Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus

Raz, Itamar; Hanefeld, Markolf; Liu, Xu; Caria, Cíntia Rabelo e Paiva; Williams-Herman, Debora; Khatami, Hootan

doi:10.1007/s00125-006-0416-z

Cited by 560 publications

(482 citation statements)

References 15 publications

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“…Furthermore, Raz et al. 15 reported that patients with a baseline duration of diabetes at or below the median (≤3.0 years) exhibited a greater reduction in HbA1c with sitagliptin than did patients with a baseline duration of diabetes >3.0 years. Consistent with these reports, multiple linear regression analysis in the present study revealed that baseline HbA1c levels ( P < 0.0001) and duration of diabetes ( P = 0.024) were independent predictors of ΔHbA1c among all patients.…”

Section: Discussionmentioning

confidence: 99%

Obesity may attenuate the HbA1c‐lowering effect of sitagliptin in Japanese type 2 diabetic patients

Bando¹,

Kanehara

Aoki

et al. 2011

J of Diabetes Invest

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Aims/Introduction: The aim of the present study was to assess the independent predictors of the HbA1c‐lowering effect of sitagliptin in Japanese type 2 diabetic patients.Materials and Methods: Data were retrieved from the medical records of 151 type 2 diabetic patients who had been taking sitagliptin 25 or 50 mg once daily for inadequate glycemic control for at least 12 weeks, with or without other oral hypoglycemic agents. Spearman’s rank correlation coefficients were calculated to investigate correlations between two independent continuous variables. Multiple stepwise regression analysis was used to identify independent predictors of reductions in HbA1c levels after 12 weeks of sitagliptin treatment (ΔHbA1c).Results: In all patients combined, Spearman’s rank correlation coefficients showed that ΔHbA1c was significantly correlated with baseline HbA1c alone (r = 0.371, P < 0.0001). However, multiple linear regression analysis among all patients using baseline variables revealed that the independent factors contributing to ΔHbA1c, in order of importance, were method of prescribing (P < 0.0001), baseline HbA1c (P < 0.0001), body mass index (BMI; P = 0.004), and duration of diabetes (P = 0.024).Conclusions: Our analysis may provide novel evidence that increased BMI contributes, in part, to attenuation of the HbA1c‐lowering effect of sitagliptin in Japanese type 2 diabetic patients. Analysis of a larger population over a longer period of time is warranted to confirm these findings. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00156.x, 2011)

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Section: Discussionmentioning

confidence: 99%

Obesity may attenuate the HbA1c‐lowering effect of sitagliptin in Japanese type 2 diabetic patients

Bando¹,

Kanehara

Aoki

et al. 2011

J of Diabetes Invest

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“…DPP-4 inhibitors are small molecules that enhance the effects of GLP-1 and GIP, increasing glucose-mediated insulin secretion and suppressing glucagon secretion. [83,84]. The first oral DPP-4 inhibitor, sitagliptin, was approved by the Food and Drug Administration in October 2006 for use as monotherapy or in combination with metformin or TZDs.…”

Section: Medicationsmentioning

confidence: 99%

“…Another DPP-4 inhibitor, vildagliptin, was approved in Europe in February 2008, and several other compounds are under development. In clinical trials performed to date, DPP-4 inhibitors lower HbA 1c levels by 0.6-0.9 percentage points and are weight neutral and relatively well tolerated [83,84]. They do not cause hypoglycaemia when used as monotherapy.…”

Section: Medicationsmentioning

confidence: 99%

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy

et al. 2008

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The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.

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“…DPP-4 inhibition has thereby been demonstrated to be anti-diabetic both in animal models of diabetes (4)(5)(6)(7) and in patients with type 2 diabetes (8)(9)(10). The antidiabetic action of DPP-4 inhibition is explained by increased insulin secretion in association with inhibited glucagon secretion with a possible long-term action to increase β-cell mass (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

DPP-4 inhibition improves glucose tolerance and increases insulin and GLP-1 responses to gastric glucose in association with normalized islet topography in mice with β-cell-specific overexpression of human islet amyloid polypeptide

Åhrén

Winzell

Wierup

et al. 2007

Regulatory Peptides

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Inhibition of dipeptidyl peptidase-4 (DPP-4) is currently explored as a novel therapy of type 2 diabetes. The strategy has been shown to improve glycemia in most, but not all, rodent forms of glucose intolerance. In this study, we explored the effects of DPP-4 inhibition in mice with β-cell overexpression of human islet amyloid polypeptide (IAPP). We therefore administered the orally active and highly selective DPP-4 inhibitor, vildagliptin (3µmol/mouse daily) to female mice with β-cell overexpression of human IAPP. Controls were given plain water, and a series of untreated wildtype mice was also included. After five weeks, an intravenous glucose tolerance test showed improved glucose disposal and a markedly enhanced insulin response in mice treated with vildagliptin. After eight weeks, a gastric tolerance test showed that vildagliptin improved glucose tolerance and markedly (approximately ten-fold) augmented the insulin response in association with augmented (approximately five-fold) levels of intact glucagon-like peptide-1 (GLP-1). Furthermore, after nine weeks, islets were isolated.Islets from vildagliptin-treated mice showed augmented glucose-stimulated insulin response and a normalization of the islet insulin content, which was reduced by approximately 50% in transgenic controls versus wildtype animals. Double immunostaining of pancreatic islets for insulin and glucagon revealed that transgenic islets displayed severely disturbed intra-islet topography with frequently observed centrally located α-cells. Treatment with vildagliptin restored the islet topography. We therefore conclude that DPP-4 inhibition improves islet function and islet topography in mice with specific ß cell transgenic overexpression of human IAPP.

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Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus

Abstract: Sitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet.

Cited by 560 publications

References 15 publications

Obesity may attenuate the HbA1c‐lowering effect of sitagliptin in Japanese type 2 diabetic patients

Obesity may attenuate the HbA1c‐lowering effect of sitagliptin in Japanese type 2 diabetic patients

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy

DPP-4 inhibition improves glucose tolerance and increases insulin and GLP-1 responses to gastric glucose in association with normalized islet topography in mice with β-cell-specific overexpression of human islet amyloid polypeptide

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