Thinking beyond HbA1c: managing CV risk in patients with T2DM

Thinking beyond HbA1c: managing CV risk in patients with T2DM

Diabetes is often oversimplified as a ‘sugar’ problem. However, over time we have learned that diabetes affects multiple organs such as the brain, the kidneys, and the heart. The good news is that we have developed various treatments aimed at improving glycaemic control in these patients, resulting in improved outcomes.1

This is according to Dr Nqoba Tsabedze, Academic Head of Cardiology at the University of the Witwatersrand, and Clinical Head of Cardiology at the Charlotte Maxeke/ Johannesburg Academic Hospital.

Dr Tsabedze presented a webinar entitled Thinking beyond HbA1c: managing CV risk in patients with T2DM, hosted by Specialist Forum and sponsored by Eli Lilly.1 Globally, the prevalence of T2DM continues to rise. In 2017, an estimated 424.9 million people were living with diabetes. This number is expected to increase to 628.6 million by 2045.2

CV risk in patients with T2DM

Although T2DM is often described in terms of a glucose pathology, many patients with the disease die as a result of cardiovascular disease (CVD).3,4 To reduce these patients’ CV burden, a number of management strategies have been developed, noted Dr Tsabedze. Current guidelines place a greater focus on patient-related issues such as CVD.1 The risk of CVD depends on the duration of T2DM. Dr Tsabedze stressed that T2DM is not a ‘single-point event’, but rather a condition that unravels over time.1 The risk of atherosclerotic CVD (ASCVD) is accelerated in individuals with metabolic syndrome (eg hypertension, central obesity and dyslipidaemia). By the time they are diagnosed with T2DM, they have a significant risk of ASCVD and after eight to ten years of living with T2DM, present with coronary heart disease.1,5

Management of T2DM

Management of T2DM is multi-pronged and should be based on shared decisionmaking between the clinician and patient. An effective management plan should incorporate a thorough assessment of key patient characteristics and factors that may impact the choice of treatment.6,7

Key patient factors include:

• Current lifestyle

• Comorbidities (eg heart failure [HF], ASCVD, chronic kidney disease [CKD])

• Clinical characteristics (eg HbA1c, weight)

• Issues such as motivation and depression

• Cultural and socioeconomic context.

Specific factors that impact the choice of treatment include:

• Individualised HbA1c target

• Impact on weight and hypoglycaemia

• Side effect profile medication

• Complexity of regimen (eg frequency and mode of administration)

• Access, cost and availability of medication.

CV trials

Numerous CV trials have been conducted aimed at improving outcomes for patients with T2DM who are at high risk of CVD. According to Dr Tsabedze, the two therapies that have shown the best CV benefits include glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose transport protein 2 inhibitors (SGLT2i).1 He highlighted the following SGLT2i studies:

• The Empagliflozin, CV Outcomes, and Mortality in T2DM study: Patients with T2DM at high risk for CV events who received empagliflozin as compared with placebo, had a lower rate of the primary composite CV outcome and of death from any cause when the study drug was added to standard care.8

• Dapagliflozin and CV Outcomes in T2DM: In patients with T2DM who had or were at risk for ASCVD, treatment with dapagliflozin resulted in a lower rate of CV death or hospitalisation for HF.9

He highlighted the following GLP-1RA studies:

• Liraglutide and CV Outcomes in T2DM: In the time-to-event analysis, the rate of the first occurrence of death from CV causes, nonfatal myocardial infarction (MI), or nonfatal stroke among patients with T2DM was lower with liraglutide than with placebo.10

• Semaglutide and CV Outcomes in Patients with T2DM: In patients with T2DM who were at high CV risk, the rate of CV death, nonfatal MI, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo.11

• Dulaglutide and CV Outcomes in T2DM: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with T2DM with either previous CVD or CV risk factors.12

• Oral Semaglutide and CV Outcomes in Patients With T2DM: Major adverse CV events occurred in 3.8% in the oral semaglutide group and 4.8% in the placebo group. Results for components of the primary outcome were as follows: death from CV causes, 0.9% in the oral semaglutide group and 1.9% in the placebo group, nonfatal myocardial infarction, 2.3% and 1.9%, respectively and nonfatal stroke, 0.8% and 1%, respectively. Death from any cause occurred in 1.4% in the oral semaglutide group and 2.8% in the placebo group.13

Key messages

• Most antidiabetic drugs show a neutral effect on CV outcomes in people with T2DM who were at an increased risk for CV events14

• Newer antidiabetic drugs are associated with a lower risk of CV events in adults with T2DM who were at high CV risk8-13

• GLP-1 RA and SGLT2i are the recommended options for individuals with T2DM and established CVD15

• SGLT-2is have shown consistent reductions in hospitalisation for HF and CKD outcomes, with benefits in terms of major CV events and all-cause mortality in some CV outcome trials (CVOTs)16

• GLP-1 RAs reportedly reduced ASCVD events, as well as all-cause mortality in some CVOTs16

• While both GLP-1 RAs and SGLT-2is have shown CV benefits in real-world studies as well, the prescription of these drugs appears to be still inadequate17-21

• The mechanisms of action of SGLT2is and GLP-1 RAs on metabolic and possibly CV/renal outcomes might be complementary22,23

• Patients often exhibit multiple needs in terms of glucose and weight control and protection of organ damage (eg heart, brain, kidney), and this requires combination therapy with both SGLT-2is and GLP-1RAs.22,24

References available on request. SF