Predictive models for cardiovascular and kidney outcomes in patients with type 2 diabetes: systematic review and meta-analyses

Heart. 2021 Dec;107(24):1962-1973. doi: 10.1136/heartjnl-2021-319243. Epub 2021 Apr 8.


Objective: To inform a clinical practice guideline (BMJ Rapid Recommendations) considering sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for treatment of adults with type 2 diabetes, we summarised the available evidence regarding the performance of validated risk models on cardiovascular and kidney outcomes in these patients.

Methods: We systematically searched bibliographic databases in January 2020 to identify observational studies evaluating risk models for all-cause and cardiovascular mortality, heart failure (HF) hospitalisations, end-stage kidney disease (ESKD), myocardial infarction (MI) and ischaemic stroke in ambulatory adults with type 2 diabetes. Using a random effects model, we pooled discrimination measures for each model and outcome, separately, and descriptively summarised calibration plots, when available. We used the Prediction Model Risk of Bias Assessment Tool to assess risk of bias of each included study and the Grading of Recommendations, Assessment, Development, and Evaluation approach to evaluate our certainty in the evidence.

Results: Of 22 589 publications identified, 15 observational studies reporting on seven risk models proved eligible. Among the seven models with >1 validation cohort, the Risk Equations for Complications of Type 2 Diabetes (RECODe) had the best calibration in primary studies and the highest pooled discrimination measures for the following outcomes: all-cause mortality (C-statistics 0.75, 95% CI 0.70 to 0.80; high certainty), cardiovascular mortality (0.79, 95% CI 0.75 to 0.84; low certainty), ESKD (0.73, 95% CI 0.52 to 0.94; low certainty), MI (0.72, 95% CI 0.69 to 0.74; moderate certainty) and stroke (0.71, 95% CI 0.68 to 0.74; moderate certainty). This model does not, however, predict risk of HF hospitalisations.

Conclusion: Of available risk models, RECODe proved to have satisfactory calibration in primary validation studies and acceptable discrimination superior to other models, though with high risk of bias in most primary studies.

Trial registration number: CRD42020168351.

Keywords: diabetes.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Cause of Death / trends
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / epidemiology
  • Global Health
  • Glucagon-Like Peptide Receptors / agonists*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / mortality*
  • Morbidity / trends
  • Prognosis
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Survival Rate / trends


  • Glucagon-Like Peptide Receptors
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors