Efficacy and safety of Jentadueto® (linagliptin plus metformin)

Scheen, André

doi:10.1517/14740338.2013.771631

Cited by 7 publications

(4 citation statements)

References 94 publications

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“…Several fixed-dose combinations (FDCs) are currently available or will be commercialized very soon 118 . Such FDCs may only be prescribed when both compounds are not contraindicated because of the presence of RI and appropriate adjustments of individual doses may be required [134][135][136] .…”

Section: Dpp-4 Inhibitors (Gliptins) Are a New Class Of Oads Belonginmentioning

confidence: 99%

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Scheen¹

2013

Expert Opinion on Drug Metabolism & Toxicology

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SUMMARYIntroduction : People with chronic kidney disease (CKD) of stages 3-5 (creatinine clearance < 60 ml/min) represent 25-30% of patients with type 2 diabetes (T2DM), but the problem is underrecognized or neglected in clinical practice. However, most oral antidiabetic agents have limitations in case of renal impairment, either because they require a dose adjustment or because they are contraindicated for safety reasons. Expert Opinion : Because of potential important PK interferences and for safety reasons, the pharmacological management of T2DM should be adjusted according to kidney function. In general, the daily dose should be reduced according to glomerular filtration rate (GFR) or even the drug is contraindicated in presence of more severe CKD. This is the case for metformin (risk of lactic acidosis) and for many sulfonylureas (risk of hypoglycemia). At present, however, the exact GFR cutoff for metformin use is controversial. New antidiabetic agents are better tolerated in case of CKD, although clinical experience remains quite limited for most of them. The dose of DPP-4 inhibitors should be reduced (except for linaglitpin) whereas both the efficacy and safety of SGLT2 inhibitors are questionable in presence of CKD.

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Section: Dpp-4 Inhibitors (Gliptins) Are a New Class Of Oads Belonginmentioning

confidence: 99%

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Scheen¹

2013

Expert Opinion on Drug Metabolism & Toxicology

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“…In contrast, the use of metformin in patients with mild to moderate CKD is either contraindicated (as stated in the labeling) or at least limited, with dose reduction and regular careful supervision of renal function as proposed more recently 3,46 . The safety aspects of using linagliptin and metformin in patients with mild to moderate CKD will be more extensively discussed in a further paper 106 .…”

Section: Safety In Patients With Ckdmentioning

confidence: 99%

“…Dose escalation should be gradual to reduce the gastrointestinal side effects associated with metformin use. Because of the presence of metformin, Jentadueto® is not recommended in hepatic impairment or hypoxic states and is contraindicated in renal impairment, although such restriction might be dampened in a near future provided that patient's careful supervision is warranted 106 .…”

Section: Linagliptin Plus Metformin Fdcmentioning

confidence: 99%

Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation

Scheen

2013

Expert Opinion on Drug Metabolism & Toxicology

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SUMMARYIntroduction : The first-choice drug therapy in the management of type 2 diabetes is metformin. However, most patients require a combined therapy to reach and/or maintain targets of glucose control. Dipeptidylpeptidase-4 (DPP-4) inhibitors, commonly referred to as gliptins, offer new options for combined therapy with metformin. Linagliptin is the most recent launched gliptin, with a unique pharmacokinetic profile characterized by negligible renal excretion, and is now also available as a fixed-dose combination (FDC) with metformin.Area covered: An extensive literature search was performed to analyze the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between linagliptin and metformin. Linaglipin and metformin may be administered together, either separately or as FDC supported by bioequivalence studies. Linagliptin and metformin are not prone to PK drug-drug interactions. Their co-administration improves blood glucose control more potently than either compound separately, without hypoglycemia and without increasing metforminrelated gastrointestinal side effects.Expert Opinion : The combination linaglitpin plus metformin, if not contraindicated (renal failure), may be used as first-line or second-line therapy in the management of type 2 diabetes.

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“…Because DPP-4 inhibitors are most often used in association with metformin, the first-line drug choice for the management of T2DM [106], several fixed-dose combinations (FDCs) are currently available [107]: sitagliptinmetformin [108], vildagliptin-metformin [52,109], saxagliptin-metformin [110], linaglipin-metformin [111] and alogliptin-metformin. Such FDCs may only be prescribed when both compounds are not contraindicated because of the presence of CKD and appropriate adjustments of individual doses may be required.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

Scheen

2014

Clin Pharmacokinet

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The prevalence of chronic kidney disease (CKD) of stages 3-5 (glomerular filtration rate [GFR] <60 mL/min) is about 25-30 % in patients with type 2 diabetes mellitus (T2DM). While most oral antidiabetic agents have limitations in patients with CKD, incretin-based therapies are increasingly used for the management of T2DM. This review analyses (1) the influence of CKD on the pharmacokinetics of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists; and (2) the efficacy/safety profile of these agents in clinical practice when prescribed in patients with both T2DM and CKD. Most DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin) are predominantly excreted by the kidneys. Thereby, pharmacokinetic studies showed that total exposure to the drug is increased in proportion to the decline of GFR, leading to recommendations for appropriate dose reductions according to the severity of CKD. In these conditions, clinical studies reported a good efficacy and safety profile in patients with CKD. In contrast, linagliptin is eliminated by a predominantly hepatobiliary route. As a pharmacokinetic study showed only minimal influence of decreased GFR on total exposure, no dose adjustment of linagliptin is required in the case of CKD. The experience with GLP-1 receptor agonists in patients with CKD is more limited. Exenatide is eliminated by renal mechanisms and should not be given in patients with severe CKD. Liraglutide is not eliminated by the kidney, but it should be used with caution because of the limited experience in patients with CKD. Only limited pharmacokinetic data are also available for lixisenatide, exenatide long-acting release (LAR) and other once-weekly GLP-1 receptor agonists in current development. Several case reports of acute renal failure have been described with GLP-1 receptor agonists, probably triggered by dehydration resulting from gastrointestinal adverse events. However, increasing GLP-1 may also exert favourable renal effects that could contribute to reducing the risk of diabetic nephropathy. In conclusion, the already large reassuring experience with DPP-4 inhibitors in patients with CKD offers new opportunities to the clinician, whereas more caution is required with GLP-1 receptor agonists because of the limited experience in this population.

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Efficacy and safety of Jentadueto® (linagliptin plus metformin)

Cited by 7 publications

References 94 publications

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease

Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

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