IN our last article we looked at some of the measures that can be used to improve the outcome of the diabetic patient and noted that cardiac and vascular disease represent the most common cause of death in the diabetics.

The incidence of heart attack, heart failure, and stroke is approximately two to four times that of the general population and cardiovascular disease represent the largest cause of mortality in diabetes.

Insulin was the first drug available to treat diabetes and this was isolated in 1922. The first oral medications for diabetes, the sulfonylureas were discovered in 1942. The management of the diabetic patient for the first 60 to 70 years concentrated on the management of the blood sugar,; however, over the last three to free decades there has been greater emphasis on preventing and managing the complications of diabetes and trying to improve morbidity and mortality. Metformin has for decades been the drug of first choice in the management of Type 2 diabetes in part because of its cardiovascular safety. The last 10 years have seen the emergence of two groups of diabetes medications with robust effects in lowering cardiovascular morbidity and mortality. We will briefly review these medications this week.

Sodium glucose transport 2 (SGLT2) inhibitors

The SGLT2 inhibitors are a class of medications that prevent reabsorption of glucose that has been filtered into the urine. This results in loss of glucose from the body thus lowering the blood sugar level. The presence of high urinary sugar increases the excretion of salt and water from the body. Initial studies of the SGLT2 inhibitors have found that in addition to improving diabetic control, these agents lower the risk of developing heart failure in diabetic patients. These agents also reduce the risk of developing heart failure, being hospitalised with heart failure and the combination of heart failure and death. Further data has found that this benefit extends to patients with heart failure who are not diabetic. Given these findings, SGLT2 inhibitors are currently considered standard treatment for most forms of heart failure. An interesting finding is that the beneficial effects of these agents are noted within weeks of initiation. They have also been demonstrated to significantly decrease the likelihood of diabetic kidney disease and are associated with a small reduction in the risks of heart attack and stroke. The drugs are safe to use with low risk of low blood sugar. The major concern, in terms of complications, is that of infection in the urinary tract, groin, and lower abdominal area.

Glucagon-like peptide receptor 1 agonists (GLP 1 receptor agonists)

These agents have multiple effects which aid in blood sugar control. They stimulate the release of insulin from the pancreas, they prevent the release of glucagon (a hormone which acts in opposition to insulin), slow stomach emptying and decrease appetite. Of most interest to the general population is the fact that these agents produce significant weight loss. The weight loss is 10-15 per cent of body weight on average and many non-diabetics have been using this drug off-label to lose weight. From a cardiac point of view, these agents decrease the risk of disease related to atherosclerosis (cardiovascular death, heart attack and stroke) by up to 24 per cent. In contrast to the SGLT2 inhibitors the effects on cardiac and vascular morbidity and mortality take place over months to years suggesting that ameliorating the effects of cholesterol deposition in vessels is an important part of their effect. The major side effects of these agents are gastrointestinal with nausea, diarrhoea and vomiting being most common. There is also a rare risk of inflammation of the pancreas.

Metformin

Metformin is one of the older agents that is used for treatment of diabetes. It has been used since the late 1950s. It is currently considered a first line medication for the newly diagnosed diabetic patient. It is safe, effective, and results in some weight loss, on average four to seven pounds. The evidence of metformin for improving cardiac outcome in the diabetic patient is mixed. Several studies have shown that it reduces the risk of dying, as well as the risk of heart attack and stroke. Most of these studies; however, are observational and not gold standard large randomised controlled trials. A recent analysis by the Cochrane group in 2020 has concluded that most of the studies demonstrating its protective effect for the heart and vascular system are limited and have suggested further research in this area. While there is some debate as to whether and how much it improves outcome there is no signal of cardiac or vascular harm.

What about aspirin?

For several decades, the use of aspirin was considered a routine part of management of the diabetic patient given the considerable risk of cardiac and vascular disease. Studies over the past 30 years have however made clear that there is a difference between aspirin use in a preventative sense i.e., patients who do not yet have vascular disease and in a secondary sense i.e., patients who are using aspirin after developing stroke, heart attack or peripheral vascular disease. There is a much greater risk reduction in the second group of patients. The use of aspirin is associated with a risk of bleeding particularly from the gastrointestinal tract and the brain, and while this risk is low, we do need to consider this risk when prescribing aspirin. In the group of patients who only have diabetes and no vascular disease the risk of bleeding is high enough and the likely benefit low enough that most professional societies have suggested that aspirin use be avoided. In contrast there is robust data that diabetic patients with stroke, heart attack or peripheral vascular disease have improved outcomes on aspirin even when considering the risk of bleeding. A grey area is patients who do not yet have vascular disease but who would be considered extremely high risk. Some experts would suggest the use of low dose aspirin along with medications to protect the stomach.

How do I reduce my cardiac and vascular risk as a diabetic patient?

It is important to remember that medical therapy should take place on a foundation of lifestyle change. Regular aerobic exercise, a heart healthy diet, good sleep hygiene, stress management, avoiding smoking, and illicit drugs, limiting alcohol and weight management are essential for good outcomes. Close attention should be paid to blood pressure as poor hypertension control in diabetic patients is a strong risk factor for heart and vascular disease. ACE inhibitors and angiotensin receptor blockers are considered first line for the management of hypertension in diabetes given the protective effects for the kidneys. Most patients with diabetes will benefit from statin therapy to lower the LDL cholesterol, so that patients should be aware of their cholesterol profile. The use of aspirin should be restricted to patients who have established vascular disease or used selectively in those who are at very high risk for vascular complications. Patients should aim for good glucose control, ideally with a medication regimen that includes a diabetic agent that lowers cardiac and vascular risk as listed above.

Dr Ernest Madu, MD, FACC and Dr Paul Edwards, MD, FACC are consultant cardiologists for the Heart Institute of the Caribbean (HIC) and HIC Heart Hospital. HIC is the regional centre of excellence for cardiovascular care in the English-speaking Caribbean and has pioneered a transformation in the way cardiovascular care is delivered in the region. HIC Heart Hospital is registered by the Ministry of Health and Wellness and is the only heart hospital in Jamaica. Send correspondence to info@caribbeanheart.com or call 876-906-2107.