Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM

Abstract

Objective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants 4.8 million patients (>= 18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.