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type 2 diabetes treatments and therapies: from insulin to glucose inhibitors

doctors have to weigh many factors before they decide which treatment to prescribe, including comorbidities, side effects, tendency for weight gain.

by robin roberts
published nov 23, 2023
last updated dec 15, 2023
read time 8 minute read
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read time 8 minute read
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type 2 diabetes treatments and therapies: from insulin to glucose inhibitors
the most widely known glp-1 receptor agonist drugs are ozempic and wegovy, which are semaglutides. getty images
if you’re one of the more than 500 canadians newly diagnosed with diabetes each day, according to the national library of medicine, you’re likely overwhelmed with questions about how it’s treated and managed. because it’s one of the most common chronic diseases — 11 million (and rising) of your fellow canadians are living with diabetes or prediabetes, according to diabetes canada — and because everyone is affected differently, there are many effective therapies to help keep it in check. the trick is to find the right medication for you.
type 2 diabetes, affecting adults, is the most common, at about 90 per cent of cases. those with type 2 can’t make enough insulin or effectively use the insulin their body does make.
type 1, which usually develops in childhood or adolescence, accounts for nine per cent of cases. those with type 1 don’t produce any insulin.
gestational diabetes, which occurs during pregnancy and is usually temporary, makes up less than one per cent. pregnant women who develop gestational diabetes can usually control their blood sugar levels with lifestyle modifications.
untreated excess blood sugar can lead to serious health conditions, such as heart disease, stroke, kidney disease, eye damage, and lower-limb amputations.

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knowing what lies ahead, understanding your treatment options, and being aware of the supports available can help ease your unease.
according to diabetes canada, people with diabetes are more than three times more likely to be hospitalized with cardiovascular disease than the general population.
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after you’ve been diagnosed, you’ll likely be referred to an endocrinologist, who will determine which treatment will benefit you best.

more diabetes medications than ever

“when i started my career, there was metformin, a class of drugs called sulfonylureas, and insulin,” says dr. peter senior, director of alberta diabetes institute. “and it was quite simple, in some ways, for doctors [to treat] but it wasn’t necessarily delivering all that patients needed in terms of making them healthier and living longer without too many side effects.
“but in the last 10 to 15 years there’s been an explosion of treatment options, including dpp-4 inhibitors, sglt2 inhibitors, glp-1 receptor agonists and a whole range of insulins. but those options bring challenges because one size won’t fit all. and the disease doesn’t stay the same. it tends to progress so you might start off with one medication but as time goes by you may need some additional [medication].”
senior says doctors have to weigh many factors before they decide which treatment to prescribe, including comorbidities, side effects, tendency for weight gain, and whether or not the patient’s health insurance will cover their medication.

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“for people who need insulin, it [could] be insulin plus some other drugs. it might be two different kinds of insulin, one at night, one with meals,” he says. “and some people are taking a bunch of other drugs for their comorbidities. it’s a complex problem and tackling it with several drugs from different angles is probably better than trying to find one magic bullet.”
the following are the more common medications used to treat type 2 diabetes. diabetes canada goes into more depth on each medicine here.

insulin

insulin is a naturally occurring hormone made by your pancreas that helps your body turn food into energy and control blood sugar levels, according to diabetes canada. without insulin, sugar builds up in the bloodstream, leading to serious health issues.
if your body can’t make enough insulin on its own, or use the insulin it does make effectively, you’ll need to inject synthetic insulin with a pen, pump or syringe. there are many types of insulin — fast-acting, long-lasting, and short-acting — and your health-care team will recommend which type will work best for you.
regardless, you’ll need to check your blood sugar levels regularly, since they vary throughout the day, to ensure they remain in the target range and to avoid hypoglycemia, or low blood sugar.
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hypoglycemia occurs when the amount of food you eat is not balanced with your dose of insulin, when you’re active without having eaten enough, if you’ve taken too much insulin or your dose or type of insulin has changed. symptoms can include sweating, trembling, nausea, headache, weakness, and anxiety.
it’s important to be aware of these symptoms, although they can be masked by other medications, which is why it’s always a good idea to keep your doctor up-to-date on how you’re feeling.
using a continuous glucose monitor, a device that measures blood sugar every few minutes using a sensor under the skin, can cut down on the number of finger pricks to test your levels.
as effective and time-tested as insulin is, many newly diagnosed people are afraid of injecting themselves.
“doctors often have a reluctance to prescribe insulin because people have a reluctance to take it,” says senior. “[they] feel they can’t inject themselves, but the [needles are] tiny, way smaller than a vaccination needle.”
he says insulin pens work better for some people but they still come with a needle attached, as does an insulin pump, a device that’s worn outside the body with a tube that connects the insulin to a catheter inserted under the skin of the abdomen and delivers specific amounts of insulin.
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drug-maker pfizer developed an inhaled insulin product a decade ago, says senior, but because the company lost money on it, it was withdrawn. other pharmaceutical companies are working on similar versions but production “has been a long, winding road; people have been talking about it forever,” says senior. he says one of the challenges for perfecting inhaled insulin is predictability of absorption.
“you need to give an awful lot to the lungs for some of it to be absorbed, and there’s been some questions about the risk of lung cancers because insulin has a growth enhancing property. if you have an early tumour in the lungs and you bathe it in insulin three times a day at high concentration, is there going to be some long-term safety risks?”
senior says any kind of insulin dosing can be complicated, because it needs to be tailored to the individual, and then to the individual’s time of day and activity level. “the dose i might need today sitting at work will be different from the weekend when i’m out hiking.”

metformin

generally the first choice glucose-lowering medication for those with type 2 diabetes, metformin has been around since the 1970s and is safe, effective, affordable and has the bonus effect of having possible heart benefits, according to diabetes canada. it also doesn’t cause weight gain and can be taken in tablet form.
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metformin works by helping your body use insulin more effectively. possible side effects include nausea and diarrhea, which usually go away after a few weeks as your body adjusts to the medication.
used in conjunction with a healthy diet and exercise, and possibly other medications to control high blood sugar, metformin also decreases the amount of sugar that your liver makes and that your stomach and intestines absorb, according to provincial government health website healthlinkbc.

dipeptidyl peptidase 4 (dpp-4) inhibitors

this group of antihyperglycemic oral drugs include linagliptin, saxagliptin, alogliptin, sitagliptin. they are all often used in combination with other medications, such as metformin, sulfonylureas, or insulin, according to the national library of medicine. these drugs lower blood sugar levels and improve the work of insulin and increase the amount of insulin secreted, according to bc diabetes.

sulfonylureas

the oldest class of oral drugs dating back to the 1950s, these include glyburide, glimepiride, chlorpropamide, glipizide and tolazamide, and work to lower blood glucose by stimulating the secretion of insulin in the body and increasing insulin in the blood.
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these medicines are used alone or in combination with other injectables or tablets, particularly metformin, which help the pancreas make more insulin and use it better. also, sulfonylureas cause weight gain and metformin causes weight loss, so they balance each other out somewhat.

sodium glucose transporter 2 inhibitors (sglt2)

these drugs include canagliflozin, dapagliflozin and empagliflozin and are designed to remove excess sugar from the body through the urine, according to health canada. they are used alone or in combination with other similar drugs, alongside diet and exercise.
health canada reviewed these drugs after they were thought to increase the risk of diabetic ketoacidosis, which happens when ketones, a type of bodily waste, builds up to toxic levels in the blood. despite the risk, the study concluded that the benefits outweighed the risks.

glp-1 receptor agonists (glucagon-like peptide-1)

the most widely known of this class of drugs, ozempic and wegovy, are semaglutides and are basically the same drug, says senior. ozempic is used to treat type 2 diabetes, and often covered by provincial health plans, and wegovy is used for management of obesity, which often is not.
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“part of the issue is that, for the longest time, obesity was perceived to be from bad choices or moral weakness and not a disease and therefore it would not be reimbursed by public payers,” says senior. that is slowly changing.
when blood sugar levels start to rise after you eat, these drugs stimulate the body to produce more insulin, which helps lower those levels, according to the mayo clinic. these drugs, most of which are injected, can also cause weight loss by slowing the movement of food from the stomach to the small intestine, which curbs hunger by making you feel full faster and longer.
research has also shown some of these meds may lower the risk of heart disease, stroke and kidney disease, and improve blood pressure and cholesterol levels.

stem cells

results from the first clinical trials at ubc, part of a larger international trial that tested the use of stem cells to treat – and possibly cure – type 1 diabetes has shown some early promise.
patients were implanted with wafer-thin devices loaded with millions of lab-grown stem cells that were encouraged to make insulin. six months later, the stem cells had not only survived, they turned into insulin-producing beta cells, which could ultimately eliminate the need to inject insulin. these trials are ongoing.
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“these are stem cell derived islet cells, which are the cells that make hormones in the pancreas and given to patients with type 1 diabetes, and there’s some interest in whether that could also apply to type 2 diabetes,” says senior.
“if the problem is a beta cell deficiency, then a cellular replacement approach makes sense. but if the problem is that obesity and other factors are overwhelming the capacity of the pancreas, it may be that giving more beta cells work for a while but they may then get exhausted and worn out too. so i think stem cell therapies will have a role for the future, but i’m not sure if it’s going to be the whole slice of the pie.”
robin roberts is a vancouver-based writer.
robin roberts
robin roberts
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