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

Abstract

Achieving target glycaemic control is essential in people with diabetes to minimize the risk of long-term complications, and many people with type 2 diabetes will ultimately require basal insulin (BI) therapy to achieve their individualized glycaemic targets. Usually, the first 12 weeks following initiation of BI therapy represents the period when the greatest dose increases and glycaemic reductions occur. Effective glycaemic control combined with minimizing the risk of hypoglycaemia is important to enable the achievement of glycaemic control in the longer term. However, substantial therapeutic inertia exists in clinical practice, both in initiation and up-titration of BI, owing to patient-, physician- and healthcare system-related barriers, including fear of hypoglycaemia and the perception of a burdensome regimen. The more prolonged duration of action, reduced glycaemic variability and lower risk of hypoglycaemia seen with second-generation versus first-generation BI analogues may help alleviate patients' and physicians' concerns and facilitate titration. In turn, optimal BI titration and subsequent metabolic benefits may help improve therapy adherence and self-management. This review details the clinical implications of prompt titration of BI to achieve early glycaemic control, and the importance of minimizing hypoglycaemia risk within the initial titration period. Facilitation of patients' self-management of BI is also addressed.

Keywords: basal insulin; glycaemic control; hypoglycaemia; insulin analogues; insulin therapy.

Figure 1

Factors contributing to therapeutic inertia of insulin. HCP, healthcare professional

Figure 2

Insulin dose titration with insulin glargine. Figure reproduced from Owens DR, et al. Diab Res Clin Pract 2014;106:264–274

Figure 3

Titration algorithms in randomized controlled trials of basal insulins. For the EDITION 1–3 studies, if a blood glucose (BG) of <3.3 mmol/L (<60 mg/dL) was recorded, the dose could be reduced by 3 units (U) or at the investigator's discretion. In BRIGHT, if a BG of <4.4 mmol/L (<80 mg/dL) was recorded, the dose could be reduced by either 2 U or at the investigator's discretion. In ATLAS, if a BG of ≤3.1 mmol/L (≤56 mg/dL) was recorded, the dose was reduced at the physician's discretion. In TAKE CONTROL, the dose was reduced by 3 U in both the physician‐managed or self‐managed titration groups if either a BG of <4.4 mmol/L (<80 mg/dL) or ≥2 symptomatic or 1 severe hypoglycaemic event(s) in the preceding week were recorded. In SENIOR, the dose was reduced by 3 U if either a BG of <5.0 mmol/L (<90 mg/dL) or ≥2 symptomatic or 1 severe hypoglycaemic event(s) in the preceding week were recorded. Phys, physician‐managed titration group; pt, patient‐managed titration group; S vs. S, simple versus stepwise titration; SMPG, self‐measured plasma glucose. *Doses were adjusted weekly; ^†doses were adjusted at every visit (AT.LANTUS: weekly during clinic visits or telephone contact visits; ATLAS: clinic visits at baseline, weeks 2, 6, 12, 16 and 24; telephone contact visits were made at weeks 1, 3, 4, 5, 8, 10 and 20; TAKE CONTROL: weekly for the first 8 weeks, biweekly until week 12, monthly until week 24); ^‡doses were adjusted every 3 days; ^§doses were adjusted twice a week; ^¶doses were adjusted daily