Effect of Basal Insulin Glargine on First and Recurrent Episodes of Heart Failure Hospitalization
The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention)
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Diabetes mellitus increases the incidence of recurrent heart failure through a variety of potential mechanisms, including ischemic myocardial damage, hyperglycemia, and the effects of the glucose-linked metabolic abnormalities on the myocardium.1 To date, randomized controlled trials of more versus less glucose lowering with a menu of drugs, including insulin, have reported a neutral effect on incident heart failure. Nevertheless, epidemiological studies and the sodium-retaining properties of insulin have fueled concerns about a possible link.2
The ORIGIN trial (Outcome Reduction With Initial Glargine Intervention) allocated 12 537 people (mean age, 64 years; 35% women) with diabetes mellitus (88%), impaired glucose tolerance, or impaired fasting glucose to either basal insulin-mediated normoglycemia or therapy without insulin and reported a neutral effect on cardiovascular events during a median follow-up of 6.2 years. People with New York Heart Association class 3 or 4 heart failure were excluded. Heart failure requiring hospitalization was a prespecified component of the primary outcome and was defined as evidence of overnight hospitalization or attendance in an acute care setting for at least 2 of the following: signs or symptoms of heart failure; radiological evidence of congestive heart failure; treated with intravenous diuretics, or a first or increased dose of an oral diuretic, intravenous or oral vasodilator, or intravenous or oral inotrope.3 Both first and recurrent episodes were prospectively collected and …