Time to insulin initiation among second-line antidiabetics in a cohort of patients with type 2 diabetes

Date of Approval
Application Number
Technical Summary

Type 2 diabetes is a common, chronic, metabolic disease that results from insulin resistance or insufficient insulin secretion. Maintaining adequate glycemia is essential for patients with type 2 diabetes to avoid the micro- and macrovascular complications of diabetes and to reduce mortality. Over the last two decades, several novel antidiabetic drug classes (e.g., DPP-4 inhibitors, GLP-1 receptor agonist, SGLT-2 inhibitors) have been introduced and are now recommended as second-line drugs for ttype 2 diabetes. Since each class of antidiabetic drugs presents unique benefits and side effects, the choice of second-line treatment should depend on patients’ characteristics and risk profiles. However, real-world evidence is limited regarding the ability of second-line antidiabetic drugs to delay the initiation of insulin therapy. Only a few studies have examined this issue but were limited to within drug class comparisons, and several had important methodological limitations. Importantly, little is known about the impact of SGLT-2 inhibitors on time to insulin initiation since this class was introduced relatively recently.

Thus, we propose to compare the ability of second-line antidiabetic agents (insulin secretagogues, thiazolidinediones, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors) to delay the time to insulin initiation in a contemporary cohort of patients with type 2 diabetes. Using CPRD Aurum, we will first establish a base cohort consisting of patients with type 2 diabetes initially treated with metformin monotherapy between 1998-2021. From this base cohort, we will select our final study cohort of patients initiating second-line treatment during 2013-2021. We will adopt an intention-to-treat approach and use inverse probability of treatment weighted Cox models to estimate the association of time to insulin initiation among these second-line antidiabetic agents. We will also compare the time to treatment failure, defined as the addition of or switching to another class of antidiabetic drugs.

Health Outcomes to be Measured

Our primary outcome of interest is the initiation of any type of insulin. The secondary outcome is time to treatment failure defined as the initiation of a new class of antidiabetic agents.


Samy Suissa - Chief Investigator - McGill University
Kristian Filion - Corresponding Applicant - McGill University
Aurelie Pare - Collaborator - McGill University
Christopher Filliter - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Qi Zhang - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Robert Platt - Collaborator - McGill University
YA-HUI YU - Collaborator - Georgia State University