Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM
Authors: Khera Rohan , Dhingra Lovedeep Singh , Aminorroaya Arya , Li Kelly , Zhou Jin J , Arshad Faaizah , Blacketer Clair , Bowring Mary G , Bu Fan , Cook Michael , Dorr David A , Duarte-Salles Talita , DuVall Scott L , Falconer Thomas , French Tina E , Hanchrow Elizabeth E , Horban Scott , Lau Wallis CY , Li Jing , Liu Yuntian , Lu Yuan , Man Kenneth KC , Matheny Michael E , Mathioudakis Nestoras , McLemore Michael F , Minty Evan , Morales Daniel R , Nagy Paul , Nishimura Akihiko , Ostropolets Anna , Pistillo Andrea , Posada Jose D , Pratt Nicole , Reyes Carlen , Ross Joseph S , Seager Sarah , Shah Nigam , Simon Katherine , Wan Eric YF , Yang Jianxiao , Yin Can , You Seng Chan , Schuemie Martijn J , Ryan Patrick B , Hripcsak George , Krumholz Harlan , Suchard Marc A 
Published: February 2024

ObjectiveTo assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.DesignFederated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting10 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.Participants4.8 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.ExposureThe exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measuresThe 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.Results4.6 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.ConclusionsDespite 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.