A Randomized Trial Evaluating the Efficacy and Safety of Fast-Acting Insulin Aspart Compared With Insulin Aspart, Both in Combination With Insulin Degludec With or Without Metformin, in Adults With Type 2 Diabetes (ONSET 9).

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp), both with insulin degludec with or without metformin, in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.

RESEARCH DESIGN AND METHODS:

This multicenter, double-blind, treat-to-target trial randomized participants to faster aspart (n = 546) or IAsp (n = 545). All available information, regardless of treatment discontinuation or use of ancillary treatment, was used for evaluation of effect.

RESULTS:

Noninferiority for the change from baseline in HbA1c 16 weeks after randomization (primary end point) was confirmed for faster aspart versus IAsp (estimated treatment difference [ETD] -0.04% [95% CI -0.11; 0.03]; -0.39 mmol/mol [-1.15; 0.37]; P < 0.001). Faster aspart was superior to IAsp for change from baseline in 1-h postprandial glucose (PPG) increment using a meal test (ETD -0.40 mmol/L [-0.66; -0.14]; -7.23 mg/dL [-11.92; -2.55]; P = 0.001 for superiority). Change from baseline in self-measured 1-h PPG increment for the mean over all meals favored faster aspart (ETD -0.25 mmol/L [-0.42; -0.09]); -4.58 mg/dL [-7.59; -1.57]; P = 0.003). The overall rate of treatment-emergent severe or blood glucose (BG)-confirmed hypoglycemia was statistically significantly lower for faster aspart versus IAsp (estimated treatment ratio 0.81 [95% CI 0.68; 0.97]).

CONCLUSIONS:

In combination with insulin degludec, faster aspart provided effective overall glycemic control, superior PPG control, and a lower rate of severe or BG-confirmed hypoglycemia versus IAsp in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.

• Authors: Wendy S Lane, Elena Favaro, Naveen Rathor, Hak C Jang, Maiken I S Kjærsgaard, Alejandra Oviedo, Ludger Rose, Peter Senior, Giorgio Sesti, Alfonso Soto Gonzalez, Edward Franek
• Journal: Diabetes care (Diabetes Care) Vol. 43 Issue 8 Pg. 1710-1716 (08 2020) ISSN: 1935-5548 [Electronic] United States
• PMID: 32209647 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the American Diabetes Association.

Chemical References

• Blood Glucose
• Drug Combinations
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Insulin, Long-Acting
• insulin degludec, insulin aspart drug combination
• insulin degludec
• Metformin
• Insulin Aspart

Topics

• Aged
• Blood Glucose (drug effects, metabolism)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Drug Combinations
• Drug Therapy, Combination
• Female
• Glycated Hemoglobin (drug effects, metabolism)
• Humans
• Hypoglycemia (chemically induced, epidemiology)
• Hypoglycemic Agents (administration & dosage, adverse effects)
• Insulin Aspart (administration & dosage, adverse effects)
• Insulin, Long-Acting (administration & dosage, adverse effects)
• Male
• Meals
• Metformin (administration & dosage, adverse effects)
• Middle Aged
• Postprandial Period (drug effects)
• Treatment Outcome