Studies have reported that people with obesity can reduce their risk of conditions such as type 2 diabetes, high blood pressure and asthma by losing weight. Few studies have looked at the clinical implications of weight loss in people with obesity and type 2 diabetes, and whether changes in blood sugar might affect the potential benefits of weight loss. The possible impact of blood sugar is important to consider in people with type 2 diabetes because long-term high or low blood sugar is also associated with increased risk of health complications.
We will use data from the Clinical Practice Research Datalink to evaluate whether people who have type 2 diabetes and obesity can reduce their risk of developing health complications by losing weight. We will also explore whether changes in blood sugar affect the association between weight loss and future health risk. The study will include adults whose medical records indicate that they had type 2 diabetes and obesity (a body mass index of at least 30 kg/m2) and that they were trying to lose weight. After a 4-year period of attempted weight loss, we will investigate how weight changes affected individuals’ risk of being diagnosed with a number of conditions, including: stroke, heart attack, kidney disease, and eye and nerve damage related to type 2 diabetes. Changes in blood sugar over the attempted weight-loss period will be taken into account. The results of this study will help to design future public health strategies for people with type 2 diabetes.
Weight is a key modifiable risk factor for T2D, and obesity management is a recommended secondary prevention strategy in patients with T2D. Real-world evidence indicates that intentional weight loss in people with obesity can reduce the risk of obesity-related complications. Data are limited on the impact of intentional weight loss on the risk of T2D-related complications. We aim to evaluate the effects of intentional weight loss on T2D-related microvascular and macrovascular complications in people with T2D and obesity, taking into account glycaemic control during the attempted weight-loss period. We will conduct a retrospective cohort study using CPRD Aurum and linked HES Admitted Patient Care, ONS Death Registration and Patient-level index of Multiple Deprivation data. The study period (1 January 2006–31 December 2022) will comprise a 4-year attempted weight-loss period, and a follow-up period for outcome evaluation. Eligible patients will be aged 18–70 years with T2D, a body mass index (BMI) of ≥30 kg/m2 (Asian patients: ≥27.5 kg/m2) at enrolment, evidence of intentional weight loss, and BMI and glycated haemoglobin (HbA1c) records in the first and last years of the attempted weight-loss period. Outcomes will be new onset T2D-related complications: myocardial infarction, stroke, peripheral artery disease, retinopathy, neuropathy and chronic kidney disease. Associations between BMI change and T2D-related complication risk will be evaluated using Cox proportional hazard regression analysis, controlling for HbA1c change during the weight-loss period. Separate models (crude and adjusted for confounders) will be fitted for each outcome pairing.
Evaluating the hypothesis that intentional weight loss can reduce complication risk in patients with T2D and obesity who achieve (or maintain) glycaemic control, will quantify the benefit of proactive weight and blood glucose management strategies in patients with T2D and obesity. The aim is to inform the design of future evidence-based secondary prevention programmes for people with T2D.
Primary outcomes
Time to diagnosis of T2D-related complications: retinopathy; neuropathy; chronic kidney disease (CKD); myocardial infarction (MI); peripheral artery disease (PAD); stroke.
Secondary outcomes
Composite endpoint of primary outcomes: T2D-related microvascular complications (i.e. retinopathy and/or neuropathy and/or CKD); T2D-related macrovascular complications (i.e. MI and/or PAD and/or stroke)
Exploratory outcomes
• Time to first diagnostic code in the follow-up period for each of the following complications associated with T2D and/or obesity: sexual dysfunction, albuminuria and/or proteinuria, asthma, hip/knee osteoarthritis, obstructive sleep apnoea (OSA), heart failure, gastroesophageal reflux disease (GERD)
• Time to first recorded intensification of diabetes treatment, defined as a first prescription for injectable or oral glucagon-like peptide-1 receptor agonist (GLP-1 RA), or for insulin therapy
• Weight-loss threshold that provides benefit (statistically significant risk reduction) versus stable weight for each endpoint of interest, while controlling for HbA1c
• Weight-loss threshold that provides benefit (statistically significant risk reduction) versus marginal weight loss for each endpoint of interest, while controlling for HbA1c
In order to assess the hypothesis that there may be greater opportunity to modify positively the risk of T2D-related complications in younger and/or more recently diagnosed patients, outcomes will be evaluated for the overall population and for the following subgroups of interest:
• Early onset T2D
– diagnosed before 40 years of age
– diagnosed before 50 years of age
• Recent onset T2D (diagnosed ≤12 months prior to enrolment)
Christian Kruse - Chief Investigator - Novo Nordisk A/S
Christian Kruse - Corresponding Applicant - Novo Nordisk A/S
Anders Boeck Jensen - Collaborator - Novo Nordisk A/S
Emil Bo Nortoft - Collaborator - Statgroup Ap S - Denmark
Nick fabrin Nielsen - Collaborator - Novo Nordisk A/S
Peter Nørgaard Kristensen - Collaborator - Novo Nordisk A/S
Runa Fenger - Collaborator - Novo Nordisk A/S
Uffe Christian Braae - Collaborator - Novo Nordisk A/S
Uffe Christian Braae - Collaborator - Novo Nordisk A/S
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation