Risk of first-time major cardiovascular event among individuals with newly diagnosed type 2 diabetes: data from Danish registers

Abstract

Aims/hypothesis: We aimed to examine whether individuals with initial omission of glucose-lowering drug treatment (GLDT), including those achieving initial remission of type 2 diabetes, may experience a higher risk of major adverse cardiovascular events (MACE) compared with well-controlled individuals on GLDT after a new type 2 diabetes diagnosis in real-world clinical practice. Furthermore, we examined whether a higher risk could be related to lower initiation of statins and renin-angiotensin system inhibitors (RASi).

Methods: In this cohort study, we used Danish registers to identify individuals with a first measured HbA_1c between 48 and 57 mmol/mol (6.5-7.4%) from 2014 to 2020. Six months later, we divided participants into four groups according to GLDT and achieved HbA_1c (<48 vs ≥48 mmol/mol [6.5%]): well-controlled and poorly controlled on GLDT; remission and persistent type 2 diabetes not on GLDT. We reported how much the standardised 5 year risk of MACE could be reduced for each group if initiation of statins and RASi was the same as in the well-controlled group on GLDT.

Results: We included 14,221 individuals. Compared with well-controlled participants on GLDT, the 5 year standardised risk of MACE was higher in the three other exposure groups: by 3.3% (95% CI 1.6, 5.1) in the persistent type 2 diabetes group not on GLDT; 2.0% (95% CI 0.4, 3.7) in the remission group not on GLDT; and 3.5% (95% CI 1.3, 5.7) in the poorly controlled group on GLDT. Fewer individuals not on GLDT initiated statins and RASi compared with individuals on GLDT. If initiation of statins and RASi had been the same as in the well-controlled group on GLDT, participants not on GLDT could have reduced their risk of MACE by 2.1% (95% CI 1.2, 2.9) in the persistent type 2 diabetes group and by 1.1% (95% CI 0.4, 1.9) in the remission group.

Conclusions/interpretation: Compared with well-controlled individuals on GLDT, individuals not on initial GLDT had a higher 5 year risk of MACE, even among those achieving remission of type 2 diabetes. This may be related to lower use of statins and RASi.

Keywords: Cardiovascular disease; Glucose-lowering drug; Glycaemic control; Remission of type 2 diabetes; Renin–angiotensin system inhibitor; Statin; Type 2 diabetes.

Fig. 1

Flow chart of the study population. ^aEnd-stage renal disease or eGFR<30 ml/min per 1.73 m²: n=1035; severe liver disease or splenomegaly: n=296; haemolytic anaemia, haemoglobinopathies, moderate anaemia, iron deficiency or B₁₂ deficiency: n=3671; alcoholism: n=1362; severe hypertriglyceridaemia or severe hyperbilirubinaemia: n=49; and intake of specific drugs: n=643. CABG, coronary artery bypass graft surgery; IHD, ischaemic heart disease; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; T2D, type 2 diabetes

Fig. 2

Crude (a) and standardised (b) absolute 5 year risk of first-time MACE according to initial GLDT and glycaemic control, 180 days after first measured HbA_1c≥48 mmol/mol (6.5%). Time zero denotes 180 days after first measured HbA_1c≥48 mmol/mol. Standardised to the distribution of all included individuals with respect to the distribution of age, sex, cohabitation status, ethnicity, income, type of requester (general practitioner or other), first measured HbA_1c level, eGFR, comorbidities, and after setting the use of statins and RASi as observed for each exposure group for all individuals. T2D, type 2 diabetes

Fig. 3

Probability of initiating statins (a) and RASi (b) according to GLDT and initial glycaemic control, 180 days after first measured HbA_1c≥48 mmol/mol (6.5%). T2D, type 2 diabetes

Fig. 4

Expected absolute reduction of standardised 5 year risk of MACE if each exposure group had the same probability of receiving statins and/or RASi as the well-controlled group on GLDT. Depicted is the absolute reduction of standardised 5 year risk of MACE for each exposure group that could be expected if they, hypothetically, were as likely to receive treatment with statins and/or RASi as the well-controlled group on GLDT. The reduction of risk was calculated for each exposure group as the difference between the risk with the observed use of statins and/or RASi (observed risk) and the risk if treatment had been the same as the well-controlled group on GLDT (risk under intervention). The use of dashes for the well-controlled group on GLDT indicates that the observed risk and risk under intervention were identical for this specific group. T2D, type 2 diabetes