Case presentation
Your patient is a 55-year-old man with a 6-year history of type 2 diabetes complicated by essential hypertension. He is an ex-smoker. Unfortunately, he has recently suffered a non-ST elevation myocardial infarction. He underwent coronary angioplasty and stenting, and a post-event echocardiogram revealed normal left ventricular function.
Examination today reveals: | |
BMI | 31 kg/m2 |
Blood pressure | 137/82 mmHg |
Bloods | Impaired renal function (eGFR 53 mL/min per 1.73 m2) |
Urinalysis | No evidence of microalbuminuria |
Current medications | Metformin 1 g bid |
bid=twice daily; BMI=body mass index; eGFR=estimated glomerular filtration rate; HbA1c=glycated hemoglobin; HDL=high-density lipoprotein; od=once daily |
After reinforcing lifestyle advice, what is your next step with respect to his glycemic control?
Case discussion
Cardiovascular disease remains the leading cause of death in those with type 2 diabetes. Individuals with type 2 diabetes have approximately twice the risk of suffering a cardiovascular event compared with those without type 2 diabetes [3].
Watch above or click here to read Dr. Fernando’s recommendations
The management of hyperglycemia in type 2 diabetes: a new consensus report from the European Association for the Study of Diabetes and American Diabetes Association
A joint task force established by the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) highlights that comprehensive cardiovascular risk reduction should remain the focus of type 2 diabetes management rather than the largely glucose-centric approach that has been adopted previously [4]. Efforts should include smoking cessation and other healthy lifestyle habits, blood pressure control, lipid management with statin treatment as appropriate and, in some circumstances, antiplatelet therapy.
The task force reiterates the importance of individualized treatment targets and strategies, with an emphasis on patient-centered care and shared decision-making. However, the 2018 consensus report from the ADA/EASD has changed the treatment paradigm again, by asking those in primary care to risk stratify individuals with type 2 diabetes according to the presence of atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease [5]. This mirrors the approach in many other national and international guidelines, including the Scottish Intercollegiate Guidelines Network (SIGN) 154: Pharmacological management of glycemic control in people with type 2 diabetes, which was published during 2017 [6]. Primary care physician Amrit Lamba gives his perspective on the ADA/EASD hyperglycemia guidelines in this interview.
This widespread change in guidance is being driven by data emerging from clinical trials analyzing the cardiovascular outcomes of diabetes medications, rather than their glucose-lowering effects. EMPA-REG OUTCOME [7] and LEADER [8] were two such landmark trials demonstrating the cardioprotective benefits of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide, respectively.
Diabetes medications with proven cardiovascular benefit
Empagliflozin demonstrated significant reductions in cardiovascular death, all-cause death, and hospitalization for heart failure compared with placebo. There was also a significant reduction in the progression of renal disease. Liraglutide demonstrated significant reductions in cardiovascular death and all-cause death compared with placebo, as well as a small but significant reduction in the progression of renal disease. There was no improvement in heart failure outcomes observed with liraglutide.
The ADA/EASD consensus report recommends the use of an SGLT2 inhibitor or GLP-1 receptor agonist with proven cardiovascular benefit in individuals with atherosclerotic cardiovascular disease, and if not at mutually agreed glycated hemoglobin (HbA1c) target [5]. At the time of writing, the following medications have shown evidence of reducing cardiovascular events:
Commercially available diabetes medications with proven cardiovascular benefit | ||
Medication class | Medication name | References |
GLP-1 receptor agonist | Liraglutide | [8] |
Semaglutide | [11] | |
Exenatide extended-release | [10] | |
SGLT2 inhibitor | Empagliflozin | [7] |
Canagliflozin | [9] | |
Dapagliflozin | [12] |
Furthermore, if an individual is at their mutually agreed HbA1c target, switching to an SGLT2 inhibitor or GLP-1 receptor agonist with proven cardiovascular benefit should be considered.
12 months later... |
|
bid=twice daily; eGFR=estimated glomerular filtration rate; HbA1c=glycated hemoglobin; NTProBNP= N-terminal prohormone of brain natriuretic peptide |
After reinforcing lifestyle advice, what is your next step with respect to his glycemic control?
Watch above or click here to read Dr. Fernando’s recommendations
The ADA/EASD consensus report recommends stratifying individuals by the presence of heart failure; if heart failure predominates, an SGLT2 inhibitor with evidence of reducing heart failure in cardiovascular outcome trials should be preferentially considered. If an SGLT2 inhibitor is not tolerated or contraindicated, or if eGFR is less than adequate, a GLP-1 receptor agonist with proven cardiovascular benefit can be considered.
All three currently available SGLT2 inhibitors have demonstrated a reduction in hospitalization for heart failure in cardiovascular outcome trials. Interestingly, the recently published DECLARE-TIMI 58 trial (dapagliflozin) suggests that this benefit extends into primary prevention populations in addition to secondary prevention populations. DECLARE-TIMI 58 steering committee member, John Wilding provides his insights in an interview here.
Summary
Cardiovascular disease in people with type 2 diabetes contributes to significant loss of life–years, and there has been a paradigm shift in diabetes guidelines with more emphasis on the cardiovascular benefits of diabetes drugs and not just their glucose-lowering properties.
Watch above or click here to read Dr Fernando’s Quality Improvement recommendation