Short-term insulin followed by oral drugs provided glucose control in new type 2 diabetes
Patients with a new diagnosis of type 2 diabetes and an HbA1c level of 8.5% or greater significantly lowered their HbA1c levels if they took insulin for two to three weeks before switching to linagliptin, metformin, or both, a randomized trial in China found.
Patients with a new diagnosis of type 2 diabetes and severe hyperglycemia may do better if treated with an “intense simplified” strategy, where short-term insulin is followed by oral antihyperglycemic drugs, a trial found.
Researchers conducted an open-label randomized trial between December 2017 and December 2020 among patients with newly diagnosed type 2 diabetes and an HbA1c level of at least 8.5%. All received short-term insulin therapy for two to three weeks, followed by 48 weeks of linagliptin, 5 mg/d; metformin, 1,000 mg/d; linagliptin plus metformin; or lifestyle modification, which served as the control. The percentage of patients whose HbA1c level fell below 7.0% by week 48 was the primary outcome, while secondary outcomes included glycemic control, beta-cell function, and variations in insulin sensitivity. The results of the study, which was funded in part by an independent research grant for investigator-initiated studies from Boehringer-Ingelheim, were published Oct. 15 by The BMJ.
A total of 412 patients at 15 hospitals in China were randomly assigned to treatment, 103 to each of the four groups, and 373 were included in the final analysis. Of these, 97 were in the linagliptin plus metformin group, 88 in the linagliptin group, 95 in the metformin group, and 93 in the control group. Mean age of the intention-to-treat population at baseline was 46.8 years, mean body mass index was 25.8 kg/m2, and mean HbA1c level was 11.0%. At week 48, 80%, 72%, and 73% of patients in the linagliptin plus metformin, linagliptin, and metformin groups, respectively, had an HbA1c level below 7.0% versus 60% of the control group (P=0.02 overall), and 70%, 68%, and 68% had an HbA1c level below 6.5% versus 48% in the control group (P=0.005 overall). The linagliptin plus metformin group was more likely to reach an HbA1c level below 7.0% after adjustment for age, gender, body mass index, and baseline HbA1c level compared with control (odds ratio, 2.78 [95% CI, 1.37 to 5.65]; P=0.005), and patients in this group also had the most improvement in fasting plasma glucose levels and indices of beta-cell function.
The researchers noted that the study was not blinded, that it was affected by the COVID-19 pandemic, and that the results may not be generalizable to all patients with type 2 diabetes. They concluded that using oral therapies after short-term insulin soon after type 2 diabetes diagnosis, especially linagliptin plus metformin, resulted in improved glycemic control and beta-cell function in patients with severe hyperglycemia.
“This proof-of-principle study also provides a new area for future exploration. More practical and feasible intensive approaches that can be applied in outpatient settings, such as multiple daily insulin injections or even regimens based on basal insulin, could be explored for the ‘intense’ module, and more convenient drugs such as fixed dose combination preparations or sodium-glucose cotransporter 2 inhibitors with benefits for complications could also be considered in the ‘simplified’ module,” they wrote. “Further data are needed to evaluate the durability of treatment effects, the strategy's impact on reducing long term complications, and its potential economic advantages.”