Thiazolidinedione Step Therapy Program

Transcription

1 Thiazolidinedione Step Therapy Program Policy Number: Last Review: 7/2018 Origination: 07/2014 Next Review: 7/2019 LoB: ACA Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for a brand name thiazolidinedione (TZD) when the following criteria are met. The brand name medications affected are: Actos (pioglitazone tablets Takeda, generics) Actoplus Met (pioglitazone/metformin tablets Takeda, generics) Actoplus Met XR (pioglitazone/metformin extended-release tablets Takeda) Avandia (rosiglitazone tablets GlaxoSmithKline) Avandamet (rosiglitazone/metformin tablets GlaxoSmithKline) Avandaryl (rosiglitazone/glimepiride tablets GlaxoSmithKline) Duetact (pioglitazone/glimepiride tablets Takeda, generics) When Policy Topic is covered Compared to the TZDs, metformin is at least as effective at lowering HbA 1C and has the advantage of being weight neutral (or resulting in modest weight loss). This step therapy program encourages the use of metformin (brand or generic), a metformin-containing combination product (brand or generic) other than the brand name TZD-containing combinations, pioglitazone (generic), or a pioglitazonecontaining combination product (generic) prior to the use of a brand TZD or TZD-containing product. If the step therapy rule is not met, coverage will be determined by prior authorization criteria. Step 1: metformin, metformin extended-release, Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet, Glucovance, metformin/glyburide, metformin/glipizide, Janumet, Janumet XR, Jentadueto, Prandimet, repaglinide/metformin, Kombiglyze XR, pioglitazone/metformin, pioglitazone, pioglitazone/glimeperide, Kazano, metformin/alogliptin, Invokamet, Synjardy, Xigduo XR. Step 2: Actos, Avandia, Actoplus Met, Actoplus Met XR, Avandamet, Duetact, Avandaryl. Criteria Exceptions can be made in patients meeting one of the following criteria: 1. Authorization may be given for a Step 2 product if the patient has tried a Step 1 product in the past. 2. No other exceptions are recommended. When Policy Topic is not covered The use of thiazolidinedione is considered investigational for all other indications. Considerations

2 Thiazolidinediones require prior authorization through the Clinical Pharmacy Department. This Blue Cross and Blue Shield of Kansas City policy Statement was developed using available resources such as, but not limited to: Food and Drug Administration (FDA) approvals, Facts and Comparisons, National specialty guidelines, Local medical policies of other health plans, Medicare (CMS), Local providers. Description of Procedure or Service The thiazolidinediones (TZDs) [Avandia and pioglitazone] and metformin are oral insulin sensitizing antidiabetic agents indicated in adjunct to diet and exercise for the treatment of type 2 diabetes mellitus. 1-10,17 Metformin (non-extended-release formulation) is indicated for use in children; neither of the TZDs are indicated in children. 1-6 Currently available therapeutic classes of oral antidiabetic agents used for the management of type 2 diabetes are the sulfonylureas, biguanides, TZDs, oral alpha-glucosidase inhibitors, non-sulfonylurea insulin secretagogues (meglitinides), dipeptidyl peptidase-4 (DPP-4) inhibitors, bromocriptine (Cycloset ) and the sodium glucose co-transporter-2 (SGLT-2) inhibitors). In addition to single entity agents, Avandia and pioglitazone are available as combination products with metformin (Avandamet and pioglitazone/metformin) and the sulfonylurea glimepiride (Avandaryl and pioglitazone/glimepiride) Pioglitazone is available as a combination with extended-release metformin (Actoplus Met XR) as well. 17 Pioglitazone is also available in combination with a DPP-4 inhibitor (Oseni [pioglitazone/alogliptin]), however this product is not part of this TZD Step Therapy policy. Metformin and metformin extended-release are indicated as monotherapy in patients aged 10 years and 17 years (Glumetza is specifically indicated for patients 18 years of age), respectively. 1-4 In addition to the combinations with TZDs mentioned above, metformin (or metformin extended-release [XR]) is also available in combination with most of the classes of oral diabetes medications mentioned above. Rationale Efficacy Achieving glycemic control is fundamental to the management of diabetes. The goal of therapy is to achieve a glycosylated hemoglobin level (HbA 1C ) as close to normal as possible while avoiding hypoglycemia. Factors that should be considered when selecting an antidiabetic agent include effectiveness at lowering blood glucose levels, the presence of any drug-specific effects independent of blood glucose lowering that may reduce long-term complications, safety profile, and tolerability. 14 Glucose-lowering effectiveness as demonstrated in clinical trials may be impacted by several factors including, but not limited to, the intrinsic characteristics of the antidiabetic agent, baseline HbA 1C, duration of diabetes, and previous therapy. 15 According to pooled data, metformin monotherapy will typically lower HbA 1C by approximately 1.0 to 2.0 percentage points and TZD monotherapy will typically lower HbA 1C by approximately 0.5 to 1.4 percentage points. 15 Overall, there high-quality clinical trial data directly comparing antidiabetic regimens are lacking. 15 The Agency for Healthcare Research and Quality (AHRQ) published a review of the oral diabetes medications that included 140 randomized controlled trials and 26 observational studies. 16 Most medications lowered HbA 1C on average by 1 absolute percentage point (metformin was more efficacious than the DPP-4 inhibitors). Two-drug combinations had similar HbA 1C reduction. Compared with metformin, TZDs and sulfonylureas had a more unfavorable effect on weight (mean difference of +2.6 kg). Metformin decreased low density lipoprotein (LDL) cholesterol relative to pioglitazone, sulfonylureas, and DPP-4 inhibitors. TZDs had an increased risk of congestive heart failure relative to sulfonylureas and bone fractures relative to metformin. Diarrhea occurred more often for metformin compared with TZD users. The report concluded that although the long-term benefits and harms of

3 diabetes medications remain unclear, the evidence supports use of metformin as a first-line agent. Comparisons of two-drug combinations showed little to no difference in HbA 1C reduction, but some combinations increased risk for hypoglycemia and other adverse events. Treatment Guidelines and Consensus Statements In general guidelines from the American Diabetes Association (ADA) and American College of Clinical Endocrinologists (AACE) for the management of diabetes recognize metformin as the cornerstone of therapy or initial therapy (after lifestyle modification) to which other agents may be added in patients with type 2 diabetes. Other classes of diabetes medications may be appropriate based on glycemic goals, specific patient factors, and comorbid conditions. According to a position statement (2012) of the ADA and the European Association for the Study of Diabetes (EASD) for the management of hyperglycemia in type 2 diabetes metformin is the preferred initial therapy. 15 If metformin cannot be used another oral agent could be chosen such as a sulfonylurea, meglitinide, pioglitazone (Avandia is not mentioned), or a DPP-4 inhibitor. Specific patient preferences, characteristics, susceptibilities to side effects, potential for weight gain, and hypoglycemia should play a role in drug selection. When addition of a second agent is warranted, the statement provides nonspecific recommendations for addition of an oral agent, a glucoagon-like peptide-1 (GLP- 1) agonist, or basal insulin. The position statement recognizes the paucity of long-term comparative effectiveness trial data available and therefore a uniform recommendation on the best agent to combine with metformin cannot be made. Rather, the advantages and disadvantages of specific drugs for each patient should be considered. The AACE Comprehensive Diabetes Management algorithm (2013) recommends monotherapy with lifestyle modification as first-line therapy in patients who present with HbA 1C < 7.5%. 18 Metformin, as monotherapy is generally the recommended first-line pharmacotherapy because it has a low risk of hypoglycemia, can promote modest weight loss, produces durable antihyperglycemic effects, and has robust cardiovascular safety; however, it cannot be used in patients with advanced renal impairment. Metformin should also be continued as background therapy when additional agents need to be added for glycemic control. Acceptable alternatives to metformin in the first-line setting include GLP-1 agonists, DPP-2 inhibitors, and alpha-glucosidase inhibitors. TZDs, SUs, and glinides may also be used, however, they should be used with caution owing to the potential for weight gain, hypoglycemia, and other risks. The algorithm notes that pioglitazone has relatively potent HbA 1C lowering properties, a low risk of hypoglycemia, possible cardiovascular disease (CVD) benefit, and durable glycemic effects. The notes side effects that have limited its use include bone fracture, elevated risk for chronic edema or heart failure, and a possible association with bladder cancer. TZDs are also mentioned for patients with prediabetes, although metformin and acarbose have more data and have been shown to reduce future diabetes incidence in patients with prediabetes by 25% to 30%. TZDs have been shown to prevent 60% to 75% of future diabetes in patients with prediabetes. Unlike metformin and acarbose however, the TZDs have safety concerns such as increased risk of bone fracture and fluid retention which may worsen underlying heart failure. Therefore, TZDs should be reserved for failures of treatment, progressive worsening of dysglycemia, despite the use of other therapies or options, or for those patients at greatest risk for future diabetes. The ADA Standards of Care (2015) recommend metformin at the time of type 2 diabetes diagnosis, along with lifestyle interventions, unless metformin is contraindicated. 14 When noninsulin monotherapy at maximal tolerated dose does not achieve or maintain the desired HbA 1C target over 3 to 6 months, a second oral agent, a GLP-1 receptor agonist, or insulin should be added. Specific therapy recommendations for the use of TZDs are not addressed. References 1. Glucophage tablets/glucophage XR extended-release tablets [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; June Glumetza extended release tablets [package insert]. Menlo Park, CA: Depomed, Inc.; April 2011.

4 3. Fortamet extended release tablets [package insert]. Florham Park, NJ:.Shionogi Inc.; January Riomet oral solution [package insert]. Jacksonville, FL: Ranbaxy Pharmaceuticals; August 5. Avandia tablets [package insert]. Research Triangle Park, NC: GlaxoSmithKline; May 6. Actos tablets [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; November Avandamet tablets [package insert]. Research Triangle Park, NC: GlaxoSmithKline; May 8. Actoplus Met [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc. July 9. Duetact tablets [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; March Avandaryl tablets [package insert]. Research Triangle Park, NC: GlaxoSmithKline; March Jentadueto tablets [package insert]. Ridgefield, CT: Boehringer Ingelheim; August Kombiglyze XR tablets [package insert]. Princeton, NJ. Bristol-Meyers Squibb Company; August Janumet XR tablets [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; August Standards of medical care in diabetes Diabetes Care. 2015;38(Suppl 1):S1-S94. Available at: _Combined_Final.6-99.pdf. Accessed on September 11, Inzucci SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: A patients centered approach. Position statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6): Bennett WL, Wilson LM, Bolen S, et al. Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update. Comparative Effectiveness Review No. 27. (Prepared by Johns Hopkins University Evidence-based Practice Center under Contract No ) AHRQ Publication No. 11-EHC038-EF. Rockville, MD: Agency for Healthcare Research and Quality. March Available at: Kazano tablets [prescribing information]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; August Garber AJ, Abrahamson MJ, Barzilay JI, et al. American Association of Clinical Endocrinologists comprehensive diabetes management algorithm 2013 consensus statement. Endocr Pract. 2013;19(Suppl 2): Actoplus Met XR[package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc; November Billing Coding/Physician Documentation Information NA Pharmacy benefit Additional Policy Key Words Policy Number: Policy Implementation/Update Information 07/2014 New Policy titled Thiazolidinedione (TZD) Step Therapy Program 07/2015 Annual review no changes made 07/2016 Annual review- no changes to policy statement 07/2017 Annual review- no changes to policy statement 07/2018 Annual review no changes to policy

5 State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.