Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial.

Abstract

OBJECTIVE:

This phase 3 confirmatory diabetes mellitus treatment study compared the safety and efficacy of Rapilin and NovoRapid insulin asparts in combination with metformin.

METHODS:

This 24-week, open-label, randomized, active-controlled, noninferiority phase 3 confirmatory study conducted across centers in China aimed to enroll patients with type 2 diabetes mellitus and blood sugar glucose inadequately controlled by oral antidiabetic drugs. Randomized patients received subcutaneous mealtime Rapilin or NovoRapid (3:1) injections, with metformin. The primary objectives were to demonstrate noninferiority (margin of 0.4%) in HbA1c change from baseline and compare safety profiles of Rapilin versus NovoRapid after 24 weeks. Secondary outcomes included 2-h postprandial plasma glucose (PPG), fasting plasma glucose (FPG), and patients achieving HbA1c <7.0% and ≤6.5%.

RESULTS:

590 patients with type 2 diabetes mellitus were randomized to Rapilin (n = 441) and NovoRapid (n = 149) groups. After 24 weeks, the mean HbA1c change from baseline was -2.20% (Rapilin) and -2.32% (NovoRapid); the estimated treatment difference based on least-square means was 0.04% (95% CI: -0.17, 0.26), meeting the noninferiority criteria for Rapilin versus NovoRapid. Comparable improvements were reported for mean 2-hour PPG (6.14 and 6.29 mmol/L), FPG (2.02 and 1.70 mmol/L), and patients with HbA1c <7.0% (52.6% and 51.0%) and ≤6.5% (34.2% and 30.9%), in the Rapilin and NovoRapid groups, respectively, with no significant safety or immunogenicity outcome differences.

CONCLUSIONS:

Rapilin demonstrated non-inferior glycemic control, and matching safety and immunogenicity to NovoRapid in patients with type 2 diabetes mellitus also receiving metformin over 24 weeks.

TRIAL REGISTRATION:

ChiCTR20003129041.

• Authors: Jun Yao, Xiaohui Guo, Li Sun, Ping Han, Xiaofeng Lv, Xiuzhen Zhang, Zhaohui Mo, Wenying Yang, Lihui Zhang, Zhanjian Wang, Lvyun Zhu, Quanmin Li, Tao Yang, Wenbo Wang, Yaoming Xue, Yongquan Shi, Juming Lu, Yongde Peng, Fan Zhang, Dewen Yan, Damei Wang, Xuefeng Yu
• Journal: Current medical research and opinion (Curr Med Res Opin) Vol. 38 Issue 11 Pg. 1797-1806 (11 2022) ISSN: 1473-4877 [Electronic] England
• PMID: 35833285 (Publication Type: Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase III, Journal Article)

Chemical References

• Insulin Aspart
• Metformin
• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents

Topics

• Humans
• Insulin Aspart (adverse effects)
• Metformin (adverse effects)
• Blood Glucose
• Glycated Hemoglobin (analysis)
• Diabetes Mellitus, Type 2 (drug therapy)
• Hypoglycemia (chemically induced)
• Hypoglycemic Agents (adverse effects)
• Treatment Outcome
• Drug Therapy, Combination