Abstract

Background: High BMI is associated with insulin resistance and greater basal insulin (BI) requirements, which can lead to increased risk of hypoglycemia. The real-life, pragmatic, randomized ACHIEVE Control study (NCT02451137) demonstrated that among insulin-naive adults with T2D ≥1 year and A1C 8–11%, those who received the 2nd-generation BI analog glargine 300 U/mL (Gla-300) were significantly more likely to achieve individualized A1C targets (<8% for participants ≥65 years or with defined comorbidities; <7% for all others) without documented symptomatic (≤70 mg/dL) and/or severe hypoglycemia versus first-generation BI analogs (insulin glargine 100 U/mL; insulin detemir) at 6 months, with the trend continuing at 12 months. Aim: This post-hoc analysis of ACHIEVE Control explored the correlation between A1C target attainment without hypoglycemia with daily insulin dose according to BMI. Method: Participants were categorized according to baseline BMI (<30, 30–<35, 35–<40, ≥40 kg/m2). Proportions of participants achieving individualized A1C targets without documented symptomatic (≤70 and <54 mg/dL) and/or severe hypoglycemia; mean daily insulin doses at 6 and 12 months were estimated. Results: The <30 kg/m2 BMI group comprised individuals who were predominantly male (61 vs 42–58%), were older (61.7 vs 55.1–59.7 years), and had longer duration of T2D (12.6 vs 9.8–11.2 years) versus those with higher BMIs. Mean A1C was 9.1–9.2% across all BMI subgroups. Background medication use was generally well balanced, except for higher GLP-1 RA use as BMI increased. The proportion of individuals with the more stringent A1C goal of <7% increased as BMI increased, likely related to their younger age. Insulin dose at 12 months (U/kg/day) was similar across all BMI categories (range: 0.351–0.395). At both 6 and 12 months, a numerically higher proportion of participants who received Gla-300 versus 1st-generation BIs achieved their individualized A1C target without documented symptomatic (at both ≤70mg/dL and <54 mg/dL) or severe hypoglycemia (except for the ≥40 kg/m2 group at 6 months) (Table). Discussion: The results of this post-hoc analysis were consistent with those of the primary endpoint of the overall ACHIEVE Control study. The trend for benefit of Gla-300 versus 1st-generation BI for achievement of individualized A1C target without documented symptomatic and/or severe hypoglycemia at 12 months was consistent regardless of BMI.

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