Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent

Diabetology & Metabolic Syndrome, Oct 2015

Objective We aimed to evaluate the efficacy and safety of the three dipeptidyl peptidase 4 (DPP-4) inhibitors (vildagliptin, sitagliptin, and linagliptin) as add-on therapy in Chinese patients with type 2 diabetes mellitus (T2DM)inadequately controlled on dual combination of insulin and metformin or acarbose. Methods A total of 535 T2DM patients who failed to achieve glycemic control with insulin and a traditional oral hypoglycemic agent were randomized to receive vildagliptin, sitagliptin, or linagliptin. Body mass index, glycosylated hemoglobin (HbA1c), fasting and postprandial plasma glucose (FPG and PPG), insulin dose, and adverse events were evaluated during the study. Results The baseline HbA1c was 9.59 ± 1.84 % (vildagliptin group), 9.22 ± 1.60 % (sitagliptin group), and 9.58 ± 1.80 % (linagliptin group). At week 12 it was 8.16 ± 1.29 % (vildagliptin), 8.56 ± 1.96 % (linagliptin), and 8.26 ± 1.10 % (sitagliptin). The changes in HbA1c from baseline were −1.33 ± 0.11 % (vildagliptin), −0.84 ± 0.08 % (sitagliptin) and −0.81 ± 0.08 % (linagliptin), the vildagliptin group had the greatest reduction in HbA1c (P < 0.05). The proportions of patients that reached target HbA1c were 66.27 % (vildagliptin), 52.73 % (sitagliptin), and 55.49 % (linagliptin), the vildagliptin group had the highest one (P < 0.05). The baseline FPG and PPG values in the three groups were at the same level. At week 12, mean FPG levels in the vildagliptin (7.31 ± 1.50 mmol/L) and linagliptin (6.90 ± 1.55 mmol/L) groups were significantly lower than in the sitagliptin group (8.02 ± 4.48 mmol/L; P < 0.05); the linagliptin group had the lowest mean PPG followed by the vildagliptin group which was also significant lower (P = 0.000) than the sitagliptin group. Additionally, the required insulin dosage in the vildagliptin group was the lowest among the groups at weeks 6 and 12. Only mild AEs were reported during the study. Conclusion The three DPP-4 inhibitors appear to be effective and safe as add-on therapy for T2DM patients on dual combination of insulin and a traditional OHA. Vildagliptin was more effective in decreasing insulin requirement and achieving glycemic control when compared to the other two.

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Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent

Tang et al. Diabetol Metab Syndr Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent Yun‑Zhao Tang 0 Gang Wang 0 Zhen‑Huan Jiang 0 TianT‑ian Yan 0 YiJ‑un Chen 0 Min Yang 0 Ling‑Ling Meng 0 YanJ‑uan Zhu 0 Chen‑Guang Li 0 Zhu Li 0 Ping Yu 0 Chang‑Lin Ni 0 0 Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University , Tongan Road 66, Heping District, Tianjin 300070 , China Objective: We aimed to evaluate the efficacy and safety of the three dipeptidyl peptidase 4 (DPP‑ 4) inhibitors (vildagliptin, sitagliptin, and linagliptin) as add‑ on therapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on dual combination of insulin and metformin or acarbose. Methods: A total of 535 T2DM patients who failed to achieve glycemic control with insulin and a traditional oral hypoglycemic agent were randomized to receive vildagliptin, sitagliptin, or linagliptin. Body mass index, glycosylated hemoglobin (HbA1c), fasting and postprandial plasma glucose (FPG and PPG), insulin dose, and adverse events were evaluated during the study. Results: The baseline HbA1c was 9.59 ± 1.84 % (vildagliptin group), 9.22 ± 1.60 % (sitagliptin group), and 9.58 ± 1.80 % (linagliptin group). At week 12 it was 8.16 ± 1.29 % (vildagliptin), 8.56 ± 1.96 % (linagliptin), and 8.26 ± 1.10 % (sitagliptin). The changes in HbA1c from baseline were −1.33 ± 0.11 % (vildagliptin), −0.84 ± 0.08 % (sitagliptin) and −0.81 ± 0.08 % (linagliptin), the vildagliptin group had the greatest reduction in HbA1c (P < 0.05). The proportions of patients that reached target HbA1c were 66.27 % (vildagliptin), 52.73 % (sitagliptin), and 55.49 % (linagliptin), the vildagliptin group had the highest one (P < 0.05). The baseline FPG and PPG values in the three groups were at the same level. At week 12, mean FPG levels in the vildagliptin (7.31 ± 1.50 mmol/L) and linagliptin (6.90 ± 1.55 mmol/L) groups were significantly lower than in the sitagliptin group (8.02 ± 4.48 mmol/L; P < 0.05); the linagliptin group had the lowest mean PPG followed by the vildagliptin group which was also significant lower (P = 0.000) than the sitagliptin group. Additionally, the required insulin dosage in the vildagliptin group was the lowest among the groups at weeks 6 and 12. Only mild AEs were reported during the study. Conclusion: The three DPP‑ 4 inhibitors appear to be effective and safe as add‑ on therapy for T2DM patients on dual combination of insulin and a traditional OHA. Vildagliptin was more effective in decreasing insulin requirement and achieving glycemic control when compared to the other two. Add‑ on therapy to insulin; Type 2 diabetes mellitus; DPP‑ 4 inhibitors; Glycemic control - Background Type 2 diabetes mellitus (T2DM) affects over 300 million people worldwide [1]. The global prevalence of T2DM was estimated to be 9 % among adults aged over 18 years in 2014 [1]. Excluding accidents, diabetes is the fifth cause of death for women and the fourth for men in the USA [2]. In China, the total diabetes prevalence was 9.7 % (92.4 million adults) according to the China National Diabetes and Metabolic Disorders Study between 2007 and 2008, while the prevalence of prediabetes was estimated to be 15.5 % (148 million adults) [3]. The increasing prevalence of diabetes has followed rapid economic growth, increases in life expectancy, and changes in lifestyle [3]. Inadequate control of blood glucose in patients correlates with a higher risk for diabetes-related micro and macrovascular complications [4, 5]. The management of diabetes aims at improving glycemic control to reduce the onset of complications [6]. Glycemic control is typically measured as reductions in glycosylated hemoglobin (HbA1c). T2DM is a progressive disease that often requires a combination of antidiabetic drugs with different mechanisms of action to achieve glycemic targets over time [7]. Dipeptidyl peptidase 4 (DPP-4) inhibitors have become a useful class of oral hypoglycemic agents (OHA) for the treatment of T2DM since 2006. DPP-4 is a transmembrane glycoprotein located on the surface of most cell types, and its multiple effects may be associated with immune regulation, cell apoptosis, and signal transduction [8]. The clinically relevant action of DPP-4 is the degradation of endogenous glucagon-like peptide 1 (GLP-1). Additionally, DPP-4 inhibitors enhance insulin secretion in a glucose-dependent manner [9]. Several clinical practice guidelines recommend a stepwise treatment pathway for diabetes. Diet control and lifestyle intervention are considered the cornerstones for treatment of DM according to these guidelines. However, dietary and lifestyle changes are difficult to implement and maintain on a large scale. Given the progress (...truncated)


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Yun-Zhao Tang, Gang Wang, Zhen-Huan Jiang, Tian-Tian Yan, Yi-Jun Chen, Min Yang, Ling-Ling Meng, Yan-Juan Zhu, Chen-Guang Li, Zhu Li, Ping Yu, Chang-Lin Ni. Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent, Diabetology & Metabolic Syndrome, 2015, pp. 91, 7, DOI: 10.1186/s13098-015-0087-3