iGlarLixi provides a higher derived time-in-range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis

Aim

To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose.

Methods

Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated.

Results

The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD₁: 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD₂: 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi.

Conclusion

iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D.     

Lower risk of severe hypoglycaemia with insulin glargine 300 U/mL versus glargine 100 U/mL in participants with type 1 diabetes: A meta-analysis of 6-month phase 3 clinical trials

Severe hypoglycaemia (SH) remains a challenge to people with type 1 diabetes (T1DM), and new-generation basal insulins may improve patient outcomes. This post hoc meta-analysis explored the risk of SH with insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in a pooled population with T1DM from three randomized, multicentre, 6-month similarly designed phase 3 trials: EDITION 4, EDITION JP 1 and EDITION JUNIOR. Endpoints included incidence and time to first occurrence of SH. Among 629 and 626 participants randomized to Gla-300 and Gla-100, respectively, glycated haemoglobin reductions were similar. Fewer participants experienced ≥1 SH event with Gla-300 (6.2%) than with Gla-100 (9.3%). From baseline to month 6, the risk of a first SH event was lower with Gla-300: hazard ratio 0.65 [95% confidence interval (CI) 0.44–0.98; stratified log-rank test P = 0.038]. SH event rates were numerically lower with Gla-300 versus Gla-100 from baseline to month 6 [relative risk (RR) 0.80 (95% CI 0.49–1.29); P = 0.356] and baseline to week 8 [RR 0.73 (95% CI 0.37–1.44); P = 0.369]. Thus, Gla-300 demonstrated similar glycaemic control with lower risk of SH versus Gla-100, particularly during the titration period.     

Hypoglycaemia risk with insulin glargine 300 U/mL compared with glargine 100 U/mL across different baseline fasting C-peptide levels in insulin-naïve people with type 2 diabetes: A post hoc analysis of the EDITION 3 trial

The relationship between baseline fasting C-peptide (FCP) and glucose control was examined in insulin-naïve people with type 2 diabetes inadequately controlled with oral antihyperglycaemic drugs commencing basal insulin glargine 300 U/mL (Gla-300) or 100 U/mL (Gla-100) in the absence of sulfonylurea/glinides. Participants with FCP measurement from the EDITION 3 trial (n = 867) were stratified according to baseline FCP (≤0.40, >0.40-1.20, >1.20 nmol/L); 11.0%, 70.9% and 18.1% contributed to each group. Glycaemic control, body weight, insulin dose and hypoglycaemia were determined at 26 weeks. Glycaemic control (HbA1c, FPG) at 26 weeks was similar in each FCP group between insulins. However, end-of-study insulin dose was greater with higher FCP for both insulins. More people with lower baseline FCP experienced hypoglycaemia with both insulins, but with numerically lower incidence for Gla-300 versus Gla-100 across all FCP groups for all definitions (time periods and levels) of hypoglycaemia. This suggests that Gla-300 might be particularly advantageous for people who are at higher risk of hypoglycaemia.     

How many people with type 2 diabetes fulfil the eligibility criteria for randomized,controlled trials of insulin glargine 300 U/mL in a real-world setting?

Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed the real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the United States, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2 and 3 (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs. insulin degludec) RCTs, we observed that only 17% (33 345/191 218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36 285/235 697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24 547) would have been eligible for the CONCLUDE (insulin degludec vs. Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs.     

Glycaemic control and hypoglycaemia risk with insulin glargine 300 U/mL versus glargine 100 U/mL: A patient-level meta-analysis examining older and younger adults with type 2 diabetes

AimOlder people with type 2 diabetes (T2DM) are at an increased risk of hypoglycaemia and its consequences. However, efficacy and safety data for basal insulin therapy are limited in these individuals. This patient-level meta-analysis assessed the treatment effects of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with T2DM ≥ 65 years old.MethodsData were pooled for patients randomised to receive Gla-300 or Gla-100 in the Phase 3a, treat-to-target EDITION 1, 2 and 3 trials. Glycaemic efficacy, hypoglycaemia, changes in body weight and insulin dosage and adverse events were examined over 6 months’ treatment with Gla-300 versus Gla-100 for participants aged ≥ 65 and < 65 years.ResultsOf 2496 participants randomised, 662 were ≥ 65 years (Gla-300, n = 329; Gla-100, n = 333). Glycaemic control was comparable for Gla-300 and Gla-100 in participants ≥ 65 years (LS mean [95% CI] difference in HbA_1c change from baseline to month 6: 0.00 [−0.14 to 0.15] %; 0.00 [−1.53 to 1.64] mmol/mol) and < 65 years (0.00 [−0.09 to 0.08] %; 0.00 [−0.98 to 0.87] mmol/mol). Fewer participants receiving Gla-300 versus Gla-100 experienced nocturnal confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemia (relative risk: ≥ 65 years: 0.70 [0.57 to 0.85]; < 65 years: 0.77 [0.68 to 0.87]). Annualised rates of nocturnal confirmed or severe hypoglycaemia were lower with Gla-300 than Gla-100 for both age groups.ConclusionGla-300 was associated with a reduced risk of nocturnal hypoglycaemia versus Gla-100, accompanied by comparable glycaemic improvement, for people aged ≥ 65 and < 65 years with T2DM.     

Insulin glargine 300 units/mL for the treatment of individuals with type 2 diabetes in the real world: A review of the DELIVER programme

Evidence from randomized controlled trials (RCTs) has shown that second-generation basal insulin (BI) analogues, insulin glargine 300 U/mL (Gla-300) and insulin degludec (IDeg), provide similar glycaemic control, with a lower risk of hypoglycaemia compared with the first-generation BI analogue insulin glargine 100 U/mL (Gla-100) in people with type 2 diabetes (T2D). However, the highly selected participants and frequent follow-up of RCTs may not be truly representative of real-life clinical practice. It is important to assess the safety and effectiveness of these second-generation BI analogues in real-life clinical practice settings. The DELIVER programme utilized electronic healthcare records from the United States to compare clinical outcomes in people with T2D who received either Gla-300 or other BI analogues in real-world clinical practice. This review provides a concise overview of the results of the DELIVER studies. Overall, Gla-300 provided similar antihyperglycaemic effectiveness and a lower risk of hypoglycaemia versus the first-generation BI analogues Gla-100 and insulin detemir in people with T2D who had switched BIs. In those who were insulin-naïve, initiation with Gla-300 versus Gla-100 was associated with significantly better antihyperglycaemic effectiveness and similar or lower hypoglycaemic risk. Both glycaemic control and hypoglycaemia risk were also shown to be similar with Gla-300 and IDeg, in people who had switched BIs and in those who were insulin-naïve. In addition, the DELIVER 2 study reported that people with T2D who switched to Gla-300 had reduced healthcare resource utilization, with an overall saving of US$1439 per person per year compared with those who switched to another BI analogue. Overall, the real-world DELIVER programme showed that the glycaemic control with a low risk of hypoglycaemia observed with Gla-300 in RCTs was also seen in standard clinical practice.     

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in insulin-naïve people with type 2 diabetes: 12-month results from the EDITION 3 trial

AimTo explore if efficacy and safety findings for insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100), observed over 6 months in insulin-naïve people with type 2 diabetes, are maintained after 12 months.MethodsEDITION 3 was a phase 3a, randomized, multicentre, open-label, parallel-group, treat-to-target study of once-daily Gla-300 versus Gla-100 (target fasting self-monitored plasma glucose, 4.4–5.6 mmol/L [80–100 mg/dL]). Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin.ResultsOf 878 participants randomized, 337/439 (77%) and 314/439 (72%) assigned to Gla-300 and Gla-100, respectively, completed 12 months of treatment. Improved glycaemic control was sustained until 12 months in both treatment groups, with similar reductions in HbA_1c from baseline to month 12 (difference: −0.08 [95% confidence interval (CI): −0.23 to 0.07] % or −0.9 [−2.5 to 0.8] mmol/mol). Relative risk of experiencing ≥ 1 confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemic event with Gla-300 versus Gla-100 was 0.86 (95% CI: 0.69 to 1.07) at night and 0.92 (0.82 to 1.03) at any time of day. For events with a glycaemic threshold of < 3.0 mmol/L (< 54 mg/dL) these numbers were 0.76 (0.49 to 1.19) and 0.66 (0.50 to 0.88). A similar pattern was seen for documented symptomatic events. No between-group differences in adverse events were identified.ConclusionOver 12 months, Gla-300 treatment was as effective as Gla-100 in reducing HbA_1c in insulin-naïve people with type 2 diabetes, with lower overall risk of hypoglycaemia at the < 3.0 mmol/L threshold.