Non-insulin drugs for treating type 2 diabetes
According to the Centers for Disease Control and Prevention (CDC), more than 30 million people in the United States have diabetes, or around 1 in 10 people. Of these, 90–95 percent have type 2 diabetes.
People with type 2 diabetes are resistant to insulin, which is the hormone that causes sugar to move from the bloodstream into the body's cells. Insulin resistance causes a person's blood sugar levels to become too high.
In this article, we look at when a person with type 2 diabetes requires insulin, and which other medications can manage the condition. We also describe useful lifestyle and dietary tips.
When does a person need insulin?
Doctors will typically only prescribe insulin for people with severe symptoms of type 2 diabetes.
In a person with type 1 diabetes, the body has stopped producing insulin. The person needs to either use an insulin pump or inject the hormone several times a day.
For people with type 2 diabetes, doctors generally recommend other medications first. They consider several factors when recommending courses of treatment, including:
- blood sugar levels
- previous treatment history
- medical history
- other ongoing health issues
Most individuals with mild-to-moderate type 2 diabetes can manage the condition with oral medications or non-insulin injectable drugs, as well as lifestyle and dietary changes.
Some people can even manage the condition with lifestyle changes alone. These can include weight management, dietary changes, and regular exercise.
However, a doctor may prescribe insulin for people with severe symptoms of type 2 diabetes or certain accompanying medical conditions.
Typically, the doctor will recommend insulin when a combination of non-insulin drugs is no longer enough to control blood sugar levels.
A wide variety of non-insulin medications are available for people with type 2 diabetes, and new drugs emerge every year.
Some of the most common oral treatment options include:
Metformin is taken orally and helps control blood sugar levels.
For people with type 2 diabetes, doctors usually prescribe metformin (Glucophage) first.
Metformin helps control blood sugar levels by reducing the amount of sugar that the liver produces and improving how the body uses the sugar.
Metformin is available in the following forms:
- Tablets: A person usually takes these two or three times a day with meals.
- Extended-release tablets: These are long-lasting, and a person usually takes one pill with their evening meal.
- A liquid: A person typically takes this once or twice a day with meals.
Initially, a doctor usually recommends a low dosage of metformin. Depending on how the individual's blood sugar levels respond to the medication, the doctor may gradually increase the dosage.
In more severe cases, the doctor may prescribe a combination of metformin and other diabetes medications, which can include insulin.
When taking metformin, or any other medication, carefully follow the doctor or pharmacist's instructions.
Although drinking alcohol in moderation with metformin is generally safe, too much can increase the risk of serious side effects, such as hypoglycemia and lactic acidosis, which is a potentially life-threating condition.
Hypoglycemia, when a person's blood sugar levels become too low, can cause symptoms such as:
Severe hypoglycemia is dangerous and requires immediate medical attention.
Common side effects of metformin include:
- stomach pain
- a loss of appetite
- a rash
- a metallic taste in the mouth
- a headache
- a runny nose
- muscle soreness
If a person experiences severe side effects, they may need to stop taking metformin temporarily.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors
SGLT2 inhibitors are a relatively new group of oral medications for type 2 diabetes.
They work by increasing the amount of sugar that the kidneys absorb from the bloodstream and pass out through the urine. This helps to lower a person's blood sugar levels.
Doctors usually prescribe SGLT2 inhibitors in combination with metformin when metformin alone cannot sufficiently lower blood sugar levels. However, a doctor may prescribe an SGLT2 inhibitor alone, especially if a person cannot take metformin.
A person typically takes an SGLT2 inhibitor once a day. Drugs available in this group include:
- canagliflozin (Invokana)
- dapagliflozin (Forxiga)
- empagliflozin (Jardiance)
Because of their effect on the kidneys, SGLT2 inhibitors increase a person's risk of contracting genital and urinary tract infections. Doctors do not recommend these drugs for people with kidney diseases.
Dipeptidyl peptidase-4 (DPP-4) inhibitors
DPP-4 inhibitors, or gliptins, are a new class of oral drug for type 2 diabetes.
They increase the production of insulin in the body and decrease the amount of sugar that the liver releases into the bloodstream. These effects help to lower a person's blood sugar levels.
Doctors usually prescribe DPP-4 inhibitors in combination with metformin, when metformin alone cannot lower blood sugar levels sufficiently. Under certain circumstances, a doctor may prescribe a DPP-4 inhibitor alone as a first-line treatment for type 2 diabetes.
A doctor may be more likely to prescribe these drugs for people who:
- have chronic kidney disease
- are older
- are of African-American descent
A person typically takes a DPP-4 inhibitor once daily. Available drugs in this class include:
- alogliptin (Nesina)
- linagliptin (Tradjenta)
- saxagliptin (Onglyza)
- sitagliptin (Januvia)
Alpha-glucosidase inhibitors (AGIs)
AGIs work by slowing digestion and reducing the absorption of sugar into the bloodstream. A person usually takes an AGI three times a day with the first bite of each meal.
Available AGIs include acarbose (Glucobay, Precose) and miglitol (Glyset). Doctors usually prescribe them in combination with other diabetes medications, such as metformin.
Sides effects of AGIs can include diarrhea, stomach upset, and gas.
These oral medications cause the pancreas to produce more insulin, which helps to regulate blood sugar levels.
There are two main types of insulin secretagogues:
- those in the sulfonylurea class, such as glimepiride, glipizide, glyburide, chlorpropamide, tolbutamide, and tolazamide
- those in the meglitinide class, such as repaglinide and nateglinide
A person usually takes sulfonylureas once or twice a day and meglitinides two to four times a day with meals.
Doctors usually prescribe insulin secretagogues in combination with other diabetes medications, such as metformin. These drugs may increase a person's risk of hypoglycemia and cause slight weight gain.
TZDs are sometimes called glitazones. They increase the body's sensitivity to insulin, which allows the hormone to regulate blood sugar levels more effectively.
Doctors usually only prescribe TZDs if other first-line treatments, such as metformin, have not achieved the desired effect.
TZDs are oral tablets, and a person usually takes them once or twice a day, with or without food. Taking these medications at the same times each day is important.
Available TZDs include rosiglitazone (Avandia) and pioglitazone (Actos). Some medications include a combination of a TZD and another diabetes drug, such as one in the sulfonylurea class or metformin.
Side effects of TZDs can include:
- body fluid retention, which can lead to swelling
- weight gain
- vision difficulties
- skin reactions
- chest infections
Many medications for type 2 diabetes, besides insulin, are available in the form of an injection, including GLP-1 agonists.
Glucagon-like peptide-1 (GLP-1) agonists
GLP-1 agonists, sometimes called incretin mimetics, they work by increasing the body's production of insulin and reducing the amount of sugar that the liver releases into the bloodstream.
These effects help to:
- lower blood sugar levels
- reduce appetite
- aid weight loss, in combination with dietary changes and exercise
Doctors often prescribe GLP-1 agonists in combination with metformin, when metformin alone cannot sufficiently control blood sugar levels.
If a person cannot take metformin, a GLP-1 agonist is often the next choice. These drugs are self-injectable, and several types are available.
The frequency of injections depends on the drug. For example:
- liraglutide (Victoza) is a once-daily injection
- exenatide (Byetta) is a twice-daily injection
- exenatide extended-release pen (Bydureon) is a once-weekly injection
- albiglutide (Tanzeum) is a once-weekly injection
- dulaglutide (Trulicity) is a once-weekly injection
A person may experience stomach upset and nausea when they begin to use a GLP-1 agonist, but this usually passes. The drugs have a low risk of causing hypoglycemia.
Common side effects of GLP-1 agonists include:
- stomach upset
- loss of appetite
Amylin analogs, or amylin agonists, work by slowing digestion and reducing the amount of sugar that the liver releases into the bloodstream. This helps to prevent blood sugar levels from rising too much after eating.
Amylin analogs also make people feel fuller for longer, which can help with weight loss.
A person needs to inject an amylin analog before meals. The only type available in the U.S. is pramlintide (Symlin). Doctors usually prescribe it alongside insulin treatment.
Some people experience nausea and vomiting when first taking this type of drug, but these side effects generally improve over time.
Guidelines published in 2018 by the American College of Cardiology recommend prescribing GLP-1 receptor agonists or SGLT2 inhibitors if a person has a diagnosis of:
- cardiovascular disease due to atherosclerosis
- chronic kidney disease
They recommend SGLT2 inhibitors specifically for people with heart failure or a risk of heart failure due to atherosclerotic cardiovascular disease.
Eating a healthful and balanced diet will help to manage type 2 diabetes.
Lifestyle and dietary changes are a crucial part of any treatment plan for type 2 diabetes. Some people can manage the condition with these changes alone.
Lifestyle tips for managing type 2 diabetes include:
- maintaining a healthy body weight, by losing weight, if necessary
- monitoring blood sugar levels regularly, as directed by a doctor
- eating a nutritious and balanced diet
- getting at least 7 hours of sleep each night
- doing at least 150 minutes of moderate-intensity exercise each week, by walking briskly, mowing the lawn, swimming, cycling, or playing sports, for example
- moderating cholesterol and blood pressure levels
- refraining from smoking
Dietary tips for managing type 2 diabetes include:
- eating fiber-rich foods, such as whole grains, nuts, leafy greens, and legumes
- eating lean meats and proteins, such as fish, poultry, and legumes
- avoiding processed foods
- avoiding sugary foods and drinks
- reducing the intake of alcohol
- eating smaller portions
- avoiding fast or fried foods
- checking the nutritional contents of food items
A doctor or dietician can give personalized advice about an individual's diet and exercise regimen. They can also provide ongoing support and monitoring.
Follow a doctor's instructions closely when taking diabetes medications.
When is insulin the only treatment option for diabetes?
Insulin is the recommended treatment option for Type 1 diabetes, but for Type 2 diabetes it is considered last-line therapy.
People with type 2 diabetes use insulin when other therapies have failed to control blood glucose. Individuals with type 2 diabetes will usually need to try multiple non-insulin medications without success before a doctor recommends insulin, but ultimately this depends on the severity of their diabetes.Dena Westphalen, PharmD Answers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.