Insulin glargine 300 U/mL versus first‐generation basal insulin analogues in insulin‐naïve adults with type 2 diabetes: 12‐month outcomes of ACHIEVE Control, a prospective, randomized, pragmatic real‐life clinical trial

Abstract

Aim: To report the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) versus standard-of-care basal insulin analogues (SOC-BI) at 12 months in the ACHIEVE Control trial, which is a prospective pragmatic randomized real-life study in insulin-naïve adults with type 2 diabetes (T2D). Methods: A total of 3304 insulin-naïve adults with T2D and glycated haemoglobin (HbA1c) concentration of 64 to 97 mmol/mol (8.0% to 11.0%) after ≥1 year of treatment with two or more antihyperglycaemic agents were randomized to Gla-300 or SOC-BI. Key secondary endpoints included HbA1c target attainment without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at 12 months. Results: At 12 months, 26.1% (Gla-300) and 23.7% (SOC-BI) of adults achieved HbA1c targets without documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.97-1.35); 33.0% and 29.5%, respectively, achieved HbA1c targets without documented symptomatic (<3.0 mmol/L [<54 mg/dL]) or severe hypoglycaemia (OR 1.19, 95% CI 1.02-1.38). The OR for HbA1c target achievement was 1.15 (95% CI 0.99-1.34), and favoured Gla-300 versus SOC-BI for absence of documented symptomatic or severe hypoglycaemia at 12 months for both ≤3.9 mmol/L (≤70 mg/dL; OR 1.21, 95% CI 1.05-1.40) and < 3.0 mmol/L (<54 mg/dL; OR 1.26, 95% CI 1.07-1.48). Conclusion: Gla-300 tended to be associated with lower hypoglycaemia risk than SOC-BI in real-world clinical practice during the 12-month follow-up.

A pragmatic randomized clinical trial of insulin glargine 300 U/mL vs first‐generation basal insulin analogues in insulin‐naïve adults with type 2 diabetes: 6‐month outcomes of the ACHIEVE Control study

“…Participation in PSPs was higher in the Gla-300 group than in the SOC-BI group (20.2% vs 8.9%), but this did not appear to influence achievement of the primary endpoint; additional analyses on the impact of PSP participation are described in the companion paper reporting the 12-month results of ACHIEVE Control. 29 Lastly, the cost of the BI analogues for both treatment arms was covered by the sponsor, which does not mirror real-world practice in the United States and Canada. While this limits the generalizability of the results, any effects should have been similar in both treatment arms.…”

“…Participation in PSPs was higher in the Gla‐300 group than in the SOC‐BI group (20.2% vs 8.9%), but this did not appear to influence achievement of the primary endpoint; additional analyses on the impact of PSP participation are described in the companion paper reporting the 12‐month results of ACHIEVE Control 29 …”

“…Regarding the two main protocol amendments, the addition of a blinded interim efficacy analysis should not have affected the outcome of the study, as care was taken to preserve the integrity of the data and the statistical analysis. The inclusion of severe hypoglycaemia would have increased the number of hypoglycaemia events for both groups similarly.Participation in PSPs was higher in the Gla-300 group than in the SOC-BI group (20.2% vs 8.9%), but this did not appear to influence achievement of the primary endpoint; additional analyses on the impact of PSP participation are described in the companion paper reporting the 12-month results of ACHIEVE Control 29. Lastly, the cost of the BI analogues for both treatment arms wascovered by the sponsor, which does not mirror real-world practice in the United States and Canada.…”

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

“…This highlights that real-world behaviour may differ substantially from that seen in a classical RCT, which should be considered when assessing results from RWE studies. 31,32 Further attempts to improve the quality of RWE include designing such studies with the same methodological rigour as RCTs, including detailed study protocols and statistical analysis plans, and comprehensive reporting of data sources, data ranges, exclusion criteria, care setting exposure to study drugs, outcomes, attrition and analytical strategies. 24,33 In addition, the validity of RWE would be further supported if consistency can be shown across studies utilizing similar data sources (e.g.…”

“…Pragmatic randomized studies can preserve the internal validity of RCTs while providing RWE from usual clinical practice 23 . Such studies include the ACHIEVE, REACH and REGAIN pragmatic real‐world studies of the effectiveness and safety of Gla‐300 31,32 . However, while findings from the 12‐month ACHIEVE study suggested lower hypoglycaemia risk with Gla‐300 than with standard of care BI, comparison of outcomes between treatment arms in the REACH and REGAIN studies was limited by suboptimal insulin dose titration.…”