Insulin Degludec Versus Insulin Glargine in Type 1 and Type 2 Diabetes Mellitus: A Meta-Analysis of Endpoints in Phase 3a Trials

Abstract

IntroductionInsulin degludec (degludec) is a basal insulin with an ultra-long, stable action profile and reduced pharmacodynamic variability. Seven phase 3a trials compared degludec with insulin glargine (glargine). Patient-level meta-analyses were performed to obtain a comprehensive overview of differences between the insulin preparations, possible because consistent outcome definitions were utilized.MethodsThree categories of trials were analyzed: basal–bolus-treated type 1 diabetes mellitus (T1DMB/B), insulin-naïve type 2 diabetes mellitus (T2DMinsulin-naïve), and basal–bolus-treated T2DM (T2DMB/B). Regression models were adjusted for baseline characteristics. Endpoints analyzed were glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), insulin dose and hypoglycemic rates analyzed in mutually exclusive groups: non-severe nocturnal, non-severe daytime, and severe.ResultsAs with previous treat-to-target trials, reductions in HbA1c were similar between degludec and glargine. Reductions in FPG were significantly greater with degludec in T1DMB/B and T2DMinsulin-naïve. Total daily insulin dose was significantly lower with degludec in T1DMB/B and T2DMinsulin-naïve. Estimated hypoglycemia rate ratios for degludec/glargine were as follows for T1DMB/B, T2DMinsulin-naïve and T2DMB/B, respectively: non-severe nocturnal 0.83, 0.64, 0.75 (all P < 0.05); non-severe daytime 1.14 [not significant (ns)], 0.89 (ns), and 0.83 (P < 0.05). Rate ratios for severe events were 1.12 (ns) (T1DMB/B); 0.14 (P < 0.05) (T2DMinsulin-naïve); and not analyzed (T2DMB/B) due to too few events.ConclusionsCompared with glargine, degludec is associated with equivalent HbA1c control and significantly lower nocturnal hypoglycemia rates. In T1DMB/B and T2DMinsulin-naïve, degludec is also associated with significantly greater reductions in FPG and lower total doses of insulin versus glargine.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0076-9) contains supplementary material, which is available to authorized users.

Randomized Clinical Trial Comparing Basal Insulin Peglispro and Insulin Glargine in Patients With Type 2 Diabetes Previously Treated With Basal Insulin: IMAGINE 5

“…The superior HbA 1c reduction achieved with BIL is noteworthy, since noninferiority has usually been observed in basal insulin treat-to-target trials (16)(17)(18). The FSG levels in glargine-treated patients were well within ranges reported in many treat-to-target trials, whereas BILtreated patients had greater reduction in FSG compared with glargine (19)(20)(21).…”

Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials

“…This was directly investigated in two studies showing no significant difference in the rate of diurnal confirmed hypoglycaemia in patients with T1D or T2D [14,16]. Further meta-analyses confirmed that the reduction in nocturnal confirmed hypoglycaemia was not accompanied by increased rates of daytime confirmed hypoglycaemia in pooled T1D, pooled T2D and pooled insulin-naïve T2D [23]. The trial protocol for insulin-experienced patients required that those who were switching from twice-daily to once-daily insulin dosing administer their total pretrial basal insulin dose in the IDeg arm, but reduce the dose by 20-30% in the IGlar arm (as per the prescribing information).…”

Hypoglycemia with New Generation Basal Analog Insulins: A Descriptive Critical Review

“…A meta-analysis of results from phase 3 trials suggests that the efficacy, in terms of lowering glycated hemoglobin (A1C), of IDeg and Gla-100 was similar in patients with T2DM [45]. Hypoglycemia event outcomes with IDeg compared with Gla-100 have been reported from the BEGIN series of phase 3 trials, in which confirmed hypoglycemia was defined as a composite of episodes with a recorded self-monitored blood glucose (SMBG) value of less than ~54 mg/dl (3.1 mmol/l) and severe episodes were defined as those requiring assistance.…”

“…In their meta-analysis of phase 3 trials of IDeg versus Gla-100, Vora et al reported that the two agents had similar efficacy in terms of reduction of A1C in T1DM patients [45].…”