Type 2 diabetes is characterized by elevated blood sugar levels. Treatments include lifestyle modification (e.g., diet, exercise), use of oral drugs, and then insulin when other treatments fail to control blood sugar levels. However, insulin can cause potential side effects, including severe low blood sugar (hypoglycemia). Recently, new insulins that stay in the body for a longer time have entered the market (long-acting insulins). These insulins are believed to have a lower risk of hypoglycemia compared to the older insulin types that stay in the body for a shorter time (intermediate-acting insulins).
Benefits of long-acting insulins were observed in clinical trials. However, these trials were conducted in highly-selected patients that are different from those seen in everyday clinical practice. Some studies have examined these new insulins using data from patients in routine clinical practice, but they had important flaws. Higher-quality studies that use clinical data are needed to evaluate the effectiveness and safety of long-acting insulins. To do this, we will use data from the Clinical Practice Research Datalink (CPRD). We will first study treatment patterns of long-acting insulins and intermediate-acting insulin in patients with type 2 diabetes. Then, we will compare the effectiveness of these insulins at reducing the risk of heart attacks, strokes, and dying of heart problems. Finally, we will compare the risk of severe hypoglycemia in patients using these different types of insulin. This study will provide regulatory agencies, clinicians, and patients with important information on the use of these insulins for the management of type 2 diabetes.
Type 2 diabetes mellitus is a disease characterized by increased levels of blood glucose, which may subsequently lead to macrovascular (myocardial infarction [MI], stroke) and microvascular (neuropathy, nephropathy, retinopathy) complications. Treatment for type 2 diabetes includes use of antidiabetic drugs and then insulin when other treatments fail to achieve glycemic control. Although effective in lowering glycaemia, insulin is associated with adverse effects in patients with type 2 diabetes, including severe hypoglycemia. Recently, new long-acting insulin analogs (glargine, detemir, degludec) have entered the market; these insulins are believed to have a lower risk of hypoglycemia and provide better weight control in comparison with human intermediate-acting insulin isophane (i.e., neutral protamine Hagedorn or NPH).
The reported benefits with long-acting insulin analogs were observed in clinical trials, but these were conducted in highly selected patient populations. Recent observational studies have provided conflicting results and many had important methodological flaws that may have introduced bias. Additional methodologically rigorous observational studies with longer follow-up are needed to evaluate the effectiveness and safety of newer insulin analogs compared to human NPH insulin. This study will aim to address the gaps in the knowledge of the utilization, effectiveness, and safety of long-acting insulin analogs vs intermediate-acting insulin. Using CPRD Aurum, Hospital Episode Statistics, and data from the Office for National Statistics, we will include all patients with a first-ever insulin prescription (either long-acting insulins or NPH) from September 1st 2002 to March 31st 2019. We will first describe the utilization of these insulins over time and patient characteristics. We will then investigate their comparative effectiveness at preventing major adverse cardiovascular events (MACE) and hospitalization for heart failure, and their safety with respect to hypoglycaemia.
Our outcomes of interest include major cardiovascular events (MACE; composite endpoint of myocardial infarction, ischemic stroke, and cardiovascular death), the individual components of MACE, all-cause mortality, hospitalization for heart failure, and severe hypoglycaemia.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
Michael Webster-Clark - 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
Vanessa Brunetti - Collaborator - Amgen Ltd
Wanning Wang - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Rachelle El Haber - Collaborator - McGill University
Shahrzad Salmasi - Collaborator - IQVIA Canada
Shahrzad Salmasi - Collaborator - McGill University
Vanessa Brunetti - Collaborator - Analysis Group, Inc.
Vanessa Brunetti - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation