Abstract

PurposeSome classes of glucose-lowering medications, including sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1-receptor agonists (GLP1-RAs) have cardio-protective benefit, but it is unclear whether this influences prescribing in the United Kingdom (UK). This study aims to describe class-level prescribing in adults with type 2 diabetes mellitus (T2DM) by cardiovascular disease (CVD) history using the Clinical Practice Research Datalink (CPRD). MethodsFour cross-sections of people with T2DM aged 18–90 and registered with their general practice for >1 year on 1st January 2017 (n = 166,012), 1st January 2018 (n = 155,290), 1st January 2019 (n = 152,602) and 31st December 2019 (n = 143,373) were identified. Age-standardised proportions for class use through time were calculated separately in those with and without CVD history and by total number of medications prescribed (one, two, three, four+). An analysis by UK country was also performed. FindingsAround 31% of patients had CVD history at each cross-section. Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines). Overall use of SGLT2is and GLP1-RAs was low, with slightly less use in patients with CVD (SGLT2i: 9.8% and 13.8% in those with and without CVD respectively; GLP1-RA: 4.3% and 4.9%, December 2019). Use of SGLT2is as part of dual therapy was low but rose throughout the study. In January 2017, estimated use was 8.0% (95% CI 6.9–9.1%) and 8.9% (8.6–9.3%) in those with and without CVD. By December 2019 this reached 18.3% (17.0–19.5%) and 21.2% (20.6–21.7%) for those with and without CVD respectively. SGLT2i use as triple therapy increased: 22.7% (21.0–24.4%) and 25.9% (25.2–26.6%) in January 2017 to 41.3% (39.5–43.0%) and 45.5% (44.7–46.3%) in December 2019. GLP1-RA use also increased, but observed usage remained lower than SGLT2 inhibitors. Insulin use remained stable throughout, with higher use observed in those with CVD (16% vs 9.7% Dec 2019). Time trends in England, Wales, Scotland and Northern Ireland were similar, although class prevalence varied. ImplicationsAlthough use of SGLT2is and GLP1-RAs has increased, overall usage remains low with slightly lower use in those with CVD history, suggesting there is opportunity to optimise use of these medicines in T2DM patients to manage CVD risk. Insulin use was substantially more prevalent in those with CVD despite no evidence of CVD benefit. Further investigation of factors influencing this finding may highlight strategies to improve patient access to the most appropriate treatments, including those with evidence of cardiovascular benefit.

Highlights

  • Cardiovascular disease (CVD) is a common comorbidity of type 2 diabetes mellitus (T2DM) globally[1] as well as in the United Kingdom, with ~35% of people with T2DM estimated to have cardiovascular disease (CVD).[2]

  • For the sodium-glucose cotransporter 2 (SGLT2) inhibitors, the EMPA-REG OUTCOME and CANVAS (Canagliflozin Cardiovascular Assessment Study) trials both showed a significant reduction in the primary end point of 3-point major adverse cardiovascular events (MACE), including CV death, nonfatal myocardial infarction, and nonfatal stroke, in a population with T2DM and increased risk for CVD, and empagliflozin showed a significant reduction in cardiovascular death.[3,4]

  • The data suggest that use of glucagon-like peptide 1-receptor agonists (GLP1-RA) has not increased at the same speed as SGLT2 inhibitors since 2017, with usage still below 20% at the end of 2019 in the majority of country/CVD status strata (Figure 3; Supplemental Figs. 3 and 4)

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Summary

Introduction

Cardiovascular disease (CVD) is a common comorbidity of type 2 diabetes mellitus (T2DM) globally[1] as well as in the United Kingdom, with ~35% of people with T2DM estimated to have CVD.[2]. All SGLT2 inhibitors showed a significant reduction in hospitalization for heart failure and the composite end point of hospitalization for heart failure or cardiovascular death.3e6 For the GLP1-RAs, 4 of the 7 cardiovascular outcome trials (LEADER [Liraglutide Effect and Action in Diabetes], SUSTAIN-6 [Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes], HARMONY Outcomes, and REWIND [Researching Cardiovascular Events with a Weekly Incretin in Diabetes]) have shown significant reductions in 3point MACE.7e13

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