Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis

Abstract

ObjectiveTo compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).DesignThis was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO.Outcome measuresChanges in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.Results41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: −0.08; 95% credible interval (CrI): −0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; −0.28 to 0.32), degludec (−0.12; −0.42 to 0.20) and premixed insulin (0.26; −0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; −0.31 to 1.71), NPH (−0.76; −1.75 to 0.21) and degludec (−0.63; −1.63 to 0.35), but significantly lower compared with premixed insulin (−1.83; −2.85 to −0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings.ConclusionsNMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.

A comparative effectiveness study of degludec and insulin glargine 300 U/mL in insulin‐naïve patients with type 2 diabetes

“…22 Given the differences in the rates of hypoglycaemia between degludec and glargine U300 treatment, it might be anticipated that this may lead to changes in prescribing, as there was a shift previously towards the use of the longer-acting insulins (glargine U100 and IDet) 28 that had lower rates of hypoglycaemia compared with their predecessors. [11][12][13][14][15][16][17][18] Such a prediction is further supported by our finding that patients treated with degludec were less likely to discontinue treatment than were patients treated with glargine U300 and, furthermore, were less likely to switch to the other treatment if discontinuing, suggesting a greater likelihood of clinical success with degludec vs glargine U300.…”

“…10 The two most recently developed basal insulins, insulin degludec (degludec) and insulin glargine 300 units/mL (glargine U300) are longer acting than first-generation basal insulin analogues (glargine 100 units/mL [glargine U100] and insulin detemir [IDet]), and these longer acting insulins have been proven to lower the risk of hypoglycaemia further still. [11][12][13][14][15][16][17][18] Despite results from both the DELIVER D+ study 19 and the BRIGHT randomized controlled trial (RCT) 20 comparing use of degludec with glargine U300, there is presently no evidence from realworld clinical practice with insulin-naïve patients that indicates a clinical advantage of degludec vs glargine U300, or vice versa. This situation, insulin-naïve patients for whom real-world data are missing, is a gap that should be bridged.…”

Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus

“…Outcome measures by network meta-analysis included changes from baseline in HbA 1c (%) and body weight (kg), and rates of documented symptomatic and/or nocturnal hypoglycemic events (per patient-year). Overall, glycemic efficacy of Gla-300 was similar to other insulins, including detemir, NPH, degludec, and premixed insulin 54. Change in body weight was comparable with Gla-300 vs detemir, NPH, and degludec (small weight increases), while weight gain with Gla-300 was significantly less than with premixed insulin.…”

rDNA insulin glargine U300 – a critical appraisal

“…However, a network meta-analysis comparing Gla-300 to degludec and other basal insulins suggests that Gla-300 exhibits comparable glycemic control, with a significantly lower risk of hypoglycemic events vs NPH, biosimilar glargine, and premixed insulin 47. There are very limited patient-oriented outcome data for the effects of Gla-300 on macrovascular or microvascular outcomes, and very limited long-term safety data for the 300 U/mL insulin glargine strength specifically.…”

“…Six-month45 and 1-year46 post hoc head-to-head comparisons of Gla-300 vs Gla-100 pooled from three randomized controlled trials (RCTs; EDITION 1, 2, and 3) in T2DM (Table 3), and an indirect head-to-head analysis comparing the efficacy and safety of Gla-300 vs other basal insulin therapies for the treatment of T2DM (that included Gla-100, biosimilar glargine, detemir, degludec, NPH, and premixed insulin) has become available 47…”