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Home , Linagliptin, Saxagliptin, Sitagliptin

STEPS New Drug Reviews

Linagliptin (Tradjenta) for the Treatment of Mellitus KAREN WHALEN, PharmD, BCPS, CDE, and KAREN R. SANDO, PharmD, CDE University of Florida College of Pharmacy, Gainesville, Florida

STEPS new drug reviews (Tradjenta) is a dipeptidyl-peptidase-4 (DPP-4) inhibitor labeled for the treat- cover Safety, Tolerability, ment of mellitus. Similar to (Januvia) and (Onglyza), Effectiveness, Price, and Simplicity. Each indepen- linagliptin delays the breakdown of endogenous hormones such as -like dent review is provided peptide 1 and glucose-dependent insulinotropic polypeptide. These hormones, when secreted by authors who have no in response to food intake, stimulate postmeal secretion, inhibit glucagon release, financial association with improve satiety, and slow gastric emptying.1,2 Linagliptin can be used alone or in combination the drug manufacturer. with (Glucophage), , (Actos), or insulin. The series coordinator for AFP is Allen F. Shaugh- nessy, PharmD, Tufts Drug Dosage Dose form Cost* University Family Medicine Residency Program at Linagliptin (Tradjenta) 5 mg daily 5-mg $254 for 30 tablets Cambridge Health Alli- ance, Malden, Mass. *—Estimated retail price of one month’s treatment based on information obtained at http://www.goodrx.com A collection of STEPS pub- (accessed October 1, 2012). lished in AFP is available at http://www.aafp.org/ afp/steps. SAFETY control should be used in patients receiving Few severe adverse effects have been associ- strong inducers of cytochrome P450 3A4 ated with linagliptin. When used alone or or P-glycoprotein, such as rifampin. Lina- with metformin or pioglitazone, linagliptin gliptin is a U.S. Food and Drug Administra- has an incidence of compa- tion category B drug.2 rable to that of placebo.1-4 Hypoglycemia is more common with linagliptin (22.9 per- TOLERABILITY cent) than with placebo (14.8 percent) when Overall, linagliptin is well tolerated, and added to the combination of metformin and reports of adverse effects are similar to those a .5 A reduction in sulfonylurea with placebo.1-5 Patients taking linagliptin or insulin dosage may be needed to decrease had slightly higher rates of back pain (9.1 the risk of hypoglycemia when linagliptin is versus 8.4 percent), arthralgia (8.1 versus added to these agents.2 As with other DPP-4 6.1 percent), and headache (6.4 versus 5.2 inhibitors, can occur, although percent) than patients treated with a sulfonyl- infrequently, with linagliptin therapy; eight urea.2 Treatment discontinuation because of cases were reported in clinical trials involving adverse effects was infrequent (1.2 to 2.9 per- 4,687 patients (0.2 percent).2 cent).1-4 Linagliptin does not affect renal func- Patients who have renal dysfunction do not tion, body weight, or waist circumference.1,3 require a dosage reduction with linagliptin, unlike with the other DPP-4 inhibitors. EFFECTIVENESS Linagliptin has no clinically relevant drug No studies have determined linagliptin’s interactions with metformin, pioglitazone, effect on diabetes-related complications and digoxin, (Zocor), or warfarin mortality. It reduces levels of A1C by 0.4 to (Coumadin). Alternative agents for glucose 0.7 percent,2,3 fasting plasma glucose (FPG) ▲

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by 20.5 to 23.4 mg per dL (1.14 to 1.30 mmol useful as an add-on therapy for patients with per L), and two-hour postprandial glucose by type 2 diabetes who require additional agents 58.4 mg per dL (3.24 mmoL per L).1,2 Add- to achieve A1C goals. Linagliptin affects ing linagliptin to metformin, sulfonylureas, measures of diabetes similarly to the other or pioglitazone will reduce A1C levels by an DPP-4 inhibitors, saxagliptin and sitagliptin, additional 0.4 to 0.6 percent,2-4 with slightly but does not require dosage adjustments in smaller reductions in FPG.2-5 When used patients with renal dysfunction. in combination with insulin (with or with- Address correspondence to Karen Whalen, PharmD, out metformin, pioglitazone, or both), lina- BCPS, CDE, at [email protected]. Reprints are not gliptin reduces A1C levels by an additional available from the authors. 0.65 percent and FPG by an additional 11 mg 2 Author disclosure: No relevant financial affiliations to per dL (0.61 mmol per L). Linagliptin has disclose. not been compared head-to-head with other DPP-4 inhibitors. REFERENCES

PRICE 1. Taskinen MR, Rosenstock J, Tamminen I, et al. Safety and efficacy of linagliptin as add-on therapy to met- A 30-day supply of linagliptin (5-mg tablets) formin in patients with type 2 diabetes: a randomized, will cost about $250. This cost is comparable double-blind, placebo-controlled study. Diabetes Obes to that of other DPP-4 inhibitors. Generic Metab. 2011;13 (1): 65-74. metformin and sulfonylureas are available 2. Tradjenta (linagliptin) tablets [prescribing information]. Ridgefield, Conn.: Pharmaceuticals, for less than $5 per month through most Inc.; 2012. http://bidocs.boehringer-ingelheim.com/ retail pharmacy discount programs. BIWebAccess/ViewServlet.ser?docBase=renetnt& folderPath=/Prescribing+Information/PIs/Tradjenta/ SIMPLICITY Tradjenta.pdf. Accessed November 26, 2012. 3. Del Prato S, Barnett AH, Huisman H, Neubacher D, Linagliptin is available in 5-mg tablets taken Woerle HJ, Dugi KA. Effect of linagliptin monotherapy once daily with or without food. It is contra- on glycaemic control and markers of β-cell function in indicated in patients with a history of hyper- patients with inadequately controlled type 2 diabetes: 2 a randomized controlled trial. Diabetes Obes Metab. sensitivity to the drug. 2011;13(3):258-267. 4. Gomis R, Espadero RM, Jones R, Woerle HJ, Dugi Bottom Line KA. Efficacy and safety of initial combination therapy Linagliptin reduces A1C levels to a lesser with linagliptin and pioglitazone in patients with inad- equately controlled type 2 diabetes: a randomized, extent than first-line therapy (metformin) double-blind, placebo-controlled study. Diabetes Obes and is significantly more expensive than Metab. 2011;13 (7): 653- 661. metformin and sulfonylureas. Importantly, 5. Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy its ability to affect diabetes-related morbid- and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metfor- ity and mortality is not known. As with min and sulphonylurea: a 24-week randomized study. other DPP-4 inhibitors, linagliptin may be Diabet Med. 2011;28 (11):1352-1361. ■

1148 American Family Physician www.aafp.org/afp Volume 86, Number 12 ◆ December 15, 2012