Impact of Being Eligible for Type 2 Diabetes Treatment on All-Cause Mortality and Cardiovascular Events: Regression Discontinuity Design Study

Irene Petersen,1,2 Sia Kromann Nicolaisen,2 Federico Ricciardi,3 Manuj Sharma,1 Reimar W Thomsen,2 Gianluca Baio,3 Lars Pedersen2 1Department of Primary Care and Population Health, University College London, London, UK; 2Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 3Department of Statistical Science, University College London, London, UKCorrespondence: Irene PetersenDepartment of Primary Care and Population Health, University College London, London NW3 2PF, UKTel +44 20 801 68032Email i.petersen@ucl.ac.ukBackground: Individuals with type 2 diabetes (T2D) have a twofold increased risk for cardiovascular events (CVE), and CVE is responsible for nearly 80% of the mortality. Current treatment guidelines state that individuals should immediately initiate antidiabetic treatment and cardiovascular risk-factor management from T2D diagnosis. However, the evidence base is sparse, and randomized trials are unlikely to be conducted. We examined the impact of being eligible for T2D treatment, as determined by the threshold of HbA1c ≥ 6.5% (≥ 48 mmol/mol), on all-cause mortality and CVE. We hypothesised that individuals who were just above this threshold had a lower risk of CVE and all-cause mortality than individuals just below.Methods and Findings: We used the regression discontinuity design (RDD), a quasi-experimental design, comparing rates of all-cause mortality and CVE in people just below and just above the eligibility for treatment threshold. We included Danish healthcare records from 43,070 individuals aged 40– 80 years with no previous T2D record and the first record of HbA1c in the range of 6.0– 7.0% (42– 53 mmol/mol) between 2006 and 2014. In total, 36,360 individuals had the first record of HbA1c between 6.0% and 6.4% (42– 47 mmol/mol), and 6710 individuals had a first record between 6.5% and 7.0% (48– 53 mmol/mol). Individuals with a measurement just above 6.5% (48 mmol/mol) had a 21% lower rate of death or CVE, compared to those just below (hazard ratio: 0.79 (95% CI 0.69– 0.90)). Few individuals received early metformin treatment. However, the chance of metformin treatment initiation within 3 months was substantially higher for individuals with an HbA1c measurement above (14%) than below (1%) the threshold.Conclusion: Individuals with first record of HbA1c measure just above treatment threshold experienced a 21% lower rate of death or CVE than those just below. Lifestyle modifications and cardiovascular risk-factor management may contribute to this reduced rate.Keywords: type 2 diabetes, glycated hemoglobin A1c, regression discontinuity design, cardiovascular event, mortality