Real-life use of novel glucose lowering agents after acute myocardial infarction and stable coronary artery disease in patients with diabetes - experience from national use in the SWEDEHEART-registry

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Abstract Background Recently Sodium Glucose Lowering Transport 2 receptor inhibitors (SGLT2i) and Glucagon Like Peptide Receptor Agonists (GLP-1 RA) have demonstrated preventive effects in patients with established diabetes and evidence of cardiovascular disease, and is recommended in guidelines regardless of glucose control. Less is known about the real uptake of these therapies and the demographic of patients prescribed these drugs. Purpose To explore trends and real-life use of novel glucose lowering agents in patients with diabetes and coronary artery disease (CAD) and these patients’ prognosis in a national perspective. Methods All patients with diabetes and CAD admitted for coronary angiography in 2010-2021 reported in the Swedish angiography and angioplasty registry (SCAAR) were included. Information on glucose lowering agents dispended within 6 months to the coronary angiography was collected from the Prescribed Drug Registry and grouped into classes. Information on comorbidities and death until December 2021 was collected from the National Patient Registry. Mortality was assessed by Cox proportional survival analysis with novel cardioprotective glucose lowering agents as a reference. Results Of 38 671 patients, mean age was 68.6 years (SD 10.6) and 67.3% (n=26 017) were men. Figure 1 depicts trends in use of glucose lowering classes 2010-2021; use of novel glucose lowering agents increased rapidly from the year 2016 with a continuously high rise (proportion 7% to 47%). This was mainly driven by the use of SGLT2i (from 4% to 38%) and less of GLP-1 RA (4% to 15%). In parallel with this, use of insulin and absence of glucose lowering treatment decreased slightly and use of sulfonylurea decreased dramatically while use of metformin slightly increased. Patients who received the new agents (SGLT2; n=3191 and GLP-1 RA; n=1570), compared to patients on other glucose lowering agents than SGLT2i or GLP-1 RA (n=25 967), were younger (mean age 66 [SD 10] vs. 68 years [SD 10]), more often men (72.8%; n=3465 vs. 67.1%; n=17 427) and with less frequent heart failure (5.0%; n=239 vs. 6.8%; n=1770) and previous myocardial infarction (7.7%; n=367 vs. 10.5%; n=2736). Cumulative event rate is depicted in Figure 2. All-cause death within 1 year occurred in 1.7% (n=79) of patients with SGLT2i and/or GLP-1 RA compared to 4.5% (n=1114) in patients without new cardioprotective agents whose adjusted associated risk for all-cause death was higher, HR 1.22 (95% CI 1.09-1.37). Conclusion The fast uptake of novel cardioprotective glucose lowering agents in patients with diabetes in Sweden is encouraging. However, there is a signal that those agents are more often prescribed to a population with lower cardiovascular risk with an associated better outcome and less often to those at high risk for new events. This may be one explanation for the lower mortality rate seen. An increased awareness is needed to use effective cardioprotective treatment also in a high-risk population.Figure 1.Use of glucose lowering agentsFigure 2.Death by glucose lowering drugs