Efficacy and safety of insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Asia Pacific insulin‐naïve people with type 2 diabetes: The EDITION AP randomized controlled trial

Abstract

Aim To compare the efficacy and safety of Gla‐300 versus Gla‐100 in insulin‐naïve people with type 2 diabetes in Asia Pacific. Materials and Methods In this open‐label, randomized, active‐controlled, 26‐week study, insulin‐naïve participants with type 2 diabetes inadequately controlled with non‐insulin antihyperglycaemic drugs were randomized (2:1) to Gla‐300 or Gla‐100. The initial daily dose of basal insulin was 0.2 U/kg and was adjusted at least weekly for 8–12 weeks to a target fasting self‐monitored plasma glucose (SMPG) of 4.4–5.6 mmol/L. Results Of the 604 participants randomized, 570 (Gla‐300, n = 375; Gla‐100, n = 195) completed the study. Non‐inferiority of Gla‐300 versus Gla‐100 in HbA1c reduction from baseline to week 26 was confirmed. In the Gla‐300 and Gla‐100 groups, 51.1% and 52.2% of participants achieved the HbA1c target of <7.0% (rate ratio [95% CI]: 0.98 [0.84 to 1.14]) and 19.1% and 21.9% achieved the target without hypoglycaemia during the last 12 weeks of treatment (rate ratio [95% CI]: 0.87 [0.63 to 1.20]). Changes in fasting plasma glucose and 24‐hour average eight‐point SMPG were comparable between groups. Incidence of hypoglycaemia at any time of day was similar between treatment groups at week 26, but incidence of any nocturnal hypoglycaemia was numerically lower with Gla‐300 than Gla‐100 over the initial 12‐week titration period and 26‐week on‐treatment period. Rates of adverse events were similar between groups and low for serious adverse events. Conclusions Glycaemic control of Gla‐300 is non‐inferior to Gla‐100 with a similar or lower incidence and proportion of hypoglycaemia in people with type 2 diabetes in Asia Pacific, reinforcing the results in the global EDITION programme.

Glycemic Variability and Time in Range During Self-titration of Once Daily Insulin Glargine 300 U/ml Versus Neutral Protamine Hagedorn Insulin in Insulin-naïve Chinese Type 2 Diabetes Patients

“…As expected, Gla-300 was associated with lower rates of hypoglycemia compared with NPH insulin. Our findings are consistent with previous results in the EDITION trials in T2D patients where Gla-300 consistently reduced nocturnal hypoglycemia compared with Gla-100 with no differences in HbA1c [ 2 , 3 ]. With comparable HbA1c and FPG achieved between treatment groups, there were notable differences in GV and TIR between the Gla-300 and NPH groups that varied by time of day.…”

“…In the NPH group, up-titration of insulin was frequently limited by hypoglycemia. The overall basal insulin requirements were lower in this trial compared with Caucasians and could be linked to ethnic differences, as has been observed in lower dose requirements in phase 3 trials of Gla-300 in Asians in a physician-titrated setting [ 3 ]. Due to ethnic differences in basal insulin requirements, our self-titration regime was designed to be less aggressive, titrating by 1 IU weekly compared with other studies where insulin was titrated every few days [ 6 ].…”

“…In phase 3 studies in insulin-naïve type 2 diabetes (T2D) patients, Gla-300 was associated with non-inferior glucose control compared with insulin glargine 100 U/ml (Gla-100) with a lower risk of nocturnal hypoglycemia [2]. These observations also extended to East Asians [3]. Use of Gla-300 resulted in similar glycemic control but lower risk of hypoglycemia when compared against another second-generation insulin analogue (insulin degludec) particularly in the initial titration period in insulin-naïve patients with T2D [4].…”

Reduced Hypoglycemia Risk in Type 2 Diabetes Patients Switched to/Initiating Insulin Glargine 300 vs 100 U/ml: A European Real-World Study

“…Our outcomes data are generally in line with those from the EDITION series of RCTs comparing Gla-300 and Gla-100. In the EDITION T2D studies, Gla-300 and Gla-100 were found to achieve similar glycemic control, but Gla-300 was associated with improvements in some hypoglycemia end points in insulin-experienced patients treated with basal-bolus therapy [ 5 ] or oral + basal therapy [ 6 , 7 ] and in insulin-naïve patients [ 8 , 9 ].…”

“…A second-generation basal insulin analog (BIA), insulin glargine 300 U/ml (Gla-300), has been associated with significant reductions in some hypoglycemia outcomes (and comparable improvements in glycemic control) in randomized controlled trials (RCTs) in patients with T2D vs. the first-generation BIA, insulin glargine 100 U/ml (Gla-100) [ 5 – 9 ], which has been confirmed in recent trial-level [ 10 ] and patient-level [ 11 , 12 ] meta-analyses. This advantage is likely due to Gla-300’s improved pharmacokinetic/pharmacodynamic (PK/PD) profile, longer half-life, and more stable bioavailability [ 13 – 15 ].…”