medwireNews: Findings from the GRADE study show that only around a third of patients with type 2 diabetes meeting the threshold for rescue insulin start the treatment within 6 weeks.
“[E]ven in the setting of a well-resourced clinical study with carefully selected participants and skilled diabetes care providers, intensifying treatment using insulin proved challenging,” say Priscilla Hollander (Baylor Scott & White Research Institute, Dallas, Texas, USA) and colleagues in Diabetes Care.
They found that despite 2387 patients with type 2 diabetes consenting at the start of the study to use daily glargine or prandial insulin aspart in addition to their assigned treatment when their glycated hemoglobin (HbA1c) rose above 7.5% (>58 mmol/mol), only 35% did so within 6 weeks and 29% after 6 weeks. It was never used in 36% of patients.
The study was conducted at 36 clinical centers across the USA and involved 5047 individuals with a diabetes duration of no more than 10 years and a baseline HbA1c of 6.8–8.5% (50.8–69.4 mmol/mol), despite taking a maximally tolerated dose of metformin 2000 mg. The participants were randomly assigned to receive insulin glargine U-100, glimepiride, liraglutide, or sitagliptin.
Among the 47.3% of participants who met the 7.5% (58 mmol/mol) threshold for rescue insulin, those most likely to start insulin were taking sitagliptin (48.0%) and had the highest mean HbA1c at that point, of 8.6% (70 mmol/mol). Patients taking glargine were the least likely to start rescue insulin within 6 weeks of reaching the threshold (16.0%), while never users were older (mean 58.9 years), had the longest diabetes duration (mean 6.8 years), and took the longest to reach the rescue insulin threshold (mean 2.8 years).
HbA1c improved in all the participants in the 2 years after meeting the threshold for rescue insulin, and to a significantly greater extent in those who started rescue insulin within 6 weeks, with a mean percentage point reduction of 0.97 (10.6 mmol/mol), compared with 0.41 (4.5 mmol/mol) in those who started after 6 weeks and 0.46 (5.0 mmol/mol) in never users.
Individuals who started rescue insulin within 6 weeks also gained a significant mean 1.10 kg in weight over the 2-year period, whereas those starting after 6 weeks and never users lost a mean 0.20 kg and 2.23 kg, respectively. Incident hypoglycemia occurred in significantly more patients commencing rescue insulin within 6 weeks, at 25% compared with 16% and 14% of those who started after 6 weeks or not at all.
The most common reasons given for delaying the use of rescue insulin beyond 6 weeks on a retrospective Non-Initiation of Insulin survey were the intention to change dietary or lifestyle behaviors and to improve adherence to current therapy, as well as not wanting to start insulin.
Commenting on the findings, Hollander et al suggest that “more needs to be done to destigmatize insulin as a treatment for type 2 diabetes.”
The researchers acknowledge that “[t]he availability of newer drugs such as sodium–glucose cotransporter 2 inhibitors and especially [glucagon-like peptide-1] receptor agonists provides more non-insulin options for many patients with type 2 diabetes.”
But they conclude that insulin “continues to be a major and too often delayed option for treating type 2 diabetes.”
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