Review: evidence for major benefits and harms of antidiabetic agents for diabetes with heart failure is limited.

M e t h o d s Data sources: MEDLINE (1966 to 2007), EMBASE/Excerpta Medica (1980 to 2007), Cochrane Central Register of Controlled Trials (1991 to 2007), 5 other databases, reference lists, and experts. Study selection and assessment: Randomized controlled trials (RCTs) or cohort studies evaluating the association between antidiabetic drugs (insulin, metformin [MET], sulfonylurea [SFU], and thiazolidinedione [TZD]) and hospitalization or all-cause mortality in patients with HF and diabetes. Quality assessment of individual studies was based on a validated checklist (maximum score 32; scores ≥ 12 indicate acceptable quality). 8 studies met the selection criteria: 1 RCT, 2 post hoc analyses from RCTs, 4 retrospective cohort studies, and 1 prospective cohort study; quality scores ranged from 13 to 22. Meta-analysis was not done because of significant statistical heterogeneity (except for studies on TZDs and hospitalization for HF). Outcomes: All-cause hospitalization, hospitalization for HF (cardiovascular morbidity), and all-cause mortality. M a i n r e s u l t s In 2 of 3 studies, MET was associated with lower risk for mortality than other drugs, and in 1 study, MET plus SFU was associated with lower risk for mortality than SFU alone (Table); groups did not differ for all-cause hospitalization. In 3 of 4 studies, insulin was associated with higher risk for mortality than other drugs (Table). In 4 studies, TZD was associated with lower risk for mortality but higher risk for hospitalization for HF than other drugs (Table). In 1 study, SFU and non-SFU drugs did not differ for mortality. C o n c l u s i o n Metformin and thiazolidinediones are associated with reduced risk but insulin is associated with increased risk for all-cause mortality in patients with heart failure and diabetes.