Medications for Type 2 Diabetes

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1 Main Page Risk Factors Symptoms Diagnosis Treatment Screening Complications Reducing Your Risk Talking to Your Doctor Living With Type 2 Diabetes Resource Guide Medications for Type 2 Diabetes by Karen Schroeder, MS, RD En Español (Spanish Version) The information provided here is meant to give you a general idea about each of the medicines listed below. Only the most general side effects are included. Ask your doctor if you need to take any special precautions. Use each of these medicines only as recommended by your doctor, and according to the instructions provided. If you have further questions about usage or side effects, contact your doctor. Some people are able to manage type 2 diabetes with diet and exercise alone. But in many cases, medicines may need to be added to this treatment plan to help you control your blood sugar. Oral antidiabetes medicines, often referred to as oral agents or oral hypoglycemic agents by doctors, are used to treat type 2 diabetes. They lower blood sugar levels in a variety of ways with many different mechanisms of action. Since each class works differently, they may be used in combination. All of these drugs work best when they are part of a total treatment program that includes a healthful diet and regular exercise. Despite diet, exercise, and oral medicines, some people with long-standing type 2 diabetes may need to take insulin, exenatide, or pramlintide to keep their blood sugar in good control. Prescription Medications Sulfonylurea Drugs Meglitinides Biguanide Thiazolidinediones Alpha-glucosidase inhibitors D-phenylalanine derivatives Dipeptidyl peptidase-4 (DPP-4) inhibitors Insulin Glucagon-like peptide-1 receptor agonists Pramlintide Sulfonylurea Drugs Common names include: Chlorpropamide (Diabinese) Glipizide (Glucotrol, Glucotrol XL) Glyburide (Micronase, Glynase PresTab, DiaBeta) Page 1 of 10

2 Glimepiride (Amaryl) Tolazamide (Tolinase) Tolbutamide (Orinase) Sulfonylurea drugs stimulate the beta cells in the pancreas to make more insulin. They also help your body's cells use insulin better. Sulfonylureas are generally taken 1-2 times per day, 30 minutes before a meal. This medicine should always be taken with food. This is to reduce the risk of developing low blood sugar. All sulfonylureas have similar effects on your blood sugar level, but they may have different side effect profiles. Based on the results of your blood sugar monitoring, your doctor will work with you to adjust your dosage. Talk to your doctor about which side effects you should watch out for. Special Considerations Sulfonylurea drugs help to control your blood sugar by stimulating the production and the release of insulin. Therefore, there is the chance that they can cause hypoglycemia (low blood sugar). Be sure to talk with your doctor and a registered dietitian about balancing the amount of food you eat with the amount of medicine you take to help reduce the risk of hypoglycemia. Some of these drugs may cause negative effects if taken with alcohol. Chlorpropamide is the most common drug to cause such effects, which include vomiting and flushing. Sulfonylurea drugs can also increase the risk of heart attack and congestive heart failure. Talk to your doctor about your individual risk factors for heart disease. Meglitinides Repaglinide (Prandin) Like sulfonylureas, repaglinide helps the pancreas produce more insulin. However, it works faster than sulfonylureas, allowing for more flexible timing of doses and meals. Also like sulfonylureas, repaglinide also carries the risk of hypoglycemia. So, you should talk with your doctor and/or a registered dietitian about balancing the amount of food you eat with the amount of medicine you take. This will help to reduce the risk of hypoglycemia. Repaglinide is usually taken 2-3 times a day, within minutes before each meal. Biguanides Metformin (Glucophage) Metformin works in the liver to make it produce less glucose and make your body more sensitive to insulin. Metformin can also lower blood fat levels and possibly lead to minor weight loss, which can ultimately help with blood sugar control. Metformin is usually taken 1-2 times a day with meals. Metformin does not cause the body to make more insulin. Therefore, when it is used alone, it rarely causes hypoglycemia (low blood sugar). However, when combined with other diabetes drugs, it can cause hypoglycemia. Special Considerations Page 2 of 10

3 Tell your doctor if you drink more than 2-4 alcoholic drinks a week, since metformin is poorly tolerated with alcohol. Also, if you are having surgery or a test that requires contrast dye for scans, make sure the doctor knows you are taking metformin. It will need to be stopped temporarily. Thiazolidinediones Common names include: Rosiglitazone (Avandia) Pioglitazone (Actos) These medicines are also called "insulin sensitizers" because they make the cells in your body more sensitive to or better able to use insulin. Specifically, they work in the muscle and fat cells. They may also help decrease the amount of glucose released by the liver. These drugs do not cause the body to make more insulin. Therefore, when they are used alone, they rarely cause hypoglycemia (low blood sugar). Pioglitazone has an added benefit of lowering cholesterol. When combined with other diabetes drugs, thiazolidinediones may cause hypoglycemia, though. This type of medicine is usually prescribed once per day. It may be taken with or without food, at about the same time each day. Special Considerations In rare cases, thiazolidinediones can harm your liver. Therefore, your doctor will regularly monitor your liver function with blood tests when you are taking one of these drugs. People who take rosiglitazone may be at an increased risk for having a heart attack. Discuss your risk with your doctor. This group of medicine may also increase the risk of fractures in women. Pioglitazone may increase your risk of bladder cancer. Alpha-glucosidase Inhibitors Common names include: Acarbose (Precose) Miglitol (Glyset) These medicines are also called "starch blockers" because they slow down the digestion of carbohydrates (starches and sugars), which are the major food sources of glucose. This slow-down in digestion leads to a slow-down in absorption, and therefore, a slower increase in blood sugar after a meal. When used alone, alpha-glucosidase inhibitors do not cause hypoglycemia, however when combined with other diabetes drugs, they may cause this side effect. Alpha-glucosidase inhibitors should be taken with the first bite of each main meal. When you initially start this medicine, your doctor may have you take it less frequently. You will build up the dose over time as your body adjusts to the medicine. Special Considerations Table sugar (sucrose) is not effective at treating hypoglycemia when you are taking these drugs because alpha-glucosidase inhibitors slow the digestion of sucrose. If symptoms of hypoglycemia occur while you are Page 3 of 10

4 taking one of these medicines, the following foods can be used to treat it: 3-4 glucose tablets 10 ounces of milk D-phenylalanine Derivatives Nateglinide (Starlix) Repaglinide (Prandin) These medicines help the pancreas to quickly produce more insulin. They can be prescribed for use with each meal and should be taken within 30 minutes before meals. Do not take a dose if you skip a meal. Although this drug works when taken alone, it may be more effective when combined with metformin. Both nateglinide and repaglinide carry a risk of low blood sugar. Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Common names include: Sitagliptin (Januvia) The FDA has warned that sitagliptin may increase the risk of acute pancreatitis. Vildagliptin (Galvus) Saxagliptin (Onglyza) Linagliptin (Tradjenta) DPP-4 inhibitors lengthen the activity of certain proteins, which increase the release of insulin after your blood sugar level rises with a meal. The medicine does this by blocking a specific enzyme (DPP-4), which is responsible for breaking down these proteins. These drugs can enhance your body s own ability to reduce the elevated blood sugar levels. This class of medicine is meant to be used together with diet and exercise to help improve the blood sugar levels. It can be used alone or added to other commonly prescribed oral antidiabetic drugs. When to Contact Your Doctor Diabetes pills do not work for everyone. Also, they may become less effective after a few months or years. Until you are well accustomed to your medicines, be sure to monitor your blood sugar levels regularly and record the information to tell your doctor. This will help you and your doctor recognize if your pills are not working properly and if you need a change in dosage or even treatment. Report the following to your doctor immediately: Fasting blood glucose (before breakfast) less than 100 milligrams per deciliter (mg/dl) [5.6 mmol/l] Symptoms of hypoglycemia: sweatiness, shakiness, and confusion When you start taking diabetes medicines, they may cause some side effects. (Each drug can cause different effects, so ask your doctor what to expect from your drug regimen.) However, many of these effects go away as your body adjusts to the medicine. If side effects persist, tell your doctor. Once your diabetes is under adequate control on oral medicines, it may not be necessary to continue monitoring your blood sugar levels on a regular basis. Many type 2 diabetes (not taking insulin) can be adequately managed by using another test called glycosylated hemoglobin or hemoglobin A1c (HbA1c), which is done in a doctor s office. Unlike blood sugar levels, HbA1c has the advantage of measuring average blood glucose levels over the last three-month period, which marks the effectiveness of diabetes management over the long-term. Most people with diabetes are recommended to keep their HbA1c levels below 7% to avoid or delay diabetic complications. Page 4 of 10

5 In a recent study of 453 moderately well-controlled type 2 diabetics who did not take insulin, researchers investigated whether patients who undertook regular self-monitoring of their blood sugar had better control over their diabetes than patients who did not monitor their blood sugar for an average of three years. They found no significant difference in HbA1c levels between the groups, suggesting that regular blood sugar testing in diabetics whose condition is under reasonably good control without insulin may not be necessary. However, you should be sure to have a discussion with your physician before discontinuing blood sugar monitoring. Insulin In almost all type 2 diabetes, the pancreas eventually no longer makes enough insulin for the body. To help control your diabetes, you may need to inject insulin. Insulin must be taken as an injection. If it were taken by mouth, it would be digested by the stomach before it reached your bloodstream where it needs to do its work. Insulin Injection Sites 2011 Nucleus Medical Media, Inc. To work properly, the amount of insulin you use must be balanced with the amount and type of food you eat, the amount of exercise you do, and the other diabetes medicines you are taking. The amount of insulin you take must be balanced with the amount and type of food you eat and the amount of exercise you do. If you change your diet, your exercise, or both without changing your insulin dose, your blood glucose level can drop too low or rise too high. Before getting insulin, you should check your blood glucose level with a blood glucose meter. This will help you to determine how much insulin you need. Current insulin treatment regimens usually employ some combination of rapid-acting and long or very long-acting insulin. Insulin is usually given before meals and at bedtime. All About Insulin The three characteristics of insulin are: Onset the length of time it takes for the insulin to reach the bloodstream and begin lowering blood glucose after it is injected Peak Time the time during which insulin is at its maximum strength in terms of lowering blood glucose levels Duration how long the insulin continues to lower blood glucose The main types of insulin available are: Page 5 of 10

6 Peak Type of insulin Onset* Duration* Notes on use time* Rapid-acting Novolog, Humalog minutes hours Regular- or Short-acting hour hours 3-5 hours Inject immediately before a meal 5-8 hours Intermediate-acting Often used in combination with hours (NPH ) hours hours short-acting insulin Long-acting Levemir hours hours Very long-acting Insulin glargine (Lantus) enters the body quickly, and has long-lasting effects hours, 1 hour n/a continuous insulin release hours; nearly Can combine a long-acting with a continuous insulin a short-acting to provide proper release peaking of insulin at mealtimes May not be mixed with other types of insulin Pre-Mixed mixture of short-acting and intermediate-acting insulins Onset* Peak time* Duration* Humulin 50/50 30 min 2-5 hours hours Humalog mix (75/25) 15 min hours hours Humulin 70/30 30 min 2-4 hours hours Novolin 70/30 30 min 2-12 hours up to 24 hours Novolog 70/ min 1-4 hours up to 24 hours *Each person has a unique response to insulin, so the times mentioned here are approximates. In the table below are types of insulin and common brand names. Type of insulin Rapid-acting Brand names Humalog (insulin lispro) NovoLog Cartridge (insulin aspart) Humulin R (regular) Iletin II Regular Regular- or Short-acting Novolin R ReliOn/Novolin R Intermediate-acting Long-acting Humulin N (NPH) Iletin II NPH Novolin N (NPH) ReliOn/Novolin N (NPH) Levemir Lantus (insulin glargine) Methods of Insulin Delivery In the past, for insulin to be used by the body, it must be moved through the outermost layer of skin and into fatty tissue. There are several different ways of getting insulin into your body by injection. Some examples are: Page 6 of 10

7 Syringe The syringes you will use are small and have fine needles with special coatings that help to make injecting as easy and painless as possible. When insulin injections are done properly, most people find that they are relatively painless. Insulin is usually given as a subcutaneous injection. This means that the needle goes into the fat layer between the skin and the muscle to deliver a certain amount of medicine. Pump This is a computerized device, about the size of a beeper that you wear on your belt or in your pocket. It delivers a steady, measured dose of insulin through a flexible plastic tube called a cannula. With the aid of a small needle, the cannula is inserted through the skin into the fatty tissue and is taped in place. In some products, the needle is removed and only a soft catheter remains in place. You control the release of insulin from the pump, based on your meals and your blood sugar level. Because the pump continuously releases tiny doses of insulin, this delivery system most closely mimics the body's normal release of insulin. Also, pumps can deliver very precise insulin doses for different times of day, which may be necessary to correct the dawn phenomenon the rise of blood sugar that occurs in the hours before and after waking. Pen The insulin pen looks very much like an old-fashioned cartridge pen, except that it has a needle and holds a cartridge of insulin. Pens are particularly useful for people who are often on the go, or whose coordination is impaired. The majority of pens are disposable. Note: Check your insulin's expiration date. If you haven't finished it before then, throw the rest away. Store unopened bottles of insulin in the refrigerator. Do not store your insulin at extreme temperatures. Keep the bottle of insulin you are using at room temperature. Injecting cold insulin can sometimes make the injection more painful. (Most pharmacists believe that insulin kept at room temperature will last for about one month.) Glucagon-like Peptide-1 Receptor Agonist Exenatide (Byetta) Liraglutide (Victoza) After eating a meal, a hormone called glucagon-like peptide-1 (GLP-1) is produced in the stomach and intestines. This hormone leads to insulin being released from the beta cells in the pancreas. Moreover, it helps to control blood glucose levels by reducing the appetite and increasing the sense of fullness. Exenatide and liraglutide belong to a family of chemicals that mimics the effects of GLP-1. GLP-1 agonists are meant to be used in people with type 2 diabetes whose blood glucose is not controlled with oral antidiabetes medicines. Side effects from these medications may include: Low blood sugar Headache Nausea, vomiting Diarrhea irritation where the shot is given There is also a concern that liraglutide may increase the risk of developing a thyroid tumor for certain patients. Discuss this with your doctor. Page 7 of 10

8 Pramlintide Pramlintide (Symlin) Amylin is a hormone produced by the same beta cells which produce insulin. Amylin is released at the same time as insulin. Moreover, amylin reduces glucagon's release and enhances the sense of fullness after eating a meal. Together with insulin, amylin helps lower the blood sugar level. Pramlintide is chemically related to amylin. And like amylin, pramlintide reduces appetite, and its use has been associated with weight loss. Pramlintide is used together with insulin in people who fail to achieve the desired blood glucose levels despite getting the optimal doses of insulin. This drug is given by injection immediately before a meal. The elderly should use this drug with special care. Special Considerations If you are taking medicines, follow these general guidelines: If you give yourself insulin injections, always use a new needle. This will reduce your risk of infection. Take your medicine as directed. Do not change the amount or the schedule. Do not stop taking them without talking to your doctor. Do not share them. Know what the results and side effects. Report them to your doctor. Some drugs can be dangerous when mixed. Talk to a doctor or pharmacist if you are taking more than one drug. This includes over-the-counter medicine and herb or dietary supplements. Plan ahead for refills so you do not run out. REFERENCES: AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Medical guidelines for the clinical practice for the management of diabetes mellitus. American Association of Clinical Endocrinologists website. Available at: Published Accessed February 12, American Diabetes Association. American Diabetes Association position statement: standards of medical care in diabetes Diabetes Care. 2010;33:S1-S99. American Diabetes Association. Executive summary: standards of medical care in diabetes Diabetes Care. 2010;33:S4-S10. American Diabetes Association website. Available at: Accessed August 14, Bohannon N. Overview of the gliptin class (dipeptidyl peptidase-4 inhibitors) in clinical practice. Postgrad Med. 2009; 121: Continuing Medical Education. The Patient-Centered Practice website. Available at: Accessed August 14, Endocrine Society website. Available at: Accessed February 12, FDA approves new drug treatment for type 2 diabetes. US Food and Drug Administration website. Available at: Published July 31, Accessed October 1, Idris I, Donnelly R. Dipeptidyl peptidase-iv inhibitors: a major new class of oral antidiabetic drug. Diab Obes Metab. 2007;9: Page 8 of 10

9 Joslin Diabetes Center website. Available at: Accessed August 16, Lexi-PALS. Exenatide. EBSCO Health Library, Lexi-PALS website. Available at: Updated March 22, Accessed October 5, Lexi-PALS. Liraglutide. EBSCO Health Library, Lexi-PALS website. Available at: Updated March 22, Accessed October 5, Ligthelm R, Davidson J. Initiating insulin in primary care-the role of modern premixed formulations. Prim Care Diabetes. 2008;2: National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health website. Available at: Accessed February 8, Sitagliptin (marketed as Januvia and Janumet) acute pancreatitis. US Food and Drug Administration website. Available at: Published September 25, Accessed August 14, Standards of medical care in diabetes. Diabetes Care. 2006;29:S4-42 Traina AN, Kane MP. Primer on pramlintide, an amylin analog. Diabetes Educ. 2011;37(3): /1/2007 DynaMed's Systematic Literature Surveillance : Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med May 21. [Epub ahead of print] 7/13/2007 DynaMed's Systematic Literature Surveillance : Farmer A, Wade A, Goyder E, et al. Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial. BMJ Jun 25. [Epub ahead of print] 1/30/2009 DynaMed's Systematic Literature Surveillance : Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ. 2009;180: Epub 2008 Dec 10. 2/12/2010 DynaMed's Systematic Literature Surveillance : Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009;339:b /5/2010 DynaMed's Systematic Literature Surveillance : Bode BW, Testa MA, Magwire M, et al. Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes. Diabetes Obes Metab. 2010;12(7): /6/2011 DynaMed's Systematic Literature Surveillance : US Food and Drug Administration. FDA approves new treatment for Type 2 diabetes. US Food and Drug Administration website. Available at: Updated May 2, Accessed May 6, /17/2011 DynaMed's Systematic Literature Surveillance : Suspension of the use of medicines containing pioglitazone. Agence française de sécurité sanitaire des produits de santé (AFSSAPS) website. Available at: Published June 9, Accessed June 17, Last reviewed September 2011 by Lawrence Frisch, MD, MPH Page 9 of 10

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