Medications For Type 2 Diabetes

Type 2 diabetes is a long-term impairment of how the body controls and uses glucose as an energy source. Individuals with type 2 diabetes have two primary interrelated problems. 

First, their pancreas does not produce enough insulin, a hormone that regulates the movement of glucose from the bloodstream into the cells. Second, their cells do not respond to insulin as they should, thus taking in less glucose and leaving more in the bloodstream. Both lead to elevated blood sugar, the hallmark of diabetes.

In the case of type 2 diabetes, the excessive glucose circulating in the blood over time can lead to complications such as nerve damage, cardiovascular disease, stroke, and kidney problems.

Medication is one of the treatment options for type 2 diabetes, but patients can also manage the condition through lifestyle modifications. Currently, there are many different medications for treating type 2 diabetes, and if you’re wondering what those might include and how they work, read on to learn more.  

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Symptoms of type 2 diabetes

If you have type 2 diabetes, your body depends on alternative energy sources found in the tissues, muscles, and organs. That happens because the body does not effectively utilize insulin, so glucose is not available for use by the cells. 

This is a chronic condition that can develop slowly, and the symptoms can be mild and easy to disregard at the beginning. Here are some of them:

  • Unintended weight loss

  • Fatigue

  • Frequent urination

  • Increased hunger

  • Dry mouth

  • Increased thirst

  • Sores that heal slowly

Causes of type 2 diabetes

The pancreas naturally secretes insulin and releases it into the bloodstream when you eat or drink. Once your food is digested and broken down into simple sugar molecules, insulin helps transport them from the blood into your cells for use as energy. 

A person with type 2 diabetes has insulin resistance, meaning their cells do not respond to the hormone efficiently. As a result, the beta cells in the pancreas may have to work harder to produce more insulin. 

Eventually, this causes sugar to accumulate in the bloodstream while the cells starve for energy. The exact triggers for that series of events are unknown, but they could be related to abnormal cell signaling and control or cell dysfunction in the pancreas. 

Risk factors of type 2 diabetes

The following risk factors can put a person at increased risk of developing type 2 diabetes

Obesity and overweight

The main risk factor for type 2 diabetes is overweight or obesity. The type of fat that predisposes one to diabetes is centered around the midsection surrounding the organs. 

Obesity is defined as a BMI ≥ 30 kg/m2 (overweight is ≥ 25 to < 30 kg/m2). Having too much weight on your body causes a chronic inflammatory state that impacts your metabolism and leads to insulin resistance. 

Additionally, the increasing need for insulin and an accumulation of fat in the pancreas results in dysfunction of the beta cells, which affects their ability to produce insulin. 

Poor diet

Diets consisting of highly refined, processed foods that are high in sugar and fat are known to contribute to the development of obesity and insulin resistance, greatly increasing diabetes risk. 

These foods tend to increase your blood glucose levels. You should instead consume foods with more nutrient and fiber content.

Family history

An individual whose parent or sibling has type 2 diabetes may be at increased risk of developing it. Certain genetic predispositions can make you more susceptible to obesity and insulin resistance. 

Research has shown that lifestyle changes, including maintaining a healthy diet and exercising, can lower your risk of obesity and diabetes but not remove it completely. 

Being inactive

Sedentary lifestyles have increased along with the incidence of obesity. Less active people are at an increased risk for developing several chronic disease conditions, including type 2 diabetes. 

Research has shown that TV viewing for more than 3 hours per day, a marker for a sedentary lifestyle, is associated with higher mortality risks from all causes. 

Exercise helps in weight control, lowers oxidative stress and inflammation, utilizes sugar as energy, and increases cells’ sensitivity to insulin.

Race and ethnicity

Insulin resistance varies among different ethnicities, and individuals with certain ethnic backgrounds may be at a higher risk of developing type 2 diabetes. 

These include Hispanic, Black, Native American, Pacific Islanders, and Asian people. Other races and ethnic variations that could contribute to type 2 diabetes include health behavior and access, social and cultural factors, and environmental contributors. 

How is type 2 diabetes treated?

The two main ways to manage type 2 diabetes are with the use of medications and by making positive lifestyle modifications. 

Healthy lifestyle options include regular exercise and a healthy diet, along with minimizing some detrimental habits, such as smoking and excessive alcohol consumption

While lifestyle changes help greatly in managing this disease, you may need medications to achieve the target blood glucose levels. Your healthcare clinician may prescribe a single medication or even a combination therapy. 

What are the medications for type 2 diabetes?

Below are some of the commonly used medications for the treatment of type 2 diabetes and their most common side effects.

Oral medications

Sulfonylureas

Sulfonylureas work by stimulating pancreatic cells to produce more insulin. Thus, they only work for patients who still have some functioning beta cells. They also help keep insulin in the circulation, keep the liver from making glucose, and help the fat and muscle cells better utilize glucose. 

These drugs have been in use for around seven decades, but the only first-generation medication still in use is chlorpropamide (Diabinese). The remaining three, glimepiride (Amaryl), glipizide (Glucotrol), and glyburide (DiaBeta, Micronase, Glynase), are second-generation medications more frequently used and given in smaller doses.  

The various forms of sulfonylurea medications have different properties, so their use is tailored for patients by prescribers. However, all of them affect the blood glucose levels similarly, lowering them by about 20%.¹ Patients typically take these drugs once or twice a day orally before meals.

The side effects of these drugs include hypoglycemia (low blood glucose), weight gain, and reduced red blood cell count.

Meglitinides

Meglitinides medications include repaglinide (Prandin) and nateglinide (Starlix). They function similarly to sulfonylureas by stimulating the pancreatic beta cells to produce insulin, but their action is shorter and a little less effective. 

Because of this, they are a little safer for people with variable mealtimes whose blood sugars can sometimes get low. They are taken before every meal. 

The side effects of these drugs include hypoglycemia and weight gain.

Dipeptidyl-peptidase 4 (DPP-4) inhibitors

DPP inhibitors augment the biological activities of glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion. They also slow down stomach emptying and inhibit the liver’s production of glucose. These effects improve the body’s glucose regulation. 

Medicines in this class are taken orally, once or twice daily, without regard to mealtimes, and they have a low risk of causing hypoglycemia. These medications also have a positive to neutral effect on cholesterol levels in the body and do not cause weight gain. 

Examples of DPP-4 inhibitors for type 2 diabetes include linagliptin (Tradjenta), saxagliptin (Onglyza), alogliptin (Nesina), and sitagliptin (Januvia). 

The side effects of these drugs include urinary tract infections, hypoglycemia, headaches, facial swelling, and fluid retention.

Thiazolidinediones

Pioglitazone (Actos) and rosiglitazone (Avandia) are examples of thiazolidinediones. These drugs help insulin function better in the fat and muscle by making the tissues more sensitive to its action. They also work by lowering insulin resistance in the fat, muscles, and liver. 

Troglitazone (Rezulin) was the first thiazolidinedione drug on the market, but it caused serious liver problems and was withdrawn. Pioglitazone and rosiglitazone do not exhibit similar problems, but initial testing and ongoing monitoring of liver function are still recommended as precautionary measures. 

The side effects of these drugs include weight gain, liver disease, fluid retention, increased risk for fractures, and increased risk for bladder cancer.

Biguanides

An example of this medication class is metformin (Fortamet, Glumetza, Riomet), which is the first-line oral drug of choice for many with type 2 diabetes. 

Drugs in this class reduce blood glucose levels by lowering the amount of glucose produced in the liver and by increasing muscle tissue sensitivity to insulin. Metformin is known to suppress inflammation in the body, which has multiple beneficial effects, including possibly prolonging one’s lifespan. Patients with type 2 diabetes often take these medications twice a day. 

The side effects of these drugs include diarrhea, decreased appetite, upset stomach, and stomach discomfort.

Alpha-glucosidase inhibitors

Alpha-glucosidase inhibitors include miglitol (Glyset) and acarbose (Precose). They inhibit certain enzymes in the breakdown of dietary starches into glucose. They also delay intestinal carbohydrate absorption.

Both of these processes help manage type 2 diabetes by slowing the spike in blood glucose levels that occurs after eating. 

Drugs from this class are often given along with metformin. They can also be used in prediabetes or for individuals at high risk for the development of diabetes. Patients should take these drugs with their first bite of food. 

The side effects of these drugs include gas, upset stomach, diarrhea, and bloating.

Bile acid sequestrants

Bile acids are made in the liver during the breakdown of cholesterol. The primary role of bile acid sequestrants is to bind bile acids, essentially stimulating the liver to produce more of them and promoting the further reduction of cholesterol. 

The exact mechanism for regulating blood sugars is still being studied, but they have also been shown to reduce blood glucose levels by blocking the liver’s production of glucose as part of the body’s normal stress response.

An example of bile acid sequestrant medication is colesevelam (Welchol). It can be given in combination with metformin to help lower the HbA1c level (a measure of blood sugar levels) or along with insulin to improve glucose control.

The side effects of these drugs include heartburn, stomach discomfort, and constipation.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors

One of the newest classes of oral medications for type 2 diabetes is the SGLT2 inhibitors. Examples of these drugs include canagliflozin (Invokana), empagliflozin (Jardiance), and dapagliflozin (Farxiga). 

Sugar in the bloodstream has to flow through the kidneys for reabsorption or excretion, and the sodium-glucose cotransporter 2 (SGLT2) proteins facilitate this process. SGLT2 inhibitor medications function by blocking their role in sugar reabsorption and promoting the removal of excess glucose in the urine as waste. 

The side effects of these drugs include yeast infections (penis and vagina), urinary tract infections, and upper respiratory tract infections.

Injectable medications

Incretin mimetics (GLP-1 analogs)

Injectable incretin mimetics include liraglutide (Victoza, Saxenda), lixisenatide (Adlyxin), albiglutide (Tanzeum), exenatide extended-release (Bydureon), dulaglutide (Trulicity), exenatide (Byetta), and semaglutide (Rybelsus, Ozempic).  

These drugs work the same way as glucagon-like peptide 1, a naturally occurring hormone in the body. Their actions include stimulating insulin production in response to sugar and hindering the secretion of glucagon, a hormone that increases blood glucose levels. The incretin mimetics also slow down the emptying of food from the stomach, thus keeping you feeling full for a longer period. 

The side effects of these drugs include nausea, vomiting, and increased risk of pancreas inflammation.

Amylin mimetics

An example of an injectable amylin mimetic is pramlintide (Symlin). This injectable medication for type 2 diabetes works by slowing the passage of food through the stomach and helping control glucose. The drug may suppress hunger and promote modest weight loss. Amylin mimetics are used along with insulin injections. 

The side effects of these drugs include hypoglycemia, nausea, and vomiting.

What is the safest medication for type 2 diabetes?

Experts consider metformin the safest medication for type 2 diabetes, even in most older individuals, since it has been in use for many decades. It is also affordable and effective.

Healthcare professionals usually prescribe metformin as the first type 2 diabetes tablet if lifestyle measures alone cannot control blood sugar levels. The drug is particularly useful for patients who are overweight since it is less likely than other glucose-lowering medicines to cause weight gain. 

Metformin also has less propensity to cause low blood sugar levels (hypoglycemia) than some of the other sugar-reducing medications. But it should not be used in patients with kidney dysfunction.

What are some complementary treatments for type 2 diabetes?

Other than medications, lifestyle adjustments can greatly help patients manage their type 2 diabetes

These include the following.

Eating healthy foods

Switching to a healthy diet is a key component of achieving blood glucose control. Consider adding more high fiber foods to help slow the absorption of sugar when it’s eaten, including fresh vegetables, fruits, and whole grains. You should also avoid refined grains, sweeteners, and highly processed, high-calorie foods. 

A registered dietitian can help you create a healthy diet plan and identify healthy options among the food items you prefer. Also, try to develop healthy eating habits such as having a regular schedule for meals and reducing portion sizes of calorie-dense foods. 

Regular physical activity

Regular exercise will help you maintain a healthy weight and regulate your blood glucose levels. It can also improve some of the commonly associated conditions, such as high blood pressure and cardiovascular disease.

You can consider aerobic exercises such as walking, running, biking, and swimming or resistance exercises such as yoga and weightlifting. Guidelines² recommend at least 150 minutes of physical activity spread over a week. However, talk to your healthcare professional for advice on a safe exercise program for you. 

Weight management 

Losing weight will improve your body’s ability to regulate glucose levels in the blood and cholesterol. Research³ has shown that, in some people, significant weight loss helped them return to normal functioning without medication or even any other lifestyle changes. 

Guidelines recommend weight loss goals of 5%⁴ of body weight. But this should be taken slowly in steps. Your dietitian and healthcare clinician can help you set weight-loss goals and recommend safe ways to achieve them.

Monitoring your blood sugar

Monitoring your blood sugar levels helps you keep them within the target range. Seek your doctor’s advice on how often to measure your blood glucose level and by what method. You can use a continuous glucose monitor (CGM) or a blood glucose meter. 

A CGM checks blood sugar levels automatically and transmits the information to a specific device, such as a phone, and can notify you when readings are too low or too high.

If you use a blood glucose meter, you will need to check your level at least once a day, before or after exercise. Your doctor may recommend you do it several times a day if you are on insulin therapy.  

When should I see a doctor?

You should see your healthcare professional if you have one or more risk factors of type 2 diabetes or notice symptoms such as frequent urination, excessive thirst and hunger, unintended weight loss, and fatigue. Because this condition develops slowly and symptoms are often mild and easy to ignore, it is good to keep up with your regular check-ups. 

Also, visit your doctor if you realize high blood glucose levels during home monitoring. 

The lowdown

Type 2 diabetes is a medical condition that occurs due to high glucose levels in the bloodstream. Lifestyle adjustments can help manage the disease, but medications are usually necessary to achieve adequate blood glucose control. 

There are quite a few medications for the treatment of type 2 diabetes, and some are taken orally while others are injected. Other ways to manage the condition include making positive lifestyle adjustments such as eating healthy, exercising regularly, and managing your weight. These also help control other associated conditions such as hypertension and cardiovascular disease. 

Blood sugars should be monitored according to your doctor’s recommendations to prevent the complications of poorly controlled diabetes.

  1. Sulfonylureas and their use in clinical practice (2015)

  2. 4. Lifestyle management | American Diabetes Association

  3. Behaviour change, weight loss and remission of Type 2 diabetes: A community‐based prospective cohort study (2020)

  4. Diabetes self-management: Facilitating lifestyle change (2017)

Other sources:

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