Reducing risk of severe hypoglycemia - iNPHORM Study

Second-generation basal insulin analogs can be used as first choice in reducing real-world severe hypoglycemia (Baseline results of the iNPHORM study, USA)

This prospective investigation of real-world hypoglycemia risk stratification in the US suggested that clinicians should prioritize second-generation BIs over first-generation BIs, whenever feasible.

Main Takeaway

• Finding from the iNPHORM study corroborate that second-generation BI analogs versus first-generation BIs reduce the rate of SH, irrespective of bolus insulin therapy.
• Daytime SH and nocturnal SH were comparable in respondents receiving first-generation versus second-generation BIs.
• Whenever possible, clinicians should prioritize second-generation BIs over first-generation BIs.

Why This Matters

• Previous trials reported that second-generation BIs reduce SH compared to first-generation BIs.
• However, owing to the tightly controlled nature of clinical trials, their applicability in real world can be limited.
• The population-based iNPHORM study assessed the effect of second-generation versus first-generation BIs on SH frequency in the real-world practice to complement RCT findings.

Key Results

• The iNPHORM study cohort comprised US participants (≥18 to ≤90 years) with T1DM and T2DM taking insulin and/or secretagogues for ≥1 year.

  • Participants were included from a probability-based internet panel: Approximately 68,000 people with diabetes

    • T1DM: n = 10,000; T2DM: n = 58,000

    • 26,387 panelists initiated screening

• Participants who were unable to understand English, currently pregnant or pregnant in the previous year, and currently enrolled in a drug trial were excluded from study.

• Overall, 2,339 participants were eligible for the study; of these, 1,694 completed the baseline questionnaire, of whom 569 reported BI use and were included in the sub-analysis (age: 52.33 [SD, 13.82] years; female: 54.5%; T1DM: 21.6%).

• Key outcomes: Crude, real-world frequency of SH* among individual taking first-generation or second-generation BIs and quantification of the potential casual effects of second- versus first-generation BIs on SH frequency

• Multivariable negative binomial regression was used to isolate the effect of second-generation versus first-generation BIs (+/- bolus insulin) on self-reportedrates of past-year total SH, daytime SH, and nocturnal SH. Confounding variables were identified from a directed acyclic graph.

• Approximately 10.0% versus 54.1% and 7.6% versus 28.3% participants reported receiving second-generation versus first-generation BIs with and without bolus insulin, respectively.

• Adjusted SH incidence rate ratios in respondents receiving first-generation versus second-generation BIs were as follows:

  • Total SH: Respondents without bolus insulin = IRR: 2.70, 95% CI: 1.07–6.84; respondents with bolus insulin = IRR: 1.17, 95% CI: 0.552–2.46

• Comparable effects were found for daytime and nocturnal SH in respondents receiving first-generation versus second-generation BIs:

  • Daytime SH: Respondents without bolus insulin = IRR: 2.26, 95% CI: 0.817–6.24; respondents with bolus insulin = IRR: 1.43, 95% CI: 0.625–3.29

  • Nocturnal SH: Respondents without bolus insulin = IRR: 3.55, 95% CI: 0.39–15.03; respondents with bolus insulin = IRR: 1.07, 95% CI: 0.38–3.03

MAT-BH-2300610/v1/October 2023