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Managing Diabetes Magazine - diabetes

New Medications to Help Manage Diabetes
How and where they work in the body

With so many medications to help manage diabetes available in Canada, keeping track of what they all do can be a challenge. New medications continue to be developed and approved. This is good news because it allows for more targeted and individualized treatment of diabetes. According to Diabetes Canada, diabetes is still on the rise, with around 11 million Canadians living with diabetes or prediabetes.

Simply put, diabetes affects people in one of three ways:
  • the body cannot make insulin (type 1 diabetes)
  • the body cannot use the insulin it makes properly (type 2 diabetes)
  • the body cannot make enough insulin or cannot use the insulin it does make properly (type 2 diabetes).

Insulin controls the amount of glucose (sugar) in the blood. This control of glucose is needed for the body to work well. If the body is not able to make or use insulin, the end result is high levels of glucose in the blood. Chronic high blood glucose levels can damage blood vessels, organs and nerves. This can cause serious problems for the eyes, kidneys, feet, heart and brain.

Complications can include blindness, heart attack, stroke, kidney failure, and problems with erections. There can be poor blood supply to the legs and problems with the feet, including severe infections, which can result in amputation.

Chronic high blood glucose levels occur due to various processes that are working in the body at the same time. The brain, kidneys, liver, pancreas, gut, intestines, and muscle cells all play a part. As our understanding of diabetes continues to expand, new medications are being developed to target these specific processes. While each class of diabetes medication works to lower blood glucose levels, they all do so in different ways.

Classes of diabetes medications

Several different classes of diabetes medications are available. Some make the liver and tissues more responsive to insulin. Others increase the amount of insulin released by the pancreas. Some help glucose to leave the body in the urine.

Classes of Diabetes medications available in Canada

DRUG CLASS EXAMPLES OF DRUGS TARGETS HOW THEY WORK
Alpha-glucosidase inhibitors Acarbose (Glucobay) Stomach Lowers blood glucose by slowing down the digestion of carbohydrates
Biguanides Metformin* (Glucophage)
Metformin Extended Release* (Glumetza)
Liver, muscle and fat cells Makes tissues more sensitive and responsive to insulin Instructs the liver to make less glucose
DPP-4 inhibitors Alogliptin* (Nesina) Linagliptin* (Trajenta) Saxagliptin* (Onglyza) Sitagliptin* (Januvia) Gut, pancreas and liver Increases insulin levels in response to high blood glucose after a meal
GLP-1 receptor agonists Dulaglutide (Trulicity)
Exenatide (Byetta)
Exenatide Extended Release (Bydureon) Liraglutide* (Victoza)
Lixisenatide* (Adlyxine)
Semaglutide (Ozempic)
Gut, pancreas, liver and brain Increases insulin levels in response to high blood glucose after a meal, and slows digestion
Sulfonylurea insulin secretagogues Gliclazide (Diamicron) Glimepiride (Amaryl) Glyburide (DiaBeta) Pancreas Helps the pancreas make more insulin
Non-sulfonylurea insulin secretagogues (meglitinide) Repaglinide (GlucoNorm) Pancreas Helps the pancreas make more insulin (short acting)
SGLT-2 inhibitors Canagliflozin* (Invokana) Dapagliflozin* (Forxiga) Empagliflozin* (Jardiance) Kidney Lowers blood glucose levels by increasing the amount of glucose passed in the urine
Thiazolidinediones Rosiglitazone (Avandia) Pioglitazone (Actos) Muscle and fat cells Helps make tissues more sensitive and responsive to insulin
Insulin** - classified by how quickly it starts working and how long the insulin lasts
Rapid acting insulin Insulin aspart (NovoRapid, Fiasp) Insulin glulisine (Apidra)
Insulin lispro (Humalog)
Cells Lowers blood glucose levels by activating insulin receptors on the outer part of the cell - this allows glucose in the blood to enter the cell, where it can be used for energy
Short acting insulin Regular insulin
(Humulin R, Novolin ge Toronto) Regular insulin pork (Hypurin Regular) Human biosynthetic insulin (Entuzity)
Cells
Intermediate acting insulin NPH insulin (Humulin N, Novolin ge NPH) NPH insulin isophane pork (Hypurin NPH) Cells
Long acting insulin Insulin determir (Levemir)
Insulin glargine* (Lantus, Basaglar, Toujeo)
Cells
Ultra long acting insulin Insulin degludec* (Tresiba) Cells
*Also available as a combination product with a second diabetes medication of a different class. **Premixed insulins are also available.

Recommending a diabetes medication

When diabetes is diagnosed, changes to lifestyle are commonly recommended first. Some people find that a healthy diet, weight loss, and regular physical activity are enough to lower blood glucose and A1C levels to healthy target ranges. However, adding a medication right away is often a good idea.

A1C, or glycated hemoglobin, is a blood test that reflects the average blood glucose level over the most recent two to three months. This is a more comprehensive measure of blood glucose levels and control than the single blood glucose readings done during the same two to three month period (and so will differ from what is on your test meter). A1C measures the percentage of glycated (sugar-coated) hemoglobin. (Hemoglobin is the part of a red blood cell that carries oxygen.) A higher A1C level may indicate that blood glucose has not been well controlled. This means higher risk of complications.

If diet and exercise are not enough to meet targets for blood glucose levels, metformin is the first choice for drug therapy to manage type 2 diabetes. It is safe, inexpensive, and good at lowering blood glucose and A1C.

If metformin and lifestyle changes are not enough to control blood glucose, additional medications will be added to the treatment. In deciding which medication to add to metformin, a doctor will consider:

  • whether the person has heart or kidney disease
  • how a new medication might interact with others the person is taking
  • the effect on body weight
  • the medication’s ability to lower blood glucose
  • the risk of hypoglycemia (abnormally low blood glucose levels)
  • cost
  • the person’s preferences.

Adding insulin or another medication is not a failure. Often, it's just how the body works, although better control can help delay this need.

Insulin is used for type 1 diabetes. It can also be very useful for people who have type 2 diabetes. With type 2 diabetes, non-insulin medications may become less effective with time. As the disease progresses, the body makes less insulin, and the cells become less sensitive to the insulin it does make. Insulin may be prescribed when:

  • targets for blood glucose cannot be met using non-insulin medications
  • another disease limits the use of non-insulin medications
  • the first A1C test a person has is high enough that insulin would be beneficial
  • symptoms of high blood glucose are present.

Your health care providers are available to answer any questions and concerns relating to managing diabetes. Research shows that scheduling a meeting with your pharmacist at least once a year to ensure you are on track is both helpful and effective.

New medications now available

Over the past several years, many new diabetes medications that work to improve blood glucose control have become available in Canada. They are meant to work along with lifestyle changes like diet and exercise. Following are the newest diabetes medications (from 2018 to present).

The newest class of medications used to treat diabetes are the SGLT-2 inhibitors, which include canagliflozin, dapagliflozin and empagliflozin. SGLT-2 inhibitors help to lower blood glucose levels by increasing the amount of glucose released in the urine. While this class of medications has been available in Canada for the past few years, they are now being prescribed more often as an add-on therapy for diabetes management. This is especially true for people with diabetes who have a history of heart disease or are overweight. Growing evidence suggests that for many people these medications will have protective effects on the heart including lowering the risks of heart attacks, stroke or heart failure in different groups of people. Furthermore, they all appear to provide protection to the kidneys and preserve their function over time.

Talk to your pharmacist or doctor at any time about the ongoing results of current research and the specific medication you have been prescribed. New evidence becomes available frequently.

Common side effects of SGLT-2 inhibitors include genital yeast infections, urinary tract infections, and increased passing of urine. They should not be taken when actively ill, especially if vomiting and diarrhea make it difficult to get adequate fluid intake. With this class of medications, the risk of hypoglycemia is low. In addition, these medications appear to be associated with weight loss and blood pressure reduction.

Ozempic (semaglutide) – This injection is given once a week under the skin (subcutaneously), in the abdomen, thigh or upper arm. It is a GLP-1 receptor agonist. It acts by slowing digestion and raising insulin levels in response to high blood glucose after a meal. It may be used to manage type 2 diabetes:

  • as an alternative if metformin cannot be used
  • in combination with metformin, or metformin and a sulfonylurea, or metformin and basal insulin, if glucose targets are not being met.

Both semaglutide and liraglutide (another GLP-1 receptor agonist) protect the heart. The effect is similar to the SGLT-2 inhibitors canagliflozin and empagliflozin. For this reason, they are often prescribed for people with known heart disease and type 2 diabetes.

Common side effects of GLP-1 receptor agonists include indigestion, nausea, diarrhea, and abdominal pain. Reactions at the injection site include pain, redness and swelling. The risk of hypoglycemia is low with these medications, and they promote weight loss.

Xultophy (insulin degludec + liraglutide) – This is a once-daily subcutaneous injection that combines a long-acting insulin and a GLP-1 receptor agonist. Liraglutide is a GLP-1 receptor agonist that works in a similar way to semaglutide. Insulin degludec is a newer ultra-long acting basal insulin. Other long-acting insulins work for 24 hours. Insulin degludec stays in your body for much longer, working for 42 hours. It helps to replace insulin that would normally be released regularly by the pancreas, producing a consistent and even glucose-lowering effect. This in turn lowers the risk of nighttime hypoglycemia and allows for more flexibility in the timing of doses.

Xultophy may be used to manage type 2 diabetes:

  • in combination with metformin, with or without a sulfonylurea, when these combined with basal insulin (less than 50 units daily) or liraglutide do not achieve glucose targets. Note that there is a limited range of dosing options available with this medication due to the components of this combination.

Common side effects are similar to those of GLP-1 receptor agonists (see semaglutide) and insulin. With any insulin, the most common side effect is hypoglycemia (low blood glucose). Other side effects include weight gain, and lipohypertrophy (the development of lumps under the skin caused by frequent injections at the same location).

Soliqua (insulin glargine + lixisenatide) This once-daily subcutaneous injection combines a long-acting insulin and a GLP-1 receptor agonist. Lixisenatide is a GLP-1 receptor agonist that works similarly to semaglutide and liraglutide. Current studies have not shown that it provides additional heart protection. Insulin glargine is a long-acting insulin that works for 24 hours, without a peak in the glucose-lowering effect. This medication may be used to manage type 2 diabetes:

  • if less than 60 daily units of basal insulin, either alone or with metformin, does not achieve glucose targets. Note that there is a limited range of dosing options available with this medication due to the components of this combination. The side effects are similar to those of Xultophy.

Medications to manage diabetes all work to lower blood glucose and A1C to prevent complications. Health Canada has already approved another handful of medications that will soon be available. New ones will continue to be developed for years to come. Your health care providers, including your pharmacists, are available to answer any questions and concerns relating to managing diabetes. Research shows that a specific meeting with your pharmacist at least once a year to ensure you are on track is both helpful and effective.

FAMILY HEALTH is written with the assistance of:
College of Family Physicans of Canada
Alberta College of Family Physicians
FAMILY HEALTH is written with the assistance of:
College of Family Physicans of Canada
Alberta College of Family Physicians
While effort is made to reflect accepted medical knowledge and practice, articles in Family Health Online should not be relied upon for the treatment or management of any specified medical problem or concern and Family Health accepts no liability for reliance on the articles. For proper diagnosis and care, you should always consult your family physician promptly. © Copyright 2018, Family Health Magazine, a special publication of the Edmonton Journal, a division of Postmedia Network Inc., 10006 - 101 Street, Edmonton, AB T5J 0S1 [DI_MDcd19]
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