Treatment of Diabetes -Antidiabetic medicines

The medicines discussed in this post are used in the treatment of diabetes.

medications used in the treatment of diabetes

Alpha glucosidase inhibitor in treatment of Diabetes

Alpha-glucosidase inhibitors delays the digestion of carbohydrates by blocking enzymes in the small intestine that breakdown of starch and sucrose to glucose. This delay means glucose enters the bloodstream slowly thereby reducing the post meal blood glucose levels and ultimately lower HbA1c. They do not have any direct effect on insulin secretion or sensitivity. Alpha-glucosidase inhibitors also increase the amount of GLP-1 after a meal. GLP-1 is a hormone which helps to delay digestion and decreases appetite. Therefore alpha-glucosidase inhibitors are less likely to cause weight gain as compared to sulfonylureas and thiazolidinediones.

Examples of alpha-glucosidase inhibitors include Glucobay (Acarbose) and Glyset (Miglitol). They should either be chewed with the first bite of a meal or swallowed whole before the meal. While it is usually used as on its own, it can also sometimes be used in combination with a sulphonylurea.

Side effects of alpha-glucosidase inhibitors include flatulence (wind) which can sometimes lead to non-adherence, but this will decrease with time as your body adjusts to the medication. Diarrhoea is also another common side effect.

Biguanide in treatment of Diabetes

Metformin is the only biguanide available and is commonly used as a first-line treatment for people with type 2 diabetes. It is available in different forms – tablets for immediate release which can be taken up to three times per day or prolonged-release which is usually taken once a day and oral solution and powder for oral solution for immediate release. Biguanides reduce blood sugar levels by stopping the liver from producing new glucose as it prevents the liver from converting fats and amino acids into glucose. It also helps to overcome insulin resistance and improve the body’s sensitivity towards insulin by activating an enzyme (AMPK). This enzyme helps cells to respond more effectively to insulin and take in glucose from the blood.

Biguanides are particularly good for people who are overweight because it does not cause weight gain. Metformin can be taken on its own or used alongside other oral or injectable diabetes medications. The most common side effects are GI disturbances especially if taken at high doses.

Using Metformin together with general anaesthesia can cause ketoacidosis. It is best to suspend metformin on the morning of surgery and restart when renal function returns to baseline (your normal levels). Using Metformin together with iodinated contrast agents can cause renal failure and precipitate lactic acidosis, it is best to suspend metformin before the x-ray and restart after 48 hours if renal function returns to baseline.

Sulphonylureas in treatment of Diabetes

Sulphonylureas reduce blood sugar levels by making the pancreas produce more insulin and by increasing the effectiveness of insulin in the body. They are usually prescribed to be taken once or twice a day, with or shortly before a meal.

Sulphonylureas are not recommended for people with significantly reduced ability to produce insulin. It can be taken on its own or in used alongside other diabetes drugs such as metformin.

Sulphonylureas are not recommended for people who are overweight or obese as it can cause weight gain due to the way it exerts its effect. Other side effects of sulphonylureas include hypoglycaemia (low blood sugar). Sulphonylureas may also cause hypersensitivity (an allergic reaction) in the first six to eight weeks of therapy.

Gliclazide, Glipizide, Glibenclamide, Glimepiride, Tolbutamide are all examples of sulphonylureas.

Thiazolidinediones (Glitazones) in treatment of Diabetes

Thiazolidinediones reduce blood sugar levels by reducing peripheral resistance to insulin. When the body’s resistance to insulin is reduced, insulin works more effectively at improving blood glucose control. It also helps to protect the insulin-producing cells in the pancreas and is taken once or twice daily with or without food. It can be taken on its own or in used alongside other diabetes drugs such as metformin, sulphonylurea or insulin but dose of sulphonylurea or insulin may need to be reduced.

Glitazones has also been found to lower blood pressure and improve lipid metabolism by increasing levels of High-density lipoprotein (HDL) which is the good cholesterol and reducing levels of triglycerides. Triglycerides are a type of fat in your blood.

Pioglitazone is an example of a thiazolidinediones.

Your doctor may prescribe you a thiazolidinedione if you type 2 diabetes and have not been able to lower your blood sugar with metformin and either sulphonylureas or Meglitinides or if you have not been able to take them.

Side effects of thiazolidinediones include weight gain, GI upset, oedema, hypoglycaemia, headache, anaemia, visual disturbances, pain in a joint, blood in urine, increased risk of infection and numbness.

Liver toxicity may occur with thiazolidinediones use. Stop treatment and see your doctor immediately if you experience severe gastrointestinal upset, fatigue, jaundice, or dark urine.

Pioglitazone should not be used in patients with heart failure or a history of heart failure. You also have the risk of heart failure increases when pioglitazone is combined with insulin. Your doctor should closely monitor you and discontinue treatment if you show any sign of deterioration in cardiac status occurs e.g. oedema, shortness of breath, fatigue, and irregular heartbeat.

Pioglitazone slightly increases your risk of having bladder cancer. Your doctor should have assessed you for this risk before starting treatment. Report immediately to your doctor if you experience any blood in urine, urinary urgency or painful or difficult urination.

Meglitinides (Glinides) in treatment of Diabetes

Glinides reduce blood sugar levels by stimulating pancreatic beta cells to produce insulin. They are taken up to three times before main meals and should be taken 30 minutes before eating to help reduce subsequent post-meal spikes in blood glucose levels. They a rapid but short acting so suitable for people whose lifestyle do not follow a routine.

Nateglinide and Repaglinide are examples of meglitinides

Side effects of Glinides include hypoglycaemia, hypersensitivity, liver problems, constipation, nausea

abdominal pain and diarrhoea.

DPP 4 inhibitors (Gliptins) in treatment of Diabetes

Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce blood sugar levels by blocking the action of DPP-4. DPP-4 is an enzyme that breaks down incretins. Incretins are a group of gastrointestinal hormones produced by the gut in response to food. Incretins trigger insulin secretion and lower glucagon secretion. They are beneficial for overweight patients as can help reduce appetite.

Your doctor may prescribe you a DPP 4 inhibitors if you type 2 diabetes and have not been able to lower your blood sugar with metformin and sulphonylureas.

Side effects of DPP-4 inhibitors include hypoglycaemia, gastrointestinal problems – including nausea, diarrhoea and stomach pain, skin reactions – painful skin followed by a red or purple rash and flu-like symptoms – headache, runny nose, sore throat, peripheral oedema and with rarely with Vildagliptin, liver dysfunction has been reported

See your doctor immediately if you have trouble breathing or a severe skin reaction.

DPP-4 inhibitors have been linked with an increased risk of pancreatitis. Discontinue treatment and see your doctor immediately if you experience severe abdominal pain, nausea, and vomiting.

DPP-4 inhibitors have been linked to liver toxicity: Discontinue treatment and see your doctor immediately if you experience symptoms of liver dysfunction occur e.g. severe gastrointestinal upset, fatigue, jaundice, or dark urine

Alogliptin, Linagliptin, Saxagliptin, Sitagliptin, Vidagliptin are examples of DPP-4 inhibitors

SGLT2 Inhibitors (Gliflozins)

SGLT2 inhibitors reduce blood sugar levels by blocking SGLT2 in the renal tubules of the kidneys to prevent the kidneys from reabsorbing glucose back into the blood and increase glucose excretion. They are taken once a day with or without food.

The kidneys usually filter glucose out of the blood and then reabsorbs glucose back into the blood. Kidneys use a protein called sodium-glucose transport proteins to reabsorb glucose. When SGLT2 inhibitors block these proteins, less glucose gets reabsorbed back into the blood and more glucose gets passed out of the body via the urine.  SGLT2 inhibitors can also have benefits for overweight patients as removal of glucose from the body can lead to weight loss.

Your doctor may prescribe you SGLT2 inhibitors if you have type 2 diabetes and have not been able to lower your blood sugar with a medication regimen such as metformin and insulin.

Your doctor should not prescribe you an SGLT2 inhibitors if you have kidney disease (nephropathy) as this prevents the drug from working well.

Side effects include of SGLT2 inhibitors constipation, thirst, nausea, lower urinary tract infection (UTI), hypoglycaemia (low blood sugar), and polyuria – when the body produces abnormally large amounts and causes you to urinate more than usual and passes excessive or abnormally large amounts of urine each time you urinate.

SGLT2 inhibitors have been associated with volume depletion. Your doctor will correct any hypovolaemia before treatment.  They may also interrupt treatment if symptoms of hypovolaemia occur. Symptoms of hypovolaemia includes postural hypotension and dizziness.

Some patients taking SGLT2 inhibitors have reported having serious and potentially life-threatening cases of diabetic ketoacidosis (DKA). It has been reported to occur with both high and normal sugar levels. You should discontinue treatment immediately and seek prompt medical attention.

Canagliflozin may increase the risk of lower-limb amputation (mainly toes). You may prevent this by taking care of your foot. You should stay well hydrated, carry out routine preventive foot care, and seek medical advice promptly if they develop skin ulceration, discolouration, or new pain or tenderness.

Canagliflozin, Empagliflozin, Dapagliflozin are examples of SGLT2 inhibitors

Glucagon-like peptide receptor agonist (Incretin mimetics)

Glucagon-like peptide 1 (GLP-1) receptor agonists also known as incretin mimetics reduce blood sugar levels by activating the GLP-1 receptor to mimic the activity of normal GLP-1 incretins. It should be injected under your skin, just before a meal. Incretins stimulate the release of insulin by the pancreas after eating, block the release of glucagon by the pancreas and slows glucose absorption into the bloodstream by slowing gastric emptying which makes you feel more satisfied after a meal.

Glucagon is a hormone that causes the liver to release its stored sugar into the bloodstream so by blocking it, glucose is not released into the blood. Increased insulin also drives glucose into the cell thereby reducing blood sugar in the blood. Slow absorption into the bloodstream means lower blood glucose in the blood.

Glucagon-like peptide 1 (GLP-1) receptor agonists have also been shown in studies to be beneficial in losing weight.

It is unlikely to cause hypoglycaemia because the effects are in direct response to the presence of carbohydrates in the gut.

Your doctor may prescribe you incretin mimetics if you have type 2 diabetes and have not been able to lower your blood sugar with a other medication.

Side effects include headaches, loss of appetite and weight loss diarrhoea, constipation nausea, vomiting, dizziness, increased sweating and indigestion.

Glucagon-like peptide 1 (GLP-1) receptor agonists have been linked with an increased risk of pancreatitis. Discontinue treatment and see your doctor immediately if you experience severe abdominal pain, nausea, and vomiting.

NEVER administer a missed dose after a meal!!

Albiglutide, Liraglutide, and Dulaglutide: administer missed dose only if there are at least three days until the next scheduled dose

Exenatide: leave the missed dose and continue with the next scheduled dose

Lixisenatide: administer missed dose 1 hour before next meal

Exenatide, Albiglutide, Dulaglutide, Liraglutide, Lixisenatide are all examples of glucagon-like peptide receptor agonist (Incretin mimetics).

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Nwasom is a pharmacy graduate and a pharmacist currently practising in the United Kingdom. I have great experience communicating with patients and their family as gained through working as a pharmacist in both the hospital and community pharmacy sector. I love writing so it was a natural thing to try and pass medical and health information on through writing.