Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control &lt;i&gt;via&lt;/i&gt; different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes

Otsuka, Yuichiro; Yamaguchi, Suguru; Furukawa, Akihiko; Kosuda, Minami; Nakazaki, Mitsuhiro; Ishihara, Hideharu

doi:10.1507/endocrj.ej14-0148

Cited by 14 publications

(10 citation statements)

References 41 publications

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“…The changes in C-peptide in this study were consistent with the above study results Furthermore, a study investigating sitagliptin as an add-on to insulin monotherapy demonstrated that postprandial blood glucose levels decreased without a change in the postprandial C-peptide levels. It was suggested that β-cell responsiveness was improved with sitagliptin treatment [24]. Thus, the increase in C-peptide levels relative to postprandial glucose levels with TNL in this study may be a class effect, similar to that with sitagliptin.…”

Section: Blood Glucose-lowering Effectsmentioning

confidence: 52%

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period

Kadowaki

Kondo

Sasaki

et al. 2017

Expert Opinion on Pharmacotherapy

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Section: Blood Glucose-lowering Effectsmentioning

confidence: 52%

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period

Kadowaki

Kondo

Sasaki

et al. 2017

Expert Opinion on Pharmacotherapy

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“…$ Significant when compared to the sitagliptin-treated diabetic group. 248 [3,[32][33][34] . DPP-IV inhibitors exert effects possibly linked to prevention or treatment of the micro-and macrovascular complications in patients with T2DM, beyond their glucose-lowering effects [2,17] .…”

Section: Discussionmentioning

confidence: 99%

Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress

Kelany

Hakami

Omar³

et al. 2016

Pharmacology

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Aims: The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms. Methods: Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology. Results: Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin. Conclusions: Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.

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“…Considering the beneficial effects of ipragliflozin on glycaemic control observed in these trials and because of the insulin‐independent nature of ipragliflozin action and its low risk of hypoglycaemia, adding ipragliflozin to insulin‐treated patients is expected to be efficacious and well tolerated without increasing the risk of hypoglycaemia and weight gain. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are commonly used in Japanese patients, and are frequently administered together with insulin, because this was reported to be an effective combination . It is important, therefore, to determine whether DPP‐4 inhibitors affect the efficacy of ipragliflozin in insulin‐treated patients.…”

Section: Introductionmentioning

confidence: 99%

“…Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used in Japanese patients, and are frequently administered together with insulin, because this was reported to be an effective combination. 8,9 It is important, therefore, to determine whether DPP-4 inhibitors affect the efficacy of ipragliflozin in insulin-treated patients.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of ipragliflozin as add‐on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi‐centre, randomized, placebo‐controlled, double‐blind study

Ishihara

Yamaguchi

Nakao

et al. 2016

Diabetes Obesity Metabolism

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AimsTo examine the efficacy and safety of add‐on ipragliflozin in Japanese patients with type 2 diabetes in the early stage of insulin therapy.MethodsPatients treated with insulin (bolus component <30% of total daily dose) with/without a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were randomized to receive placebo (n = 87) or ipragliflozin (n = 175) for 16 weeks. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline. Secondary endpoints included changes in fasting plasma glucose (FPG) and metabolic hormones. Safety endpoints were also examined.ResultsThe changes in HbA1c were 0.27% and −0.79% (2.9 and −8.7 mmol/mol) in the placebo and ipragliflozin groups, respectively (baseline: 8.62% vs 8.67% [70.8 vs 71.2 mmol/mol]), corresponding to an adjusted mean difference of −1.07% (95% confidence interval −1.24, −0.91) or −11.7 mmol/mol (−13.5, −9.9), p < .001. Ipragliflozin reduced FPG and serum C‐peptide levels and body weight (all p < .001), and increased serum adiponectin levels (p = .022). There was a statistically significant interaction for use/non‐use of a DPP‐4 inhibitor × treatment group for the change in HbA1c (p = .042). Hypoglycaemia was the only treatment‐related adverse event reported in >5% of patients (14.9% vs 29.1%). Events consistent with urinary tract infection (placebo 1.1% vs ipragliflozin 2.3%) or genital infection (0.0% and 4.0%, respectively) occurred in <5% of patients.ConclusionIpragliflozin was well tolerated and effective in insulin‐treated patients, especially when used with a DPP‐4 inhibitor.

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Addition of sitagliptin or metformin to insulin monotherapy improves blood glucose control <i>via</i> different effects on insulin and glucagon secretion in hyperglycemic Japanese patients with type 2 diabetes

Cited by 14 publications

References 41 publications

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period

Efficacy and safety of teneligliptin add-on to insulin monotherapy in Japanese patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled trial with an open-label period

Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress

Efficacy and safety of ipragliflozin as add‐on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi‐centre, randomized, placebo‐controlled, double‐blind study

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