Comparison of Protein Binding Rate of DPP- 4 Inhibitor LGT- 6 in Different Species of Plasma / 中国药房

OBJECTIVE：To establish the method for determining protein binding rate of dipeptidyl peptidase- 4 inhibitor LGT- 6 in different species of plasma ，and to compare their difference. METHODS ：By equilibrium dialysis ，LGT-6（3，30，300，3 000 nmol/L）was equilibrated in rat ，monkey and human plasma （i. e. internal dialysis solution ）for 48 h，using phosphate buffer as the external dialysis solution. The concentration of LGT- 6 in internal and external dialysis solution was determined by UPLC-MS/MS using tolbutamide as internal standard ，and the plasma protein binding rate was calculated. The determination was performed on ACQUITY UPLC HSS T 3 column with water （containing 0.01％ formic acid ）-acetonitrile（containing 0.01％ formic acid ）as mobile phase at the flow rate of 0.6 mL/min. The column temperature was 40 ℃，and the sample size was 2 μL. The ion source was electrospray ion source ，and the multiple ion monitoring mode was used to carry out positive ionization scanning. The ion pairs for quantitative analysis were m/z 487.0→434.3（LGT-6），m/z 271.1→172.0（internal standard ），respectively. RESULTS ：At the concentrations of 3，30，300，and 3 000 nmol/L，the protein binding rates of LGT- 6 in rat plasma were （96.25±0.97）％，（84.16± 1.24）％，（78.25±0.61）％，（66.63±0.95）％；the protein protein binding rates in monkey plasma were （98.54±0.58）％，（87.27± 1.01）％，（79.35±0.86）％，（66.69±0.54）％；the protein binding rates in human plasma were （99.40±1.03）％，（84.48± 1.15）％，（77.62±0.77）％，（66.93±0.48）％. At the same concentration ，the protein binding rates of LGT- 6 in rat ，monkey and human plasma had no significant difference （P＞0.05）. In the same species of plasma ，there were significant differences in the plasma protein binding rates of different concentration of LGT-6 among those groups （P＜0.05），and it decreased with 才〔2016〕4015） the increase of drug concentration. CONCLUSIONS ： The method for the determination of plasma protein binding rate of LGT-6 is successfully established. The data revealed that the protein binding rate of LGT- 6 is concentration-dependent ， there was no obvious spec ies difference on protein binding rates of LGT- 6 in rat ，monkey and human plasma under the same concentration.

Efficacy of evogliptin and cenicriviroc against nonalcoholic steatohepatitis in mice: a comparative study

Dipeptidyl peptidase (DPP)-4 inhibitors, or gliptins, are a class of oral hypoglycemic drugs that have been widely used as a second-line treatment for type 2 diabetes. Gliptins, which were introduced for clinical use a decade ago, have been shown to be beneficial against nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) in animals and humans. Cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor type 2 and 5, is currently under investigation against NASH and fibrosis. It was previously discovered that evogliptin (EVO) reduces hepatic steatosis in diet-induced obese animals but the effectiveness of EVO on NASH remains unexplored. Here, we compared the effectiveness of EVO and CVC against NASH and fibrosis in mice fed a high-fat and high-fructose diet (HFHF). Biochemical and histological analyses showed that mice fed a HFHF for 20 weeks developed severe hepatic steatosis and inflammation with mild fibrosis. Administration of EVO (0.2% wt/wt) for the last 8 weeks of HFHF feeding significantly reduced hepatic triglyceride accumulation, inflammation, and fibrosis as well as restored insulin sensitivity, as evidenced by lowered plasma insulin levels and the improvement in insulin tolerance test curves. Treatment of mice with CVC (0.1% wt/wt) inhibited hepatic inflammation and fibrogenesis with similar efficacy to that of EVO, without affecting hepatic steatosis. CVC treatment also reduced plasma insulin concentrations, despite no improvement in insulin tolerance. In conclusion, EVO administration efficiently ameliorated the development of NASH and fibrosis in HFHF-fed mice, corroborating its therapeutic potential.

Short-term outcomes of patients with Type 2 diabetes mellitus treated with canagliflozin compared with sitagliptin in a real-world setting

<p><b>INTRODUCTION</b>We aimed to evaluate the effectiveness and safety of canagliflozin as compared to sitagliptin in a real-world setting among multiethnic patients with Type 2 diabetes mellitus (T2DM) in Singapore.</p><p><b>METHODS</b>This was a new-user, active-comparator, single-centre retrospective cohort study. Patients aged 18-69 years with T2DM and estimated glomerular filtration rate ≥ 60 mL/min/1.73 m were eligible for inclusion if they were initiated and maintained on a steady daily dose of canagliflozin 300 mg or sitagliptin 100 mg between 1 May and 31 December 2014, and followed up for 24 weeks.</p><p><b>RESULTS</b>In total, 57 patients (canagliflozin 300 mg, n = 22; sitagliptin 100 mg, n = 35) were included. The baseline patient characteristics in the two groups were similar, with overall mean glycated haemoglobin (HbA1c) of 9.4% ± 1.4%. The use of canagliflozin 300 mg was associated with greater reductions in HbA1c (least squares [LS] mean change -1.6% vs. -0.4%; p < 0.001), body weight (LS mean change -3.0 kg vs. 0.2 kg; p < 0.001) and systolic blood pressure (LS mean change: -9.7 mmHg vs. 0.4 mmHg; p < 0.001), as compared with sitagliptin 100 mg. About half of the patients on canagliflozin 300 mg reported mild osmotic diuresis-related side effects that did not lead to drug discontinuation.</p><p><b>CONCLUSION</b>Our findings suggest that canagliflozin was more effective than sitagliptin in reducing HbA1c, body weight and systolic blood pressure in patients with T2DM, although its use was associated with an increased incidence of mild osmotic diuresis-related side effects.</p>

Research progress of dipeptidyl peptidase 4 inhibitors on healing of chronic diabetic foot ulcers / 中国修复重建外科杂志

Objective: To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers. Methods: The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly. Results: DPP-4 inhibitors can accelerated the ulcer healing. The mechanisms probably include inhibiting the expression of the matrix metalloproteinase (MMP) and restoring the balance of the wound MMP and the tissue inhibitors of MMP; promoting recruitment of endothelial progenitor cells and augmenting angiogenesis; optimizing extracellular matrix construction and the immune response to persistent hypoxia in chronic diabetes wounds, and so on. At present, clinical researches show that DPP-4 inhibitors may be considered as an adjuvant treatment for chronic diabetic foot ulcers. Conclusion: DPP-4 inhibitors show promise in the local wound healing of chronic diabetic foot ulcers. However, more strictly designed, adequately powered, long-term follow-up, and high-quality randomized control trials are needed to further verify their efficacy and safety for chronic diabetic foot ulcers.

Effects of DPP-4 inhibitors on cardiovascular risk in type 2 diabetic patients / 中华内分泌代谢杂志

As diabetes is a major independent risk factor for the development of cardiovascular disease (CVD), cardiovascular safety should be taken into account when it refers to the treatment of type 2 diabetes (T2DM). Relevant evidence has suggested that dipeptidyl peptidase 4 (DPP-4) inhibitors could regulate cardiovascular system function by multiple various mechanisms,with inconsistent results among clinical trials. Meta-analysis showed that DPP-4 inhibitors could significantly reduce the CVD risk factors. However,the results from three large scale cardiovascular safety studies were of non-inferiority results. The baseline elder age of participants with longer duration of diabetes and more risk factors of CVD could contribute to the non-inferiority cardiovascular outcomes of DPP-4 inhibitors. Recent clinical trials further indicated that alogliptin and sitagliptin could attenuate atherosclerosis progression of patients with T2DM,which would bring new implications for the clinical use of DPP-4 inhibitors. More research should be designed to further explore the specific mechanism.

Therapeutic effect of dipeptidyl peptidase-4 inhibitor on patients with type 2 diabetes mellitus with nonalco-holic fatty liver disease / 实用医学杂志

Objective To explore therapeutic effect of dipeptidyl peptidase IV inhibitor on type 2 diabetes mellitus with nonalcoholic fatty liver disease. Methods 120 patients suffering type 2 diabetes mellitus with nonal-coholic fatty liver disease from October 2014 to March 2016 in our hospital were randomly divided into two groups:treatment group and control group. Both groups were given type 2 diabetes conventional treatment ,and the treat-ment group was given dipeptidyl peptidase IV inhibitor in addition. Height,weight,waist circumference,hip cir-cumference were measured. Lipid metabolism and,function index,FPG,2 h PG,HbA1c,Ins,C peptide were detected. HOMA-IR was calculated. Results The total effective rate of clinical treatment of fatty liver in the treat-ment group(88.3%)was higher than the control group(78.3%). The difference was statistically significant. FPG , 2hPG,HbA1c,HOMA-IR,LDL-C,TC,TG,AST,ALT andγ-GT in the treatment group were lower than the con-trol group. The difference was also statistically significant. Conclusion The efficacy of sitagliptin in the treatment of type 2 diabetes with nonalcoholic fatty liver was significant. It can also significantly reduce blood glucose and in-sulin resistance. Furthermore ,it has a better effect on the patients with blood glucose control and lipid metabolism regulation.

Value of dipeptidyl peptidase 4 inhibitor in the treatment of type 2 diabetes mellitus / 中国综合临床

Objective To investigate the efficacy and safety of dipeptidyl peptidase 4(DDP-4)inhibitor in the treatment of diabetes mellitus.Methods Eighty-six cases patients with poor glycemic control in type 2 diabetes mellitus in Shunde First People's Hospital of Foshan from May 2015 to May 2016 were selected as the research objects and divided into two groups according to random number table method,each group with 43 cases.The control group with acarbose(50 mg/times,3 times/d,with the same as the 3 meals,sustained medication for 12 weeks)to control blood sugar,while the observation group used DPP-4 inhibitors sitagliptin(100 mg/times,1 times/d,sustained medication for 12 weeks),compared the blood glucose,blood lipid indexes and adverse reactions of two groups before and after treatment.Results After treatment,FPG,2 hPG,HbAlc level of observation group were respectively(6.71±0.65)mmol/L,(8.10±0.17)mmol/L,(7.12±0.41)％,significantly lower than control group((7.86±0.72)mmol/L,(9.20±0.65)mmol/L,(7.51±0.52)％,the differences were statistically significant(P＜0.01).After treatment,there were no significant differences in terms of TC,TG,HDL-C,LDL-C between two groups(P＞0.05).Treatment for 12 weeks,the blood glucose compliance rate of observation group was 88.37％(38/43),the control group was 67.44％(29/43),the observation group was significantly higher than the control group(P=0.019).After treatment,the HOMA-IR value of the observation group was 4.42±0.17,significantly lower than the control group(4.91±0.24),HOMA-beta value was 88.20±6.31,significantly higher than that of the control group(80.21±5.67),the differences were significant(P＜0.01).Conclusion DDP-4 inhibitor in the treatment of type 2 diabetes,can effectively reduce the level of blood glucose and glycosylated hemoglobin,and have no significant adverse reactions,is effective and safe hypoglycemic drugs.

Potential benefit of the combination therapy of dipeptidyl peptidase-4 inhibitor with sodium-glucose cotransporter-2 inhibitor in patients with type 2 diabetes mellitus: From the standpoint of renoprotection / 中华内分泌代谢杂志

Both dipeptidyl peptidase-4(DPP-4)inhibitor and sodium-glucose cotransporter-2(SGLT-2) inhibitor have been approved for the treatment of type 2 diabetes mellitus(T2DM). In preclinical or clinical studies, DPP-4 inhibitor shows a potential beneficial effect on renal architecture damage,whereas SGLT-2 inhibitor has a role in renoprotection by improving renal hemodynamics. Therefore,the combination therapies with DPP-4 inhibitor and SGLT-2 inhibitor not only improve metabolic control, but also may have a synergistic or complementary effect in protecting renal structure and function in patients with T2DM. This combination therapy provides a novel option for raising the comprehensive management level in patients with T2DM.

Predictive Factors for the Therapeutic Response to Concomitant Treatment with DPP-4 Inhibitors in Type 2 Diabetes with Short-Term Follow-Up / 고신대학교의과대학학술지

OBJECTIVES: To evaluate the efficacy and predictive factors of Dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus (T2DM) patients who were not well controlled with other oral antidiabetic drugs or insulin in real clinical practice. METHODS: From December 2012 to January 2014, retrospective longitudinal observation study was conducted for patients with T2DM who were not reached a glycemic target (glycated hemoglobin [HbA1c] > 6.5%) with other oral antidiabetic drugs or insulins. Type 1 diabetes or other types of diabetes were excluded. Responders were eligible with decreased HbA1c from baseline for more than 5% during follow up period. RESULTS: Of total 135 T2DM patients having an average 9.0 months follow-up period, 84 (62.2%) of patients were responder to DPP-4 inhibitors. After concomitant treatment with DPP-4 inhibitors, patients had a mean decrease in HbA1c of 0.69 ± 1.3%, fasting plasma glucose of 13 ± 52 mg/㎗, and postprandial plasma glucose of 29 ± 85 mg/㎗ from baseline (all P < 0.05). Independent predictive factor for an improvement of glycemic control with DPP-4 inhibitors was higher baseline HbA1c (odds ratio 2.07 with 95% confidence interval 1.15-3.72) compared with non-responders. CONCLUSIONS: A clinical meaningful improvement in glycemic control was seen when DPP-4 inhibitors were added to other anti-diabetic medications in patients with T2DM regardless of age, duration of T2DM, type of combination treatment regimen. Patients who had higher HbA1c were more easily respond to DPP-4 inhibitors treatment in short-term follow-up period.

Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin

BACKGROUND: We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes. METHODS: The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin. RESULTS: The mean changes in HbA1c levels from baseline were -0.94% in the vildagliptin group and -0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were -60.2 mg/dL in the vildagliptin group and -38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was -0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002). CONCLUSION: As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Dipeptidyl peptidase-4 inhibitor impacts the expression of Bcl-2 and Bax throughγamino acid bwtyric acid in pancreas islets / 中华内分泌代谢杂志

Objective To explore the effects of dipeptidyl peptidase ( DPP-4 ) inhibitor on proteins expression of Bcl-2 and Bax of islet β-cells through increasing the expression of islet γ amino acid butyric acid ( GABA) . Methods A total of 50 rats of clean grade were studied. Among them, ten rats were randomly selected as normal controls, the remaining forty rats were fed with high-fat diet and then intraperitoneal injection with streptozotocin, the diabetic rats models were then established. Rats were randomly divided into three groups:i. e. diabetic control group, DPP-4 inhibitor group, and antagonist group ( DPP-4 inhibitor and GABA receptor antagonist). Six weeks later, blood glucose, serum insulin, glucagon, and the proteins expression of GABA, Bcl-2, and Bax of islet β-cells were measured. Results ( 1 ) Compared with diabetic control group, serum insulin was increased(P<0.05),bloodglucoseandserumglucagonweredecreasedinDPP-4inhibitorgroup(P<0.05). (2) Compared with DPP-4 inhibitor group, serum insulin was decreased(P<0. 05), blood glucose and serum glucagon were increased(P<0. 05) in antagonist group. (3) Compared with diabetic control group, the expression of GABA was increased(P<0. 05), the expression of Bcl-2 protein was increased (P<0. 05) in pancreatic β-cells in DPP-4 inhibitor group. ( 4 ) Compared with diabetic control group, the expression of GABA in pancreatic β-cells was increased in antagonist group(P<0. 05) . Compared with DPP-4 inhibitor group, the expression of Bax protein in pancreaticβ-cells was increased in antagonist group(P<0. 05) , while the expression of Bcl-2 protein was decreased (P<0. 05). Conclusions DPP-4 inhibitor could increase the secretion of insulin, decrease the secretion of glucagon, up-regulate expression of anti-apoptosis protein Bcl-2, and down-regulate expression of apoptosis protein Bax in pancreatic β-cells through increasing the expression of GABA, inhibiting pancreatic β-cells apoptosis and protecting the damagedβ-cells in type 2 diabetic rats.

An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass

Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans.

Effect of sitagliptin on lipopolysaccharide-induced changes in the mass and function of islet β cells / 中华内分泌代谢杂志

Objective To investigate the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor on lipopolysaccharide (LPS)-induced changes in the mass and function of pancreatic β-cells.Methods RINm cells were cultured and treated with LPS alone or combined with different concentrations of sitagliptin for 24 h.The proliferation of RINm cells was detected by CCK-8 assay.Apoptotic rate was determined by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide flow cytometry.Insulin secretion was measured by enzyme-linked immunosorbent assay.The expression of IL-6 mRNA was displayed by RT-PCR.Results LPS significantly stimulated the proliferation of RINm cells (0.89 ± 0.04 vs 1.14 ± 0.08,P＜0.01),while LPS+sitagliptin showed no significant difference compared with LPS group.The cell apoptotic rate in LPS + 10-1 mmol/L sitagliptin group was significantly lower than that in LPS group.There were no significant differences in basal insulin secretion among all groups,but after the high/low glucose stimulation,LPS increased insulin secretion as compared with the control.The IL-6 mRNA expression in LPS+sitagliptin group was significantly lower than that in LPS group (0.77 ± 0.33 vs 1.30 ± 0.41,P =0.006).Conclusions DPP-4 inhibitor has no influence on LPS-induced proliferation of pancreatic β-cell,but it can inhibit LPS-induced apoptosis and insulin secretion,and IL-6 may be involved in the process.

Effect of DPP-4 inhibitor on serum adiponectin and hs-CRP in patients with type 2 diabetes mellitus / 中国生化药物杂志

Objective To investigate the effects of dipeptidyl peptidase 4(DPP-4) inhibitor on serum adiponectin (APN) and high sensitivity C-reactive protein (hs-CRP) in patients with type 2 diabetes mellitus.Methods 45 cases were type 2 diabetes were collected from department of endocrinology,wuxi second People's hospital of jiangsu province from January 2015 to April 2015.45 patients with type 2 diabetes mellitus were randomly divided into treatment group (n=23) and control group (n =22) , treatment group was treated with metformin combined with DPP-4 inhibitor and control group was treated without DPP-4 inhibitor.Before and after treatment,fasting plsma glucose(FPG),postprandial 2h glucose(2hPG),adiponectin, hs-CRP and homeostasis model assessment for insulin resistance(HOMA-IR) were measured.Results Adiponectin was significantly higher in treatment group than before(P<0.05),FPG,2hPG,hs-CRP and HOMA-IR were significantly lower than before(P<0.05).Adiponectin in treatment group was significantly higher than control group post-treatment(P<0.05).2hPG,hs-CRP and HOMA-IR in treatment group were siginificantly lower than control group post-treatment (P<0.05).Conclusion DPP-4 inhibitor could improve insulin resistance in type 2 diabetes mellitus by increasing serum adiponectin and decreasing serum Hs-CRP and HOMA-IR.

Comparative Effectiveness between Dipeptidylpeptidase-4 Inhibitors and Sulfonylureas in Combination with Metformin in Type 2 Diabetes Mellitus Patients

OBJECTIVE: Treatment with sulfonylureas in combination with metformin improves glycemic control in type 2 diabetes mellitus (T2DM), but is associated with hypoglycemia and weight gain. This retrospective study aims to compare the effectiveness of dipeptidylpeptidase-4 (DPP-4) inhibitors and sulfonylureas as an add-on therapy to metformin in patients with T2DM. METHODS: Data from medical records of 355 T2DM patients received therapy either DPP-4 inhibitors (DPP-4 inhibitor group) or sulfonylurea (SU group) in combination with metformin from 1 March 2009 to 30 September 2011 were retrospectively reviewed. Of total 355 patients, 231 patients were in DPP-4 inhibitor group and 124 patients were in SU group. Baseline Hemoglobin A1c (HbA(1c)) level in SU group was higher than DPP-4 inhibitor group with a statistically significant difference (8.6% vs. 7.8%). Comparative analysis between DPP-4 inhibitor group and SU group was performed for HbA(1c) values, amounts of HbA(1c) changes, and rates of HbA(1c) changes from baseline at 6-month intervals and incidence rates of major cardiocerebral events. RESULTS: SU group showed larger HbA(1c) changes in both amounts and rates compared to DPP-4 inhibitor group, although statistical significance was not found in all study periods. Proportions of patients with stable HbA(1c) <6.5% or 7% were significantly higher in DPP-4 inhibitor group than SU group (<6.5%: 30.4% vs. 13.4%, <7%: 72.3% vs. 41.2%). Time to achieve stable HbA(1c) <6.5% was not significantly different, but time to achieve stable HbA(1c) <7% was shorter in DPP4 inhibitor group than SU group with a significant difference. The incidence rate of cardiocerebral events in group of patients with or without previous events was 1.7%, not significantly lower than that in DPP-4 inhibitor group (4.0%). For newly encountered cardiocerebral events during the treatment, incidence rates of two groups did not differ significantly. CONCLUSION: DPP-4 inhibitors were as effective as sulfonylureas in achieving the HbA(1c) goal of less than 6.5% or 7% and cardiocerebral event rates did not differ between the two drugs.

Effect of Dipeptidyl Peptidase-4 Inhibitor on All-Cause Mortality and Coronary Revascularization in Diabetic Patients

BACKGROUND: Anti-atherosclerotic effect of dipeptidyl peptidase-4 (DPP-4) inhibitors has been suggested from previous studies, and yet, its association with cardiovascular outcome has not been demonstrated. We aimed to evaluate the effect of DPP-4 inhibitors in reducing mortality and coronary revascularization, in association with baseline coronary computed tomography (CT). METHODS: The current study was performed as a multi-center, retrospective observational cohort study. All subjects with diabetes mellitus who had diagnostic CT during 2007-2011 were included, and 1866 DPP-4 inhibitor users and 5179 non-users were compared for outcome. The primary outcome was all-cause mortality and secondary outcome included any coronary revascularization therapy after 90 days of CT in addition to all-cause mortality. RESULTS: DPP-4 inhibitors users had significantly less adverse events [0.8% vs. 4.4% in users vs. non-users, adjusted hazard ratios (HR) 0.220, 95% confidence interval (CI) 0.102-0.474, p = 0.0001 for primary outcome, 4.1% vs. 7.6% in users vs. non-users, HR 0.517, 95% CI 0.363-0.735, p = 0.0002 for secondary outcome, adjusted variables were age, sex, presence of hypertension, high sensitivity C-reactive protein, glycated hemoglobin, statin use, coronary artery calcium score and degree of stenosis]. Interestingly, DPP-4 inhibitor seemed to be beneficial only in subjects without significant stenosis (adjusted HR 0.148, p = 0.0013 and adjusted HR 0.525, p = 0.0081 for primary and secondary outcome). CONCLUSION: DPP-4 inhibitor is associated with reduced all-cause mortality and coronary revascularization in diabetic patients. Such beneficial effect was significant only in those without significant coronary stenosis, which implies that DPP-4 inhibitor may have beneficial effect in earlier stage of atherosclerosis.

Role of cardiovascular protection played by dipeptidyl peptidase 4 inhibitors / 中华内分泌代谢杂志

Cardiovascular disease is a common complication of type 2 diabetes,causing considerable fatality.Dipeptidyl peptidase 4 (DPP-4) inhibitors are new drugs for treatment of diabetes.Current studies have demonstrated that these drugs play an important role in cardiovascular protection.DPP-4 inhibitors can lower blood pressure,regulate blood lipid,and suppress inflammation and atherosclerosis.Treatment with DPP-4 inhibitors results in reduced size of myocardial infarct,reduced myocardial ischemia/reperfusion injury,increased myocardial cell regeneration,and improved heart function,etc.Recent studies have also found that DPP-4 inhibitors are able to mobilize progenitor cells to the sites of cardiovascular injury and thus to promote tissue repair.

Dipeptidyl Peptidase-4 Inhibitor / 대한내과학회지

Recent advances in incretin biology have led to the development of a new class of oral anti-diabetic drugs. To date, there are two known incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), of which the former is a more important therapeutic target for type 2 diabetes. GLP-1 is secreted by intestinal L-cells in response to oral nutrient intake, and it stimulates insulin secretion and suppresses glucagon secretion in a glucose-dependent manner. However, both GLP-1 and GIP are rapidly degraded by dipeptidyl peptidase-4 (DPP-4), a multifunctional type II transmembrane glycoprotein. Thus, several DPP-4 inhibitors with different pharmacologic features are now available and can be used either as monotherapy or in combination with other anti-diabetic agents for the treatment of type 2 diabetes. In both therapeutic regimens, DPP-4 inhibitors have been shown to reduce hemoglobin A1c levels by approximately 0.5-0.8%. In clinical trials, DPP-4 inhibitors were generally well-tolerated, posed a low risk of hypoglycemia, and did not increase body weight. Despite some reports of a possible increased risk of pancreatitis with GLP-1 receptor agonists and DPP-4 inhibitors, no causal associations have been found. Recent randomized controlled clinical trials have shown that DPP-4 inhibitors did not increase or decrease the rates of major adverse cardiovascular events in patients with type 2 diabetes at high risk of cardiovascular disease, even though this class of anti-diabetic agents had various salutary effects in many studies involving animals or healthy and diabetic humans. Additional studies will be required to resolve these disparate conclusions.

Effectiveness and Tolerability of Vildagliptin in Indian Patients with Type 2 Diabetes Mellitus: Results From Edge−A Real-World Observational Study.

Objective: To assess the effectiveness and tolerability of vildagliptin in combination with another oral antidiabetic drug (OAD) versus any other two-agent OAD combinations in Indian patients with type 2 diabetes mellitus (T2DM) in a real-world setting. Study design: This was a post hoc analysis of a multicenter, prospective, 1-year, observational EDGE study for patients enrolled in India. The primary efficacy endpoint of the study was proportion of patients achieving glycosylated hemoglobin (HbA1C) reduction of >0.3% without peripheral edema, hypoglycemic event, discontinuation due to a gastrointestinal event or weight gain. One of the secondary efficacy endpoints was proportion of patients achieving HbA1C <7% without hypoglycemia and weight gain. Results: The mean age, body mass index, HbA1C and duration of T2DM were 51.8 years, 26.6 kg/m2, 8.6% and 4.3 years, respectively. The proportion of patients achieving the efficacy endpoints was significantly higher in the vildagliptin cohort compared with the comparator cohort (p < 0.0001). The vildagliptin cohort showed a numerically greater reduction in HbA1C than the comparator cohort (1.4 vs 1.1%; analysis not pre-specified). Adverse events were comparable in both groups (4.2% vs 4.9%). Conclusion: In India, in a real-world setting, vildagliptin showed better overall clinical benefits compared with comparator OADs in patients with T2DM.

Predictive Clinical Parameters and Glycemic Efficacy of Vildagliptin Treatment in Korean Subjects with Type 2 Diabetes

BACKGROUND: The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. METHODS: In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. RESULTS: Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (DeltaHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment. CONCLUSION: Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.