Dataset Information

Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.

ABSTRACT: The prevalence of type 2 diabetes mellitus is high and growing rapidly. Suboptimal glycemic control provides opportunities for new treatment options to improve the morbidity and mortality of this progressive disease. Saxagliptin, a selective DPP-4 inhibitor, increases endogenous incretin levels and incretin acitivty. In controlled clinical trials saxagliptin reduces both fasting and postprandial glucose and works in monotherapy and in combination with metformin, TZDs and sulfonylureas. Saxagliptin has a very favourable side effect profile and may have other beneficial non-glycemic effects. The authors review the current available evidence for the safety, efficacy and saxagliptin's place in therapy for type 2 diabetes mellitus. As understanding of the incretin hormones (GLP-1, GIP) expand we may see additional important non-glycemic effects that may affect the chronic management of type 2 diabetes mellitus.

SUBMITTER: Shubrook J

PROVIDER: S-EPMC3411543 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.

Shubrook Jay J Colucci Randall R Guo Aili A Schwartz Frank F

Clinical medicine insights. Endocrinology and diabetes 20110112

The prevalence of type 2 diabetes mellitus is high and growing rapidly. Suboptimal glycemic control provides opportunities for new treatment options to improve the morbidity and mortality of this progressive disease. Saxagliptin, a selective DPP-4 inhibitor, increases endogenous incretin levels and incretin acitivty. In controlled clinical trials saxagliptin reduces both fasting and postprandial glucose and works in monotherapy and in combination with metformin, TZDs and sulfonylureas. Saxaglipt ...[more]

PMID: 22879789

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Project description:Dipeptidyl peptidase IV inhibitor (DPP-4i) has been shown to act either as a promoter or as a suppressor for cancer. Although epidemiologic studies suggest that DPP-4i does not correlate with the development of malignancies, its effects on cancer metastases are controversial. We evaluated the impact of DPP-4i on postoperative outcomes of the diabetic patients with colorectal cancer and microscopic features of the resected tumors. In 260 consecutive patients with type 2 diabetes mellitus (T2DM) who underwent curative resection of colorectal cancer, the correlation between DPP-4i use and prognosis was retrospectively examined. Expression of Zeb1 on tumor cells and density of infiltrating immune cells were quantitatively evaluated with multicolor IHC in 40 tumors from DPP-4i users, 40 tumors from propensity score-matched users, and 40 tumors from nonusers. Postoperative disease-free survival (DFS) was significantly lower in 135 patients treated with DPP-4i compared with 125 nontreated patients [5-year DFS, 73.7% vs. 87.4%; HR, 1.98; 95% confidence interval (CI), 1.05-3.71; P = 0.035]. IHC revealed that the number of Zeb1+ tumor cells increased in tumors from DPP-4i-treated patients than tumors from nonusers (P < 0.01). The densities of CD3+ and CD8+ T cells were significantly lower in tumors from DPP-4i users (P < 0.01) with decreased density of tertiary lymphoid structures (P < 0.001). However, the density of M2-type tumor-associated macrophages with CD68+ CD163+ phenotypes was significantly higher (P < 0.01) in tumors from DPP-4i users. Exposure of colorectal cancer to DPP-4i may accelerate epithelial-to-mesenchymal transition (EMT) creating a tumor-permissive immune microenvironment, which might impair the outcomes of the patients with colorectal cancer and T2DM.SignificanceDPP-4i has been shown to enhance the antitumor effects of immunotherapy. However, we found that DPP-4i significantly impairs the outcomes of patients with colorectal cancer who underwent curative resection, possibly through acceleration of EMT and creation of a tumor-permissive immune microenvironment. This suggests that DPP-4i must be used with caution until its safety is fully confirmed by further studies of the mechanistic effects on existing cancers in humans.

Dataset Information

Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.

Publications

Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.

Similar Datasets

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