Time to Insulin Initiation Among Patients With Type 2 Diabetes Treated With Second‐Line Antidiabetic Drugs

Objective To examine the effect of second‐line treatments (insulin secretagogues, thiazolidinediones, glucagon‐like peptide‐1 (GLP‐1) receptor agonists, dipeptidyl peptidase‐4 (DPP‐4) inhibitors or sodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors) on time to insulin initiation among patients with type 2 diabetes. Research Design and Methods We conducted a retrospective cohort study using the Clinical Practice Research Datalink (CPRD) Aurum. Initiation of metformin monotherapy (1998–2021) defined base cohort entry, and initiation of second‐line treatment (2013–2021) defined study cohort entry (time zero). After propensity score trimming, we applied inverse probability of treatment weighted Cox models to estimate the association between second‐line agents and time to insulin initiation. The secondary outcome was time to treatment modification, defined as the addition of or switch to another antidiabetic drug class. Results Our analytic cohort included 64 404 patients; 44% initiated DPP‐4 inhibitors, 36% insulin secretagogues, 18% SGLT‐2 inhibitors, 1% thiazolidinediones and 3% GLP‐1 receptor agonists. Over a mean follow‐up of 2.9 years, initiation of TZDs, DPP‐4 inhibitors, or SGLT‐2 inhibitors was associated with a lower risk of insulin initiation than initiation of insulin secretagogues (HR [95% CI]: 0.59 [0.43–0.83], 0.75 [0.69–0.80] and 0.62 [0.56–0.68], respectively). For treatment modification, the risk was higher among TZD and DPP‐4 inhibitor initiators, and slightly lower among SGLT‐2 inhibitor initiators and GLP‐1 receptor agonist initiators than among insulin secretagogue initiators. Conclusion This study provides real‐world evidence that TZDs, DPP‐4 inhibitors and SGLT‐2 inhibitors may offer an advantage over insulin secretagogues in delaying insulin initiation after metformin monotherapy.