Association between intensification of metformin treatment with insulin vs sulfonylureas and CV events and all-cause mortality among patients with diabetes

Roumie CL, Greevy RA, Grijalva CG, et al. Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes. JAMA. 2014;311(22):2288-2296.

This study compared time to nonfatal CVD or mortality among subjects who intensified antihyperglycemic treatment with insulin vs sulfonylurea added to metformin.

Subjects: retrospective cohort of VHA patients already taking metformin who filled a prescription for

  • Insulin (long-acting, premixed, or short/fast-acting; n=2,436*)
  • Sulfonylurea (glyburide, glipizide, or glimepiride; n=12,180*)

The primary composite outcome was acute MI, stroke hospitalization, or all-cause mortality. Secondary outcomes included acute MI + stroke, all-cause mortality, and a composite of acute MI, stroke, and CV mortality. Median follow-up after treatment intensification was 14 months. 

Click on slide thumbnail to view larger. Slide available for download in the slide library.
Nonfatal CVD and All-Cause Mortality With Insulin Vs Sulfonylurea As Add-On to Metformin Design  
Nonfatal CVD and All-Cause Mortality With Insulin Vs Sulfonylurea as Add-On to Metformin: Design  

Primary outcome
Results for the primary composite outcome, acute MI, stroke hospitalization, or all-cause mortality, showed an increased risk with insulin treatment vs sulfonylurea (rate per 1,000 person-years):

  • Metformin + Insulin (n=2,436*): 42.7 (172 events)
  • Metformin + Sulfonylurea (n=12,180*): 32.8 (634 events)
  • Adjusted HR, 1.30; 95% CI, 1.07-1.58; P=0.009

Click on slide thumbnail to view larger. Slide available for download in the slide library.
Increased Risk of Nonfatal CVD and All-Cause Mortality With Insulin Vs Sulfonylurea As Add-On to Metformin  
Increased Risk of Nonfatal CVD and All-Cause Mortality With Insulin Vs Sulfonylurea As Add-On to Metformin 

Secondary outcomes
Results for secondary CV outcomes and all-cause mortality (rate per 1,000 person-years):

  • Acute MI + stroke
    • Metformin + Insulin (n=2,436*): 10.2 (41 events)
    • Metformin + Sulfonylurea (n=12,180*): 11.9 (229 events)
    • Adjusted HR, 0.88; 95% CI, 0.59-1.30; P=0.052
     
  • All-cause mortality
    • Metformin + Insulin (n=2,436*): 33.7 (137 events)
    • Metformin + Sulfonylurea (n=12,180*): 22.7 (444 events)
    • Adjusted HR, 1.44; 95% CI, 1.15-1.79; P=0.001
     
  • Composite of acute MI, stroke, and CV mortality
    • Metformin + Insulin (n=1,865*): 22.8 (54 events)
    • Metformin + Sulfonylurea (n=9,145*): 22.5 (258 events)
    • Adjusted HR, 0.98; 95% CI, 0.71-1.34; P=0.087   
Click on slide thumbnail to view larger. Slide available for download in the slide library.
Nonfatal CVD and All-Cause Mortality With Insulin Vs Sulfonylurea As Add-On to Metformin  
Nonfatal CVD and All-Cause Mortality With Insulin Vs Sulfonylurea As Add-On to Metformin 

*After propensity-score matching due to size differences between treatment groups; 1:5 matching for metformin + insulin to metformin + sulfonylurea

MI=myocardial infarction; VHA=Veterans Health Administration 

 
 
  

Any pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

June 2014 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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Last Modified: 8/4/2014