Diabetes mellitus is one of the most prominent chronic health conditions in the United States.

In diabetes, the body either does not make enough insulin or is not as responsive to insulin as it should be. Typically, the pancreas produces insulin so the body can store and use the sugar and fat from one’s diet. When someone does not produce enough insulin or is not as sensitive to insulin, their blood sugar levels can increase in the bloodstream. Therefore, it is critical that patients properly manage their diabetes with lifestyle changes and medication.

Historically, most diabetic patients have had to turn to injectable insulin medications to manage their disease. However, there are now numerous medications available on the market that offer different routes of administration, including oral medications.

Patients now have the option to use non-insulin injectable medications for their type II diabetes before going on insulin. The choice of a diabetes medication regimen should be individualized based on the specific patient and the medications themselves. Medication characteristics that affect a provider’s choice in therapy include efficacy in lowering blood glucose, side effects, tolerability, adherence, cost, and safety.

It is important that patients are aware of the different treatment options available for diabetes, including the differences between oral and injectable medications, so that they can be informed and make decisions with their diabetes care team about the best plan of care.

Brands of Oral and Injectable Medications

Twelve different classes of antihyperglycemic agents exist, with varying characteristics including some fixed-dose combinations of oral therapies and fixed-ratio combinations of injectable therapies.

With so many types of diabetes agents available on the market, treatment can oftentimes be overwhelming for patients. It is important that patients have some familiarity with the different brands of medications, their routes of administration, and what classes they fall into so that patients are able to follow their regimen appropriately.

Below is a list of common diabetes medications, organized by oral versus injectable medications:

Common Names of Diabetes Medications

**Brand names in parentheses

Oral MedicationsInjectable Medications
  • Sulfonylureas: Glimepiride (Amaryl), glipizide (Glucotrol), glyburide (Diabeta)
  • Biguanides: Metformin (Glucophage),
  • Alpha-glucosidase inhibitors: acarbose (Precose)
  • Thiazolidinediones: pioglitazone (Actos), rosiglitazone (Avandia)
  • Meglitinides: repaglinide (Prandin), nateglinide (Starlix)
  • DPP-4 inhibitors: alogliptin (Nesina), sitagliptin (Januvia), linagliptin (Tradjenta)
  • SGLT-2 inhibitors: canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance)

Indications for Oral vs. Injectable Medications

It is important to note that oral medications can only be used when treating patients with type II diabetes mellitus.

In type I diabetes, the pancreas is unable to produce insulin to control the body’s blood glucose levels. Thus, patients must supplement their body’s insulin through the use of injectable insulin to manage their blood sugar. Oral medications are therefore ineffective for these patients.

Selection of the appropriate medication should take into account the patient’s medical history, behaviors, risk factors, and environment.

Typically, most diabetic patients will at least be on an oral agent as monotherapy to control their disease. For monotherapy, metformin is the recommended agent for all patients unless it is contraindicated or not tolerated.

If a patient’s hemoglobin A1C increases to greater or equal to 7.5%, they will then require dual or triple therapy that may include the addition of injectable insulin.

Administration of Oral vs. Injectable Medications

Most patients are familiar with oral medications and how they should be taken.

Oral diabetes medications are not much different than any other pill that is taken by mouth. However, certain drugs might need to be taken with or without food, at a certain time of day, or multiple times a day.

Contrastingly, injectable insulin is a bit more complex in its administration, and it can be taken in a variety of ways. Injections can be taken using a basic needle and syringe by drawing up the insulin into the syringe and injecting it under the skin.

Insulin pens are a bit easier to use and more convenient than a needle and syringe. Pens are prefilled, and like needles, should be inserted under the skin. The benefit of pens is that they are usually less painful to use than needles.

Other ways to inject insulin include methods such as using an insulin pump or an infuser.

Side Effects for Oral vs. Injectable Medications

Each diabetes agent carries its own benefits and risks of treatment. An important factor to consider when picking a medication regimen are the side effects of a drug and a patient’s tolerability of these side effects. Patients can experience adverse events with both oral and injectable diabetes medications, but the side effect profiles vary between the two.

The chart below outlines common symptoms associated with the use of oral and injectable treatments:

Common Side Effects of Diabetes Medications

Oral MedicationsInjectable Medications
  • Sulfonylureas: itching, weight gain, skin rash, low blood sugar, upset stomach
  • Biguanides/Metformin: kidney complications, dizziness, upset stomach, tiredness, metal taste, sickness with alcohol
  • Alpha-glucosidase inhibitors: bloating, gas, diarrhea
  • Thiazolidinediones: liver disease risk, anemia risk, leg or ankle swelling, weight gain
  • Meglitinides: low blood sugar, weight gain
  • DPP-4 inhibitors: nausea, diarrhea, flu-like symptoms
  • SGLT-2 inhibitors: infection, joint pain, nausea, increased urination
  • Low blood sugar
  • Weight gain
  • Headache
  • Flu-like symptoms
  • Injection-site reactions

While there is some overlap in side effect profiles, there are differences in the frequency of these side effects between oral and injectable agents. Typically, agents with little or no risk for hypoglycemia or weight gain are preferred. For that reason, metformin is the usual starting agent for those with type II diabetes because it is much less likely to cause these side effects.

With a multitude of diabetes treatment options available to patients, it is important that healthcare providers and patients understand the similarities and differences between oral and injectable diabetes medications.

Patients should feel empowered to understand their treatment options so that they can make informed decisions about their plan of care and be educated about their therapy.