T2DM from January 2008 to June 2013 and received a prescription for MF in combination with a sulfonylurea (SU; n = 9419), thiazolidinedione (TZD; n = 1846), dipeptidyl peptidase-4 inhibitor (DPP-4i; n = 1487), or a glucagon-like peptide-1 receptor agonist (GLP-1a; n = 433). Multivariate Cox models with propensity analysis were used to compare cohorts, with MF+SU serving as the comparator group.


RESULTS
The mean (±SD) age was 60.6 ± 12.6 years, with 54.6% male and 75.8% Caucasians. The median follow-up was 4 years. There were 1077 deaths, 1733 CAD events, and 528 CHF events in 55,100 person-years of follow-up. A higher risk of CHF was observed with MF+DPP-4i use (hazard ratio [HR] 1.104; 95% confidence interval [CI] 1.04-1.17; P = 0.001). A trend towards improved overall survival for users of MF+TZD (HR 0.86; 95% CI 0.74-1.0; P = 0.05) and MF+GLP-1a (HR 0.569; 95% CI 0.30-1.07; P = 0.08) was observed. No significant differences in the risk of CAD were identified.


CONCLUSIONS
Consistent with recent studies, our results raise concern for an increased risk of CHF with use of DPP-4i.
Department of Endocrinology, Diabetes and Bariatric Medicine, Narayana Health City, Bangalore, India.
Subramanian
S
Kannan
Department of Endocrinology and Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Kevin M
KM
Pantalone
Department of Endocrinology and Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Simone
S
Matsuda
Translational Science Institute Medical Center, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Brian J
BJ
Wells
Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Matthew
M
Karafa
Department of Endocrinology and Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Robert S
RS
Zimmerman
D000368:Aged; D003324:Coronary Artery Disease / Q000139:chemically induced / Q000401:mortality*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000627:therapeutic use; D006333:Heart Failure / Q000139:chemically induced / Q000401:mortality*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D015996:Survival Rate; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1; D008687:Metformin; C089946:2,4-thiazolidinedione
congestive heart failure; dipeptidyl peptidase-4 inhibitors; mortality; sulfonylureas; thiazolidinediones; 二肽基肽酶-4抑制剂; 充血性心力衰竭; 噻唑烷二酮类; 死亡率; 磺酰脲类