Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24‐week, randomized, open‐label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape)

Abstract

In long-standing type 2 diabetes with suboptimal glycaemia despite oral therapies and basal insulin, the basal plus regimen was non-inferior to biphasic insulin for biomedical outcomes, with a similar overall hypoglycaemia rate but more nocturnal events.

Premixed insulin regimens for type 2 diabetes

“…Similarly, the recently published GALAPA-GOS study demonstrated that in insulin-naive patients, premixed insulin once or twice daily reduced HbA 1c by a further 0.16 % (confidence interval 0.04 to 0.27) compared with insulin glargine with or without insulin glulisine [10]. Finally, in a subgroup analysis in insulin-naïve patients, premixed regimen had no difference with basal-bolus regimens (-0.15 %; -0.52 to 0.22) [11].For patients already on basal insulin, results from the LanScape study suggested that basal-plus regimens (glargine plus insulin glulisine once daily) are non-inferior to premixed insulin (biphasic insulin aspart 30 twice daily) in reducing HbA 1c [12]. However, a recent meta-analysis by Wang et al concluded that basal-bolus regimens have superior glycemic efficacy to premix insulin in non-insulinnaïve patients (-0.22 %; -0.42 to -0.02) [11].…”

“…Similarly, body weight increase in insulin-naive patients in the GALA-PAGOS trial was comparable between those randomized to insulin glargine with or without insulin glulisine once daily and those treated with a premixed insulin regimen once or twice daily (LS mean difference -0.3 kg; p = 0.12) [10]. Likewise, in the LanScape trial, there was no difference in weight gain between basal-plus and biphasic insulin regimens (-0.44 kg; -1.12 to 0.23) in patients inadequately controlled on basal insulin and oral antidiabetic agents [12]. These results are verified in the meta-analysis by Giugliano et al including both insulin-naive patients and patients already on insulin, verifying the lack of any significant difference in body weight change between premixed insulin and basal-bolus regimens based on results from nine studies (-0.21 kg; -0.61 to 0.19) [7].…”

“…However, data from the GALAPAGOS study which was not included in the aforementioned meta-analysis suggest that, in insulin-naïve patients, biphasic insulin aspart 30 is associated with an increased risk both for overall or nocturnal symptomatic hypoglycemia compared with basal insulin or a basal-plus regimen (22 vs. 35.2 % and 7.3 vs. 18.7 %, respectively) [10]. On the contrary, results from an RCT in patients already treated with basal insulin showed no difference in the incidence rate of any hypoglycemia between basal-plus and premixed insulin regimens (estimated rate ratio 0.84; 0.64-1.11) [12]. This result was corroborated by the latest meta-analysis by Giugliano et al supporting there is no difference in the event rate for overall hypoglycemia between basal-bolus and premixed insulin regimens (0.16 episode/patient/year; -2.07 to 2.38), based on data from nine studies assessing variable insulin dosing schemes [7].…”

“…For patients already on basal insulin, results from the LanScape study suggested that basal-plus regimens (glargine plus insulin glulisine once daily) are non-inferior to premixed insulin (biphasic insulin aspart 30 twice daily) in reducing HbA 1c [12]. However, a recent meta-analysis by Wang et al concluded that basal-bolus regimens have superior glycemic efficacy to premix insulin in non-insulinnaïve patients (-0.22 %; -0.42 to -0.02) [11].…”

Comment on American Diabetes Association. Approaches to Glycemic Treatment. Sec. 7. In Standards of Medical Care in Diabetes—2016. Diabetes Care 2016;39(Suppl. 1):S52–S59

“…23 in Eng et al [3]) demonstrated the superiority of basal insulin plus GLP-1-RA. At least two recent randomized controlled trials (4,5) had the specific aim to compare a basal-plus regimen with a twice-daily premixed insulin regimen in long-standing type 2 diabetes with suboptimal glycemia despite oral therapies and basal insulin: the basal-plus regimen was found to be noninferior (5) or inferior (4) to a premixed regimen in terms of reduction of HbA 1c and was associated with more nocturnal hypoglycemic events (5). The evidence so far produced indicates that the three options are at least equally effective and should have the same scientific dignity.…”