In patients with poorly controlled type 2 diabetes, glucagon-like peptide-1 receptor agonist (GLP-1 RA) is proven to be overall effective without prior glycemic control with insulin. However, prior glycemic control with insulin might overcome glucose toxicity-induced GLP-1 resistance in cases with insulinopenic type 2 diabetes.

• This is an open-label, parallel trial with poorly controlled type 2 diabetes patients who were randomly assigned to receive once-daily insulin therapy, degludec (Insulin–GLP-1 RA relay group, mean 16.8 ± 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP-1 RA, liraglutide (GLP-1 RA first group, 0.9 mg), for 24 weeks.

• Prior to the study, median fasting plasma glucose and glycated hemoglobin (HbA1c) were 210.0 mg/dL and 9.8%, respectively.

• At week 24, significant reduction in the levels of fasting plasma glucose and HbA1c was achieved in the Insulin–GLP-1 RA relay group (P < 0.001) and GLP-1 RA first group (P < 0.001), although there were no intergroup differences.

• In the Insulin–GLP-1 RA relay group, HbA1c decrease tended to be larger compared to that in the GLP-1 RA first group in the lowest CPR (C-peptide immunoreactivity) quartile.

• Adverse events comprised gastrointestinal issues, followed by hypoglycemia.