Cardiovascular disease and type 2 diabetes in older adults: a combined protocol for an individual participant data analysis for risk prediction and a network meta-analysis of novel anti-diabetic drugs.

INTRODUCTION: Older and multimorbid adults with type 2 diabetes (T2D) are at high risk of cardiovascular disease (CVD) and chronic kidney disease (CKD). Estimating risk and preventing CVD is a challenge in this population notably because it is underrepresented in clinical trials. Our study aims to (1) assess if T2D and haemoglobin A1c (HbA1c) are associated with the risk of CVD events and mortality in older adults, (2) develop a risk score for CVD events and mortality for older adults with T2D, (3) evaluate the comparative efficacy and safety of novel antidiabetics.

METHODS AND ANALYSIS: For Aim 1, we will analyse individual participant data on individuals aged ≥65 years from five cohort studies: the Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People study; the Cohorte Lausannoise study; the Health, Aging and Body Composition study; the Health and Retirement Study; and the Survey of Health, Ageing and Retirement in Europe. We will fit flexible parametric survival models (FPSM) to assess the association of T2D and HbA1c with CVD events and mortality. For Aim 2, we will use data on individuals aged ≥65 years with T2D from the same cohorts to develop risk prediction models for CVD events and mortality using FPSM. We will assess model performance, perform internal-external cross validation, and derive a point-based risk score. For Aim 3, we will systematically search randomized controlled trials of novel antidiabetics. Network meta-analysis will be used to determine comparative efficacy in terms of CVD, CKD, and retinopathy outcomes, and safety of these drugs. Confidence in results will be judged using the CINeMA tool.

ETHICS AND DISSEMINATION: Aims 1 and 2 were approved by the local ethics committee (Kantonale Ethikkommission Bern); no approval is required for Aim 3. Results will be published in peer-reviewed journals and presented in scientific conferences.

STRENGTHS AND LIMITATIONS: We will analyse individual participant data from multiple cohort studies of older adults who are often not well represented in large clinical trials.By using flexible survival parametric models, we will be able to capture the potentially complex shapes of the baseline hazard functions of cardiovascular disease (CVD) and mortality.Our network meta-analysis will include recently published randomised controlled trials on novel anti-diabetic drugs that have not been included in previous network meta-analysis and results will be stratified by age and baseline HbA1cAlthough we plan to use several international cohorts, the external validity of our findings and particularly of our prediction model will need to be assessed in independent studiesOur study will help guide CVD risk estimation and prevention among older adults with type 2 diabetes.