Health benefits of sustained weight loss in people with overweight or obesity

Date of ISAC Approval: 
Lay Summary: 
People who are overweight or have obesity have a higher risk of developing a number of diseases during lifetime (such as diabetes, hypertension, sleep apnoea and degeneration of joint cartilage and the underlying bone), in comparison to people with normal weight. Some of these diseases may be followed by even more serious conditions like heart diseases, hip or knee replacement, or death. While it is generally well accepted that weight loss can reduce the overall health status, it is not clear how effective a moderate weight loss is in preventing particular diseases. With currently available weight loss medication, 10% weight loss over the duration of one year can be expected, typically in combination with lifestyle changes (such as diet and exercise). Body Mass Index (BMI) is used to describe weight in relation to official recommendations and takes height into account (kg/m2). In this study we aim to estimate the risks associated with higher BMI and to quantify the benefit of moderate weight loss in people who are overweight or have obesity. In particular, we will investigate whether weight loss may reduce the risk of complications to a level similar to the risk observed in persons with comparable low stable weight.
Technical Summary: 
The aim of this study is to assess the risk of various disease outcomes in persons with excess body weight and to evaluate the effect of a moderate weight loss. We will compare a cohort of subjects with sustained weight loss, i.e., 10% weight loss during one year followed by stable weight during the following year, with a control cohort of subjects with a 2-year stable weight period. We will use Cox proportional hazard models to quantify the relative risk reduction due to the weight loss on a number of obesity comorbidities. In the Cox proportional hazard models, age will be the underlying time scale. Follow-up will be censored at the first outcome diagnosis, death, transfer-out date, or study end, whichever occurs first. In particular, we will look at: - primarily weight-related outcomes (sleep apnoea, osteoarthritis, asthma) - cardiovascular risk factors and cardio-metabolic diseases (hypertension, type 2 diabetes, heart failure and chronic kidney disease) - Hard endpoints (myocardial infarction, stroke, and death) - Hip/knee replacement All applicable endpoints will also be included as comorbidities if diagnosed before start of follow-up in order to adjust for these known risk factors in the models.
Health Outcomes to be Measured: 
- Type 2 diabetes - Dyslipidaemia - Transient ischemic attack - Asthma - Atrial fibrillation - Stroke - Sleep apnoea - Osteoarthritis - Hypertension - Atherosclerosis - Heart failure - Chronic kidney disease - Unstable angina - Myocardial infarction - Hip/knee replacement - Cardiovascular (CV) death

Kirsten Eriksen - Chief Investigator - Novo Nordisk
Altynai Satylganova - Collaborator - Novo Nordisk
Christiane Lundegaard Haase - Collaborator - Novo Nordisk
Kirsten Eriksen - Corresponding Applicant - Novo Nordisk
Professor Phil McEwan - Collaborator - Health Economics & Outcomes Research Ltd(HEOR Ltd)
Philip Kittel - Collaborator - Novo Nordisk
Sandra Lopes - Collaborator - Novo Nordisk
Volker Schnecke - Collaborator - Novo Nordisk

HES Admitted;ONS