Linagliptin

Pharmacologic Category

Antidiabetic Agent, Dipeptidyl Peptidase 4 (DPP-4) Inhibitor

Dosing: Adult

Diabetes mellitus, type 2: Oral: 5 mg once daily

Concomitant use with insulin and/or insulin secretagogues (eg, sulfonylureas): Reduced dose of insulin and/or insulin secretagogues may be needed.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Use: Labeled Indications

Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes as monotherapy or in combination with other antidiabetic agents

* See Uses in AHFS Essentials for additional information.

Class and Related Monographs

Dipeptidyl Peptidase-4 Inhibitors

Comparative Efficacy

• LINAGLIPTIN

Clinical Practice Guidelines

Diabetes Mellitus:

American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE), “Consensus Statement on the Comprehensive Type 2 Diabetes Management Algorithm - 2019 Executive Summary,” January 2019

American Diabetes Association, “Standards of Medical Care in Diabetes - 2019,” January 2019

American Diabetes Association and the European Association for the Study of Diabetes Consensus Report, “Management of Hyperglycemia in Type 2 Diabetes, 2018,” December 2018

Diabetes Canada, “Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada,” 2018

Administration: Oral

May be administered with or without food.

Dietary Considerations

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Storage/Stability

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

Frequently reported side effects of this drug

• Sore throat

• Stuffy nose

• Runny nose

• Cough

• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out

• Skin blisters

• Skin breakdown

• Persistent joint pain

• Severe joint pain

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/201280s014lbl.pdf#page=14, must be dispensed with this medication.

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity) to linagliptin or any component of the formulation

Canadian labeling: Additional contraindications: Use in type 1 diabetes mellitus or diabetic ketoacidosis

Warnings/Precautions

Concerns related to adverse effects:

• Arthralgia: Severe and disabling arthralgia has been reported with DPP-4 inhibitor use; onset may occur within one day to years after treatment initiation and may resolve with discontinuation of therapy. Some patients may experience a recurrence of symptoms if DPP-4 inhibitor therapy resumed.

• Bullous pemphigoid: DPP-4 inhibitor use has been associated with development of bullous pemphigoid; cases have typically resolved with topical or systemic immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Advise patients to report development of blisters or erosions. Discontinue therapy if bullous pemphigoid is suspected and consider referral to a dermatologist.

• Hypersensitivity reactions: Rare hypersensitivity reactions (including anaphylaxis, angioedema, and exfoliative skin conditions) have been reported in patients treated with linagliptin; events have generally been noted within the first 3 months of therapy and may occur with the initial dose. Discontinue if signs/symptoms of hypersensitivity reactions occur. Use with caution if patient has experienced angioedema with other DPP-4 inhibitor use.

• Pancreatitis: Cases of acute pancreatitis, including fatalities, have been reported with use. Monitor for signs/symptoms of pancreatitis; discontinue use immediately if pancreatitis is suspected and initiate appropriate management. Use with caution in patients with a history of pancreatitis as it is not known if this population is at greater risk.

Disease-related concerns:

• Bariatric surgery:

– Altered absorption: Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery (Mechanick 2013; Melissas 2013).

– Glucagon-like peptide-1 exposure and therapeutic efficacy: Closely monitor for signs and symptoms of pancreatitis; gastric bypass and sleeve gastrectomy may increase endogenous secretion of glucagon-like peptide-1 (Korner 2009; Peterli 2012). A single-dose, placebo-controlled study evaluated short-term therapy (4 weeks) with sitagliptin in gastric bypass patients having persistent or recurrent type 2 diabetes and found it to be well tolerated and provided a small but significant reduction in postprandial blood glucose (Shah 2018).

• Cardiovascular disease: In cardiovascular outcome trials of patients with type 2 diabetes and atherosclerotic cardiovascular disease, treatment with other DPP-4 inhibitors has been associated with HF. However, in a randomized, double-blind, placebo-controlled trial of patients with type 2 diabetes mellitus and high cardiovascular and renal risks, the occurrence of the primary composite cardiovascular outcome (cardiovascular death, nonfatal MI, nonfatal stroke) with linagliptin was found to be noninferior to placebo. In addition, the rate of hospitalization for HF did not differ from placebo, including in patients with preexisting HF. Median follow-up was 2.2 years (McGuire 2018; Rosenstock 2018). The ADA suggests DPP-4 inhibitors (except saxagliptin) may be considered in patients with HF (ADA 2019).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Not indicated for use in patients with type 1 diabetes mellitus (insulin dependent, IDDM) or with diabetic ketoacidosis (DKA).

• Patient education: Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

According to the manufacturer, ~26% of participants in clinical trials were ≥65 years of age; ~3% were ≥75 years of age. No difference in efficacy or safety was noted between younger and older patients. However, it has been noted in a cohort of adults over the age of 70 that linagliptin in combination with a sulfonylurea can significantly increase the risk of hypoglycemia (Barnett 2013). Intensive glucose control (HbA1c <6.5%) has been linked to increased all-cause and cardiovascular mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly" to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be based on several factors, including the patient's functional and cognitive status, how well he/she recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other disease states. An HbA1c <7.5% is an acceptable endpoint for a healthy older adult, while <8% to 8.5% is acceptable for elderly patients, patients depending on the level of comorbities, functional and cognitive status and living situation (eg, caregiver present to assist, long-term care facility). For elderly patients with diabetes who are relatively healthy, attaining target goals for aspirin use, blood pressure, lipids, smoking cessation, and diet and exercise may be more important than normalized glycemic control (ADA 2018b).

Pregnancy Considerations

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia (ACOG 201 2013). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Agents other than linagliptin are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).

Breast-Feeding Considerations

It is not known if linagliptin is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Lexicomp Pregnancy & Lactation, In-Depth

• LinaGLIPtin

Briggs' Drugs in Pregnancy & Lactation

• Linagliptin

Adverse Reactions

Incidences may include use in combination therapy regimens.

1% to 10%:

Endocrine & metabolic: Hypoglycemia (7%), increased uric acid (3%)

Gastrointestinal: Increased serum lipase (8%; >3x upper limit of normal)

Respiratory: Nasopharyngitis (7%), cough (2%)

Frequency not defined:

Dermatologic: Urticaria

Neuromuscular & skeletal: Myalgia

Respiratory: Bronchoconstriction

Postmarketing: Acute pancreatitis, anaphylaxis, angioedema, bullous pemphigoid, exfoliation of skin, oral mucosa ulcer, rhabdomyolysis, severe arthralgia, severe hypersensitivity, skin rash, stomatitis

* See Cautions in AHFS Essentials for additional information.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Exceptions: Danazol. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Dipeptidyl Peptidase-IV Inhibitors may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy

Antihepaciviral Combination Products: May increase the serum concentration of LinaGLIPtin. Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Risk C: Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Insulins: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Risk X: Avoid combination

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of LinaGLIPtin. Management: Strongly consider using an alternative to any P-glycoprotein inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider therapy modification

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Risk C: Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Ritonavir: May increase the serum concentration of LinaGLIPtin. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Sulfonylureas: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Genes of Interest

• Cytochrome P450 3A4
• P-Glycoprotein

Monitoring Parameters

HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2019]), serum glucose; signs/symptoms of pancreatitis; signs/symptoms of heart failure

Reference Range

Recommendations for glycemic control in nonpregnant adults with diabetes (ADA 2019):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics)

Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics)

Peak postprandial capillary blood glucose: <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics)

Recommendations for glycemic control in older adults (≥65 years) with diabetes (ADA 2019):

HbA1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very complex/poor health) (individualization may be appropriate based on patient and caregiver preferences)

Preprandial capillary blood glucose: 90 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health)

Bedtime capillary blood glucose: 90 to 150 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health)

Advanced Practitioners Physical Assessment/Monitoring

Obtain HbA1c (twice yearly in stable patients and quarterly in unstable patients) and serum glucose. Monitor blood pressure. Observe for signs of pancreatitis. Refer patient to diabetes educator for instruction if needed.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor blood pressure. Watch for signs of hypoglycemia. Refer patient to diabetes educator for instruction if needed. Educate patient about increased risk of pancreatitis and to report any signs or symptoms.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tradjenta: 5 mg [contains corn starch]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Trajenta: 5 mg

Anatomic Therapeutic Chemical (ATC) Classification

• A10BH05

Generic Available (US)

No

Pricing: US

Tablets (Tradjenta Oral)

5 mg (per each): $18.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Linagliptin inhibits dipeptidyl peptidase 4 (DPP-4) enzyme resulting in prolonged active incretin levels. Incretin hormones (eg, glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production. Under normal physiologic circumstances, incretin hormones are released by the intestine throughout the day and levels are increased in response to a meal; incretin hormones are rapidly inactivated by the DPP-4 enzyme.

Pharmacodynamics/Kinetics

Distribution: Extensive

Protein binding: 70% to 80%; concentration dependent

Metabolism: Not extensively metabolized

Bioavailability: ~30%

Half-life elimination: Effective (therapeutic): ~12 hours; Terminal (DPP-4 saturable binding): >100 hours

Time to peak: 1.5 hours

Excretion: 80% feces unchanged; 5% urine unchanged

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Linagliptin-dependent patients with diabetes should be appointed for dental treatment in the morning in order to minimize chance of stress-induced hypoglycemia.

Effects on Bleeding

No information available to require special precautions

Related Information

• Oral Antidiabetic Agents Comparison Table

Index Terms

BI-1356; Trajenta

FDA Approval Date

May 02, 2011

References

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American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64.[PubMed 29370047]

American Diabetes Association (ADA). Diabetes Care. 2019;42(suppl 1):S1-S193. http://care.diabetesjournals.org/content/42/Supplement_1. Accessed January 24, 2019.[PubMed 29222377]

American Diabetes Association (ADA). Standards of medical care in diabetes–2020. Diabetes Care. 2020;43(suppl 1):S1-S212. https://care.diabetesjournals.org/content/43/Supplement_1. Accessed January 22, 2020.

Barnett AH, Huisman H, Jones R, von Eynatten M, Patel S, Woerle HJ. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9902):1413-1423. doi: 10.1016/S0140-6736(13)61500-7.[PubMed 23948125]

Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249. doi: 10.1210/jc.2013-2465.[PubMed 24194617 ]

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes. 2013;35(suppl 1):1-212.

FDA Safety Alert. DPP-4 Inhibitors. Food and Drug Administration website. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm460238.htm. Accessed August 28, 2015.

Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan. Endocr Pract. 2011;17(suppl 2):1-53.[PubMed 21474420]

Kirkman MS, Briscoe VJ, Clark N, et al; Consensus Development Conference on Diabetes and Older Adults. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012;60(12):2342-2356. doi: 10.1111/jgs.12035.[PubMed 23106132]

Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond). 2009;33(7):786-795. doi: 10.1038/ijo.2009.79.[PubMed 19417773]

McGuire DK, Alexander JH, Johansen OE, et al; CARMELINA Investigators. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA [published online ahead of print November 11, 2018]. Circulation. doi: 10.1161/CIRCULATIONAHA.118.038352.[PubMed 30586723]

Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis. 2013;9(2):159-191. doi: 10.1016/j.soard.2012.12.010.[PubMed 23537696]

Melissas J, Leventi A, Klinaki I, et al. Alterations of global gastrointestinal motility after sleeve gastrectomy: a prospective study. Ann Surg. 2013;258(6):976-982. doi: 10.1097/SLA.0b013e3182774522.[PubMed 23160151]

Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740-748. doi: 10.1007/s11695-012-0622-3.[PubMed 22354457]

Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P; Clinical Guidelines Committee of the American College of Physicians. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians [published correction appears in: Ann Intern Med. 2012;156(10):756. Ann Intern Med. 2012;157(2):152]. Ann Intern Med. 2012;156(3):218-231. doi: 10.7326/0003-4819-156-3-201202070-00011.[PubMed 22312141]

Rosenstock J, Perkovic V, Johansen OE, et al; CARMELINA Investigators. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial [published online ahead of print November 9, 2018]. JAMA. doi: 10.1001/jama.2018.18269.[PubMed 30418475]

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Shah A, Levesque K, Pierini E, et al. Effect of sitagliptin on glucose control in type 2 diabetes mellitus after Roux-en-Y gastric bypass surgery. Diabetes Obes Metab. 2018;20(4):1018-1023. doi: 10.1111/dom.13139.[PubMed 29072800]

Tradjenta (linagliptin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals and Indianapolis, IN: Eli Lilly and Company; July 2019.

Trajenta (linagliptin) [product monograph]. Burlington, Ontario, Canada: Boehringer Ingelheim (Canada) Ltd; November 2019.

Brand Names: International

Glitin (BD); Glucoliptin (EG); Ligatin (BD); Linajenta (EG); Linax (BD); Lino (BD); Prevaglip (EG); Tradjenta (BB); Trajenta (AE, AT, AU, BE, BH, CH, CY, CZ, DK, EE, EG, ES, FR, GB, HK, HR, HU, ID, IE, IL, IN, IS, JO, KR, KW, LB, LT, LU, LV, MT, MY, NL, NO, PH, PL, PT, QA, RO, SA, SE, SG, SI, SK, TH, TW, VN); Traneta (BD); Trayenta (AR, BR, CL, CO, CR, CU, DO, EC, GT, HN, MX, NI, PA, SV); Trazenta (JP)

Last Updated 3/19/20