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

Objective: To 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).

Design: This 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 measures: Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.

Results: 41 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; 0.19 to 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.

Conclusions: NMA 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.

Keywords: DIABETES & ENDOCRINOLOGY.

Figure 1

(A) PRISMA flow diagram for studies comparing basal insulin therapies in type 2 diabetes mellitus (T2DM; N=41). ^aCochrane Library (eg, the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effectiveness (DARE)), MEDLINE and MEDLINE In-Process (using Ovid platform), Embase (using Ovid Platform) and PsycINFO; If applicable, relevant results from clinical trial registry were included. Zinman et al report 2 distinct studies within 1 publication. ^bFor title/abstract and full-text review, articles were excluded based on inclusion/exclusion criteria as specified in the systematic literature review. ^cTwo articles analysed the same trial. ^dConferences searched included EASD and ADA 2011–2013, and IDF 2011. IDF 2013 was assessed when the CD-ROM became available—the end of February. Multiple abstracts examined the same trial and 14 trials were extracted. ^eStudies must include at least two treatment arms in the network, including: U300, insulin glargine, insulin detemir, insulin NPH, insulin degludec and premix insulin. (B) Evidence network diagram for BOT studies (n=25) reporting HbA1c (%) change from baseline. Each insulin treatment is a node in the network. The links between the nodes represent direct comparisons. The numbers along the lines indicate the number of trials or pairs of trial arms for that link in the network. Reference numbers indicate the trials contributing to each link. BOT, basal insulin-supported oral therapy; HbA1c, glycated haemoglobin; NPH, neutral protamine Hagedorn.

Figure 2

NMA findings for Gla-300 versus other basal insulins in the BOT population: (A) change in HbA1c (%); (B) change in body weight (kg); (C) risk of nocturnal hypoglycaemia; (D) risk of documented symptomatic hypoglycaemia. BOT, basal insulin-supported oral therapy; CrI, credible interval; DET, =insulin detemir; DEG, insulin degludec; HbA1c, glycated haemoglobin; NMA, network meta-analysis; NPH, neutral protamine Hagedorn; PREMIX, premixed insulin; RR, risk ratio.

Figure 2

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