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30-01-2019 | Cardiovascular outcomes | Case study | Article

Cardiovascular risk reduction in type 2 diabetes

Author: Kevin Fernando

Author bio | Disclosures

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)
Non-HDL cholesterol 4.2 mmol/L
HbA1c 64 mmol/mol (8%) – up from 50 mmol/mol (6.7%) 12 months ago

Urinalysis

No evidence of microalbuminuria

Current medications

Metformin 1 g bid
Gliclazide 160 mg bid
Lisinopril 20 mg bid
Atorvastatin 80 mg od
Aspirin 75 mg od
Clopidogrel 75 mg od (for 12 months post-stent)

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.

Editor's recommendation
Files

17-10-2017 | GLP-1 agonists | At a glance | Article

Round up of the GLP-1 receptor agonist CV outcome trials

medwireNews provides a brief overview of the published and ongoing glucagon-like peptide-1 receptor agonist cardiovascular outcomes trials.

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.

Editor's recommendation
Files

10-11-2018 | SGLT2 inhibitors | At a glance | Article

Round-up of the SGLT2 inhibitor CV outcome trials

With DECLARE-TIMI 58 now published, medwireNews rounds up the SGLT2 inhibitor cardiovascular outcome trials so far.


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...
  • Your patient re-presents with a 6-month history of worsening shortness of breath on exertion and associated ankle swelling.
  • Physical examination reveals:
    • Pitting edema to both ankles
    • Bi-basal crackles on auscultation
  • Investigations reveal:
    • Elevated NTProBNP at 700 pg/mL
    • Echocardiogram reveals left ventricular systolic dysfunction with an ejection fraction of 35%
  • The patient is reviewed by cardiology and commenced on:
    • Furosemide 80 mg bid
    • Carvedilol 3.125 mg bid
  • HbA1c remains above target at 60 mmol/mol (7.6%) and eGFR has improved to 63 mL/min per 1.73 m2
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

Literature
  1. Jardiance: EPAR - Product Information. Available at www.ema.europa.eu/documents/product-information/jardiance-epar-product-information_en.pdf. [Accessed 26 November 2018].
  2. Invokana: EPAR - Product Information. Available at www.ema.europa.eu/documents/product-information/invokana-epar-product-information_en.pdf. [Accessed 26 November 2018].
  3. The Emerging Risk Factors Collaboration, Sarwar N, Gao P et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375:2215–2222.
  4. Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38: 140–149.
  5. Davies MJ, D'Alessio DA, Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2018; 61: 2461–2498.
  6. SIGN 154: Pharmacological management of glycaemic control in people with type 2 diabetes. Available at www.sign.ac.uk/assets/sign154.pdf. [Accessed 26 November 2018].
  7. Zinman B, Wanner C, Lachin J et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117–2128.
  8. Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375: 311–322.
  9. Neal B, Perkovic V, Mahaffey K et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644–657.
  10. Holman RR, Bethel MA, Mentz R et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017; 377: 1228–1239.
  11. Marso SP, Bain SC, Consoli A et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375: 1834–1844.
  12. Wiviott SD, Raz I, Bonaca MP et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2018; Advance online publication. doi:10.1056/NEJMoa1812389.

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