No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects

Smulders, Ronald A.; Zhang, W.; Veltkamp, Stephan A.; Dijk, Jan van; Krauwinkel, Walter; Keirns, James J.; Kadokura, Takeshi

doi:10.1111/j.1463-1326.2012.01624.x

Cited by 25 publications

(10 citation statements)

References 19 publications

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“…PK properties of ipragliflozin and sitagliptin, pioglitazone or glimepiride were investigated in three separate open-label, randomized, two-way crossover design trials in healthy subjects [31]. These studies demonstrated that acutely, administration of ipragliflozin to sitagliptin, pioglitazone or glimepiride does not change the PK [33] Fonseca et al [40] Wilding et al »31 kg/m 2 , T2DM diagnosis: »5 years) participated in a double-blind, randomized placebo-controlled trial conducted in multiple centers [33].…”

Section: Pks and Metabolismmentioning

confidence: 99%

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Hedrington

2015

Expert Opinion on Drug Metabolism & Toxicology

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Section: Pks and Metabolismmentioning

confidence: 99%

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Hedrington

2015

Expert Opinion on Drug Metabolism & Toxicology

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“…Ipragliflozin, a sodium-glucose co-transporter 2 inhibitor [1], improves glycaemic control by promoting urinary glucose excretion in patients with type 2 diabetes mellitus (T2DM) [2][3][4][5][6]. Western studies have shown that ipragliflozin in combination with metformin improves glycaemic control with a low incidence of adverse events [7,8].…”

Section: Introductionmentioning

confidence: 99%

Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double‐blind, placebo‐controlled study

Kashiwagi

Kazuta

Goto

et al. 2014

Diabetes Obesity Metabolism

116

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research letterIpragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study This multicenter, double-blind, placebo-controlled study examined the efficacy and safety of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with metformin in Japanese patients with type 2 diabetes mellitus (T2DM). Patients were randomized in a 2 : 1 ratio to 50 mg ipragliflozin (n = 112) or placebo (n = 56) once daily for 24 weeks, followed by a 28-week open-label extension in which all patients received 50 or 100 mg ipragliflozin, while continuing metformin. The primary outcome was the change in glycated haemoglobin (HbA1c) from baseline to week 24. HbA1c decreased significantly in the ipragliflozin group (−0.87%; adjusted mean difference from placebo: −1.30%; p < 0.001). The overall incidence of treatment-emergent adverse events was similar in both groups, although pollakiuria and constipation were more common in the ipragliflozin group; thus, ipragliflozin significantly improved glycaemic control and reduced body weight without major safety issues in Japanese patients with T2DM.

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“…Similarly, multiple doses of sitagliptin did not change the pharmacokinetics of a single dose of ipragliflozin (Table 5). Thus, no dose-adjustments are likely to be required when ipragliflozin is given in combination with sitagliptin in patients with T2D [69] .…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…To investigate the effect of ipragliflozin on the pharmacokinetics of sitagliptin and vice versa, ipragliflozin 150 mg and sitagliptin 100 mg were administered alone or in combination in two cohorts of 32 healthy subjects [69] . Multiple doses of ipragliflozin did not change the AUC inf and C max of a single dose of sitagliptin : geometric mean ratio (GMR) and 90% CI for AUC inf and C max , with and without ipragliflozin, were within the predefined range of 80-125 % (Table 5).…”

Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes

Scheen

2016

Clin Pharmacokinet

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SUMMARYType 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2i, known as gliflozin) and a dipeptidyl peptidase-4 inhibitor known as gliptin) appears to be an attractive strategy because of complementary modes of action.This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with a SGLT2i (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and a DPP-4i (linagliptin, saxagliptin, sitagliptin, teneligliptin). Drug-drug pharmacokinetic interaction studies do not show any significant changes in peak concentrations (C max ) and total exposure (area under the curve of plasma concentrations or AUC) of either drug when they were given orally together compared to corresponding values when each of them was absorbed alone. Some fixed-dose combinations (FDC) are already available (dapagliflozin-saxagliptin, empagliflozin-linagliptin) or in development (ertugliflozin-sitagliptin), and preliminary results showed bioequivalence of the two medications given as FDC tablets when compared with co-administration of the individual tablets. Dual therapy is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. SGLT2i and DPP-4i could be used as initial combination or in a stepwise approach. The additional glucose-lowering effect appears to be more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Combining the two pharmacological options is safe and does not induce hypoglycaemia. Key-words : Combined therapy -DPP-4 inhibitor -Fixed-dose combination -SGLT2 inhibitor -Type 2 diabetesKey points -The combination of a sodium-glucose cotransporter type 2 inhibitor (SGLT2i), which promotes glycosuria and improves glucose tolerance independently of insulin, and a dipeptidyl peptidase-4 inhibitor (DPP-4i), an incretin-based therapy that corrects islet dysfunction, is an attractive approach for the management of type 2 diabetes.-Both dapagliflozin plus saxagliptin and empagliflozin plus linagliptin combined therapies have been tested as separate tablets (no clinically relevant pharmacokinetic drug-drug interactions) and as fixed-dose combination (FDC: bioequivalence studies); such combined therapies are more efficacious than either monotherapy to control blood glucose, without worsening of the safety profile.-Other combinations of a SGLT2i and a DPP-4i have been evaluated in studies that also showed the absence of drug-drug pharmacokinetic interactions and better glucose control compared to either therapy alone. An ertugliflozin-sitagliptin FDC is in current development.-Initial SGLT2i -DPP-4i combination may be considered or one medication may be added to the other, with apparently better results when the SGLT2i was added to the DPP-4i compared with the reverse sequence. However, which glucose-lowering agent sh...

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No pharmacokinetic interaction between ipragliflozin and sitagliptin, pioglitazone, or glimepiride in healthy subjects

Cited by 25 publications

References 19 publications

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Ipragliflozin, a sodium–glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes

Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double‐blind, placebo‐controlled study

Pharmacokinetic Characteristics and Clinical Efficacy of an SGLT2 Inhibitor Plus DPP-4 Inhibitor Combination Therapy in Type 2 Diabetes

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