Cardiovascular Safety of Gla-100: Reflections From the ORIGIN and ORIGINALE Trials

Cardiovascular diseases (CVD) risk in people with type 2 diabetes mellitus (T2DM) is two to four folds higher than in individuals without T2DM. Insulin therapy was speculated to be atherogenic- thereby aggravating CVD risk years ago. However, cardiovascular outcome trials (CVOTs) such as the Outcome Reduction with Initial Glargine Intervention (ORIGIN), and its extended follow-up study - ORIGIN and Legacy Effects (ORIGINALE) conclusively established the long-term cardiovascular (CV) safety of basal insulin, such as insulin glargine 100 U/mL (Gla-100). Moreover, these studies hinted at the possible benefits of early insulin therapy-including stalling the progression of diabetes with minimal weight gain and hypoglycemia risk. This review highlights the background developments which led to the ORIGIN trial. Additionally, it also dwells on the critical insights to emerge from this trial pertaining to the CV safety of basal insulin Gla-100 in high CV risk individuals with T2DM.