Medications to Treat Type 2 Diabetes

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The first step in controlling your blood sugar is to receive diabetes self-management education so that you can understand the fundamental factors that can help you to achieve good blood sugar control. Depending upon how elevated your blood sugars are at diagnosis, the first line of treatment is lifestyle changes—eating a balanced modified carbohydrate diet, adequate exercise and weight loss are critical steps in achieving blood sugar control. Even small changes can make a big difference. But, there is a chance, you will need to take medication to get your blood sugars under control.

If your blood sugar stays high for a long time, you may have an increased risk of developing diabetes complications such as heart attack, stroke, kidney damage, blindness, and amputations. Keeping your blood sugar at a good level might reduce or prolong your chance of these problems.

The American Diabetes has an algorithm to which medications should be chosen. There are first-line agents, second line, and so on. Diabetes medications can vary greatly across classes—they all do different things and can vary significantly. It's important for your physician to keep in mind—your overall health, weight, lifestyle and economic status before prescribing a medication. 

Quick Facts About Diabetes Medications

  • Different classes of diabetes medications work on specific parts of your body to control your blood sugar (blood glucose).
  • Sometimes more than one medication is needed to control blood sugar. In this case you can take a combination medication or two different kinds of medicine. 
  • Combining two kinds of medicine can sometimes make it more likely that your blood sugar will drop too low (hypoglycemia).
  • Some diabetes medicines can cause weight gain. If you are overweight, these types of medications are not ideal because excess weight is an indepedent risk factor for elevated blood sugars. 
  • Some diabetes medicines are injectable (but are not insulin) and can help to achieve blood sugar control and weight loss.
  • It is not uncommon for people who have had diabetes for a very long time to be prescribed insulin. 

Available Oral Medications

Here we look at seven classes of oral medications for the treatment of type 2 diabetes as well as combinations of drugs from different classes:

Biguanides

Metformin, a biguanide, remains the most widely used first-line type 2 diabetes drug. 

Available biguanides include: 

  • Fortmate
  • Glucophage
  • Glucophage XR
  • Glumetza
  • Riomet (Liquid Metformin)

Possible adverse effects of the biguanides include the following:

  • nausea, diarrhea, or an upset stomach when you first start taking this type of medicine—these side effects are likely to go away after a while
  • rarely, a serious condition called lactic acidosis

Sulfonylureas

Sulfonylureas stimulate your pancreas to make more insulin, which helps lower your blood glucose. They have been around for a long time and are usually used as a second agent to help reduce mealtime blood sugars. They should be used with caution in the elderly because this population is at increased risk of developing low blood sugars.

Available sulfonylureas include:

  • Glimepiride (Amaryl) 
  • Glyburide  (Diabeta, Micronase)
  • Glipizide (Glucotrol, Glucotrol XL)

Possible adverse effects of the sulfonylureas include the following:

  • low blood glucose
  • upset stomach
  • skin rash
  • weight gain

Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors work by slowing down the digestion of foods high in carbohydrates, such as rice, potatoes, bread, milk, and fruit. Available alpha-glucosidase inhibitors include:

  • Miglitol (Glyset)
  • Acarbose (Precose)

Possible adverse effects of the alpha-glucosidase inhibitors are:

  • stomach pain, gas, bloating, or diarrhea—these symptoms usually go away after you have taken these pills for a while

Thiazolidinediones

Thiazolidinediones make you more sensitive to insulin. Available thiazolidinediones include:

  • Actos (pioglitazone)
  • Avandia (rosiglitazone)

If you have heart failure, you should not take this type of pill. This type of pill can cause congestive heart failure or make it worse. Studies have shown that Avandia is associated with an increased risk of heart attacks and chest pain or discomfort from blocked blood vessels.

In September 2010, the FDA restricted the use of Avandia and any drug combinations including Avandia due to increased cardiovascular risk. The FDA withdrew some of these restrictions in 2013, and the rest in 2015, as the result of newer clinical trials (particularly the RECORD trial). However, despite it's availability in the U.S., most doctors avoid prescribing Avandia. In fact, new patients should be prescribed Avandia only if they can't achieve glucose control taking any other drug. Furthermore, Actos is the preferred drug in this class for new patients.

If you are currently taking Avandia and benefiting from this medication, you may be able to continue taking it; however, you must discuss this option with your physician. If you haven't already done so, it's imperative that you meet with your physician and discuss any associated risks.

Possible adverse effects of the thiazolidinediones include:

  • congestive heart failure is the most serious side effect
  • anemia
  • an increased risk of getting pregnant even if you’re taking birth control pills
  • increased risk of bone fracture in women

Meglitinides

Meglitinides are similar to sulfonylureas in that they increase insulin output, but they are shorter acting. These medicines are typically good for older patients who need help with lowering their meal-time sugars. However, they must be taken three times a day and can be hard to comply with. 

  • Prandin (Repaglinide)
  • Starlix (Nateglinide)

Possible adverse effects of Prandin include:

  • low blood glucose
  • weight gain
  • upset stomach
  • back pain or a headache

DPP4 Inhibitors

DPP4 Inhibitors are typically used as a second line agent to help lower after-meal sugars. DPP4 Inhibitors lower your blood glucose by helping your body make more insulin when it’s needed, especially right after meals. It also helps keep your liver from putting stored glucose into your blood. DPP4 Inhibitors include:

  • Januvia (Sitagliptin)
  • Trajenta (Linagliptin)
  • Onglyza (Saxagliptin)
  • Nesina (Alogliptin) 

Possible adverse effects include:

  • upper respiratory infection
  • runny nose
  • sore throat
  • headache

SLGT-2 Inhibitors

Works with your kidneys to help remove excess glucose (sugar) from your body when you urinate. SLGT-2 Inhibitors include:

  • Canagliflozin (Invokana®)
  • Dapagliflozin (Farxiga®)
  • Empagliflozin (Jardiance®)

Possible adverse side effects include: 

  • Urinary tract infection or yeast infections
  • dehydration
  • bladder cancer
  • Canaglifozin may increase the risk of amputation, but may reduce the risk of cardiovascular disease

Combination Diabetes Pills

Combination pills contain two different types of diabetes pills. Many combination pills are available, including:

Actoplus Met (pioglitazone/metformin)

Avandamet (rosiglitazone/metformin)

Avandaryl  (rosiglitazone/glimepiride)

Duetact (pioglitazone/glimepiride). 

Glucovance (glyburide/metformin)

Glyxambi (jardiance/tradjenta)

Invokamet (canagliflozin/metformin HCl)

Janumet and Janumet (XR) (sitagliptin/metformin). 

Jentadueto (linagliptin/metformin HCl)

Juvisync (sitagliptin and Simvastatin)

Kazano (alogliptin/metformin)

Kombiglyze XR (saxagliptin/metformin)

Metaglip (glipizide/metformin). 

Oseni (alogliptin/pioglitazone)

Synjardi (metformin/jardiance)

Xigudo XR (dapagliflozin/metformin HCl)

Non Insulin Injectables: GLP-1 Agonists

GLP-1 receptor agonists are a type of non-insulin injectable medication that has become increasingly popular and prominent, making its’ way into the forefront of diabetes care and research. Studies have shown that these types of medicines, when used in combination with diet and exercise, both short acting and long acting, help patients with type 2 diabetes lose weight, reduce their hemoglobin A1C (3 month average of their blood sugar), as well as potentially reduce the rate of cardiovascular death. These types of medications are not typically used as a first line treatment, but can be used in combination with oral medicines and have been shown to be non inferior to combination regimens such as basal insulin (long acting insulin), plus GLP-1 agonist versus basal insulin, plus rapid acting insulin. 

GLP-1 agonists stimulate glucose dependent insulin release, which reduces post meal blood sugars. They also act on the stomach, brain, pancreas and liver to increase feelings of fullness which promotes weight loss. 

There are short acting and long-acting GLP-1 agonists. Some are injected once or twice daily and others once weekly. More and more of these types of medicines continue to be approved by the FDA and we will continue to look for these approvals. 

Some of these include: 

  • Byetta (Exenatide): injected twice daily. 
  • Victoza (Liraglutide): injected once daily. 
  • Adlyxin (Lixisenatide): injected once daily. 
  • Bydureon (Exenatide long acting form of Byetta)L injected once weekly.
  • Tanzeum (Albiglutide): injected once weekly. 
  • Trulicity (Dulaglitide): injected once weekly. 
  • Ozembic (Semaglutide) - just received FDA approval as a once weekly injectable, but is not available yet

Possible side effects: 

  • nausea, vomiting, diarrhea (more common with shorter acting agents)
  • rodent studies have shown an increased risk in thyroid c-cell tumors
  • small increased risk of pancreatitis

How to Know Which Diabetes Medications to Take

Because of the large number of medications available to treat type 2 diabetes, you may be confused about which medication is best for you. 

The American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) have established algorithms based on individual characteristics, such as age, length of diabetes diagnosis, blood glucose control and other health issues to help physicians and their patients determine which medication is best. Sometimes, you may start with one medication, only to realize that it is not working efficiently and you'll either have to add another type or switch entirely. Your physician will work with you to determine the most appropriate drug or combination of drugs depending on your individual circumstances. All the while, it's important that you make lifestyle modifications, such as eating a healthy diet and making it a point to exercise daily. Diabetes medications are meant to be an adjunct to diet and exercise and if lifestyle changes are not made, medications will likely need to be increased and tweaked. For more information on why, when, and how to take your diabetes medications: All About Oral Diabetes Medications

What About Insulin? 

People who have had diabetes for a long time or those that are unable to control their blood sugars with oral or non-insulin injectables may need to take insulin to control their blood sugars. Sometimes insulin is introduced to a person's diabetes regimen and once the persons glucose toxicity resolves the regimen can be subsequently simplified. For more information on how different types of insulin work: How Do Different Types of Insulin Work?

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View Article Sources
  • American Diabetes Association. Standards of Medical Care in Diabetes – 2017. Diabetes Care. 2017 Jan; 38 (Suppl 1): S1-132. 
  • Jonas D, Van Scoyoc E, Gerrald K, et al. Portland (OR): Oregon Health & Science University