Type 1 diabetes (T1DM) is a chronic condition that stops the body from producing insulin, an important protein responsible for the regulation of blood sugar levels. It affects 9 million people worldwide. Patients with T1DM commonly develop many complications that affect the health of their eyes, kidneys, nerves, and heart. These complications reduce the life expectancy of patients with T1DM by 8 to 13 years. T1DM is managed by lifelong injection of insulin multiple times per day. A new type of synthetic insulin (long-acting insulins) entered the market that offer longer insulin coverage, lower variability in blood sugar, better blood sugar control, and a lower chance of dangerous drops in blood sugar levels compared to neutral protamine Hagedorn (NPH) insulin, albeit at a much higher price. The main goal of insulin therapy, however, is the prevention of diabetic complications. To date, no studies have investigated if long-acting insulins are better at reducing the rates of T1DM complications compared to NPH. Additionally, evidence is lacking on the trends of insulin utilization in T1DM. We will compare the rates of long-term complications and hypoglycemia between patients who use long-acting insulin and those who use NPH insulin using data from the Clinical Practice Research Datalink linked to hospitalization and vital statistics data. We will describe the utilization of each insulin in terms of annual trends, patterns of use and switching, and the characteristics of users. Findings of this study will add to our understanding of the long-term benefits of long-acting insulins versus NPH.
Type 1 diabetes mellitus (T1DM) is characterized by deficient insulin production and an inability to regulate blood glucose levels. It affects over 9 million people globally. Micro- (retinopathy, nephropathy, neuropathy) and macrovascular complications (cardiovascular) are common in these patients and associated with substantial morbidity and mortality. Management of T1DM involves lifelong insulin injections. Landmark trials have demonstrated that compared to neutral protamine Hagedorn (NPH) insulin, long-acting insulins offer more stable and longer insulin coverage, reduced risk of hypoglycemia, and better glycemic control, albeit at a much higher price than NPH ($7.19 vs $4.68/day). However, the main goal of insulin therapy is the prevention of the diabetic complications. To date, no studies have examined the comparative effectiveness of long-acting insulin and NPH for the prevention of these complications. There is also currently no head-to-head comparison of long-acting insulins. Additionally, evidence is lacking on patterns of insulin utilization over time in T1DM. Our objective is to compare the effectiveness of long-acting insulin versus NPH insulin for the prevention of micro- and macrovascular complications and their safety in terms of severe hypoglycemia among patients with T1DM, and to describe their utilization in terms of trends over time, trajectories of use, treatment switching, and characteristics of users.
We will conduct a cohort study with a prevalent new user design using CPRD AURUM and its linked databases. From a cohort of patients with T1DM, we will match new users of long-acting insulin to users of NPH on history of T1DM, calendar time, and time-conditional propensity score. The primary outcome will be major adverse cardiovascular events (MACE, a composite endpoint of myocardial infarction, ischemic stroke, and cardiovascular death). Secondary outcomes will be a composite of microvascular complications, the individual components of MACE and microvascular complication endpoints, all-cause mortality, hospitalization for heart failure and annual prescription rate.
• Macrovascular complications (a composite outcome of MACE including cardiovascular death, MI, and ischemic stroke)
• Microvascular complications (a composite outcome of retinopathy, amputation, and nephropathy).
• Cardiovascular death
• MI
• Ischemic stroke
• All-cause mortality
• Retinopathy
• Below-knee amputations
• Nephropathy
• Severe Hypoglycemia
• Annual prescription rate
• Daily dose Trajectories
• Treatment switching
• Characteristics of long-acting insulin initiators
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
Antonios Douros - Collaborator - McGill University
In-Sun Oh - Collaborator - McGill University
James Brophy - 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
Rachelle El Haber - Collaborator - McGill University
Robert Platt - Collaborator - McGill University
Samuel Igweokpala - Collaborator - McGill University
Shahrzad Salmasi - Collaborator - IQVIA Canada
WANG-CHOI TANG - Collaborator - McGill University
Wanning Wang - Collaborator - McGill University
Shahrzad Salmasi - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data