Efficacy and Hypoglycemia Profile of Once-weekly Insulin Icodec vs Once-daily Comparators Across Demographic Subgroups

Abstract

Objective: This post hoc analysis evaluated the impact of age, ethnicity, and race on efficacy and hypoglycemia outcomes with once-weekly insulin icodec (icodec) vs once-daily (OD) basal insulin comparators, leveraging data from the ONWARDS 1 to 5 phase 3a clinical trials.

Methods: Efficacy and hypoglycemia outcomes were assessed within each trial in insulin-naive (ONWARDS 1, 3, and 5) and insulin-experienced (ONWARDS 2 and 4) adults (≥18 years) with type 2 diabetes across subgroups of age (<55, 55-64, and ≥65 years), ethnicity (Hispanic/Latino and non-Hispanic/Latino), and race (Asian, Black/African American, White, Other). The primary outcome was the change in glycated hemoglobin (HbA1c) from baseline to planned end of treatment. Other outcomes assessed included the achievement of HbA1c <7% (<53 mmol/mol) without clinically significant or severe hypoglycemia and the number of clinically significant or severe hypoglycemic episodes.

Results: Across all trials, the estimated treatment differences for change in HbA1c and the odds ratios for achieving HbA1c <7% (<53 mmol/mol) without clinically significant or severe hypoglycemia were similar across age, ethnicity, and race subgroups with icodec vs OD insulin (no statistically significant treatment by subgroup interactions were observed; P > .05 in all instances). Hypoglycemia rates were numerically low for both treatment groups and consistent across age, ethnicity, and race subgroups.

Conclusion: The efficacy and hypoglycemia profile of icodec vs OD comparators was consistent across trial populations irrespective of age, ethnicity, or race.

Keywords: demographic analyses; ethnicity; long-acting basal insulin; race; type 2 diabetes.

Figure 1.

Estimated treatment differences in change in HbA_1c (percentage points) from baseline to planned EOT by (A) age, (B) ethnicity, and (C) race. Planned EOT: ONWARDS 1, week 78; ONWARDS 2-4, week 26; ONWARDS 5, week 52. Mean change in HbA_1c is the estimated change. The “Other” race subgroup included American Indian or Alaska native, and native Hawaiian or other Pacific Islander. *The P value is for test of no treatment interaction by subgroup. Modeled using an analysis of covariance model with treatment, region, subgroup, treatment by subgroup interaction, and, if applicable, additional relevant factors as fixed factors and baseline response as covariate. ^†In ONWARDS 5, participants in the OD comparator arm received OD degludec, glargine U100, or glargine U300 at the investigators’ discretion. Abbreviations: Aspart, insulin aspart; degludec, insulin degludec; EOT, end of treatment; ETD, estimated treatment difference; glargine U100, insulin glargine U100; glargine U300, insulin glargine U300; HbA_1c, glycated hemoglobin; icodec, insulin icodec; OD, once daily.

Figure 2.

Estimated odds ratios for the achievement of HbA_1c <7% at planned EOT without clinically significant or severe hypoglycemia in the previous 12 weeks by (A) age, (B) ethnicity, and (C) race. Planned EOT: ONWARDS 1, week 78; ONWARDS 2-4, week 26; ONWARDS 5, week 52. Clinically significant hypoglycemia: blood glucose of <54 mg/dL (<3.0 mmol/L), confirmed by blood glucose meter. Severe hypoglycemia: hypoglycemia associated with severe cognitive impairment requiring external assistance for recovery. The “Other” race subgroup included American Indian or Alaska native, and native Hawaiian or other Pacific Islander. *The P value for treatment interaction by subgroup was calculated using a logistic regression model (logit link) with treatment, region, subgroup, treatment by subgroup interaction, and, if applicable, additional relevant factors as fixed factors and the baseline HbA_1c value as covariate. ^†In ONWARDS 5, participants in the OD comparator arm received OD degludec, glargine U100, or glargine U300 at the investigators’ discretion. Abbreviations: Aspart, insulin aspart; degludec, insulin degludec; EOR, estimated odds ratio; EOT, end of treatment; glargine U100, insulin glargine U100; glargine U300, insulin glargine U300; HbA_1c, glycated hemoglobin; icodec, insulin icodec; OD, once daily.