Dr Angela Murphy helps us understand the recent changes in the guidelines for treating diabetes.
The purpose of treating diabetes is to improve the symptoms which result from high glucose levels and to prevent other complications in the future. Diabetes is a risk for heart disease, stroke, kidney failure, amputations and loss of vision. In fact, heart disease is the most common complication of diabetes, encompassing angina, heart attack and heart failure.
With good control, these conditions can be avoided. Achieving good control is the challenge for both patient and healthcare provider (HCP). We must never under estimate the benefit of a healthy lifestyle and this is always the building block in any treatment algorithm.
Controlled portions, choice of unrefined carbohydrates and good fats, as well as regular exercise are essential to have a holistic approach to managing diabetes.
When insulin was first discovered in 1922, it seemed the only feasible treatment for diabetes. It remains the cornerstone of treatment for Type 1 diabetes to this day. Although, there have been advances in types of insulin and ways to deliver it.
The initiation of treatment for Type 2 diabetes is generally straightforward in that most patients will be counselled regarding a healthy lifestyle and given metformin. Metformin reduces levels of blood glucose by decreasing the amount of glucose produced by the liver. It also improves the action of insulin, secreted by the pancreas, at the level of the muscle cell.
Many people, particularly those eating and exercising correctly, may control their blood glucose levels on metformin indefinitely. However, if the glucose levels and HbA1c start to rise, further treatment will need to be added.
At this point, the choice of medication becomes quite extensive. The critical question the HCP must now ask is: what is the right medication for the patient in front of me?
What is the right medication for the patient?
There are eight groups of diabetic medications with various types within each group. This means that the possible combinations of drug types and dosages can count into the hundreds. HCPs have for many years looked to clinical practice guidelines to assist in their choice.
The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) are sentinel voices in the world of diabetes. Many experts over many years have come together to work out diabetes management guidelines.
Most countries, including South Africa, will consult the content of these guidelines when drawing up local recommendations. In recent years, the experts from ADA and EASD have come together on several occasions to issue a Combined Consensus Statement on the management of Type 2 diabetes. The latest one, published at the end of 2018, suggested some basic changes to our approach of diabetes management.
2018 guidelines
The reason for the new guidelines is that it recognises the excess risk of cardiovascular disease in diabetic patients and takes into consideration the evolution of diabetes drugs, particularly with the advent of the sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.
SGLT2 inhibitors
SGLT2 inhibitors (Forxiga; Jardiance), also known as the gliflozins, act by blocking the re-uptake of glucose that has been filtered through the kidney. This results in excess glucose being excreted in the urine. The advantage of this glucose loss from the body is that this translates into a calorie loss as well which helps with some weight loss in the patient.
As the name of the medication suggests, not only excess glucose but sodium is excreted. The lowering of sodium helps reduce blood pressure and has beneficial effects on the heart.
Jardiance is registered in America for the indication of cardiovascular death reduction in the patient with Type 2 diabetes and previous cardiovascular disease (angina, heart attack, need for stents).
Forxiga has recently been shown to improve heart function in patients with heart failure; in both diabetic and non-diabetic subjects.
GLP-1 receptor agonists
GLP-1 (Byetta; Victoza) is a hormone secreted by the cells in the wall of the small intestine in response to food. The GLP-1 then stimulates the pancreas to secrete insulin and, thus, lowers post-meal glucose levels. The GPL-1 receptor agonist drugs also delay the emptying of the stomach and increase the sense of fullness which results in weight loss.
In addition, Victoza has proven to reduce the risk of a heart attack, stroke or death from these causes in Type 2 diabetic patients who have already had an event. The Federal Drug Agency (FDA) in America have added this benefit to the indications for the use of Victoza.
Cardiac protection changes how Type 2 diabetes patients are managed
The incredible cardiac protection these new medications offer in addition to diabetes control is so important that it has initiated a change in how we mange Type 2 diabetes.
It is crucial that HCPs identify the patients who would benefit from these medications as soon as possible. For this reason, the 2018 guidelines now advise that after initiation of metformin, patients should be divided into two groups.
The first group is those patients with atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD); i.e. patients who have already suffered from a heart attack or angina, had coronary stents, a stroke or have chronic decrease in kidney function.
The second big group is the patients who have not had heart or kidney disease to date. The latter group then gets subdivided into three main groups aiming for treatment that addresses a patient’s most pressing concern.
The groups identify those patients struggling with hypoglycaemia (low blood glucose), obesity, and those patients who need to keep costs of treatment down.
It makes sense that those patients with established ASCVD and CKD be given one of the classes of medication which have been proven to protect the heart from further events or a deterioration in heart function. As one would expect with a ‘designer drug’, the cost is significant and reimbursement from medical aids is not guaranteed.
SGLT2 inhibitors and GLP-1 receptor agonists do not cause hypoglycaemia. So, they would be possible choices in patients who need to avoid hypoglycaemia.
Dipeptidyl peptidase-4 inhibitors
Another group of medications, called dipeptidyl peptidase-4 inhibitors, also increase the natural GLP-1 levels and do not cause hypoglycaemia. The class of drugs most effective with weight loss is the GLP-1 receptor agonists, especially Victoza. However, much higher doses need to be used for weight loss management than just for diabetes management. A higher dose pushes up the cost.
South African setting
In South Africa, where most of the diabetes patients receive healthcare from the state and, in the current climate of escalating costs in the private healthcare system, cost effective medicine is essential.
The oldest group of oral medications used in Type 2 diabetes are the sulphonylureas (SUs) which increase insulin secretion from the pancreas.
The South African diabetes guidelines, drawn up by Society of Endocrinology and Metabolism of South Africa (SEMDSA), advocate the use of the newer generation SUs, such as gliclazide MR (Diamicron MR, Diaglucide MR and other generic formulations), as acceptable second-line treatment for Type 2 diabetes.
More than two million South Africans are living with diabetes. To improve their present and future health aiming for good glucose control is important. However, with increasing types of medication available to manage Type 2 diabetes, choosing the right drug for the right patient is becoming ever more important.
The newer agents have made it possible to improve long-term complications from the outset, by mechanisms other than just glucose lowering. It may not be necessary, or possible, for everyone to access these medications at present but the guidelines from both local and international societies will continue to guide the diabetes community to make the correct choice.
MEET OUR EXPERT
Dr Angela Murphy is a specialist physician working in the field of Diabetes and Endocrinology in Boksburg. She is part of the Netcare Sunward Park Bariatric Centre of Excellence and has a busy diabetes practice.