Rates of Hypoglycemia Predicted in Patients with Type 2 Diabetes on Insulin Glargine 300 U/ml Versus First- and Second-Generation Basal Insulin Analogs: The Real-World LIGHTNING Study

Abstract

Introduction The LIGHTNING study applied conventional and advanced analytic approaches to model, predict, and compare hypoglycemia rates of people with type 2 diabetes (T2DM) on insulin glargine 300 U/ml (Gla-300) with those on first-generation (insulin glargine 100 U/ml [Gla-100]; insulin detemir [IDet]) or second-generation (insulin degludec [IDeg]) basal-insulin (BI) analogs, utilizing a large real-world database. Methods Data were collected between 1 January 2007 and 31 March 2017 from the Optum Humedica US electronic health records [EHR] database. Patient-treatments, the period during which a patient used a specific BI, were analyzed for patients who switched from a prior BI or those who newly initiated BI therapy. Data were analyzed using two approaches: propensity score matching (PSM) and a predictive modeling approach using machine learning. Results A total of 831,456 patients with T2DM receiving BI were included from the EHR data set. Following selection, 198,198 patient-treatments were available for predictive modeling. The analysis showed that rates of severe hypoglycemia (using a modified definition) were approximately 50% lower with Gla-300 than with Gla-100 or IDet in insulin-naïve individuals, and 30% lower versus IDet in BI switchers (all p < 0.05). Similar rates of severe hypoglycemia were predicted for Gla-300 and IDeg, regardless of prior insulin experience. Similar results to those observed in the overall cohorts were seen in analyses across subgroups at a particularly high risk of hypoglycemia. PSM (performed on 157,573 patient-treatments) revealed comparable reductions in HbA 1c with Gla-300 versus first- and second-generation BI analogs, alongside lower rates of severe hypoglycemia with Gla-300 versus first-generation BI analogs ( p < 0.05) and similar rates versus IDeg in insulin-naïve and BI-switcher cohorts. Conclusions Based on real-world data, predicted rates of severe hypoglycemia with Gla-300 tended to be lower versus first-generation BI analogs and similar versus IDeg in a wide spectrum of patients with T2DM. Funding Sanofi, Paris, France. Electronic supplementary material The online version of this article (10.1007/s13300-019-0568-8) contains supplementary material, which is available to authorized users.

Comparable glycaemic control and hypoglycaemia in adults with type 2 diabetes after initiating insulin glargine 300 units/mL or insulin degludec: The DELIVER Naïve D real‐world study

“…However, in contrast to the current study, the BRIGHT trial, and other recent real‐world studies, the CONFIRM observational study has reported contradictory results. The CONFIRM study examined the EMRs of insulin‐naïve adults with T2D from the same database as the current study (Explorys; IBM Watson Health), but reported that IDeg was associated with a significantly larger mean HbA1c reduction and significantly greater “reductions in the change in the likelihood of hypoglycaemia” than Gla‐300 .…”

“…Results from the current study are also in line with those from three real‐world, observational studies that have compared outcomes among insulin‐naïve or insulin‐experienced adults with T2D. The real‐world, observational LIGHTNING study of EMRs (Optum Humedica database) included adults with T2D who newly initiated or switched to Gla‐100, insulin detemir (IDet), Gla‐300, or IDeg .…”

“…Results from the current study are also in line with those from three real‐world, observational studies that have compared outcomes among insulin‐naïve or insulin‐experienced adults with T2D. The real‐world, observational LIGHTNING study of EMRs (Optum Humedica database) included adults with T2D who newly initiated or switched to Gla‐100, insulin detemir (IDet), Gla‐300, or IDeg . The LIGHTNING study reported comparable HbA1c reductions and severe hypoglycaemia event rates among propensity score‐matched patients who newly initiated Gla‐300 or IDeg, and among those who switched to Gla‐300 or IDeg.…”

“…LIGHTNING also used machine learning methodology to develop a model to predict severe hypoglycaemia rates among vulnerable subgroups of patients. Using this model, no significant differences in severe hypoglycaemia were predicted with Gla‐300 versus IDeg among insulin‐naïve patients or among those who switched to Gla‐300 versus IDeg for patients at increased hypoglycaemic risk, those with moderate/severe renal impairment, or those aged ≥65 or ≥ 75 years . In DELIVER D, all patients switched from Gla‐100 to Gla‐300 or IDeg, while in DELIVER D+, patients switched from Gla‐100 or IDet to Gla‐300 or IDeg.…”

Efficacy and safety of insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Asia Pacific insulin‐naïve people with type 2 diabetes: The EDITION AP randomized controlled trial

“…The DELIVER 2 study showed that, in patients previously treated with basal insulin, Gla‐300 provided comparable HbA1c reductions with other basal insulins, but with lower rates of severe hypoglycaemia . LIGHTNING predicted lower rates of severe hypoglycaemia with Gla‐300 versus first‐generation basal insulin analogues, Gla‐100 and insulin detemir, in insulin‐naïve people with T2D …”