Type 2 diabetes is a chronic condition in which the body does not respond properly to the hormone insulin and causes blood sugar to rise. Many people with type 2 diabetes need two or more drugs or combination therapy to keep blood sugar levels within target ranges and avoid complications associated with diabetes.
Combination therapy for type 2 diabetes can help a person control their blood sugar levels. Some have weight loss benefits as well as heart and kidney health benefits.
Read on to learn more about combination therapy and the different types available.
Combination therapy is a treatment that uses two or more drugs to treat different health conditions, such as type 2 diabetes.
Type 2 diabetes is a chronic disease that occurs when blood sugar levels rise due to problems with the use or production of insulin in the body. Untreated high blood sugar levels can over time lead to complications such as heart or kidney disease.
In addition to lifestyle changes, metformin is the first line of treatment for type 2 diabetes. This oral medication improves the body’s response to insulin, which lowers blood sugar. People who cannot tolerate metformin well may take another type of diabetes medication.
However, a drug alone is not always enough to keep blood sugar levels within the target range. People with type 2 diabetes often find it harder to control blood sugar levels over time. Therefore, combination therapy may be more effective.
Doctors may prescribe combination therapy for people with type 2 diabetes who have high blood sugar levels, even though they are dependent on treatment with metformin or another drug.
“Metformin is still the usual first line of treatment,” said Dr. Barbara Keber, Chair of Family Medicine at Glen Cove Hospital on Long Island, NY, told Medical News Today Levels Appropriate. “
People with type 2 diabetes, who are at greater risk of complications related to diabetes, receive combination therapy even if their blood sugar levels are within the target range. This includes people:
- coronary artery disease or high risk of developing it
- chronic kidney disease
- Heart failure
The American Diabetes Association (ADA) recommends combination therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) or a sodium-glucose transport protein-2 inhibitor (SGLT2) for people with these diseases.
A doctor can prescribe both drugs together.
Combination therapy usually uses metformin with one or more of the following drugs:
GLP-1 RAs or DPP-4 inhibitors
The liver produces, stores, and releases glucose into the bloodstream based on the instructions that insulin sends. This means that the liver plays an essential role in regulating and stabilizing the body’s blood sugar levels.
GLP-1 RAs are incretins. After a person ingests food, incretins increase the release of insulin from the pancreas and decrease glucagon. This lowers the level of glucose that is released from the liver.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are drugs that block DPP-4. DPP-4 is an enzyme that destroys GLP-1 incretins. These are hormones that help control the release of insulin.
GLP-1 RAs and DPP-4 inhibitors:
- Decrease appetite
- promote a sense of fullness
- Support of efficient insulin production
- Reduce the amount of glucose the liver releases
A Cochrane review of studies reports that GLP-1-RAs are among the most effective drugs for lowering blood sugar levels. Studies also link most types of GLP-1 RAs to weight loss.
DPP-4 inhibitors tend to be less effective in lowering blood sugar levels. They may or may not contribute to some weight loss.
“DPP-4 inhibitors are useful in some patients but do not help lower A1C as much as the GLP-1 RA or SGLT2 inhibitors,” said Dr. Keber. “They shouldn’t be used in conjunction with GLP-1 RA as they work the same way,” she added.
A1C is a measure of your average blood sugar level over the past three months.
One of the functions of the kidneys is to filter the blood. They also remove waste and excess water to make urine.
By blocking the SGLT protein, SGLT2 inhibitors prevent the kidneys from reabsorbing glucose into the bloodstream. Instead, glucose is released in the urine. This will help lower blood sugar levels.
“Glucose is allowed to be removed from the blood at a higher rate than normal,” said Dr. Minisha Sood, an endocrinologist at Lenox Hill Hospital in New York, NY.
The Cochrane study found that SGLT2 inhibitors tended to have less of an impact on blood sugar levels than GLP-1 RAs. However, studies have more consistently linked SGLT2 inhibitors to weight loss.
Combination therapy may include other drugs:
- Thiazolidinediones (TZDs): These drugs make the body more sensitive to insulin, which helps lower blood sugar levels. They also reduce the amount of glucose the liver releases into the bloodstream.
- Sulphonylureas (SUs): This group of drugs helps the pancreas make and release insulin.
- Basal insulin: This medicine supplements the insulin that the body produces on its own.
“Sometimes insulin is needed in addition to metformin or other drugs when blood sugar is very high,” said Dr. Keber.
The ADA recommends insulin if a person with type 2 diabetes:
- has A1C levels greater than 10% or blood sugar levels of 300 milligrams per deciliter or higher
- has symptoms of hyperglycemia or high blood sugar
- experienced inexplicable weight loss
Sometimes doctors can prescribe insulin to lower glucose levels before gradually reducing the prescribed dose and removing insulin from a person’s treatment plan.
In other cases, a person may need to take insulin continuously.
Combination therapy can help lower blood sugar levels and keep them within the target range. This, in turn, lowers the risk of complications related to diabetes.
GLP-1 RAs and SGLT2 inhibitors offer additional benefits.
GLP-1 RAs can help:
- Support weight loss
- Lower blood pressure
- Prevent coronary artery disease
- Prevent the coronary artery disease from worsening
SGLT2 inhibitors can help:
- Facilitate weight loss
- Lower blood pressure
- prevent kidney damage from diabetes
- prevent heart failure from getting worse
The ADA reports that GLP-1 RAs and SGLT2 inhibitors may also reduce the risk of death from cardiovascular causes, including heart attack and stroke.
Some medications may not be safe for people with certain health conditions. For example, people with medullary thyroid cancer should not take GLP-1 RAs or DPP-4 inhibitors.
In addition, people with heart failure or liver disease should not take TZD.
Any drug for type 2 diabetes carries some risk of side effects. Common side effects are:
- Hypoglycemia: Any drug that lowers blood sugar levels can cause them to fall below what doctors consider safe. Insulin and SUs also carry a higher risk of hypoglycemia than other diabetes drugs.
- Weight gain: TZDs, SUs, and insulin can lead to weight gain.
People with diabetes should always consult a doctor about the potential benefits and risks of any medication before taking it.
When deciding which type of combination therapy is best for a person, doctors consider the following:
- whether the person has coronary heart disease, chronic kidney disease, or heart failure
- whether they have a history of hypoglycaemia
- how the treatment will affect their weight
- the risk of side effects from treatment
- the person’s treatment priorities and goals
- the treatment costs
A person should always seek advice from a doctor if they do not understand why they are receiving a particular therapy or if they have other questions about their treatment plan.
Combination therapy can help keep blood sugar levels within the target range. This will reduce a person’s risk of developing complications from type 2 diabetes.
Some types of combination therapy also provide weight loss, heart health, or kidney health benefits.
A healthcare professional can explain the potential risks and benefits of different types of combination therapy.