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Time to Insulin Initiation Among Patients With Type 2 Diabetes Treated With Second-Line Antidiabetic Drugs
Ya-Hui Yu1, Qi Zhang2, Estefania Zapata-Bravo2,3
1Department of Epidemiology, Rollin School of Public Health, Emory University, Atlanta, Georgia, USA.
Diabetes, Obesity & Metabolism
|August 7, 2026
Summary
Second-line treatments like thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors may delay insulin initiation in type 2 diabetes patients more effectively than insulin secretagogues. This real-world evidence supports their use in managing type 2 diabetes progression.
Area of Science:
- Endocrinology
- Pharmacology
- Clinical Medicine
Background:
- Type 2 diabetes management often requires escalating therapy beyond metformin.
- Second-line antidiabetic agents play a crucial role in delaying the need for insulin therapy.
- Understanding the comparative effectiveness of different second-line drug classes is essential for optimizing treatment strategies.
Purpose of the Study:
- To compare the effectiveness of various second-line treatments in delaying insulin initiation among patients with type 2 diabetes.
- To evaluate the impact of thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors versus insulin secretagogues.
Main Methods:
- Retrospective cohort study utilizing the Clinical Practice Research Datalink (CPRD) Aurum.
- Inclusion of patients initiating metformin monotherapy followed by second-line treatment.
- Propensity score trimming and inverse probability of treatment weighted Cox models were applied to analyze time to insulin initiation and treatment modification.
Main Results:
- Initiation of TZDs, DPP-4 inhibitors, or SGLT-2 inhibitors was associated with a significantly lower risk of insulin initiation compared to insulin secretagogues.
- Hazard ratios (95% CI) for insulin initiation were: TZDs 0.59 (0.43-0.83), DPP-4 inhibitors 0.75 (0.69-0.80), and SGLT-2 inhibitors 0.62 (0.56-0.68).
- Treatment modification risks varied, with higher risks for TZD and DPP-4 inhibitor initiators and slightly lower risks for SGLT-2 inhibitor and GLP-1 receptor agonist initiators compared to insulin secretagogues.
Conclusions:
- Real-world evidence suggests TZDs, DPP-4 inhibitors, and SGLT-2 inhibitors are more effective than insulin secretagogues in delaying insulin initiation in type 2 diabetes.
- These findings support the use of TZDs, DPP-4 inhibitors, and SGLT-2 inhibitors as preferred second-line agents after metformin to prolong the time to insulin therapy.
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