Management of patients with type 2 diabetes and mild/moderate renal impairment: profile of linagliptin

Gallwitz, Baptist

doi:10.2147/tcrm.s67076

Cited by 7 publications

(8 citation statements)

References 57 publications

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“…DPP-4 inhibitors can be administered in patients with impaired kidney function due to the good safety and tolerability. Except for linagliptin, which is eliminated via a biliary route, all other DPP-4 inhibitors are excreted in the urine (22, 29, 32, 33). Dose adjustments have to be observed for the various DPP-4 inhibitors with renal elimination in dependence of the compound used and the severity of renal impairment (21, 22, 29, 32).…”

Section: Dpp-4 Inhibitors and Their Clinical Characteristicsmentioning

confidence: 99%

Clinical Use of DPP-4 Inhibitors

2019

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DPP-4 inhibitors were introduced for the treatment of type 2 diabetes in 2006. They stimulate insulin secretion and inhibit glucagon secretion by elevating endogenous GLP-1 concentrations without an intrinsic hypoglycaemia risk. Their efficacy potential to lower HbA1c is in the range between 0.5 and 1.0% and their safety profile is favorable. DPP-4 inhibitors are body weight neutral and they have demonstrated cardiovascular safety. Most compounds can be used in impaired renal function. Guidelines suggest the additional use of DPP-4 inhibitors after metformin failure in patients that do not require antidiabetic therapy with proven cardiovascular benefit. Recently, DPP-4 inhibitors have increasingly replaced sulfonylureas as second line therapy after metformin failure and many metformin/DPP-4 inhibitor fixed dose combinations are available. In later stages of type 2 diabetes, DPP-4 inhibitors are also recommended in the guidelines in triple therapies with metformin and SGLT-2 inhibitors or with metformin and insulin. A treatment with DPP-4 inhibitors should be stopped when GLP-1 receptor agonists are used. DPP-4 inhibitors can be used as monotherapy when metformin is contraindicated or not tolerated. Some studies have shown value of initial metformin-DPP-4 inhibitor combination therapy in special populations. This article gives an overview on the clinical use of DPP-4 inhibitors.

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Section: Dpp-4 Inhibitors and Their Clinical Characteristicsmentioning

confidence: 99%

Clinical Use of DPP-4 Inhibitors

2019

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“…Therefore, it is important to determine the fundamental pharmacological mechanism of each inhibitor to use the appropriate drug for suitable patients. Linagliptin is the only bile-excreted, anti-diabetic oral DPP-4 inhibitor; therefore, its dose reduction is unnecessary [ 6 – 8 ]. Moreover, linagliptin decreased the risk of cardiovascular and cerebrovascular diseases, which are associated with systemic atherosclerosis and related prognostic factors of diabetes [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Linagliptin inhibits lipopolysaccharide-induced inflammation in human U937 monocytes

et al. 2018

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BackgroundAtherosclerosis and inflammation are more common in patients with diabetes than in patients without diabetes, and atherosclerosis progression contributes to inflammation. Therefore, anti-inflammatory therapy is important for the prognosis of patients with diabetes. Linagliptin is the only bile-excreted, anti-diabetic oral dipeptidyl peptidase-4 (DPP-4) inhibitor. Although the anti-inflammatory effects of DPP-4 inhibitors in vivo and in vitro have been reported, few in vitro studies have examined the effects of linagliptin using monocytes, which play a central role in arteriosclerosis-related inflammation. Herein, we assessed the anti-inflammatory effects of linagliptin in human U937 monocytes.MethodsU937 cells at densities of 1 × 106 cells/mL were cultured in Roswell Park Memorial Institute medium supplied with 10% fetal bovine serum and treated with 100 nM phorbol myristate acetate for 48 h for differentiation into macrophages. The media were replaced, and the cells were pretreated with 1, 5, 10, 50, and 100 nM linagliptin for 1 h or were left untreated. The media were then replaced again, and the cells were treated with 1 μg/mL lipopolysaccharide (LPS) or 10 nM interleukin (IL)-1β only, in combination with 1, 5, 10, 50, and 100 nM linagliptin or were left untreated. The extracted media were used to measure IL-6 and tumor necrosis factor (TNF)-α levels using enzyme-linked immunosorbent assay kits.ResultsLPS alone significantly increased IL-6 and TNF-α production compared with the control treatment. The treatment of cells with linagliptin at all concentrations significantly inhibited the LPS-stimulated IL-6 and TNF-α production. Meanwhile, IL-1β alone significantly increased IL-6 production compared with the control treatment. No significant difference in IL-6 production was noted between the cells treated with IL-1β and simultaneous treatment with IL-1β and linagliptin.ConclusionsLinagliptin inhibited LPS-induced inflammation in human monocytic U937 cells.

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“…In patients with T2D where first‐line metformin monotherapy does not provide sufficient glycaemic control or is not indicated, guidelines recommend the introduction of one of a number of different therapeutic options, including sulphonylureas, sodium–glucose co‐transporter‐2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase‐4 (DPP‐4) inhibitors, basal insulin or glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) . The extent of clinical experience with these drug classes in patients with renal disease varies, with many of these treatment options contraindicated or not recommended in patients with moderate or severe impairment; specific concerns have been raised regarding the use of certain sulphonylureas and SGLT2 inhibitors in this population. With regard to GLP‐1 RAs, there is a relative lack of data investigating their use in patients with impaired renal function .…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of lixisenatide in patients with type 2 diabetes and renal impairment

Hanefeld¹,

Arteaga

Leiter

et al. 2017

Diabetes Obesity Metabolism

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AimsThis post hoc assessment evaluated the efficacy and safety of once‐daily, prandial glucagon‐like peptide‐1 receptor agonist lixisenatide in patients with type 2 diabetes (T2D) and normal renal function (estimated glomerular filtration rate ≥90 mL/min), or mild (60‐89 mL/min) or moderate (30‐59 mL/min) renal impairment.MethodsPatients from 9 lixisenatide trials in the GetGoal clinical trial programme were categorized by baseline creatinine clearance: normal renal function (lixisenatide n = 2094, placebo n = 1150); renal impairment (mild: lixisenatide n = 637, placebo n = 414; moderate: lixisenatide n = 122, placebo n = 68). Meta‐analyses of placebo‐adjusted mean differences between baseline renal categories were performed for efficacy and safety outcomes.Results HbA1c, 2‐hour postprandial plasma glucose and fasting plasma glucose were comparably reduced in lixisenatide‐treated patients with normal renal function, and mild and moderate renal impairment. The most common adverse events (AEs) in all renal function categories were gastrointestinal (GI), predominantly nausea and vomiting. A 14% higher incidence of GI AEs and a 10% higher incidence of nausea and vomiting were seen with mild impairment vs normal function (P = .003 for both), but no significant differences were observed between the mild and moderate impairment categories (P = .99 and P = .57, respectively), or between the moderate impairment and normal categories (P = .16 and P = .65, respectively). Additionally, the incidence of hypoglycaemia was similar in all categories.ConclusionsThis study demonstrates that baseline renal status does not affect efficacy outcomes in lixisenatide‐ vs placebo‐treated patients, and that no lixisenatide dose adjustment is required for patients with T2D with mild or moderate renal impairment.

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Management of patients with type 2 diabetes and mild/moderate renal impairment: profile of linagliptin

Cited by 7 publications

References 57 publications

Clinical Use of DPP-4 Inhibitors

Clinical Use of DPP-4 Inhibitors

Linagliptin inhibits lipopolysaccharide-induced inflammation in human U937 monocytes

Efficacy and safety of lixisenatide in patients with type 2 diabetes and renal impairment

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