Novo Nordisk hosted a virtual summit last year on glucagon-like peptide-1 receptor agonist (GLP-1RA). One of the keynote speakers was Prof Mpiko Ntsekhe, head of the Cardiology Division at the University of Cape Town. Prof Ntsekhe discussed diabetes as a cardiometabolic disease and looked at the role of semaglutide, a GLP-1RA, in preventing and managing cardiovascular diseases (CVDs) in patients with type 2 diabetes (T2DM). 

Atherosclerotic CVD (ASCVD) – in particular stroke, myocardial infarction (MI), peripheral vascular disease and HF – is the main cause of morbidity and disability-adjusted life years in patients with T2DM. 

T2DM doubles, and in some cases triples, the risk of MI and stroke, relative to age and gender-matched controls. The absolute risks of ASCVD in patients with T2DM depends on: 

• Age
• Gender
• Hypertension
• Lipid profile
• Smoking
• Duration of diabetes
• Presence of microvascular complications
• Use of specific risk lowering medications (eg statins). 

CVD in T2DM  

T2DM is commonly associated with peripheral arterial disease (PAD) and heart failure (HF). T2DM was positively associated with PAD, ischaemic stroke, stable angina, HF, and non-fatal myocardial infarction (MI).  

The aim of the 2020 International Survey of the Occurrence of Cardiovascular Disease Among Patients with T2DM (CAPTURE) was to estimate the contemporary (2019) prevalence of established CVD in people with T2DM across 13 countries from five continents. In total, 9 823 adults with T2DM managed in primary as well as specialist care, participated. Overall CVD prevalence was 34.8%, with most (85.8%) categorised as ASCVD (31.8%). Overall coronary heart disease prevalence was 17.7%, carotid artery disease was 8.4%, and cerebrovascular disease was 7.2%. The overall prevalence of HF was 2.4%, driven by a relatively low prevalence in China (0.2%).  

Prevalence estimates were similar across primary and specialist care settings. The researchers concluded that in 2019, about one in three adults with T2DM attending a primary or specialist healthcare visit, had established CVD. In the CAPTURE study patients were treated with GLP-1RAs such as semaglutide, and sodium-glucose cotransporter-2 inhibitors (SGLT-2is). Most guidelines now recommend early introduction of these agents as second-line therapy in combination with metformin in patients who are at high risk or have established CVD, explained Prof Ntsekhe.   

THE ROLE OF SEMAGLUTIDE  

Semaglutide has an extended half-life of about seven days, allowing for one weekly dosing. Its efficacy and safety have been shown in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6).  

Prof Ntsekhe noted that most patients in the study had established CVD – either past MI or stroke. But what are the implications for patients who were considered high risk, but did not have a history of CVD?  

In a post-hoc analysis of SUSTAIN-6, time to major adverse cardiovascular events (MACE) and its individual components (CV death, non-fatal MI, nonfatal stroke), hospitalisation for unstable angina or HF, and revascularisation (coronary and peripheral) were analysed for all subgroups.   

Compared with placebo, semaglutide reduced the risk of the first occurrence of MACE and each MACE component consistently across all subgroups (gender, age, and baseline CV risk profile). Revascularisations, HbA1c and body weight were also reduced consistently across all subgroups compared with placebo. 

In this post-hoc analysis of SUSTAIN-6, once-weekly semaglutide vs placebo reduced the risk of MACE in all subjects included in the trial, regardless of gender, age, or baseline CV risk profile, noted Prof Ntsekhe. The findings of this study have important implications. Newer agents like semaglutide offer major opportunities for better patient care and outcomes, said Prof Ntsekhe.  

TAKE-HOME MESSAGES 

1. The burden of diabetes is high and growing – particularly in geographical regions such as sub-Saharan Africa
2. The burden of CVD in patients with T2DM is high with ASCVD predominating as the main manifestation
3. It is important to view diabetes as a cardiometabolic disease rather than a disorder of dysglycaemia
4. Early use of once weekly semaglutide provides opportunity to improve CVD outcomes beyond traditional risk factor control.

References available on request.