Back to Basics: How Your Type-2 Diabetes Medication Actually Work

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Diabetes is a disease condition where the body is resistant to, does not produce or produces too little of the substance required to break down sugar. This substance is a hormone called insulin. Insulin was first isolated by Frederick Banting and Charles Best with contributions from James Collip and J.J.R. Macleod had brought about a dramatic breakthrough as one of medical research’s earliest successes. Frederick Banting and JJR. Macleod were awarded a Nobel prize for this discovery in 1923.

There are two types of Diabetes: Type 1 and type 2. In type 1 diabetes, no insulin is produced at all while in type 2, it is produced but in insufficient quantities and or the body is not able to utilize it fully. Therefore, diabetic medications are aimed at either replacing the insulin hormone, stimulating the production of insulin, or regulating the body's response to insulin.

It is important to keep blood sugar within normal levels because excessively high blood sugar for a prolonged time may lead to complications that involve the small blood vessels, large blood vessels and nerves of multiple organs and body systems. Heart disease is the most common cause of death in patients with diabetes because of the significant impact of diabetes on various body functions and hence the need to pay close attention to treatment and management of diabetes.

Insulin is the only drug that works in type 1 diabetes while there are several classes of medications that are effective in the treatment of type 2 diabetes. The following are the pharmacologic classifications of type-2 diabetic medications and a quick rundown of how they work.

Biguanides

Metformin is the medication of first choice for newly diagnosed and uncomplicated type 2 diabetes. It decreases the amount of sugar produced by the liver, increases the uptake of sugar into body cells and also improves sugar breakdown by the body. In addition, the medication is very cost effective which makes it a very popular choice. Caution must however be observed in patients with reduced kidney function due to the possibility of acute renal failure. Metformin may also cause vitamin B12 deficiency resulting in anemia and nerve problems. Thus, supplementation with vitamin B12 may be needed while on Metformin.

Alpha-glucosidase Inhibitors

Acarbose and miglitol inhibit an enzyme in the intestines called alpha-glucosidase. This group of drugs causes a delay in digestion of sugar-producing foods and ultimately a reduction in blood sugar levels especially after a meal. Therefore, acarbose should be taken with the first bite of the main meal. Common side effects include flatulence, abdominal discomfort and diarrhoea.

Dipeptidyl Peptidase-4 Inhibitors

This group of diabetic medications are also known as the Gliptins such as Alogliptin, Linagliptin, Saxagliptin (Onglyza) and Sitagliptin (Januvia). They work by increasing the availability of a substance called GLP-1 (Glucagon Like Peptide 1) as well as other potentially active substances involved in sugar balance such as incretin. Incretins are a group of metabolic hormones that are secreted after food intake which in turn stimulates the release of insulin from the pancreas. They are mostly used as second or third-line agents when blood sugar is not controlled with metformin. Caution must be taken in people with pancreas issues because this group of drugs can induce pancreatitis, ie inflammation of the pancreas.

Glucagon-Like Peptide-1 Receptor Agonists

Dulaglutide, Semaglutide, Liraglutide, Lixisenatide and Exenatide are the currently available medications in this class. These agents work by mimicking the actions of the Glucagon Like Peptide 1 (GLP-1) which increases insulin secretion and also increases satiety. This results in better control of sugar levels and even weight loss. These agents are available as short-acting injections used daily, long-acting injections used once weekly and as oral tablets used daily. Some of these agents like semaglutide (Rybelsus) also have proven evidence of preventing heart disease. Common side effects of drugs in this class are nausea and vomiting, thus should be started at lower doses. These drugs are not recommended in patients that have pancreatitis or thyroid tumors.

Insulin Secretagogues: Sulfonylureas and Meglitinides

These agents: gliclazide, glimepiride, glyburide and tolbutamide stimulate the pancreatic cells to produce more insulin than they would normally do on their own. There is also repaglinide which has a shorter duration of action.

They are very good at reducing blood sugar but could also drop the blood sugar too low causing a state commonly referred to hypoglycemia. Symptoms of hypoglycemia include headaches, dizziness, confusion and even fainting. Every diabetic patient should be aware of the signs and symptoms of hypoglycemia and quickly use a source of sugar to bring the blood sugar back to normal levels.

Sodium-Glucose Cotransporter 2 Inhibitors

These agents include canagliflozin, dapagliflozin, empagliflozin and ertugliflozin. They work by blocking up to 90% of sugar reabsorption in the kidneys. This leads to an increased excretion of sugar through the kidneys and a corresponding reduction in blood glucose. They have a low risk of hypoglycemia and their actions are very dependent on kidney function. Due to increased sugar excretion from the kidneys, there is an increased risk of urinary tract infections especially yeast infections. Some of these agents like the Dapagliflozin (Farxiga) and the Empagliflozin (Jardiance) have been shown to lower risk of kidney failure and heart diseases.

Thiazolidinediones (TZDs)

Pioglitazone (Actos) and rosiglitazone, also called insulin sensitizers, influence the way the body cells act and respond to insulin and thereby lowering blood sugar. When used as a single medication, the risk of hypoglycemia is low. This risk however increases when combined with insulin secretagogues and or insulin. Some analyses have called into question the heart safety of thiazolidinediones even though various studies have failed to prove this.

Insulin for Type 2 Diabetes

Type 2 diabetes disease is progressive in nature and eventually, all non-insulin regimens gradually lose their efficacy over the years. Insulin therefore is very important as it also does not adversely affect the heart.

Insulin is usually the last drug of choice but may be used as the first line in some cases such as

1. Pregnancy

2. Very high blood sugar levels

3. End organ damage such as kidney failure

Insulin is associated with weight gain and a lot of patients are also hesitant because of the frequent needle pricks.

In conclusion, there are a variety of drug options in type 2 diabetes and treatment can easily be tailored to each patients’ preferences, tolerance and lifestyle. As effective as medications are, the importance of self education, exercise, proper diet and regular blood sugar monitoring cannot be over emphasized in diabetes management. Remember, proper diet and exercise can be used as medicine in treating and reducing risks linked with diabetes. Always keep in touch with your diabetes management and care team such as your doctor, endocrinologist, dietitian/nutritionist or health coach.

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