2012年1月30日，礼来公司和勃林格殷格翰公司宣布美国食品药品管理局(FDA)已批准Jentadueto(利拉利汀/盐酸二甲双胍)用于改善成人2型糖尿病患者的血糖控制。该药适合作为饮食和运动疗法的辅助用药，用于同时适宜采用利拉利汀和二甲双胍治疗的患者。Jentadueto既可以单独用药，也可以与磺酰脲联合用药。
FDA批准利拉利汀/二甲双胍复方制剂是基于评价利拉利汀和二甲双胍作为单独片剂治疗糖尿病的临床试验结果。在最大剂量下，利拉利汀/二甲双胍组的血红蛋白A1c相对于安慰剂组的降幅达到1.7%(安慰剂组为+0.1%，利拉利汀/二甲双胍组为-1.6%)。健康受试者联合服用利拉利汀片和二甲双胍片显示与服用利拉利汀/二甲双胍复方制剂具有生物等效性。
Jentadueto治疗组中有≥ 5%的患者报告发生不良反应，该比例大于安慰剂对照组，不良反应包括鼻咽炎和腹泻。Jentadueto+磺酰脲联合治疗组与安慰剂+磺酰脲+二甲双胍联合治疗组相比，其报告发生低血糖的患者比例较高(分别为22.9% vs. 14.8%)。在这些研究中，服用利拉利汀/二甲双胍与任何明显的体重变化均无相关性。
Jentadueto的说明书中包含一个有关乳酸酸中毒的黑框警告。
Jentadueto是一种口服片剂，每日服用2次。
JENTADUETO- linagliptin and metformin hydrochloride tablet, film coated
Boehringer Ingelheim Pharmaceuticals, Inc.
 

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use JENTADUETO safely and effectively. See full prescribing information for JENTADUETO.

Jentadueto® (linagliptin and metformin hydrochloride) tablets
Initial U.S. Approval: 2012
WARNING: RISK OF LACTIC ACIDOSIS
See full prescribing information for complete boxed warning.
Lactic acidosis can occur due to metformin accumulation. The risk increases with conditions such as renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure. (5.1)
Symptoms include malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate. (5.1)
If acidosis is suspected, discontinue JENTADUETO and hospitalize the patient immediately (5.1)
RECENT MAJOR CHANGES
Indications and Usage  
Important Limitations of Use (1.2) 6/2013
Dosage and Administration  
Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin (2.2) 9/2013
Contraindications (4) 5/2014
Warnings and Precautions  
Pancreatitis (5.2) 6/2013
Use with Medications Known to Cause Hypoglycemia (5.5) 9/2013
Hypersensitivity Reactions (5.6) 5/2014
INDICATIONS AND USAGE
JENTADUETO is a dipeptidyl peptidase-4 (DPP-4) inhibitor and biguanide combination product indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both linagliptin and metformin is appropriate (1.1)
Important limitations of use:
Not for treatment of type 1 diabetes or diabetic ketoacidosis (1.2)
Has not been studied in patients with a history of pancreatitis (1.2)
DOSAGE AND ADMINISTRATION
Individualize the starting dose of JENTADUETO based on the patient's current regimen (2.1)
The maximum recommended dose is 2.5 mg linagliptin/1000 mg metformin twice daily (2.1)
Should be given twice daily with meals, with gradual dose escalation to reduce the gastrointestinal side effects due to metformin (2.1)
DOSAGE FORMS AND STRENGTHS
Tablets:
2.5 mg linagliptin/500 mg metformin hydrochloride
2.5 mg linagliptin/850 mg metformin hydrochloride
2.5 mg linagliptin/1000 mg metformin hydrochloride (3)
CONTRAINDICATIONS
Renal impairment (4)
Metabolic acidosis, including diabetic ketoacidosis (4)
History of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity (4)
Hypersensitivity to metformin (4)
WARNINGS AND PRECAUTIONS
Lactic acidosis: Warn against excessive alcohol use. JENTADUETO is not recommended in hepatic impairment or hypoxic states and is contraindicated in renal impairment. Ensure normal renal function before initiating and at least annually thereafter. (5.1, 5.3, 5.4, 5.8, 5.9)
There have been postmarketing reports of acute pancreatitis, including fatal pancreatitis. If pancreatitis is suspected, promptly discontinue JENTADUETO. (5.2)
Temporarily discontinue JENTADUETO in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids (5.3)
Hypoglycemia: When used with an insulin secretagogue (e.g., sulfonylurea (SU) or insulin, consider lowering the dose of the insulin secretagogue or insulin to reduce the risk of hypoglycemia (2.2, 5.5)
There have been postmarketing reports of serious hypersensitivity reactions in patients treated with linagliptin (one of the components of JENTADUETO) including anaphylaxis, angioedema, and exfoliative skin conditions. In such cases, promptly discontinue JENTADUETO, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. (5.6)
Vitamin B12 deficiency: Metformin may lower vitamin B12 levels. Monitor hematologic parameters annually (5.7)
Macrovascular outcomes: No conclusive evidence of macrovascular risk reduction with JENTADUETO or any other antidiabetic drug (5.10)
ADVERSE REACTIONS
Adverse reactions reported in ≥5% of patients treated with JENTADUETO and more commonly than in patients treated with placebo are nasopharyngitis and diarrhea (6.1)
Hypoglycemia was more commonly reported in patients treated with the combination of JENTADUETO and SU compared with those treated with the combination of SU and metformin (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or 1-800-459-9906 TTY, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Cationic drugs eliminated by renal tubular secretion: May reduce metformin elimination. Use with caution. (7.1)
Strong P-glycoprotein/CYP3A4 inducer: The efficacy of JENTADUETO may be reduced when administered in combination (e.g., rifampin). Use of alternative treatments is strongly recommended. (7.2)
USE IN SPECIFIC POPULATIONS
Pregnancy: There are no adequate and well-controlled studies in pregnant women. JENTAD