Comparison between a basal‐bolus and a premixed insulin regimen in individuals with type 2 diabetes–results of the GINGER study

Abstract

Aim:To compare the efficacy and safety of an intensified insulin regimen, using insulin glargine (glargine) once daily and pre-meal insulin glulisine (glulisine) (basal-bolus), with a conventional therapy, using premixed insulin (premix) twice daily. Methods:This 52-week, open-label, randomized, multinational, multicentre trial included 310 subjects with type 2 diabetes (T2D) on premix, with or without metformin, who were randomized to a basal-bolus regimen with glargine and glulisine (n = 153; mean ± s.d. age 60.2 ± 7.5 years; HbA1c 8.6 ± 0.8%; weight 87.0 ± 15.1 kg; T2D duration 12.8 ± 5.8 years) or twice-daily premix (n = 157; age 60.9 ± 7.8 years; HbA1c 8.5 ± 0.9%; weight 84.3 ± 15.0 kg; T2D duration 12.5 ± 6.8 years). The primary endpoint was change in HbA1c from baseline to endpoint. Results:Mean decrease in baseline-to-endpoint HbA1c for basal-bolus vs. premix was −1.31 vs. −0.80% (difference: −0.476%; 95% Cl: −0.714, −0.238; p = 0.0001, ANCOVA). More subjects reached HbA1c ≤7.0% in the basal-bolus group than in the premix group [68 (46.6%) vs. 43 (27.9%); p = 0.0004], while they also experienced significantly lower mean ± s.d. daytime (−2.7 ± 2.3 vs. −2.3 ± 2.5 mmol/l; p = 0.0033) and postprandial (−3.1 ± 2.6 vs. −2.5 ± 2.8 mmol/l; p < 0.0001) blood glucose. Endpoint daily insulin doses were 98.0 ± 48.7 vs. 91.3 ± 44.3 IU (p = 0.2104); mean weight gain was +3.6 ± 4.0 vs. +2.2 ± 4.5 kg (p = 0.0073). Mean number of overall hypoglycaemic events with basal-bolus and premix was 13.99 and 18.54 events/patient year, respectively (difference: −3.90; 95% CI: −10.40, 2.60; p = 0.2385). Conclusions:An intensified basal-bolus regimen using glargine/glulisine results in a significantly superior glycaemic control vs. premix therapy in a population with long-standing insulin-treated T2D, with no increase in the rates of hypoglycaemia.

Incidence of Hypoglycaemia in Patients with Type 2 Diabetes – A Subgroup Analysis from the GINGER study

“…The demographics and baseline characteristics of the two groups were well matched. 3 The glargine plus glulisine group had a greater change from baseline in both groups (data not shown).…”

“…3 In this post-hoc analysis of the GINGER study, actual rates of overall hypoglycaemia were determined as a function of endpoint HbA1c for patients in each of the two groups. Using a negative binomial regression model, 4 the predicted rates for the basal-bolus group were compared with those of the overall premixed insulin group.…”

“…3 The primary endpoint of the GINGER study was the change in HbA1c from baseline to endpoint. Secondary endpoints included the rate of hypoglycaemia.…”

Efficacy of switching from premixed insulin to insulin glargine regimen in Type 2 diabetes mellitus patients with different islet functions

“…Currently, ~80% of patients with T2DM receive premixed insulin and insulin analogues in the form of two subcutaneous injections, one in the morning and the other in the evening, and a number of clinical studies have proven the effectiveness of such regimen on glycaemic control (4)(5)(6)(7)(8)(9). This is a simplified approach in DM treatment, which minimizes the number of injections patients must receive daily.…”

“…This is a simplified approach in DM treatment, which minimizes the number of injections patients must receive daily. However, it is limited by its fixed ratio, which does not fulfil normal physiological needs or provide enough flexibility, and it is associated with increasing the risk of hypoglycaemia (4,8). The key application of premixed insulin enabling regular monitoring of blood glucose, which allegedly establishes good glycaemic control.…”