Linagliptin plus metformin: a pharmacokinetic and pharmacodynamic evaluation

Scheen, André

doi:10.1517/17425255.2013.767892

Cited by 11 publications

(10 citation statements)

References 103 publications

(132 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When T2DM patients cannot be well controlled by lifestyle and single oral antidiabetic drugs, it may be necessary to consider combination therapy with two or more antidiabetic drugs such as a thiazolidinedione plus metformin or a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin 115, 116. The combination therapy has several advantages over monotherapy: (1) greater efficacy with lower-dose; (2) reduced risk of negative effect; (3) lower costs; (4) improved medication concordance 117.…”

Section: Treatment Of T2dmmentioning

confidence: 99%

Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention

Wu¹,

Ding²,

et al. 2014

View full text Add to dashboard Cite

Type 2 diabetes is a serious and common chronic disease resulting from a complex inheritance-environment interaction along with other risk factors such as obesity and sedentary lifestyle. Type 2 diabetes and its complications constitute a major worldwide public health problem, affecting almost all populations in both developed and developing countries with high rates of diabetes-related morbidity and mortality. The prevalence of type 2 diabetes has been increasing exponentially, and a high prevalence rate has been observed in developing countries and in populations undergoing “westernization” or modernization. Multiple risk factors of diabetes, delayed diagnosis until micro- and macro-vascular complications arise, life-threatening complications, failure of the current therapies, and financial costs for the treatment of this disease, make it necessary to develop new efficient therapy strategies and appropriate prevention measures for the control of type 2 diabetes. Herein, we summarize our current understanding about the epidemiology of type 2 diabetes, the roles of genes, lifestyle and other factors contributing to rapid increase in the incidence of type 2 diabetes. The core aims are to bring forward the new therapy strategies and cost-effective intervention trials of type 2 diabetes.

show abstract

Section: Treatment Of T2dmmentioning

confidence: 99%

Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention

Wu¹,

Ding²,

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Linagliptin did not change the pharmacokinetic steady state of ethinyl estradiol and levonorgestrel, 147 digoxin, 148 warfarin, 149 glyburide, 150 pioglitazone, 151 simvastatin, 152 and metformin. 117 Rifampicin, in turn, can reduce the exposure to linagliptin, suggesting that linagliptin efficacy may be reduced by concomitant use with rifampicin. 107 Thus, inducers of CYP3A4 or P-gp (e.g., rifampin) should not be used in combination with linagliptin to avoid therapeutic failure.…”

Section: In Vivo Studiesmentioning

confidence: 99%

Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Chen

Zhou

et al. 2015

Clin Exp Pharma Physio

View full text Add to dashboard Cite

SUMMARYDipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM). The eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM. DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucoselowering agents such as metformin, thiazolidinediones, or sulfonylureas. Although DPP-4 inhibitors have the same mode of action, they differ by some important pharmacokinetic and pharmacodynamic properties that may be clinically relevant in some patients. The main differences between the eight gliptins include: potency, target selectivity, oral bioavailability, elimination half-life, binding to plasma proteins, metabolic pathways, formation of active metabolite(s), main excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions. As a drug class, the DPP-4 inhibitors have become accepted in clinical practice due to their excellent tolerability profile, with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing. It is unknown if DPP-4 inhibitors can prevent disease progression. More clinical studies are needed to validate the optimal regimens of DPP-4 inhibitors for the management of T2DM when their potential toxicities are closely monitored.

show abstract

“…Metformin is mainly excreted by the kidneys whereas linagliptin has a negligible renal excretion. This part of the present review will focus on the PK interactions between linagliptin and metformin 38 . Only limited DDIs have been described with metformin and with linagliptin both in healthy volunteers and in T2DM patients 35,39,40 .…”

Section: Pharmacokinetic Evaluationmentioning

confidence: 99%

“…The two antidiabetic agents exert their glucose-lowering effects via different mechanisms, metformin essentially independently of insulin secretion whereas linagliptin primarily (although not exclusively) via its incretin action on insulin secretion 38,46 . The antihyperglycemic effect of metformin is already marked in the fasting state, by inhibiting overnight gluconeogenesis 47 whereas the DPP-4 inhibitor generally exerts a greater glucoselowering effect in the postprandial state than after an overnight fast 48 .…”

Section: Pharmacodynamic Evaluationmentioning

confidence: 99%