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Type 2 Diabetes Medications to Manage Blood Glucose

Over the last 20 years, the understanding of type 2 diabetes as well as its management has advanced by leaps and bounds. It's now well known that type 2 is a progressive disease, which means that to stay healthy over the years, you'll likely need to transition from taking no medications or one blood glucose-lowering medicine to adding several types of medications, such as insulin. 

  • Know Your Blood Glucose-Lowering Meds

    It’s important to work with your health care provider over time to track your treatment to keep your blood glucose (blood sugar) in control. It’s keeping your blood sugar, cholesterol, and blood pressure in control that will help you minimize complications and stay healthy.

    The best first step to long-term diabetes management success is to understand how each of the blood glucose-lowering medications you take works. It’s also essential to take them according to your health care provider's instructions. If you are unable to take any of your medications for whatever reason, discuss this with your provider.

    Other positive steps to ensure you’re receiving quality care:

    • Stay informed. Ask your health care providers or pharmacist if you don't understand something about one or more of the medications you take.

    • Ask about how long it will take for a new medication to start to lower your blood sugar and become maximally effective. Some start working immediately, while others take longer to become maximally effective.

    • Ask about how many points (milligrams/deciliter, or mg/dl) you can expect a new blood glucose-lowering medication to lower your blood sugar and your A1C (average blood glucose over time, given as a percentage). Ask what the maximum dose of the medication is so you'll know if you are taking a small dose or the most that can be prescribed.

    • Know the possible side effects (positive and negative), how to deal with them, and when to alert your provider if you have problems.

    • Realize that your provider prescribes medications based on your health history and the other medications (prescribed or over-the-counter) you take. Be honest about all the medications, dietary supplements, etc., that you take or use. That’s the only way your provider can make sure that the medications prescribed are safe for you.

    • Check your blood sugar as directed, and learn how your prescribed medication changes might affect it.

  • The Need for Blood Glucose-Lowering Medication

    When you have type 2 diabetes, two problems are occurring and progressing:

    • The function of the beta cells in your pancreas that make the hormone insulin are slowly dwindling. More than likely, by the time you were diagnosed with type 2 diabetes, you had already lost at least half of your beta cells. By 10 years after a type 2 diagnosis, many people need to take insulin because their pancreas no longer makes enough insulin.

    • People with type 2 diabetes have insulin resistance, which means that the insulin you do make is not adequately able to lower your blood glucose. During the first few years you have type 2, your body likely continues to make some insulin. A small amount of weight loss and physical activity can help decrease insulin resistance and help your body make better use of the insulin you still make.

    • Recommendations from the American Diabetes Association and other related organizations suggest that most people with type 2 diabetes begin taking a medication that sensitizes the body to insulin. The medication these groups most commonly recommend is metformin.

    Most people with type 2 diabetes need a progression of blood glucose-lowering medications over the years to keep blood sugar levels in the desirable target range and stay healthy. Read on for the latest on the blood glucose-lowering medications for type 2 approved for use in the United States.

  • Biguanides

    Generic Name: metformin 
    Trade Names: Glucophage, Glucophage XR, Fortamet, Riomet Liquid, Glumetza

    How Metformin Works: When you have type 2 diabetes, your cells are resistant to insulin. This causes the liver to increase glucose production, especially overnight, leading to higher blood sugar levels. Metformin helps to stop the liver from generating this extra glucose. It also helps the muscles use up some of the excess glucose. Metformin is available as a generic medication, has a long history of safety and effectiveness, and is the most commonly recommended and prescribed as an initial medication for type 2 diabetes. It does not cause hypoglycemia unless taken with another blood glucose-lowering medication that can cause hypoglycemia. It is also increasingly being prescribed for people diagnosed with prediabetes, though this remains an off-label use (meaning not an approved use by the FDA).

    Side Effects: Some people might experience upset stomach or a metallic taste, but for most people this resolves after a few weeks. It is important for your provider to prescribe a small amount of this medication and increase the dose slowly to build tolerance, minimize side effects, and adequately control your blood sugar. Metformin may help you lose a few pounds when you start to take it. It should not be prescribed to people who have chronic kidney disease or are binge drinkers of alcohol.  In some people, long-term use of metformin can cause a slight vitamin B-12 deficiency. Discuss with your provider whether you should have your B-12 level checked.  

  • DPP-4 Inhibitors

    Generic Names/Trade Names: sitagliptan/Januvia, saxagliptin/Onglyza, linagliptin/Tradjenta, alogliptin/Nesina
     

    How DPP-4 Inhibitors Work: Dipeptidyl peptidase 4 (DPP-4) is an enzyme responsible for inactivating a group of hormones made in your intestines called incretins. Incretins normally help slow stomach emptying and thereby slow the rise of blood glucose after you eat, delay the release of glucose into the bloodstream, promote fullness, and prevent the release of glucagon (the hormone that puts more glucose into the bloodstream) from the pancreas. People with type 2 diabetes typically make decreasing amounts of incretins. By slowing the breakdown of the DPP-4 enzyme that inactivates incretins, the DPP-4 inhibitors keep more of the incretin called GLP-1 in circulation, helping enable the amount of this incretin you make on your own to work properly. This medication does not cause hypoglycemia unless taken with another blood glucose-lowering medication that can cause hypoglycemia.

    Side Effects: These medications have minimal side effects. A small percentage of people in the drug-approval studies experienced headache, sore throat, stomach discomfort, diarrhea, or upper respiratory tract infection.

  • SGLT-2 Inhibitors

    Generic Names/Trade Names: canagliflozin/Invokana, dapagliflozin/Farxiga, empagliflozin/Jardiance
     

    How SGLT-2 Inhibitors Work: The sodium-glucose cotransporter 2 (SGLT-2) inhibitors category of medication targets the kidneys by blocking the reabsorption of glucose by the kidneys. In doing so, the medication increases the amount of glucose excreted by the kidneys through the urine to lower elevated blood sugar levels. In some studies, these medications have been shown to assist with some weight loss, because more calories are lost in the urine. It's the first category of blood glucose-lowering medication to target the kidneys. You will know a medication is in this category because the name will end in "gliflozin."

    The first drug approved in the category, canagliflozin, was cleared by the U.S. Food and Drug Administration (FDA) in March 2013 for treatment of type 2 diabetes. Two other drugs in this category have since been approved. They are all once-a-day pills.

    These medications can be used as a sole blood glucose-lowering medication or can be used along with metformin, sulfonylureas, pioglitazone, and/or insulin. The FDA noted in its approval that SGLT-2 inhibitors shouldn't be used in people with severe kidney impairment, with end-stage kidney disease, or on dialysis.

    Side Effects: Increased urination, dehydration, urinary tract infections, vaginal yeast infections in women and yeast infections in the skin around the penis in men who aren’t circumcised. Hypoglycemia if taken with another glucose-lowering medication that can cause low blood sugar.

  • Insulin

    Generic Names: none 
    Trade Names: There are about four types of insulin (all insulins remain brand names). Each type of insulin has varied times of onset, peak (or no peak at all), and duration or length of action. There are several combinations of insulins that come premixed. Typically, rapid-acting and longer-acting insulins are premixed.

    How Insulin Works: Insulin lowers blood sugar by allowing glucose to get into cells and be used for energy. Due to the progression of type 2 diabetes, many people will need to take one or two kinds of insulin one or more times a day beginning about 10 years after the type 2 diabetes diagnosis.

    Side Effects: An excess of insulin can cause hypoglycemia. Insulin in excess can also cause hunger and weight gain. However, insulin is an exceedingly safe medication because it simply replaces the insulin normally made in the pancreas.

    News About Insulins: Inhaled ultra-rapid-acting insulin inhalation powder (Afrezza) was approved for adults with diabetes by the FDA in 2014. Afrezza is taken with meals several times a day using a handheld inhaler device. Single-use cartridges are available in doses of 4 or 8 units. It shouldn’t be used by people with chronic lung disease or asthma, or by people who smoke.

    Long-acting basal insulin (Lantus/glargine) in a more concentrated form (u300) was approved by the FDA in early 2015. The trade name will be Toujeo. Like other basal insulins, Toujeo lowers glucose slowly and over the course of a day. It will be available using a disposable prefilled pen, which contains a total of 450 units of insulin. The most common concentration of insulin today is u100.

  • Incretin Mimetics

    Generic Names/Trade Names: exenatide/Byetta (taken twice a day), liraglutide/Victoza (taken once a week), exentatide extended-release/Bydureon (once weekly), dulatglutide/Trulicity (once weekly), albiglutide/Tanzeum (once weekly)

    How Incretin Mimetics Work: Incretin mimetics, also called glucagon-like peptide-1 (GLP-1) analogs, put more of the incretin hormone GLP-1 into circulation to help control blood sugar. Their actions are similar to the DPP-4 inhibitors but are more powerful in their effect on lowering blood glucose. They slow stomach emptying and thereby slow the rise of blood glucose after eating, delay the release of glucose into the bloodstream, promote fullness, and prevent the release of glucagon (the hormone that puts glucose into circulation) from the pancreas. An incretin mimetic must be taken by injection because it's a protein. This medication does not cause hypoglycemia unless taken with another blood glucose-lowering medication.

    Side Effects: Some people might experience nausea and/or vomiting when they start taking this category of medication. For most people this resolves quickly, but for some it does not. This category of medications can help people achieve some weight loss.

  • Glitazones (TZDs)

    Generic Names/Trade Names: pioglitazone/Actos, rosiglitazone/Avandia

    How TZDs Work: TZDs reduce the cells' resistance to insulin and allow insulin to enter the cells more easily, helping to control blood glucose levels. They do not cause hypoglycemia unless taken with another blood glucose-lowering medication. TZDs might take a few weeks to start working to lower your blood sugar.

    Side Effects: Some people might experience weight gain, water retention (edema), headaches, dizziness, diarrhea, or nausea. An increased risk of developing congestive heart failure is associated with TZDs. They can also cause some weight gain. If weight gain is excessive, alert your provider. TZDs can cause your liver enzymes to increase. Your provider is encouraged to follow your liver enzyme levels by checking your liver function with a blood test before you start on a TZD and periodically thereafter. For premenopausal women who have stopped experiencing ovulation, TZDs may cause ovulation to resume. Some research shows that TZDs might increase the risk of bone fractures. If you are at risk for or have osteoporosis, a TZD may not be the best medication choice.

  • Alpha Glucosidase Inhibitors

    Generic Names/Trade Names: acarbose/Precose, miglitol/Glyset

    How Alpha Glucosidase Inhibitors Work: Alpha glucosidase inhibitors prevent the digestive system from absorbing glucose. By blocking an enzyme that breaks down glucose, they prevent glucose from being digested normally, delay the digestion of carbohydrate, and prevent blood glucose from rising after meals. They do not cause hypoglycemia unless taken with another blood glucose-lowering medication. If hypoglycemia occurs, it should be treated with a pure form of glucose, like glucose tablets, and not other forms of carbohydrate. The digestion of these will be slowed by the medication.

    Side Effects: Some people might experience gas, diarrhea, bloating, nausea, flatulence, or abdominal discomfort.

    Take Note: This category of blood glucose-lowering medications is less frequently prescribed.

     

  • Meglitinides

    Generic Names/Trade Names: repaglinide/Prandin, nateglinide/Starlix

    How Meglitinides Work: Meglitinides stimulate the pancreas to secrete more insulin within a few hours after you take the medication and eat. If you don't eat, don't take that dose. The main goal of these medications is to control the rise of blood sugar after you eat. They act like sulfonylureas but lower blood glucose more quickly.

    Side Effects: Some people might experience headache, nausea, diarrhea, sweating, tremors, dizziness, hyperglycemia, or hypoglycemia.

    Take Note: It's important to take these medications as prescribed with food. If you take them when you don't eat, your blood glucose can drop too low.

  • Sulfonylureas

    Generic Names/Trade Names: glyburide/Glynase PresTabs/Diabeta/Micronase, glipizide/Glucotrol, glimepiride/Amaryl 

    How Sulfonylureas Work: This is the oldest category of blood glucose-lowering medications. There are several generic ones available, and they're relatively inexpensive. These medications stimulate the pancreas to release more insulin. This in turn decreases the amount of glucose in your blood.

    Side Effects: Some people might experience nausea, hypoglycemia, heartburn, diarrhea, dizziness, headache, or constipation. You might also experience some weight gain due to increased hunger or treating hypoglycemia, a potential side effect. Most providers start these medications at a low dose if a maximum dose of metformin is not controlling blood sugar, and then increase the dose gradually to minimize side effects. If your blood glucose is regularly low or you have other side effects, alert your provider. This could indicate that the dose is too high.

    Take Note: Do not take sulfonylureas if you are allergic to sulfa drugs. Sulfonylureas may cause sensitivity to the sun's rays, so wear a hat and use protective sunscreen when outdoors. To minimize unwanted weight gain, monitor your calories and increase your activity.

  • How Blood Glucose-Lowering Medications Can Help

    Blood glucose-lowering medications can improve one or more of the problems that arise with type 2 diabetes.

    1. Decreased number and proper functioning of beta cells: Occurs when your pancreas can no longer produce sufficient insulin amounts.

    2. Insulin resistance: Occurs when the body can't properly use the insulin it continues to make, which can worsen due to excess weight. The body's insulin-making beta cells sense that blood glucose levels are high and in turn produce more insulin. The cells can't use this insulin effectively, so eventually the beta cells no longer produce extra insulin, and blood glucose levels climb.

    3. After-meal high blood glucose levels: Occurs when the body doesn't have enough insulin to utilize carbohydrate from food. This can result in a blood glucose spike a few hours after eating in people with diabetes.

    4. Inadequate glucagon regulation: Occurs when glucagon—a hormone released from the pancreas that causes the breakdown of liver and muscle stores of glucose (glycogen) and an increase in blood glucose levels—doesn't get the normal hormonal feedback from insulin to shut off.

    5. Inadequate production of incretin hormones: A number of incretins are produced in the intestines, and people with type 2 diabetes have a dwindling supply of incretins. This causes problems with appetite control and elevation of blood glucose after eating.

  • Combinations of Blood Glucose-Lowering Medications and Mixtures of Insulins

    With the number of blood glucose-lowering medications available today, there are many options for you and your provider to achieve optimal control. This is good news, because as type 2 diabetes progresses over time, you will need to add and/or change the medications you take in an effort to continue to reach your blood glucose targets.

    Some of the oral medications are available in a combination of two types of medications. These combination pills are often available in two or three dosage levels. Some providers, but not all, like using combination medications. Ask your provider for his or her opinion.

    When the FDA approves blood glucose-lowering medications, it also provides guidance for what other medications in this category they can be used with or if they should be used alone. These recommendations are based on the research that pharmaceutical companies provide the FDA in their request for approval.

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