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WORKING TOGETHER TO MANAGE DIABETES DIABETES MEDICATIONS SUPPLEMENT

SECTION A DIABETES MEDICATIONS Agent Class Primary Action Typical Dosage Side Effects Tolbutamide (Ornase TM ) Tolazamide (Tolinase TM ) Chlorpropamide (Diabenese TM ) Sulfonylureas (1st generation) Increases insulin production in pancreas Tolbutamide: 0.25 2.0 g/day in divided doses; maximum, 3 g/day Tolazamide: 100 1,000 mg/day in divided doses; maximum, 1 g/day Chlorpropamide: 100 500 mg/day twice a day; maximum, 750 mg/day Hypoglycemia, weight gain, hyperinsulinemia Disulfiram reaction with alcohol Glyburide (Micronase TM, Diabeta TM, Glynase TM ) glipizide (Glucotrol, Glucotrol XL TM ), glimepiride (Amaryl TM ) Repaglinide (Prandin TM ) Sulfonylureas (2nd generation) Meglitinide Increases insulin production in pancreas Increases insulin release from pancreas Glyburide: 1.25 2.50 mg/day twice a day; Hypoglycemia, weight maximum 29 mg/day gain, hyperinsulinemia Glynase: 0.75 12.0 mg/day; maximum 20 mg/day Glipizide: 2.5 20.0 mg/day twice a day; Maximum, 40 mg/day; or XL* 2.5 10.0 mg/day twice a day; maximum, 20 mg/day Glimepiride: 1 8 mg/day; maximum, 8 mg/day Hypoglycemia, weight New diagnosis or HbAlc <8% 0.5 mg gain, hyperinsulinemia before meals 2 4 times a day HbA1c >8: 1 2 mg, 15 30 min after each meal; increase weekly until results are obtained; maximum, 16 mg/day Nateglinide (Starlix TM ) Phenylalanine derivative Increases insulin release from pancreas 120, or 60 mg 3 times a day before meals Hypoglycemia, weight gain, hyperinsulinemia Metformin (Glucophage TM ) Biguanide Increases insulin sensitivity 500 mg/day twice a day with meals increase by 500 mg every 1 3 wk, twice or three times a day; usually most effective at 2,000 mg/day; maximum, 2,550 mg/day Nausea, diarrhea, metallic taste, very rare lactic acidosis Rosiglitazone (Avandia TM ) Thiazolidinedione Increases insulin sensitivity 4 mg/day in single or divided doses Increase to 8 mg/day in 12 wk, if needed; maximum, 8 mg/day with or without food Weight gain, fluid retention, edema Pioglitazone (Actos TM ) Thiazolidinedione Increases insulin sensitivity 15 or 30 mg/day; Maximum with or without food 45 mg for monotherapy 30 mg for combination therapy Weight gain, fluid retention, edema Acarbose (Precose Miglitol (Glyset ) TM TM ) Alpha-glucosidase inhibitor Blocks gut absorption of complex sugars 25 mg/day; increase by 25 mg/day every 4 6 wk; maximum, split dose before meals with first bite of food 300 mg/day (150 mg/day for weight <60 kg) Gas and bloating, sometimes diarrhea for both drugs Combinations Glucovance TM glyburide and metformin Decreases hepatic glucose production and increases insulin secretion. Initial, 1.25 mg/250 mg once or twice a day with meals; increase every 2 wk by 1.25 mg/250 mg per day; 2nd line, 2.5mg/500 mg or 5 mg glyburide/ 500 mg twice a day with meals; maximum, 20 mg/2000 mg per day Possible hypoglycemia, nausea, diarrhea, abdominal pain for this combination drug Metaglip TM glipizide and metformin Decreases hepatic glucose production and increases insulin secretion Initial, 2.5 mg/250 mg once or twice a day with meals. Increase every 2 wk to maximum of 10 mg/1000 mg or 10 mg/2000 mg per day. 2nd line, 2.5 mg/500 mg or 5 mg/500 mg twice a day with meals. Maximum, 20 mg/2000 mg per day Diarrhea, nausea/ vomiting, headache for this combination drug Avandamet TM rosiglitazone and metformin Decreases hepatic glucose production, increases glucose uptake, and decreases insulin resistance 1 mg/500 mg, 2 mg/500 mg or 4 mg/500 mg twice a day; dosage individualized based on current therapy. Maximum, 8 mg/2000mg per day Diarrhea, edema, anemia for this combination drug Adapted from 2002 The Diabetes Center, Old Saybrook, CT, used by permission. ALT = alanine aminotransferase CHF = congestive heart failure GI = gastrointestinal HbA1c = glycated hemoglobin XL = extended release 1 WORKING TOGETHER TO MANAGE DIABETES

TABLE 1. ORAL AGENTS TO TREAT TYPE 2 DIABETES* Precautions Chlorpropamide remains active for up to 60 hours. Use extreme caution with elderly patients or patients with hepatic or renal impairment. Critical Tests Metabolized in liver. Periodic evaluation of liver function tests. Comments Use of these agents is not recommended unless the patient has a well-established history of taking them. Second-generation sulfonylureas provide more predictable results with fewer side effects and more convenient dosing. Clearance may be diminished in patients with hepatic or renal impairment. Metabolized in liver. Periodic evaluation of liver function tests. Glipizide is preferred with renal impairment. Doses >15 mg should be split. Should not be used in patients with diabetic ketoacidosis and known hypersensitivity to drug or its inactive ingredients. Metabolized in liver. Periodic evaluation of liver function tests. Patients should be instructed to take medication δ30 min before a meal. If meals are skipped or added, medication should be skipped or added as well. Should not be used in patients with diabetic ketoacidosis and known hypersensitivity to drug or its inactive ingredients. Metabolized in liver. Periodic evaluation of liver function tests. Patients should be instructed to take medication δ30 min before a meal. If meals are skipped or added, medication should be skipped or added as well. Nateglinide is approved only as monotherapy or in combination with Metformin. Should not be used in patients who use alcohol frequently, liver, kidney disease or CHF because of risk of lactic acidosis. Contraindicated if serum creatinine is: >1.5 mg/dl in men or >1.4 mg/dl women, or use if creatinine clearance is abnormal. Monitor hematological and renal function annually. Metformin is especially beneficial in obese patients due to potential for weight loss, improved lipid profile, and lack of potential for hypoglycemia requiring supplemental carbohydrate intake. Discontinue for 48 hr after procedure using contrast dye. Should not be used in patients with CHF or hepatic disease. Can cause mild-to-moderate edema. Clearance may be diminished in patients with hepatic or renal impairment. Should not be used if GI disorders are concurrent. Avoid initiation with patients with increased baseline liver enzyme levels (ALT >2.5 times upper limit of normal). Liver enzymes monitored every 2 months for 12 months, then periodically. If ALT levels increase to >3 times the upper limit of normal, discontinue use and recheck liver enzyme levels. Avoid initiation with patients who have liver disease or ALT levels >2.5 times the upper limit of normal. Patients with mildly elevated liver enzymes (ALT levels 1 2.5 times the upper limit of normal) should be evaluated. Discontinue if >3 times the upper limit of normal. Rosiglitazone is approved for use as monotherapy and in combination with metformin or sulfonylureas. Pioglitazone is approved for use as monotherapy or with metformin, sulfonylureas, or insulin. Should not be used if frequent alcohol use, liver or kidney disease, or CHF is suspected. Avoid if serum creatinine is >2.0 mg/dl. Monitor serum transaminase every 3 months for 1st year of therapy. Contraindicated if serum creatinine is >1.5 mg/dl in men or 1.4 mg/dl in women, or if creatinine clearance is abnormal. Monitor hematological and renal function annually. May use 1.25mg/250mg and 2.5mg/500mg doses at different times of day for best glucose control. Incidence of hypoglycemia is higher for combination than for single agent use. Should not be used if frequent alcohol use, liver or kidney disease, or CHF is suspected. Contraindicated if serum creatinine is >1.5 mg/dl in men, or >1.4 mg/dl in women, or if creatinine clearance <60 75 ml/min. Monitor hematologic and renal function annually. May use 1.25mg/250mg and 2.5mg/500mg doses at different times of day for best glucose control. Incidence of hypoglycemia is higher for combination than for single agent use. Should be avoided in patients with hepatic disease, CHF, renal disease. Contraindicated if serum creatinine is >1.5 mg/dl in men or >1.4 mg/dl in women, or if creatinin clearance is abnormal. Agent is less expensive than its components separately. Decrease in GI upset is reported with metformin compared with rosiglitazone alone. *Agents in a class of medicines share mechanisms of action, require similar precautions, and generally have similar side effects. For proper usage, please read label. Agents should not be used in patients with type 1 diabetes. DIABETES MEDICATIONS SUPPLEMENT 2

TABLE 2. IMPORTANT INSULIN INFORMATION* Insulin Onset Peak Effective Maximal Duration Duration Human Lispro (humalog) Aspart (novalog) Regular NPH Lente Ultralente 70/30 <15 min <15 min 0.5 1 hr 2 4 hr 3 4 hr 6 10 hr 0.5 1 hr 1 2 hr 1 3 hr 2 4 hr 4 10 hr 4 12 hr Minimal 2 10 hr 2 4 hr 3 5 hr 3 5 hr 10 16 hr 12 18 hr 18 20 hr 10 16 hr 3 5 hr 4 6 hr 4 8 hr 14 18 hr 16 20 hr 20 30 hr 14 18 hr Comments Must be taken just before or immediately after eating. Best if administered 30 min before meal. Frequently used instead of NPH in children. Humalog mix 75/25 <15 min 1 2 hr 10 16 hr 14 18 hr Must be taken before or immediately after eating. Insulin glargine (Lantus ) TM 4 6 hr None 24 hr 24 hr Administered at bedtime once a day. Cannot be mixed in same syringe and should not be given with use of same needle in same place as previous injection. Animal Source Regular NPH Lente 0.5 2 hr 4 6 hr 4 6 hr 3 4 hr 8 14 hr 8 14 hr 4 6 hr 16 20 hr 16 20 hr 6 8 hr 20 24 hr 20 24 hr Adapted from 2002, The Diabetes Center, Old Saybrook, CT, used by permission. *Site rotation for injections is necessary for all types of insulin. Change over to human insulin recommended. Dose changes required; consult physician. TABLE 3. RECOMMENDED INSULIN STORAGE Recommended Insulin Storage Refrigerated (36 F 46 F) Room Temperature (59 F 86 F) VIAL Humalog, novolog, humulin, novolin Novalog (release pending) Lantus TM (10 ml) Lantus TM (5 ml) PENS/CARTRIDGES Humalog Humulin R (cartridge) Humulin N Humulin 70/30 Humalog Mix 75/25 Novolog Novolin R (prefilled and 1.5-mL cartridge) Novolin R (3-mL cartridge) Novolin N (prefilled and 1.5-mL cartridge) Novolin N (3-mL cartridge) Novolin 70/30 (prefilled and 1.5-mL cartridge) Novolin 70/30 (3-mL cartridge) Lantus TM Self-filled syringes Opened Unopened until expiration date until expiration date until expiration date until expiration date Not in use 14 days* Adapted from 2002, The Diabetes Center, Old Saybrook, CT, used by permission. *Suggested, not clinically established Opened 14 days In use 14 days 10 days 10 days 30 days 7 days 14 days 7 days 10 days 7 days* Unopened 14 days 3 WORKING TOGETHER TO MANAGE DIABETES

TABLE 4. GLUCOSE LOWERING ACTIVITY ORAL DIABETES AGENT Medication Blood Glucose Most Affected SMBG* Testing to Recommend Greatest Risk for Hypoglycemia Sulfonylureas Fasting and postprandial 2 3 times per day, 4 6 hr after meal and fasting especially fasting Meglitinide phenylalanine derivative Postprandial 2 hr after meal 2 3 hr after meal Biguanide Alpha-glucosidase inhibitor Thiazolidinedione Glucovance Fasting Postprandial Fasting and postprandial Fasting and postprandial Fasting 2 hr after meal 2 3 times per day, especially fasting 2 3 times per day, especially fasting Adapted from 2002, The Diabetes Center, Old Saybrook, CT, used by permission. SMBG = self-monitoring of blood glucose None if used as single agent None if used as single agent After exercise when used with sulfonylureas or insulin 4 6 hr after meal and fasting TABLE 5. MEASURES TO CONTROL GLYCEMIA Biochemical Index Normal Goal Action Suggested Before meals (mg/dl) plasma whole blood Bedtime (mg/dl) plasma whole blood HbA1c* <110 <100 <120 <110 <6 90 130 80 120 110 150 100 140 Adapted from 2002, The Diabetes Center, Old Saybrook, CT, used by permission. HbA1c = glycated hemoglobin <7 <90, >150 <80, >140 <110, >180 <100, >160 >8 Diagnosis: Diabetes On what was supposed to be one of the happiest days of our lives, my husband, Tim Hanf, collapsed to the floor during our wedding reception. He had diabetes which was left undiagnosed until that night. Too much champagne and wedding cake caused his glucose levels to spike landing him in the emergency room. I don t have to tell any of you how painfully scary this can be. What can be equally as intimidating is the plethora of information received from the doctors and nurses. Unfortunately, over-information and misinformation were a big part of the problem. One doctor recommended a certain type of drug while other doctors recommended a different type while still others spoke out against drugs all together. This prompted me to do some research myself. After talking with doctors, nurses, dieticians, and numerous patients who had beaten the disease, I discovered how my husband could be naturally cured of this disease without the use of medications. DIABETES MEDICATIONS SUPPLEMENT 4

Side Effects As you can see from the charts detailing today s current treatments, there are numerous medications for assisting diabetics in keeping their glucose levels in check. You can also see the myriad of side-effects and precautions involved with each of them. Hypoglycemia - Hypoglycemia, also called low blood sugar, occurs when your blood glucose (blood sugar) level drops too low to provide enough energy for your body's activities. In adults or children older than 10 years, hypoglycemia is uncommon except as a side effect of diabetes treatment. Hyperinsulinemia - Hyperinsulinemia is a disorder characterized by a failure of our Blood Sugar Control System to work properly. This occurs when insulin progressively loses its effectiveness in removing the blood glucose from the blood stream into the cells that constitute our bodies. Edema - Edema is the swelling caused by fluid in your body's tissues. It commonly occurs in the feet, ankles and legs, but it can involve your entire body. Anemia - Anemia is a condition where there is a lower than normal number of red blood cells in the blood, measured by a decrease in the amount of hemoglobin. Hemoglobin is the oxygen-carrying part of red blood cells. Nausea, diarrhea, fluid retention, gas, bloating, headaches, vomiting and weight can are also common side-effects to many diabetic medications. Precautions & Procedures Along with side-effects, each medication offers precautions and procedures for its use. Having other health issues may limit your ability to take certain prescriptions. You and your doctor must also consider other medications you are taking and how they interact. You have to consider the time of day at which you take each medication, whether you ve eaten, and the proper storage of each one. The Cure Diabetes and the management of the disease could easily take over your life. This was not the life my husband and I wanted for us. We didn t want to spend every waking moment thinking about or treating this disease. Through research, trial and tribulation, we were able to eliminate his diabetes through natural methods. Today Tim is diabetes free and takes no medications to regulate his glucose levels. Through proper nutrition, exercise and dietary supplements, diabetes is no longer a part of our daily lives. He is active, healthy and has more energy than ever before. Talk to your doctor and discover if a natural treatment is right for you. Instead of living your life dealing with diabetes, you can live a naturally healthy life. 5 WORKING TOGETHER TO MANAGE DIABETES

Centers for Disease Control and Prevention. Working Together to Manage Diabetes: Diabetes Medications Supplement. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, 2004. NDEP-54-S

ii WORKING TOGETHER TO MANAGE DIABETES