All Cause and Cardiovascular Mortality in type 2 diabetes patients using Detemir or Glargine

Date of ISAC Approval: 
Lay Summary: 
Considering the large number of patients who require treatment for diabetes , a potential survival benefit of a particular type of treatment would have major clinical and public health implications. This study will examine the influence of the diabetes treatments named basal insulins Detemir and Glargine on risk of death from diseases of the heart or vascular system ; and on the risk of and death from all causes in patients treated by their general practitioner in United Kingdom (UK). The patients included in the present study have type 2 diabetes, they are 40 years of age or above at time of initiating basal insulin therapy in January 2004- December 2018. These patients will be assessed through registers (i.e. the Clinical Practice Research Datalink (CPRD)), with comprehensive data on deaths, deaths from heart and vascular system, and background disease and social-economic variables. The study will provide knowledge of the risk of death in users of the diabetes treatment “insulin Detemir”, compared to risk of death in users of the diabetes treatment named “insulin Glargine”.
Technical Summary: 
The impact of different types of basal insulins in patients with type 2 diabetes on risk of death and death from cardiovascular diseases is unclear. Therefore, the aim of this study is to estimate the differences in all-cause and cardiovascular mortality rates between first time users of basal insulins (Detemir vs Glargine) in a population-based study in UK. Patients with type 2 diabetes aged ≥40, who initiated basal insulin therapy (Detemir or Glargine) in 2004-2018 will be identified from Clinical Practice Research Datalink (CPRD), with comprehensive data on mortality, cause of death, and background variables. The estimates will be adjusted for relevant patient characteristics at time of treatment initiation. Follow-up time will be up to 14 years (median 4 years). Exposure variables are defined in two ways: - “ITT (Intention to treat)” where patients are allocated to the first used basal insulin throughout follow-up. - “On treatment of the first drug used” where patients are followed while they are on the first used drug and until time of first switch to another treatment, where they are censored. A “lag time of one year” for each treatment episode is used. The fully adjusted Cox’s Proportional Hazard (PH) model will include the exposures of interest and adjustment variables such as age, calendar year, sex, diabetes duration, Body Mass Index (BMI), history of Cardiovascular Disease (CVD), CVD medication and non-insulin glucose-lowering medications at time of insulin initiation. Time dependent variables are assessed i.e. “non-insulin glucose-lowering medications,” bolus insulin” and “smoking status”. The study will provide knowledge of comparative mortality among users of insulin detemir compared to users of insulin glargine in real clinical practice. Considering the large number of patients who require
Health Outcomes to be Measured: 
All-cause mortality; cardiovascular mortality

Lina Steinrud Morch - Chief Investigator - Novo Nordisk
Lina Steinrud Morch - Corresponding Applicant - Novo Nordisk
Dr Lise Lotte Nystrup Husemoen - Collaborator - Novo Nordisk
Niels Vaever Hartvig - Collaborator - Novo Nordisk
Rikke Salbol Brandt - Collaborator - Novo Nordisk
Thue Johansen - Collaborator - Novo Nordisk

ONS;Patient IMD;Practice IMD (Standard)