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

Abstract

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.

Comparative Effectiveness of Switching From First-Generation Basal Insulin to Glargine 300 U/ml or Degludec 100 U/ml in Type 1 Diabetes: The RESTORE-1 Study

“…As for safety the reduction in the proportions of patients with at least one hypoglycemic event and in the incidence rates of hypoglycemia (BG B 70 mg/dl and \ 54 mg/dl) during 6 months in both groups documents that the switch from 1BI to a 2BI is safe. A recent meta-analysis in T1D demonstrated similar glycemic control with lower risk of severe hypoglycemia of Gla-300 versus Gla-100, particularly during the titration period [37].…”

Clinical research of insulin glargine U300 in type 1 diabetes mellitus patients with frequent hypoglycaemia: real-world experience

“…Taken together, these findings indicate that although a minimal increase occurred in the insulin dosages of the patients, a reduction occurred in the frequency of hypoglycaemia. Previous randomized open-label studies reported that although switching to IGlar U300 led to a significant reduction in the frequency of hypoglycaemia, it provided suboptimal blood glucose control [11,12]. In the Edition 4 study, which included 274 patients randomized to Gla-300 and 275 to Gla-100, and a patient follow-up of 6 months, the change in HbA 1c was equivalent in the 2 treatment groups (difference 0.04%, 95% CI: -0.10 to 0.19) (0.4 mmol/mol, -1.1 to 2.1), Percentage and Gla-300 was thus deemed noninferior.…”

“…Moreover, IGlar U300 provides more steady-state pharmacokinetics (PK) and pharmacodynamics (PD) profiles and a longer duration of action than IGlar U100, extending blood glucose control well beyond 24 h [ 10 ]. On the other hand, IGlar U300 has been shown to be as effective for glycaemic control as IGlar U100 in patients with long-term T1DM and to have a lower risk of hypoglycaemia and weight gain than IGlar U100 [ 11 , 12 ]. In a retrospective trial (SPARTA), IGlar U300 reduced the incidence of hypoglycaemic events while providing better blood glucose control [ 13 ].…”

New Insulins, Biosimilars, and Insulin Therapy

“…Risk of hypoglycaemia with insulin degludec versus insulin glargine U300 in insulin-treated patients with type 2 diabetes: the randomised, head-to-head CONCLUDE trial Philis-Tsimikas A 1 , Klonoff DC 2 , Khunti K 3 , Bajaj HS 4 , Leiter LA 5 , Hansen MV 6 , Troelsen LN 6 , Ladelund S 6 , Heller S 7 , Pieber TR 8 , on behalf of the CONCLUDE Study Group 1 Scripps Whittier Diabetes Institute, San Diego, CA; 2 Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA; 3 Diabetes Research Centre, University of Leicester, Leicester, UK; 4 LMC Diabetes and Endocrinology, Brampton, ON, Canada; 5 Li Ka Shing Knowledge Institute, Division of Endocrinology & Metabolism, St Michael's Hospital, University of Toronto, ON, Canada; 6 Novo Nordisk A/S, Søborg, Denmark; 7 Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Sheffield, UK; 8 Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria Diabetologia 2020; 63: 698-710…”