Hypoglycaemia risk in the first 8 weeks of titration with insulin glargine 100 U/mL in previously insulin‐naive individuals with type 2 diabetes mellitus

Abstract

Patient characteristics associated with hypoglycaemia frequency during insulin glargine 100 U/mL (Gla-100) titration and clinical outcomes at Week 24 were examined using participant-level data from 16 treat-to-target trials involving individuals with type 2 diabetes mellitus who were inadequately controlled with oral antidiabetes drugs and were initiating Gla-100 (n = 3549). Hypoglycaemia (plasma glucose <3.9 mmol/L or severe) during the first 8 weeks of titration was stratified by number of events (0, 1-3 and ≥4), resulting in 72.5%, 20.6% and 6.9% of participants in each group, respectively. Changes in glycaemia, body weight and insulin dose from baseline to Weeks 12 and 24 were analysed. Hypoglycaemia was more common in participants with lower BMI and fasting C-peptide, and in those undergoing sulfonylurea treatment. Glycaemic outcomes at Week 24 were similar in each hypoglycaemia group, despite the fact that the Week 24 mean daily dose and dose increase for Gla-100 were highest in participants without hypoglycaemia and were lowest in those experiencing ≥4 events. The risk of hypoglycaemia during Gla-100 titration depends mainly on patient characteristics and on sulfonylurea use and may delay dose titration, which apparently has little effect on short-term glycaemic control in a clinical trial setting.

The importance of the initial period of basal insulin titration in people with diabetes

“…Results showed that the incidence of anytime (24 hours) hypoglycaemic events within the maintenance period (weeks 13–24) was lower for individuals who did not experience hypoglycaemia within the initial 12‐week titration period compared with those who did (38.2% vs. 75.4%) . Additionally, an analysis of 16 RCTs of Gla‐100 initiation showed that a higher risk of hypoglycaemia during titration was associated with a continued higher risk of non‐severe and severe hypoglycaemia for up to 6 months …”

New Digital Health Technologies for Insulin Initiation and Optimization for People With Type 2 Diabetes

“…For example, experiencing hypoglycemia early after the initiation of basal insulin (BI) is associated with a higher long-term risk of hypoglycemia or BI discontinuation. 8,9 Clinician concerns about hypoglycemia may result in suboptimal treatment 10 and contribute to many people with T2D not achieving the target glycated hemoglobin (HbA1C) levels. 11 The adjustment of insulin doses in patients with T2D is often led by healthcare providers (HCPs), but access to timely and appropriate HCP resources and education to support effective self-titration remain challenging.…”

Similar glycaemic control and less hypoglycaemia during active titration after insulin initiation with glargine 300 units/mL and degludec 100 units/mL: A subanalysis of the BRIGHT study

“…7 Therefore, reducing the risk of hypoglycaemia during this period may be particularly beneficial, 6 as both randomized controlled trials and real-world evidence have shown an association between experiencing hypoglycaemia soon after initiating BI therapy and a higher risk of hypoglycaemia and BI discontinuation in the longer term. [8][9][10] In addition, reducing hypoglycaemia during the titration period may increase confidence to up-titrate BI. This is important because failure to reach an HbA1c of <7.0% by 3 months is associated with an increased risk of failing to achieve this target at 24 months.…”

“…Previous real‐world studies have also shown that active titration of basal insulin (BI) typically occurs during the first 12 weeks, after which there is little further titration . Therefore, reducing the risk of hypoglycaemia during this period may be particularly beneficial, as both randomized controlled trials and real‐world evidence have shown an association between experiencing hypoglycaemia soon after initiating BI therapy and a higher risk of hypoglycaemia and BI discontinuation in the longer term . In addition, reducing hypoglycaemia during the titration period may increase confidence to up‐titrate BI.…”