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.