A Multicenter Observational Study of Incretin-based Drugs and Heart Failure

Claire Rummage, Mercer University College of Pharmacy


Incretin-based drugs include dipeptidyle peptidase four (DPP-4) inhibitors and glucagon- like peptide one (GLP-1) analogs. [1] The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) guidelines recommend that incretin-based drugs be used as second-line or third-line therapy for type two diabetes. [2] Approximately 12 percent of type two diabetic patients are reported to be prescribed an incretin-based drug. [3]



A Multicenter Observational Study of Incretin-based Drugs and Heart Failure [4]
Design Multicenter, cohort-control, retrospective study; N= 1,499,650
Objective To determine whether the use of incretin-based drugs, as compared with oral antidiabetic-drug combinations, in routine clinical practice is associated with an increase risk of heart failure (HF)
Study Groups Patients with diabetes who were hospitalized for heart failure (n= 23,205) and matched controls (n= 435,777) and patients with diabetes who had a history of heart failure (n= 6,536) and matched controls (n= 100,480)
Methods The study obtained healthcare data on patients with diabetes from databases for multiple sites. The base cohort included patients with first-ever prescription for noninsulin antidiabetic drugs from the earliest to the last date of prescription drug information at each site. From the base cohort, the study formed a study cohort consisting of all patients who began to receive a new antidiabetic drug during the year in which incretin-based drugs entered the market and thereafter. They matched each patient who was hospitalized for heart failure with up to 20 controls from the same cohort based on sex, age, date of study-cohort entry, duration of treated diabetes and duration of follow up. Cohort-specific hazard ratios for hospitalization due to heart failure among patients receiving incretin-based drugs were compared with those receiving oral antidiabetic-drug combinations.
Duration N/A
Primary Outcome Measure The risk of hospitalization for heart failure with incretin-based drugs as compared with oral antidiabetic drug combinations
Baseline Characteristics   No history of HF History of HF
  Case Patients (n= 23,205) Controls (n= 435,777) Case patients (n= 6,536) Controls (n= 100,480)
United States, n 74.2% 74.2% 58.7% 58.7%
Mean age, y 68.7 68.6 74.2 74.1
Male sex, n 56.7% 56.7% 58.9% 58.9%
Meanduration of treated diabetes, y 0.7 0.7 1.8 1.8
Hypertension 77.4% 71.8% 88.9% 88.5%
Dyslipidemia 52.6% 56.0% 61.1% 62.8%
Results   Hospitalizations for HF in patients without a history of HF Hospitalizations for HF in patients with a history of HF
  Case Patients (n= 23,205) Controls (n= 435,777) Hazard Ratio (95% Confidence interval) Case patients (n= 6,536) Controls (n= 100,480) Hazard Ratio (95% Confidence interval)
Two or more oralantidiabetic drugs 13.6% 11.9% 1.00 10.5% 10.6% 1.00
Incretin-based dr
10.6% 9.8% 0.82 (0.67-1.00) 14.4% 12.3% 0.86 (0.62-1.19)
DPP-4 inhibitors 9.6% 8.9% 0.84 (0.69-1.02) 13.8% 11.6% 0.87 (0.63-1.21)
GLP-1 analogues 1.0% 0.9% 0.95 (0.83-1.10) 0.5% 0.7% 0.75 (0.22-2.51)
AdverseEvents Common Adverse Events: N/A
Serious Adverse Events: N/A
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions In this analysis of data from large cohorts of patients with diabetes, incretin-based drugs were not associated with an increased risk of hospitalization for heart failure, as compared with commonly used combinations of oral antidiabetic drugs.


The findings of this study were consistent for patients with or without a history of heart failure, as well as those taking DDP-4 inhibitors or GLP-1 analogues. However, the data gathered in the study did not include ejection fraction. For the ability to examine the type of heart failure present and adjust for it, subsequent studies should include ejection fraction. Furthermore, the reference group included many patients who were taking sulfonylureas. The use of sulfonylureas may have caused an increased risk of adverse cardiovascular effects in this study group.





  1. Zoulay Laurent, Filion Kristian B, Platt Robert W,Dahl Matthew, Dormuth Colin R, Clemens Kristin K et al. Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study BMJ 2016; 352 :i581.


  1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Associated (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35:1364-79.


  1. McGill University. No increased Heart Failure with Incretin-Based Drugs. Drug Discovery and Development website. http://www.dddmag.com/news/2016/03/no-increased-heart-failure-incretin-based-drugs. March 29, 2016. Accessed March 29, 2016.


  1. Filion KB, Azoulay L, Platt RW, et al. A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. N Engl J Med. 2016;374(12):1145-54.





Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s