Matching algorithm

We applied a three-step matching algorithm to enhance the comparability of baseline patient characteristics between two study group (Supplementary Figure ¹)^12,14. To keep as many IAHI users (the study drug group) as possible in the analyses and match them to the most comparable LAIA users (the comparator drug group) with similar baseline patient characteristics, the stable use sets from the LAIA group were re-used through the matching process.

We first aligned the cohort entry time of the study groups to avoid differences in time-related biases and confounding effects that arise from the evolution of clinical treatment and practice over time. For each stable use set of IAHI, we identified the LAIA stable use set with an index date falling within ± 180 days of the index date of the IAHI stable use set. Then, because the utilization patterns of GLAs prior to the IAHI or LAIA use could be an important indicator of diabetes progression and severity, we adjusted for the history of past GLA use, including metformin, sulfonylureas, meglitinides, thiazolidinediones, acarbose, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, short-acting/rapid-acting insulins, IAHI, LAIA, and premixed insulins, within the year before the index date. The previous 1-year GLA utilization patterns for the matched pairs of IAHI and LAIA users had to meet two criteria: (1) being exposed to the same GLA classes, and (2) having a difference in the total number of days’ supply of less than 90 (± 45 days) for each specific GLA. Lastly, one-to-one 8-digit greedy propensity score (PS) matching was used to adjust for other baseline patient characteristics (e.g., demographics, diabetes-related complications, comorbidities, and other medication use; Table ​Table1)1) between the two study groups.

Baseline patient characteristics before and after application of the matching algorithm.

IAHA, intermediate-acting human insulin; LAIA, long-acting insulin analogue; SMD, standardized mean difference; GLA, glucose-lowering agent; SD, standard deviation; MPR, medication possession ratio; CIC, Chronic Illness with Complexity; CVD, cardiovascular disease; RAAS, renin–angiotensin–aldosterone system.