The prevalence of diabetes in the United States in

Medical Management of Type 2 Diabetes Celia Levesque, CNS-BC ABSTRACT More than 20 million Americans have type 2 diabetes. Managing blood glucose is an important component in delaying, slowing, or preventing acute and long-term diabetes complications. Numerous diabetes medications are on the market for this purpose, making it difficult for the advanced practice nurse to know where to begin. This article reviews published algorithms for glucose management of type 2 diabetes and the diabetes medication classes and agents within each class. Knowing how each class works and how to initiate, titrate, and combine diabetes medications is vital when customizing a diabetes medication regimen to meet target glycemic goals. Keywords: diabetes algorithms, diabetes management, diabetes medications, type 2 diabetes 2011 American College of Nurse Practitioners The prevalence of diabetes in the United States in 2007 was an estimated 23.6 million. 1 Of those, 90% to 95% (more than 20 million) had type 2 diabetes mellitus (T2DM). Characterized by a combination of insulin resistance and relative insulin deficiency that leads to elevated blood glucose, T2DM carries a high risk for both macrovascular and microvascular complications; therefore, proper management is critical. Numerous medications are available to control blood glucose. Like hypertension management, glucose management often requires a combination of different classes of antidiabetes medications. Choosing an initial diabetes medication regimen and modifying it if the glycemic target is not achieved can be challenging. The purpose of this article is to review the diabetes medication classes and the published algorithms for T2DM management. The algorithms discussed include those promulgated by the American Diabetes Association (ADA) with the European Association for the Study of Diabetes (EASD), the American Association of Clinical Endocrinologists (AACE), and the Texas Diabetes Institute (TDI). Each agency has slightly different glycemic target ranges and algorithms but is very similar in recommendations. When creating an initial T2DM treatment regimen, nurse practitioners (NPs) should first choose a target hemoglobin A1c (HbA1c) level and blood glucose range appropriate for the patient. The goal is to choose a safe target. A lower target is acceptable if the patient is generally healthy, highly motivated to achieve tight glucose control, and not at high risk for severe hypoglycemia. A higher target is appropriate for people with unstable cardiovascular disease, severe microvascular complications, chronic kidney disease, frequent hypoglycemia episodes, hypoglycemia unawareness, cognitive impairment, high risk of falling, dependence on others for care, and limited life expectancy. Table 1 summarizes HbA1c and blood glucose target recommendations. When creating a diabetes medication regimen that is safe and effective, it is imperative to know how each class of medication works, initial dosing and titration methods, contraindications to the drugs, and guidelines for combining medications of different classes. Table 2 shows the different medications used for T2DM. CLASSES OF ANTIDIABETIC MEDICATIONS Biguanide The biguanide class is the most widely used oral diabetes class. Metformin is the only drug in this class. The brand names include Glucophage (immediate release), Glucophage XR (extended release), Fortamet (extended 492 The Journal for Nurse Practitioners - JNP Volume 7, Issue 6, June 2011

Table 1. Glycemic Goals Goals ADA/EASD AACE TDC HbA1c goals 7% 6.5% or as near normal as possible without inducing clinically significant hypoglycemia Fasting blood glucose goals Fasting 70-130 mg/dl Postprandial 180 mg/dl Less than 6%-7% if no unstable cardiovascular disease, severe microvascular complications, frequent hypoglycemia episodes, or hypoglycemia unawareness and in newly diagnosed patients Less than 7%-8% if severe microvascular complications, hypoglycemia unawareness, or frequent or severe hypoglycemia and in patients with impaired cognition or history of falling 110 mg/dl 100 mg/dl if the HbA1c goal is 6% 120 mg/dl if the HbA1c goal is 7% 140 mg/dl if the HbA1c goal is 8% HbA1c hemoglobin A1c; ADA American Diabetes Association; EASD European Association for the Study of Diabetes; AACE American Association of Clinical Endocronologists; TDC Texas Diabetes Institute. release), and Riomet (liquid metformin). Even though its mechanism of action is not fully understood, metformin is known to decrease hepatic glucose output, lower fasting plasma glucose and fasting plasma insulin levels, and increase insulin sensitivity. Since metformin does not cause insulin secretion, it has a low risk of hypoglycemia and does not promote weight gain when used as a monotherapy. Common side effects include nausea and diarrhea. Contraindications include renal disease with elevated creatinine, hepatic disease, diabetic ketoacidosis, shock, myocardial infarction, sepsis, and hypoxemia. Metformin should be restricted during and for 48 hours after surgery or tests involving intravenous iodinated contrast agents. Unless metformin is contraindicated, it is used as a firstline agent in all of the treatment algorithms reviewed in this article. Metformin is a pregnancy category B drug. Sulfonylurea The commonly used sulfonylurea agents include glipizide (Glucotrol), glipizide XL (Glucotrol XL), glyburide (Diabeta and Micronase), micronized glyburide (Glynase), and glimepiride (Amaryl). Sulfonylureas cause increased insulin secretion by binding to an adenosine- 5 -triphosphate dependent potassium channel on the cell membrane of pancreatic beta cells. This class of antidiabetic medications also increases the pancreatic beta cells sensitivity to glucose. Common side effects include hypoglycemia and weight gain. Contraindications include diabetic ketoacidosis and type 1 DM (T1DM). Sulfonylureas should be used with caution in patients with renal disease, hepatic disease, and adrenal or pituitary insufficiency, as well as in malnourished and elderly patients. Sulfonylureas are pregnancy category C drugs. Glitinide The glitinides on the market include nateglinide (Starlix) and repaglinide (Prandin). Their action is similar to that of sulfonylurea in that they cause increased insulin secretion by binding to a different site of the adenosine-5 - triphosphate dependent potassium channel on the cell membrane of pancreatic beta cells. Glitinides have a shorter duration of action than do sulfonylureas and should be taken with meals. Common side effects include hypoglycemia and weight gain. Contraindications include diabetic ketoacidosis, T1DM, creatinine clearance (CrCl) less than 20 ml per minute, and hemodialysis. Caution should be used when prescribing glitinides to patients using insulin, the elderly, patients who are debilitated or malnourished, and those with adrenal, pituitary, hepatic, or renal insufficiency. Glitinides are pregnancy category C drugs. Thiazolidinedione Thiazolidinediones (TZD) on the market include pioglitizone (Actos) and rosiglitazone (Avandia). These drugs increase insulin sensitivity by binding to peroxisome proliferator-activated receptors, specifically peroxisome proliferator-activated receptor-gamma. They also modify adipocyte www.npjournal.org The Journal for Nurse Practitioners - JNP 493

Table 2. Classes of Diabetes Medications Class/Agent How Supplied Initial Dose Titrate Maximum Dose Bigunide/Metformin (Glucophage) Bigunide/Metformin extended release (Glucophage XR, Glumetza, Fortamet) Bigunide/Liquid form of metformin (Riomet) Sulfonylurea/Glipizide (Glucotrol) Glipizide XL (Glucotrol XL) Sulfonylurea/ Glyburide (Diabeta, Glynase, Micronase) Sulfonylurea/ Glimepiride (Amaryl) Glitinide/Repaglinide (Prandin) Glitinide/Nateglinide (Starlix) TZD/Pioglitazone (Actos) TZD/Rosiglitazone (Avandia) Alpha-glucosidase inhibitor/acarbose (Precose) Alpha-glucosidase inhibitor/miglitol (Glyset) 500, 850, 1,000 mg 500 mg BID or 850 mg day If adding to insulin: 500 mg/day and reduce insulin 25%- 50% 500, 750 mg 500 mg BID or 750 mg/day 100 mg/ml 5 ml BID or 8.5 ml/day 2.5, 5, 10 mg extended release 1.25, 2.5, 5 mg 2.5-5 mg day with breakfast Elderly/debilitated: 1.25 mg day 1 mg 1-2 mg/day with breakfast 500 or 850 mg/day Weekly 5 mg with breakfast Usual range 5-10 mg/day 0.5, 1, 2 mg If HbA1c 8% or CrCl 20-40 ml/min: 0.5 mg ac If HbA1c 8%: 1-2 mg ac 60, 120 mg HbA1c near goal: 60 mg ac; HbA1c above goal: 120 mg ac 15, 30, 45 mg 15 or 30 mg/day Reduce insulin or sulfonylurea dose, if needed 2, 4, 8 mg 4 mg/day or in 1 or divided doses 2.55 g/day in 2 or 3 divided doses 500 or 750 mg/day 2.55 g/day in 2 or 3 divided doses 5 or 8.5 ml/day 2.55 g/day in 2 or 3 divided doses Increase by 2.5 mg weekly; maintenance: 1.25-20 mg/day in single or divided doses Consider divided doses if more than 10 mg/day Increase by 2 mg at 1- or 2-wk intervals after reaching 2 mg Double the dose after at least 1 wk Increase to 45 mg, if needed Increase after 8-12 wks 25, 50, 100 mg 25 mg ac Increase at 4- to 8-wk intervals, if needed 25, 50, 100 mg 25 mg ac Increase at 4- to 8-wk intervals, if needed 20 mg/day 20 mg/day 8 mg/day 16 mg/day 360 mg 45 mg/day 8 mg/day 60 kg: 50 mg ac 60 kg: 100 mg ac 100 mg ac 494 The Journal for Nurse Practitioners - JNP Volume 7, Issue 6, June 2011

Table 2. Classes of Diabetes Medications (continued) Class/Agent How Supplied Initial Dose Titrate Maximum Dose DPP-4 inhibitor/ Sitagliptin (Januvia) DPP-4 inhibitor/ Saxagliptin (Onglyza) Glucagon-like peptide-1 analog/ Exenatide (Byetta) Glucagon-like peptide-1 analog/ Liraglutide (Victoza) Amylin agonist/ Pramlintide (Symlin) 25, 50, 100 mg 100 mg/day; renal insufficiency: CrCl 30-50 ml/min 50 mg/day; CrCl 30 ml/min or dialysis: 25 mg/day 2.5, 5 mg 2.5 or 5 mg/day Moderate/severe renal impairment, CrCL 50 ml/min or concomitant CYP3A4/5 inhibitors: 2.5 mg/day Give dose after hemodialysis 250 μg/ml pen 5 μg before AM and PM meals None None May increase to 10 μg before AM and PM meals after 1 month 6 mg/ml pen 0.6 mg/day After 1 week, increase dose to 1.2 mg/day May increase to 1.8 mg/day 0.6 mg/ml vial and pen T2DM: 60 μg ac (T1DM has a different initial dose and titration schedule) T2DM: after 3-7 days, increase to 120 μg ac, if no significant nausea 100 mg/day 5 mg/day 10 μg before AM and PM meals 1.8 mg/day 120 μg ac Insulin/ Action Onset Peak Duration Aspart (Novolog) Rapid-acting analog 10-20 min 60-120 min 3-5 h Glulisine (Apidra) Rapid-acting analog 10-20 min 1-2 h 3-4 h Lispro (Humalog) Rapid-acting analog 15 min 30-90 min 3-5 h Regular Short-acting 0.5-1 h 2-3 h 4-12 h NPH Medium-acting 1.5-4 h 4-12 h Up to 24 h Glargine (Lantus) Long-acting analog 1-2 h Flat 24 h Detemir (Levemir) Long-acting analog 0.8-2 h 3.2-9.3 h (dosedependent) Up to 24 h All proprietary names are italicized and in parentheses. BID twice a day; HbA1c hemoglobin A1c; ac before meals; TZD thiazolidinedione; DPP-4 dipeptidyl peptidase-4 inhibitor; CrCl creatinine clearance; T2DM type 2 diabetes mellitus; T1DM type 1 diabetes mellitus. differentiation, inhibit vascular endothelial growth factorinduced angiogenesis, decrease leptin levels, and increase adiponectin levels. When used as a monotherapy, TZDs carry a low risk of hypoglycemia because they do not increase insulin secretion. Common side effects include fluid retention, edema, and weight gain. Contraindications include New York Heart Association class III or IV heart failure, T1DM, diabetic ketoacidosis, and alanine transaminase (ALT) levels greater than 2.5 times the upper limit of normal. Caution should be used when prescribing TZDs to patients with symptomatic heart failure, New York Heart Association class II heart failure, edema, hepatic disease, and ALT levels 1.0-2.5 times www.npjournal.org The Journal for Nurse Practitioners - JNP 495

the upper limit of normal. The patient s ALT level should be monitored closely and the TZDs discontinued if the level is more than 3 times the upper limit of normal or if jaundice occurs. As of September 23, 2010, rosiglitazone has additional safety labeling instructions and prescribing restrictions. NPs should review the black box warnings and the Food and Drug Administration guidelines before prescribing rosiglitazone. TZDs are pregnancy class C drugs. Alpha-Glucosidase Inhibitors The alpha-glucosidase inhibitors (AGI) on the market include acarbose (Precose) and miglitol (Glyset). AGIs slow carbohydrate digestion and reduce postprandial blood glucose. This class does not cause insulin secretion and carries a low risk of hypoglycemia when used as a monotherapy. Common side effects include flatulence and diarrhea. Contraindications include diabetic ketoacidosis, inflammatory bowel disease, colonic ulceration, intestinal obstruction, cirrhosis, and chronic intestinal disease. Caution should be used when prescribing AGIs to patients with a creatinine level over 2 mg/dl. If hypoglycemia occurs, use glucose rather than sucrose to treat. These drugs are pregnancy category B. Dipeptidyl Peptidase-4 Inhibitors The dipeptidyl peptidase-4 (DPP-4s) on the market include sitagliptin (Januvia) and saxagliptin (Onglyza). They increase glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), inhibit glucagon, increase insulin secretion, and decrease gastric emptying. Since DPP-4s augment insulin secretion in a glucose-dependent manor, when used as a monotherapy, there is a low risk for hypoglycemia and weight gain. Common side effects include nasopharyngitis, headache, and nausea. Contraindications include T1DM and ketoacidosis. Caution should be used when prescribing DDP-4 inhibitors to patients with renal or hepatic insufficiency. DPP-4 inhibitors are pregnancy category B drugs. GLP-1 Analog GLP-1 analogs augment insulin release in a glucosedependent manner, suppress glucagon, and slow gastric emptying. The GLP-1s on the market include exenatide (Byetta) and liraglutide (Victoza). Exenatide is injected subcutaneously just before the 2 largest meals of the day, and liraglutide is injected subcutaneously once daily in the morning. Common side effects include nausea, vomiting, indigestion, and other gastrointestinal distress. Although not common, pancreatitis has been added to exenetide s warning label. Contraindications include T1DM, diabetic ketoacidosis, and end-stage renal disease. Liraglutide should not be used for patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, type 2. Caution should be used when prescribing GLP-1 analogs to patients with moderate renal impairment (CrCl 30-50 ml/min), a history of pancreatitis, severe gastrointestinal disorders, or gastroparesis. GLP-1 analogs are pregnancy category C drugs. Amylin agonist The only amylin agonist on the market is pramlintide (Symlin). This drug slows gastric emptying, promotes satiety, inhibits inappropriate secretion of glucagon, and helps to regulate postprandial blood glucose levels. It is injected subcutaneously just before each meal. Although amylin itself does not cause hypoglycemia, its use in combination with mealtime insulin can cause hypoglycemia. Common side effects include nausea, anorexia, headache, and insulin-dependent hypoglycemia. Contraindications include gastroparesis, hypoglycemia unawareness, HbA1c level over 9%, recurrent severe hypoglycemia in the past 6 months, and use of drugs that increase gastric motility. Caution should be used when prescribing amylin agonists to patients on dialysis. Amylin agonists are pregnancy category C drugs. PUBLISHED ALGORITHMS FOR T2DM MANAGEMENT American Diabetes Association/European Association for the Study of Diabetes The ADA and the EASD published a consensus algorithm with 2 tiers of recommendations. Tier 1 consists of wellvalidated core therapies, and tier 2 consists of less well-validated therapies. The recommended HbA1c level is less than 7% for most patients with T2DM, although they do recognize that some patients might not need such stringent control, such as patients with a limited life expectancy, a history of frequent or severe hypoglycemia, or a history of cardiovascular disease. Tier 1 recommends therapeutic lifestyle interventions plus metformin at diagnosis. If after 496 The Journal for Nurse Practitioners - JNP Volume 7, Issue 6, June 2011

Table 3. ADA/EASD Algorithm for T2DM Management HbA1c Goal 7% Fasting Blood Glucose Postprandial Blood Glucose Goal 70-130 mg/dl Goal 180 mg/dl Tier 1: Well-Validated Step 1 Step 2 Step 3 At diagnosis: Lifestyle 2-3 months after Step 1, 2-3 months after Step 2 regimen, interventions metformin if HbA1c target: add a if HbA1c target: (if tolerated) sulfonylurea to the Step 1 If insulin was not initiated regimen if HbA1c 8.5% or in Step 2, initiate insulin initiate insulin if HbA1c 8.5% If insulin was initiated in Step 2, intensify the insulin regimen Tier 2: Less Well-Validated Step 1 Step 2 Lifestyle metformin pioglitazone Lifestyle metformin pioglitazone sulfonylurea or or Lifestyle metformin GLP-1 Lifestyle metformin basal insulin ADA American Diabetes Association; EASD European Association for the Study of Diabetes; T2DM type 2 diabetes mellitus; HbA1c hemoglobin A1c; GLP-1 glucagon-like peptide-1 agonist. The ADA goals for HbA1c and blood glucose apply to most people with T2DM. More-stringent or less-stringent goals may be applied, depending on the patient s individual needs. 2-3 months the HbA1c level is above target but less than 8.5%, a sulfonylurea should be added. If the HbA1c level is greater than 8.5%, insulin therapy should be started and metformin continued. If after 2-3 additional months the HbA1c level is still above target and insulin was not initiated at the previous visit, insulin therapy should begin. If insulin was initiated, the regimen should be intensified. 2, 3 Tier 2, step 1 recommends therapeutic lifestyle changes plus metformin and either pioglitazone or a GLP-1 at diagnosis. 2,3 If after 2-3 months the glycemic targets are not being met, sulfonylurea or basal insulin should be added. 3 Table 3 presents an overview of the current ADA and EASD algorithm for T2DM management. 2,3 ADA/EASD Recommendations for Insulin Therapy for Patients with T2DM The suggested initial basal insulin dose is 10 units or 0.2 units/kg of weight daily. The dose may be given in the morning or the evening and may be increased by 2 units every 3 days until the fasting blood glucose is 70-130 mg/dl. If the fasting blood glucose level is greater than 180 mg/dl, the dose may be increased by more than 2 units. If hypoglycemia occurs or the fasting blood glucose level is less than 70 mg/dl, the dose may be reduced by 4 units or 10% of the total dose. Once the fasting blood glucose is at target, NPs should have the patient measure the blood glucose before lunch, before supper, and at bedtime. If the blood glucose level before lunch is consistently higher than target, rapid-acting insulin may be added at breakfast. If the blood glucose level before supper is consistently higher than target, NPH insulin may be added at breakfast or rapid-acting insulin may be added at lunch. If the blood glucose level at bedtime is consistently higher than the target range, rapid-acting insulin may be added at supper. 2,3 American Association of Clinical Endocrinologists The AACE algorithm begins with medical nutrition therapy, physical activity, weight management, diabetes selfmanagement education, and either monotherapy or combination therapy, depending on the HbA1c. 4 If the initial HbA1c level is 6%-7%, monotherapy should be initiated using either metformin, TZDs, sulfonylureas, glitidides, DPP-4s, or AGIs. If the HbA1c level is not met after 2-3 months on monotherapy, NPs should add a second agent. If the initial HbA1c level is 7%-8%, combination therapy is recommended. If the initial HbA1c level is 8%-10%, NPs should initiate/intensify combination therapy to target both fasting and postprandial hyperglycemia. If the HbA1c level is over 10%, NPs should initiate/intensify insulin therapy using a combination of long- and short-acting insulin. If the patient is being treated with maximum oral combination therapy or oral agents combined with a GLP-1 and the HbA1c level is 6.5%-8.5%, he or she should begin insulin therapy. 4 Table 4 presents an overview of the AACE algorithm. www.npjournal.org The Journal for Nurse Practitioners - JNP 497

Table 4. AACE Algorithm for T2DM Management HbA1c Goal 6.5% Fasting Blood Glucose Goal 70-130 mg/dl Postprandial Blood Glucose Goal 180 mg/dl Medication Recommendations Based on HbA1c Initial HbA1c 6%-7%: initiate monotherapy Initial HbA1c 7%-8%: initiate combination therapy Initial HbA1c 8%-10%: initiate/intensify combination therapy to treat fasting and postprandial hyperglycemia Initial HbA1c 10%: initiate insulin therapy using a basal bolus method Subsequent HbA1c 6.5%-8.5%: intensify combination therapy or add insulin therapy Subsequent HbA1c 8.5%: initiate basal-bolus insulin Recommend Options for Monotherapy Metformin or TZD or Secretagogue (a sulfonylurea or glitinide) or DPP-4 inhibitor or Alpha-glucosidase inhibitor Recommended Options for Dual Therapy Secretagogue (a sulfonylurea or glitinide) metformin or Secretagogue (a sulfonylurea or glitinide) alpha-glucosidase inhibitor or TZD metformin or DPP-4 metformin or Secretagogue (a sulfonylurea or glitinide) metformin TZD or Combination pill/fixed dose or TZD metformin or TZD secretagogue (a sulfonylurea or glitinide) or Secretagogue (a sulfonylurea or glitinide) metformin or Insulin may be used with oral agents. The type of insulin used should match the patient s glucose pattern Recommended Options for Triple Therapy GLP-1 a secretagogue (a sulfonylurea or glitinide) and metformin or Secretagogue (a sulfonylurea or glitinide) metformin and a TZD or Pramlintide used in combination with prandial insulin or If the HbA1c is 6.5%-8.5% and the patient is on maximum combination therapy using oral agents or Oral agents with a GLP-1, begin insulin therapy AACE American Association of Clinical Endocrinologists; T2DM type 2 diabetes mellitus; HbA1c hemoglobin A1c; TZD thiazolidinedione; DPP-4 dipeptidyl peptidase-4 inhibitor; GLP-1 glucagon-like peptide-1 agonist. AACE Recommendations for Insulin Therapy for Patients with T2DM AACE recommends a basal-bolus method as the most effective initial insulin therapy. However, if patients are hesitant to begin insulin, the association recommends beginning with a less intensive regimen. Common insulin regimens include a long-acting insulin analog once or twice daily, a long-acting insulin with a rapidacting insulin administered with the largest meal of the day, once daily premixed insulin administered at the largest meal of the day, long-acting insulin with a rapidacting insulin given twice daily at breakfast and supper, or premixed insulin given twice daily at breakfast and supper. The recommended initial dose is 10 units per injection and the titrating the dose up based on glucose patterns. The morning insulin is adjusted based on the presupper blood glucose, and the evening insulin is adjusted based on the morning blood glucose. If the patient is not adequately controlled on once-daily long-acting insulin and twice-daily premixed insulin is desired, NPs need to divide the total dose in half and give half at breakfast and half at supper. The patient should begin the new regimen 18-24 hours after the last dose of longacting insulin. If the patient is on once-daily premixed insulin and twice daily is desired, simply divide the total daily dose in half and give half at breakfast and half at supper. Then titrate doses until the desired blood glucose range is achieved. If the patient is on once-daily long-acting insulin and 1 injection of rapid acting insulin needs to be added to the largest meal, give 10% of the total dose as rapid-acting insulin before the largest meal and reduce the long-acting 498 The Journal for Nurse Practitioners - JNP Volume 7, Issue 6, June 2011

Table 5. Texas Diabetes Council Algorithm for T2DM Management HbA1c Goal Fasting Blood Glucose Goal Postprandial Blood Glucose Goal 6%-7% if no unstable cardiovascular disease, severe microvascular complications, frequent hypoglycemia episodes, or hypoglycemia unawareness and in newly diagnosed patients Less than 7%-8% if severe microvascular complications, hypoglycemia unawareness, or frequent or severe hypoglycemia and in patients with impaired cognition or a history of falls Diabetes Treatment Algorithm 100 mg/dl if the HbA1c goal is 6% 120 mg/dl if the HbA1c goal is 7% 140 mg/dl if the HbA1c goal is 8% 140 mg/dl At Diagnosis 3 Months After Diagnosis 6 Months After Diagnosis DSME TLC Monotherapy if HbA1c 1% above goal Dual therapy if HbA1c 1% above goal Recommended Options for Dual Therapy Metformin + TZD or Metformin + DPP-4 or Metformin + sulfonylurea or Metformin + GLP-1 or Metformin + glitinde or Metformin + Colesevelam Recommended Options for Triple Therapy Metformin TZD or SU GLP-1 or DPP-4 or AGI or colesevelam Metformin TZD or DPP-4 or AGI or SU5 or colesevelam Insulin If HbA1c 1% above goal on monotherapy, begin dual therapy If HbA1c 1% above goal on dual therapy, begin triple therapy If HbA1c 1% above goal on monotherapy, begin dual therapy If HbA1c 1% above goal on dual therapy, begin triple therapy Goal not met after optimizing therapy, add or intensify insulin Consider referring to an endocrinologist/diabetes specialist T2DM type 2 diabetes mellitus; HbA1c hemoglobin A1c; DSME diabetes self-management education; TLC therapeutic lifestyle changes; TZD thiazolidinedione; DPP-4 dipeptidyl peptidase-4 inhibitor; GLP-1 glucagon-like peptide-1 agonist; SU sulfonylurea; AGI alpha-glucosidase inhibitors. insulin dose by 10%. If the patient is transitioning from premixed insulin twice daily to a basal-bolus method, he or she should begin by dividing the total daily insulin dose in half. The initial basal insulin dose is 80% of half of the total daily dose. The bolus insulin dose for meals is half of the previous total daily dose divided between the meals. Texas Diabetes Council The TDC algorithm recommends at diagnosis diabetes education, self-monitoring of blood glucose, medical nutrition therapy, weight control, exercise, monotherapy if HbA1c level is less than 1% above target glycemic goals, and dual therapy if the HbA1c level is 1% or higher than target. If after 3 months the HbA1c level is less than 1% above goal and the patient is on monotherapy, a second agent (oral agent or GLP-1 agonist) should be added. If the patient is on dual therapy and the HbA1c level is less than 1% above goal, triple therapy should begin. If the patient s HbA1c level is equal to or greater than 1% above target and on monotherapy, dual therapy should www.npjournal.org The Journal for Nurse Practitioners - JNP 499

Table 6. Algorithm for T2DM Management Monotherapy Options Dual-Therapy Options Triple-Therapy Options Meformin Metformin TZD Metformin TZD GLP-1 SU Glitinide Metformin DPP-4 Metformin TZD DPP-4 TZD AGI Metformin SU or glitinide Metformin TZD 1 AGI GLP-1 DPP-4 Metformin GLP-1 Metformin TZD Colesevelam Metformin Glitinide Metformin Colesevelam Metformin SU or glitinide GLP-1 Metformin SU or glitinide DPP-4 Metformin SU or glitinide AGI Metformin SU or glitinide Colesevelam Metformin TZD insulin Metfomim DPP-4 insulin Metformin AGI insulin Metformin SU or glitinide insulin Metformin Colesevelam insulin T2DM type 2 diabetes mellitus; TZD thiazolidinedione; GLP-1 glucagon-like-1 agonist; SU sulfonylurea; DPP-4 dipeptidyl peptidase-4 inhibitor; AGI alpha-glucosidase inhibitor. 500 The Journal for Nurse Practitioners - JNP Volume 7, Issue 6, June 2011

begin with either an additional oral agent, or a GLP-1 agonist, or basal insulin. If the patient is on dual therapy and the HbA1c level is equal to or greater than 1% above goal, triple therapy should start. If after 3 additional months the HbA1c is not at goal, insulin therapy should be started (if the patient is not already on insulin) or intensified (if the patient is). NPs should consider referring the patient to an endocrinologist or diabetes specialist. 5 Table 5 presents an overview of the TDC algorithm. CONCLUSION Using published algorithms that are supported by evidencebased medicine gives the NP guidance in selecting a T2DM diabetes medication regimen. The algorithms discussed in this article have a step-wise approach, are similar in their recommendations, and are effective in achieving target glycemic goals in the patient with T2DM. References 1. Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2008. 2. Nathan D, Buse J, Davidson M, Heine R, Holman R, Sherwin R, Zinman B. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29:2816-2818. 3. Nathan D, Buse J, Davidson M, Ferrannini E, Holman R, Sherwin R, Zinman B. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32:193-203. 4. Rodbard HW, Blonde L, Braithwaite SS, et al, AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(suppl 1):1-68. 5. Texas Diabetes Council. Glycemic control algorithm for type 2 diabetes mellitus in children and adults. Publication number: E45-11265. http://www.dshs.state.tx.us/diabetes/pdf/algorithms/type%202%20glycemic %20Control.pdf. Revised July 22, 2010. Accessed August 1, 2010. Celia Levesque, MSN, RN, CNS-BC, CDE, BC-ADM, is an advanced practice nurse at MD Anderson Cancer Center in Houston, TX, in the endocrine neoplasia and hormonal disorders department. She is also a certified diabetes educator and has a board certification in advanced diabetes management; she can be reached at clevesqu@mdanderson.org. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conflict of interest. 1555-4155/11/$ see front matter 2011 American College of Nurse Practitioners doi:10.1016/j.nurpra.2011.01.005 www.npjournal.org The Journal for Nurse Practitioners - JNP 501