Stepwise intensification of insulin therapy in Type 2 diabetes management—exploring the concept of the basal‐plus approach in clinical practice

Abstract

Basal insulin provides an effective method for initiating insulin therapy in people with Type 2 diabetes, resulting in significant improvements in glycaemic control, lower rates of hypoglycaemia and less weight gain than either prandial or premixed insulin regimens. However, the progressive nature of Type 2 diabetes and the inability of basal insulin to correct excessive postprandial glucose excursions mean that insulin therapy will eventually need to be intensified, typically by adding prandial insulin as part of a basal–bolus or premixed insulin regimen. The aim of this review is to summarize recent clinical evidence for a staged ‘basal-plus’ strategy for insulin intensification where one, two or three prandial insulin injections are added to basal insulin according to individual need. In the early stages of insulin therapy, most individuals seem to achieve favourable glycaemic control with basal insulin alone, or in combination with a single prandial insulin injection. The addition of a single prandial insulin injection at the largest meal is well tolerated and associated with significant improvements in glycated haemoglobin (HbA1c), low rates of hypoglycaemia and limited weight gain. More people achieve recommended HbA1c targets with a basal-plus strategy, compared with twice-daily premixed insulin therapy, with lower rates of hypoglycaemia. The data indicate that a step-by-step approach with the basal-plus strategy is a promising alternative method of insulin intensification that allows for individualization of treatment and may delay progression to a full basal–bolus insulin replacement therapy for many individuals.

Management of Type 2 Diabetes – Methods for Addition of Prandial to Basal Insulin

“…37 Previous studies have suggested that, when prandial coverage becomes necessary, physician-led stepwise addition and titration of bolus insulin doses is an effective way to intensify basal-only insulin therapy, and that the additional boluses can be added to meals based on the estimated size of the meal. [42][43][44][45][46][47] FullSTEP showed that stepwise treatment intensification, using patient-led dose titration under medical supervision and guidance, is noninferior to full basal-bolus therapy in terms of change in HbA 1c after 32 weeks, with less hypoglycaemia and greater patient satisfaction compared with full basal-bolus therapy (also using patient-led dose titration). 18 The easy-to-use '1-0-1' titration algorithm and straightforward approach may reduce the inertia toward treatment intensification that can occur in clinical practice.…”

“…[42][43][44][45][46][47] The implications of these studies are briefly discussed here, and are also considered in the primary FullSTEP study report. 18 In the 48-week Step-wise RCT, a bolus dose of insulin aspart was incrementally added to basal insulin detemir for each 12-week phase that ended in inadequate glycaemic control (HbA 1c ≥7.0 %).…”

Efficacy and safety of a premixed versus a basal-plus insulin regimen as intensification for type 2 diabetes by timing of the main meal

“…Several approaches are available for insulin intensification. These include adding a rapid-acting analogue to the regimen, administered before the main meal (usually the meal associated with the largest postprandial glycemic excursion or highest postprandial glucose level; 'basalplus' regimen), or switching to a premixed insulin analogue, which is administered two or three times a day [6][7][8][9][10][11][12][13][14][15][16] . Reasons for the preference for the basal-plus strategy include its perceived flexibility and the fact that insulin can be given with the main meal.…”

Similar glucose control with basal–bolus regimen of insulin detemir plus insulin aspart and thrice-daily biphasic insulin aspart 30 in insulin-naive patients with type 2 diabetes: Results of a 50-week randomized clinical trial of stepwise insulin intensification

“…challenge to both T2DM patients and their treating physicians [1][2][3]. Patients who are unable to achieve HbA 1c targets, regardless of insulin initiation, require more intensified regimens.…”

“…The guidelines consider single-dose basal insulin a suitable strategy to begin with. Alternatively, one of the most widely used options is to start with twice-daily premixed insulin [1]. However, some patients may still not achieve their HbA 1c goals despite up-titration of insulin or, sometimes, titration may become difficult due to ensuing hypoglycaemia.…”