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Patients with heart failure and diabetes: clinical outcomes with Metformin and sulfonylurea therapies


The objective of a study was to characterize associations between initiation of Metformin and sulfonylurea therapy and clinical outcomes among patients with comorbid heart failure ( HF ) and diabetes ( overall and by ejection fraction [ EF ] phenotype ).

Metformin and sulfonylureas are frequently prescribed to patients with diabetes for glycemic control. The impact of these therapies on clinical outcomes among patients with comorbid heart failure and diabetes is unclear.

Researchers have evaluated Medicare beneficiaries hospitalized for heart failure in the Get With The Guidelines - Heart Failure Registry between 2006 and 2014 with diabetes and not prescribed Metformin or sulfonylurea before admission.
In parallel separate analyses for metformin and sulfonylurea, patients with newly prescribed therapy within 90 days of discharge were compared with patients not prescribed therapy.

Multivariable models landmarked at 90 days have evaluated associations between prescription of therapy, and mortality and hospitalization for heart failure ( HHF ) at 12 months.

Negative control ( falsification ) endpoints included hospitalization for urinary tract infection, hospitalization for gastrointestinal bleed, and influenza vaccination.
Prespecified subgroup analyses were stratified by ejection fraction less than or equal to 40% versus more than 40%.

Of 5,852 patients, 454 ( 7.8% ) were newly prescribed Metformin and 504 ( 8.6% ) were newly prescribed sulfonylurea.

After adjustment, Metformin prescription was independently associated with reduced risk of composite mortality / hospitalization for heart failure ( HR: 0.81; 95% CI: 0.67-0.98; P = 0.03 ), but individual components were not statistically significant. Findings among patients with ejection fraction less than 40% accounted for associations with mortality / hospitalization for heart failure ( HR: 0.68; 95% CI: 0.52-0.90 ) and hospitalization for heart failure ( HR: 0.58; 95% CI: 0.40-0.85 ) endpoints ( all P for interaction less than or equal to 0.04 ).

After adjustment, sulfonylurea initiation was associated with increased risk of mortality ( HR: 1.24; 95% CI: 1.00-1.52; P = 0.045 ) and hospitalization for heart failure ( HR: 1.22; 95% CI: 1.00-1.48; P = 0.050 ) with nominal statistical significance.

Associations between sulfonylurea initiation and endpoints were consistent regardless of ejection fraction ( all P for interaction more than 0.11 ).
Neither Metformin initiation nor sulfonylurea initiation were associated with negative control endpoints.

In conclusion, in this population of older U.S. adults hospitalized for heart failure with comorbid diabetes, Metformin initiation was independently associated with substantial improvements in 12-month clinical outcomes, driven by findings among patients with ejection fraction more than 40%.
By contrast, sulfonylurea initiation was associated with excess risk of death and heart failure hospitalization, regardless of ejection fraction. ( Xagena )

Khan MS et al, JACC Heart Fail 2022; 10: 198-210

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