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

Date of Approval: 
2021-05-25 00:00:00
Lay Summary: 
Type 2 diabetes, a common disease characterized by elevated blood sugar levels, results from insulin resistance or insufficient insulin secretion. Maintaining adequate blood glucose is essential to avoid complications such as having a heart attack or stroke. Over the last two decades, several new types of drugs were introduced to treat type 2 diabetes (e.g., dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors). These drugs are now among the recommended second-line treatments for type 2 diabetes when metformin alone is insufficient to control blood sugar. Treatment guidelines emphasize that second-line drug choice should depend on patients' characteristics since each drug class has different benefits and side effects. Little is known about the impact of these different drug classes on the time to initiate insulin therapy. The initiation of insulin, an injectable drug used among those with severe diabetes and in those whom oral antidiabetic drugs are no longer able to control blood sugar levels, is recognized as an important milestone in the disease course, posing challenges in clinical management and quality of life. We propose a study to compare the time to insulin initiation with different second-line antidiabetic drugs (DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, thiazolidinediones, and insulin secretagogues) in a contemporary cohort of patients with type 2 diabetes who were previously using metformin monotherapy using data from the CPRD. We will also compare the time to treatment failure (defined as starting a new type of antidiabetic drugs) among these different second-line antidiabetic drugs.
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.
Application Number: 
21_000450
Collaborators: 

Samy Suissa - Chief Investigator - McGill University
Kristian Filion - Corresponding Applicant - McGill University
Aurelie Pare - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Robert Platt - Collaborator - McGill University
Ya-Hui Yu - Collaborator - McGill University