Indiana Medicaid Drug Utilization Review Board Newsletter

Transcription

1 Indiana Medicaid Drug Utilization Review Board Newsletter Indiana Medicaid DUR Board Room W382 Indiana State Government Center, South Introduction The Management of Type 2 Diabetes Deborah K. Brokaw, Pharm.D., BCACP Diabetes is a chronic, progressive, metabolic disease that affects over West Washington million people in the United States. An additional 7 million are estimated to be Street undiagnosed. 1 It is the seventh leading cause of death and is associated with significant morbidity, such as kidney failure, blindness, non-traumatic lowerlimb amputations, cardiovascular disease and stroke. 1 In 2007, estimated Indianapolis, Indiana diabetes costs in the United States totaled $174 billion, with $116 billion attributed directly to medical costs. 1 The increasing prevalence of type 2 DUR Board Members diabetes (T2DM) mirrors the changes in lifestyle (lack of diet and exercise) and rising obesity rates in the U.S. population. 2 This newsletter will review pertinent information on the management of type 2 diabetes, current guideline recommendations, and highlight the importance of medication adherence.!"# # $ # # % # &' (!)% *! () Inside this Issue The Management of Type 2 Diabetes Top 25 Drug Lists for 3Q2012 Epidemiology Type 2 diabetes accounts for 90-95% of patients with the diagnosis of diabetes. 1 Although T2DM is referred to as adult onset diabetes, the incidence in children and adolescents has been increasing. 1 During , an estimated 3,600 youth were newly diagnosed on an annual basis with type 2 diabetes. 1 Risk factors for the development of T2DM include: older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity (African Americans, Hispanic/Latino Americans, American Indians, Asian Americans, and Pacific Islanders). 1,3 Diagnosis Diabetes can be diagnosed using four different measures (Table 1). These include using the fasting plasma glucose (FPG), 2-hour value in the oral glucose tolerance test (OGTT), and hemoglobin A1c (A1C). 3 If an A1C is being used for diagnosis, it should be performed in a laboratory setting using a method that is certified using the National Glycohemoglobin Standardization Program or traceable to the Diabetes Control and Complications Trial reference assay. 3

2 VOLUME 16 ISSUE 1 PAGE 2 Table 1. Criteria for the Diagnosis of Diabetes 3 Any of the following: A1C > 6.5%* FPG > 126 mg/dl* 2-h plasma glucose > 200 mg/dl following a 75g glucose load* Random plasma glucose > 200 mg/dl in a patient with classic symptoms of hyperglycemia *If the patient has a test result that is diagnostic for diabetes, the result should be confirmed, preferably using the same test, on a subsequent day. Lifestyle Modifications All patients with T2DM benefit from physical activity and improvements in diet. These benefits include weight loss, improvements in blood glucose, and also reductions in cardiovascular risk factors. 2,3 Upon diagnosis, patients should be educated and receive encouragement on increasing physical activity and personalized dietary advice. This should be reassessed and reinforced at subsequent visits. In general, patients with T2DM should spend at least 150 min/week on moderate-intensity aerobic activity, spread over at least 3 days per week with no more than 2 consecutive days without exercise. 3 Patients should also be encouraged to engage in resistance training twice a week in the absence of contraindications. 3 Medical nutrition therapy is an integral part of diabetes management and patients should be encouraged to meet with a certified diabetes educator or dietician to receive education on healthy eating and individualized dietary recommendations. Patients should be reminded that lifestyle modifications enhance the efficacy of pharmacologic therapy and even modest weight loss (5-10%) can significantly improve glycemic control. 2,3 Diabetes Pharmacotherapy The goal of drug therapy is to lower blood glucose in an effort to minimize long-term complications while avoiding hypoglycemia. 2,4 Effective management of diabetes is important, because the risk of microvascular and macrovascular complications increase as the A1C increases. 2,3 To delay the onset and/or progression of these complications a multifactorial approach is needed, since glycemic control is critical. In patients with T2DM there are several pathophysiologic defects that contribute to hyperglycemia. These include: increased hepatic glucose production, abnormal islet cell function (pancreatic - and -cell dysfunction), abnormalities in the incretin system, and insulin resistance in target tissues (liver, myocardium, skeletal muscle, adipose tissue). 2-4 Current drug therapy targets these underlying physiological defects and can be divided into three general categories: therapies that increase insulin levels, improve insulin sensitivity, and those with other actions (Table 2).

3 VOLUME 16 ISSUE 1 PAGE 3 adapted from references 3,4 Table 2. Pharmacologic Therapies for Type 2 Diabetes Medication Class Action(s) Expected A1C Lowering Oral Advantages Disadvantages Biguanides (Metformin) hepatic glucose production intestinal glucose absorption action of insulin % No weight gain, no hypoglycemia (monotherapy), improvements in lipid panel, reduction in cardiovascular events, combination products available, cost Gastrointestinal intolerance, increased risk of lactic acidosis (rare), vitamin B 12 deficiency, contraindicated in patients with renal impairment 2 nd generation Sulfonylureas (Glyburide, Glipizide, Glimepiride) insulin secretion % Well tolerated, combination products available, cost Hypoglycemia, weight gain Thiazolidinediones (Pioglitazone, Rosiglitazone) Meglitinides (Nateglinide, Repaglinide) peripheral insulin sensitivity % No hypoglycemia (monotherapy), improvements in HDL and triglycerides (pioglitazone), combination products available insulin secretion % Short duration of action, hepatic clearance, targets postprandial hyperglycemia, combination tablets available Weight gain, edema, heart failure, increased risk of fractures, potential risk of bladder cancer and cardiovascular events (rosiglitazone), cost Hypoglycemia, weight gain, dosing frequency, cost Alpha-glucosidase inhibitors (Acarbose, Miglitol) slowed intestinal carbohydrate digestion and absorption % Targets postprandial hyperglycemia Gastrointestinal intolerance, dosing frequency DPP-4 inhibitors (Linagliptin, Saxagliptin, Sitagliptin) active GLP-1 and GIP concentrations insulin secretion % No weight gain, no hypoglycemia (monotherapy), combination products available, infrequent adverse effects Unknown long-term safety, reported cases of pancreatitis and angioedema, cost Bile acid sequestrant (Colesevelam) glucagon secretion unknown 0.5% No hyperglycemia, LDL lowering Constipation, drug interactions, dosing frequency, may increase triglycerides, cost D2 dopamine-receptor agonist (Bromocriptine rapid release) alters hypothalamic metabolism regulation insulin sensitivity 0.5% Hypoglycemia rare Adverse effects (gastrointestinal, fatigue, dizziness, rhinitis), unknown long-term safety, cost DPP: dipeptidyl peptidase; GLP-1: glucagon-like peptide-1; GIP: glucose-dependent insulinotropic polypeptide

4 VOLUME 16 ISSUE 1 PAGE 4 adapted from references 3,4 Continued. Table 2. Pharmacologic Therapy for Type 2 Diabetes Injectable GLP-1-receptor agonist (Exenatide, Exenatide ER, Liraglutide) insulin secretion (dosedependent) glucagon secretion (dosedependent) % No hypoglycemia (monotherapy), weight loss Gastrointestinal intolerance, reported cases of pancreatitis, thyroid C-cell hyperplasia and tumors in rodents (exenatide ER and liraglutide), injection, unknown long-term safety, cost Slowed gastric emptying satiety Amylin analogue (Pramlintide) glucagon secretion (dosedependent) Slowed gastric emptying % Weight loss, targets postprandial hyperglycemia Hypoglycemia with insulin use, nausea and vomiting, injection, dosing frequency, unknown long -term safety, cost satiety Insulin (Aspart, Glulisine, Lispro, Regular, NPH, Detemir, Glargine) glucose disposal hepatic glucose production % Effective in all patients, potent hypoglycemic effect, (theoretically unlimited), several preparations, combination products available Hypoglycemia, weight gain, Injection, cost (newer agents), patient education needed with use GLP-1: glucagon-like peptide-1; ER: extended-release Therapies which increase the levels of insulin include: sulfonylureas, meglitinides, glucagon-like peptide- 1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and exogenous insulin. With the exception of the GLP-1 agonists and the DPP-4 inhibitors, these agents are available generically and can cause weight gain and hypoglycemia when used as monotherapy. 2,4 The meglitinides have a shorter duration of action, target primarily postprandial blood glucose, but require dosing at meals and bedtime. 2,4 The GLP-1 agonists and DPP-4 inhibitors are newer incretin agents which offer several advantages. As monotherapy they lack the risk of hypoglycemia and are not associated with weight gain. 2,4 The GLP-1 agonists promote weight loss, but cause nausea and vomiting upon initiation, and have been associated with acute pancreatitis. 2,4,9 DPP-4 inhibitors are weight neutral and have an adverse effect profile similar to placebo. 4,9 However, concerns over post-marketing reports of severe hypersensitivity reactions are associated with their use. 9 This lack of longterm safety data with the incretin therapies is a disadvantage associated with their use. Insulin is the most potent agent for lowering blood glucose and can be used in T2DM patients as monotherapy or in combination with oral anti-diabetic agents to lower blood glucose. 4 Insulin is often required in patients with T2DM, as a result of progressive β-cell dysfunction, to reach and maintain glycemic goals. 2 Since there are several formulations of insulin on the market (long-, short-, and rapid-acting), patient characteristics (lifestyle, exercise/dietary habits) and blood glucose trends from self-monitoring of blood glucose (SMBG) should be taken into consideration when insulin therapy is initiated. 2 A common initial strategy is the addition of a basal insulin (i.e., NPH, glargline, detemir) to the existing treatment regimen (often at bedtime) to suppress hepatic glucose production in between meals and at nighttime. 2,4 If glycemic goals are not reached, rapid-acting insulin can be utilized. 2,4

5 VOLUME 16 ISSUE 1 PAGE 5 Therapies such as metformin and thiazolidendiones (TZDs) enhance insulin sensitivity. Unlike the TZDs, metformin is not associated with weight gain and may result in weight loss. In addition to being first-line therapy, it offers several advantages in the treatment of T2DM. It is available in combination products with many anti-diabetic agents and as an extended-release product which helps simplify complicated drug therapy regimens. 2,3 Even though TZDs enhance insulin sensitivity in peripheral tissues, their adverse effect profile and long-term safety is concerning. These include: exacerbation of heart failure, increased risk of bone fractures, and recent associations of bladder cancer with pioglitazone. 2,4 While pioglitazone continues to be available, rosiglitazone can only be obtained through a restricted assess program due to concerns over increased risk of myocardial infarction. 9 Other therapies available for T2DM work through alternative mechanisms to lower blood glucose, and have lower utilization due to modest lowering of A1C levels and/or adverse effects. Alpha-glucosidase inhibitors slow the absorption of carbohydrates from the intestines, but their use is limited by their dosing regimen and gastrointestinal adverse effects. 2,4 Bromocriptine is a dopamine agonist which increases insulin sensitivity through an unknown mechanism. 4 Its place in the therapy for T2DM has yet to be determined, and because only the immediate-release formulation of bromocriptine is approved for this indication, cost may be an issue. 4 Colesevelam is a bile acid sequestrant which reduces hepatic glucose production by an unknown mechanism and also increases incretin levels. 2,4 Even though patients have to take 6 tablets per day to get a small reduction in A1C, colesevelam can positively impact LDL and HDL cholesterol levels. 2,4,9 The amylin mimetic pramlintide stimulates amylin receptors, and like GLP-1 agonists, is an injectable therapy that causes weight loss, decreases appetite, delays gastric emptying, and decreases glucagon secretion (independent of glucose levels). 2 It is indicated for use in patients with either type 1 or type 2 diabetes who use mealtime insulin therapy. 9 When used in conjunction with insulin, especially in patients with type 1 diabetes, severe hypoglycemic episodes have been reported. 9 Treatment Approach The American Diabetes Association (ADA) recommends an individualized patient-centered approach to treat T2DM. This involves using lifestyle modifications (diet and exercise) and pharmacologic therapy to achieve an A1C goal of < 7%, for most individuals. 2,3 If initiated soon after the diagnosis of diabetes, lowering the A1C to < 7% has been shown to reduce microvascular complications of diabetes, and has been associated with long-term reduction in macrovascular disease. 3 Unfortunately, data from the National Health and Nutrition Examination Survey ( ) published in 2009 showed that only 57% of adults with diabetes achieved an A1C < 7%. 5 Some patient populations may require a higher or lower A1C goal therefore, healthcare providers should take into consideration patient-specific characteristics (e.g., concomitant disease states, disease duration, life expectancy, patient attitude, patient resources, and risks associated with hypoglycemia) when deciding on glycemic goals for their patients. 2,,3 Because the achievement of glycemic goals requires active patient participation, involving patients in the decision making process can be helpful and may improve adherence to the management plan. 6 The recently updated ADA and European Association for the Study of Diabetes treatment guidelines recommend early intervention with metformin in combination with lifestyle changes. 2,3 Unless contraindications exist, metformin should be considered the optimal first-line drug. This recommendation is based upon metformin s effect on A1C, absence of weight gain or hypoglycemia, generally low level of adverse effects, relatively low cost, and potential beneficial effects on cardiovascular disease. 2,7,8 To minimize gastrointestinal symptoms during treatment initiation, metformin should be given with meals and titrated up from a low dose. In addition, because metformin can increase the risk of lactic acidosis, its use is contraindicated in patients with renal impairment (serum creatinine > 1.4mg/dl in females, > 1.5 mg/dl in males) and should not be used in patients at risk for lactic acidosis (e.g., alcoholism, acute/chronic metabolic acidosis, acute or unstable congestive heart failure). 9 Patients with a high baseline A1C ( > 9%) may require combination therapy with two oral agents or insulin. 2

6 VOLUME 16 ISSUE 1 PAGE 6 Because T2DM is a chronic, progressive disease, patients will ultimately need combination drug therapy to achieve and maintain target A1C levels. In these instances factors such as cost, concomitant conditions, drug therapy, and lifestyle should be taken into consideration since there is not a consensus on which therapy should be added to metformin. 2,3 If after 3 months of monotherapy at maximal tolerated doses the A1C is not at target levels, and medication adherence is not a contributing factor, a second therapy should be considered. Options could include adding on a second oral agent, a GLP-1 agonist, or basal insulin. 2,3 In general, the addition of an oral agent provides a further A1C reduction of approximately 1%. 2 However, if initial therapy did not produce any clinically significant lowering of the A1C, it should be replaced with an agent with a different mechanism of action. 2 It is important to note, that the greater the A1C lowering that a patient needs, the more likely the addition of insulin will be needed. This is especially true when the addition of a third agent is needed to achieve glycemic control. Monitoring The A1C should generally be monitored twice a year in patients meeting their glycemic goals and quarterly in patients requiring drug therapy changes or who have not achieved their goal A1C. 2,3 Patients and healthcare providers can also utilize SMBG to assess glycemic control, especially postprandial blood glucose targets, in those patients using multiple insulin injections. 3 The optimal frequency and timing of SMBG in patients with T2DM has yet to be determined. Recommended goals include pre-prandial plasma glucose levels of mg/dl and postprandial plasma glucose levels < 180 mg/dl. 3 Medication Adherence Medication adherence is an important component in achieving glycemic goals. Poor glycemic control is associated with worse patient outcomes, including increased risk of hospitalizations, and potentially increased treatment costs. 5 Even though A1C levels improve as medication adherence increases, adherence rates as low as 65% for oral anti-diabetic medications have been reported. 6 Commonly reported reasons for non-adherence with anti-diabetic medications include: adverse effects (e.g., hypoglycemia, weight gain, gastrointestinal symptoms), medication cost, fear of self-injections (with injectable therapies), complex treatment regimens, and lack of patient understanding of medication regimen. 6 Unfortunately, healthcare providers are often not aware of non-adherence; therefore, it is important for them to ask about and discuss medication adherence with patients. This can result in a more open dialogue between the patient and provider and create an opportunity for providers to openly discuss issues related to patient adherence and potential barriers. In addition to involving patients in the decision-making process with their medications, ways to improve medication adherence include, selecting medications with less frequent daily dosing (e.g. once daily with ER formulations), decreasing the number of tablets taken daily by using combination tablets if available, using generic products, and titrating the dose of the medication slowly to improve tolerability (e.g., metformin, GLP- 1 agonist). 6 Discussions regarding potential adverse effects and their management, dosing regimen, and cost are additional ways to encourage adherence with patients. 6 Conclusion Diabetes is a chronic, progressive disease that affects many people and has a large impact on healthcare costs. Several medications can be used to manage diabetes and the symptoms associated with it. Current treatment guidelines recommend metformin, in addition to lifestyle modifications, as first-line therapy. However, many patients will require additional add-on therapies to achieve and maintain optimal glycemic control. For successful, comprehensive, and ongoing treatment, patients with diabetes should take an active role in managing their disease and build strong partnerships with their doctor and other healthcare providers.

7 VOLUME 16 ISSUE 1 PAGE 7 For additional information on Diabetes and patient education materials, please visit the following websites: American Academy of Family Physicians American Diabetes Association Centers for Disease Control and Prevention National Diabetes Education Program References 1. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2012;35: American Diabetes Association. Position Statement: Standards of Medical Care in Diabetes Diabetes Care 2012;35(Suppl 1):S11-S Ismail-Beigi. Glycemic management of type 2 diabetes mellitus. N Engl J Med 012;366(14): Wild H. The Economic Rationale for Adherence in the Treatment of Type 2 Diabetes Mellitus. Am J Manag Care. 2012;18:S43-S Nau D. Recommendations for Improving Adherence to Type 2 Diabetes Mellitus Therapy Focus on Optimizing Oral and Non-Insulin Therapies. Am J Manag Care. 2012;18:S49-S Turner RC, Holman RR, Cull CA, et al;uk Prospective Diabetes Study (UKPDS) Group. Effect of intensive bloodglucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352: Lamanna C, Monami M, Marchionni N, et al. Effect of metformin on cardiovascular events and mortality: a metaanalysis of randomized clinical trials. Diabetes Obes Metab 2011;13(3): Individual package insert

8 VOLUME 16 ISSUE 1 PAGE 8 Top 25 Drugs For 3rd Quarter 2012 Top 25 Drugs 3rd Quarter 2012 Ranked by Total Number of Paid Claims Drug # Paid Claims Avg. Amount Paid/Claim LORATADINE 10 MG TABLET 49,028 $4.75 PROAIR HFA 90 MCG INHALER 48,948 $50.11 HYDROCODON-ACETAMINOPHEN ,893 $2.78 OMEPRAZOLE DR 20 MG CAPSULE 35,636 $6.09 HYDROCODON-ACETAMINOPHEN ,688 $8.65 TRAMADOL HCL 50 MG TABLET 29,596 $2.72 ALPRAZOLAM 1 MG TABLET 25,851 $2.57 CETIRIZINE HCL 10 MG TABLET 25,841 $6.89 AMOXICILLIN 400 MG/5 ML SUSP 23,301 $8.49 CYCLOBENZAPRINE 10 MG TABLET 22,287 $2.41 HYDROCODON-ACETAMINOPHN ,071 $14.63 ALBUTEROL 0.083% INHAL SOLN 21,964 $14.61 DOK 100 MG CAPSULE 20,949 $2.19 FERROUS SULFATE 325 MG TABLET 20,846 $0.44 CLONAZEPAM 1 MG TABLET 20,366 $2.56 MAPAP 325 MG TABLET 20,072 $1.65 ALPRAZOLAM 0.5 MG TABLET 19,407 $2.31 FLUTICASONE PROP 50 MCG SPRAY 19,084 $22.47 CLONAZEPAM 0.5 MG TABLET 18,746 $1.93 CEPHALEXIN 500 MG CAPSULE 17,044 $4.02 AZITHROMYCIN 250 MG TABLET 16,856 $5.05 ASPIRIN 81 MG CHEWABLE TABLET 16,508 $1.44 OMEPRAZOLE DR 40 MG CAPSULE 16,189 $12.47 IBUPROFEN 800 MG TABLET 15,342 $3.34 HYDROCODON-ACETAMINOPH ,301 $6.76

9 VOLUME 16 ISSUE 1!"# PAGE 9 Top 25 Drugs 3rd Quarter 2012 Ranked by Amount Paid Drug Total Amount Paid Avg. Amount Paid/Claim ABILIFY 5 MG TABLET $3,197, $ CYMBALTA 60 MG CAPSULE $3,138, $ ABILIFY 10 MG TABLET $2,545, $ PROAIR HFA 90 MCG INHALER $2,452, $50.11 ADVATE UNITS VIAL $2,367, $34, METHYLPHENIDATE ER 36 MG TAB $1,986, $ LANTUS 100 UNITS/ML VIAL $1,812, $ SPIRIVA 18 MCG CP-HANDIHALER $1,641, $ ABILIFY 20 MG TABLET $1,601, $ INCIVEK 375 MG TABLET $1,579, $17, SUBOXONE 8 MG-2 MG SL FILM $1, $ ABILIFY 15 MG TABLET $1,433, $ INTUNIV ER 2 MG TABLET $1,398, $ VYVANSE 30 MG CAPSULE $1,289,076,85 $ METHYLPHENIDATE ER 54 MG TAB $1,203, $ ADVATE UNITS VIAL $1,186, $31, SINGULAIR 10 MG TABLET $1,179, $ DEXTROAMP-AMPHET ER 20 MG CAP $1,162, $ PULMOZYME 1 MG/ML AMPUL $1,139, $2, COPAXONE 20 MG INJECTION KIT $1,131, $4, CYMBALTA 30 MG CAPSULE $1,100, $ ABILIFY 2 MG TABLET $1,098, $ DEXTROAMP-AMPHET ER 30 MG CAP $1,093, $ ATRIPLA TABLET $1,087, $2,352.97

10 VOLUME 16 ISSUE 1 PAGE 10 PDL Listing The Indiana Medicaid PDL listing may be found at the following Web site: Program Assistance All prior authorization requests or questions regarding the PDL should be directed to the Xerox (formerly ACS) Clinical Call Center at The article in this issue of the DUR Newsletter was authored by Debbie Brokhaw PharmD, Clinical Pharmacist, Xerox The content of this newsletter was approved by the Indiana Medicaid DUR Board