These drugs are GLP-1 agonists and SGLT-2 inhibitors.
Cardiovascular Outcome Trial (CVOT) studies of these two antidiabetic treatments demonstrate (for most GLP1-RA and SGLT-2i) a very significant benefit and protection mainly from cardiovascular disease.
Specifically documented:
• Significant reduction in major cardiovascular events (MACE point: non-fatal myocardial infarction, non-fatal stroke and cardiovascular death), in secondary prevention patients (patients with known cardiovascular disease) with most agonists GLAT-1RA, d SGLT-2i inhibitors (empa, cana, dapagliflozin).
• Significant reduction of renal endpoint with SGLT-2i and GLP-1RA (provided, however, that albuminuria – a sign of diabetic renal disease – is included in renal endpoint).
• Significant reduction in hospitalization risk for heart failure with SGLT-2i.
“Because the two comparable groups (intervention group – control group) in the cardiovascular safety studies had similar glycemic regulation (similar mean levels of glycosylated hemoglobin, as was the design of the studies) it is obvious that the particular pleiotropic, systemic effects of GLP-1RA and SGLT-2i contributed particularly to these favorable results “, says Dr. Andreas Melidonis, Coordinating Director of the Diabetological and Cardiometabolic Center of the Metropolitan Hospital, President of EKO. WITH. Ν.
At the same time, the analysis of cardiovascular safety studies revealed other interesting conclusions:
• There was no reduction in major cardiovascular events in primary prevention patients (ie patients who had only risk factors but no disease). In the corresponding meta-analyzes of these antidiabetic treatments but also in the individual cardiovascular safety analyzes, with the exception of dulaglutide, in the REWIND study, no analysis showed a reduction of major cardiovascular events in the population of primary prevention patients.
• There was no significant reduction in microangiopathic complications and more specifically diabetic retinopathy in the cardiovascular safety assays of GLP-1RA and SGLT-2i.
“However, as the particular and ongoing focus on the benefits of GLP-1RA and SGLT-2i treatments seems to coexist with a relative ‘degradation’ of glycemic control value, it would be good to (re) look at its documented consequences.” explains the doctor.
Consequences of intensive glycemic control
Recent meta-analysis data from all prospective randomized trials (RCTs) investigating the effect of intensive versus conventional glycemic control on major cardiovascular events were recently published. According to the meta-analysis, this intensive regulation significantly reduced the incidence of major cardiovascular events compared to conventional regulation.
Particularly important was the reduction of the incidence of major cardiovascular events in:
• Primary prevention patients
• Patients with a duration of diabetes <10 years
• Patients with follow-up duration> 10 years.
In contrast, the reduction in the incidence of major cardiovascular events in:
• Secondary prevention patients (patients with cardiovascular disease)
• Patients with a duration of diabetes> 10 years.
Regarding the effects of glycemic regulation on microangiopathic complications, the effect of strict regulation on reducing the incidence of these complications is striking:
• In diabetes mellitus 1, the Diabetes Control and Complications Trial-DCCT study (the only randomized controlled trial-RCT in type 1 diabetes mellitus) showed a significant reduction in the incidence of all microangiopathic complications (60% reduction in diabetic neuropathy, 54% of diabetic neuropathy). , 63% of diabetic retinopathy) in the intensive care unit. This significant reduction in all complications was demonstrated in the follow-up to the DCCT study, the observational study Epidemiology of Diabetes Interventions and Complications (EDIC).
• In diabetes mellitus 2, in the UK Prospective Diabetes Study-UKPDS study there was a significant 25% (27% of diabetic retinopathy) reduction of microangiopathic complications in the intensive care unit that remained significant even 10 years after intervention.
The value of glycemic control in the prevention of serious complications and fatalities has been clearly demonstrated in the treatment of COVID-19 diabetic patients.
In a study of 7,300 hospitalized diabetic patients with COVID-19, it was shown that patients who had adequate glycemic control (sugars <180mg / dl) during their treatment showed a dramatic reduction in the risk of death (HR = 0.14 p = 0.008) compared with patients who remained unregulated during hospitalization. That is, they showed a reduction of 86% of fatalities in hospitalization, as a result of good glycemic control.
They also showed a significant reduction in the risk of acute renal failure (acute renal failure) and acute heart failure.
It is also worth noting that in-hospital diabetic patients were significantly better-regulated before hospitalization (glycosylated hemoglobin = 7.1% vs. glycosylated hemoglobin = 8.3% of non-hospital diabetics).
In-hospital hyperglycemia (but also hypoglycemia) particularly impairs immune function, promotes the secretion of adhesion molecules and inflammatory cytokines and therefore the “cytokine storm” associated with the severe progression of COVID-19 disease and the risk. Glycemic regulation and the anabolic effect of insulin in hospitalization obviously contribute to the beneficial effects shown by the studies.
“In conclusion, glycemic regulation is important and irreplaceable for the prevention of cardiovascular complications in newly diagnosed individuals with diabetes and primary prevention of diabetes, as well as for the prevention and reduction of microangiopathic complications and the prevention of acute illness.
“In diabetic patients with established cardiovascular disease, glycemic control must be done with new, proven cardiovascular benefit treatments, such as GLP-1RA and SGLT-2i, to provide cardiovascular and renal protection for them,” concludes Dr. Melidon.
Writes:
Dr. Andreas Melidonis, Coordinating Director of the Diabetological and Cardiometabolic Center of the Metropolitan Hospital, President of EKO. WITH. Ν.
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