口服二甲双胍血糖控制不佳的2型糖尿病患者联合西格列汀治疗的有效性和安全性

目的评价口服二甲双胍血糖控制不佳的2型糖尿病患者联合西格列汀治疗的有效性与安全性。方法采用随机、开放、格列美脲平行对照的研究方法。102例口服二甲双胍控制不佳的2型糖尿病患者随机分为早餐前口服西格列汀100 mg（n=52）或早餐前口服格列美脲1~4 mg（n=50）两组,同时继续口服二甲双胍,进行为期24周的观察。结果①基线时两组口服二甲双胍的时间及其他指标相似;②24周时,西格列汀组与格列美脲组的平均HbA1c分别下降了1.41%和1.38%,日平均血糖降幅分别为5.28 mmol/L和4.56 mmol/L;③试验结束时,西格列汀组和格列美脲组分别有3.80%和10.00%的患者发生症状性低血糖（3次和18次）,其中严重低血糖事件,西格列汀组为0次,格列美脲组有4.00%患者（3次）,夜间低血糖西格列汀组为0次,格列美脲组有4.00%患者（2次）,两组间差异有统计学意义（均P〈0.05）;④试验结束时西格列汀组患者平均体重下降1.0 kg,格列美脲组平均增加1.2 kg,两组间差异有统计学意义（P〈0.01）。结论与格列美脲相比,西格列汀联合二甲双胍可使2型糖尿病患者的血糖得到有效控制,且低血糖发生率明显降低,体重下降;因此,作为控制2型糖尿病血糖的二线用药,西格列汀优于格列美脲。     

磷酸西格列汀联合二甲双胍治疗2型糖尿病临床疗效探究

目的研究分析磷酸西格列汀联合二甲双胍治疗2型糖尿病临床疗效。方法对86例于2018年10月—2019年10月入院就诊2型糖尿病患者进行该次研究,通过随机分组,将患者平均分成常规组和联合组两组,每组43例患者。常规组患者使用二甲双胍进行治疗,联合组患者采用磷酸西格列汀联合二甲双胍进行治疗,治疗实施后,对比两组患者数据评分结果。结果治疗后,联合组患者临床治疗效果、治疗成效、用药反应、2型糖尿病疾病控制有效率等均优于常规组患者,差异有统计学意义(P<0.05)。结论对2型糖尿病患者使用磷酸西格列汀联合二甲双胍进行治疗,可以有效控制患者血糖水平,提高临床治疗效果,对2型糖尿病具有显著的临床应用价值。     

恩格列净和西格列汀治疗肥胖的2型糖尿病患者的临床效果比较

目的比较恩格列净联合二甲双胍和西格列汀联合二甲双胍治疗合并肥胖的2型糖尿病患者的疗效和安全性。方法选取2019年3月—2020年3月该院诊治的合并肥胖的2型糖尿病患者48例,按随机数字表将患者分为两组,A组24例,予恩格列净联合二甲双胍治疗,B组24例,予西格列汀联合二甲双胍治疗,疗程12周;对比两组患者治疗后的临床效果。结果治疗后两组患者的FPG、2 hPG、HbA1c水平均显著低于治疗前,差异有统计学意义(P<0.05),但两组间差异无统计学意义(P>0.05)。治疗后A组的三酰甘油、体质指数低于B组,差异有统计学意义(P<0.05);治疗后A组的高密度脂蛋白胆固醇水平高于B组,差异有统计学意义(P<0.05);治疗后A组总胆固醇、低密度脂蛋白胆固醇水平与治疗前及B组比较差异无统计学意义(P>0.05)。两组患者均未发生明显不良反应。结论二甲双胍单药治疗效果不佳的、合并肥胖的2型糖尿病患者用恩格列净和西格列汀治疗降糖效果相当,均不易发生低血糖,但恩格列净还可降低患者体重,改善血脂。     

西格列汀联合二甲双胍治疗肥胖型2型糖尿病的疗效及对体脂含量情况分析

目的 研究肥胖型2型糖尿病患者联合采用西格列汀、二甲双胍治疗的临床效果.方法 选择2018年10月—2020年4月该院100例肥胖型2型糖尿病患者为研究对象,采用随机数表法分成常规组和治疗组,每组50例.常规组予二甲双胍治疗,治疗组予二甲双胍+西格列汀治疗.比较两组治疗效果、血糖指标、体脂含量、胰岛功能指标及不良反应....     

Efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes switched from glinides

Aims/Introduction

The efficacy and safety of sitagliptin, a dipeptidyl peptidase (DPP)‐4 inhibitor, were compared with those of glinides in Japanese patients with type 2 diabetes.

Materials and Methods

The participants were 82 patients with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.0% and <10%) under treatment with glinides for glucose control. The participants were randomly assigned to a group (n = 44) receiving continuous treatment with glinides and a group (n = 38) switched to sitagliptin. Patients were followed for 12 weeks to evaluate glucose control. A meal tolerance test was carried out in weeks 0 and 12 to examine the pancreatic secretory response to postprandial hyperglycemia.

Results

The changes in HbA1c from week 0 to week 12 were −0.25 and −0.05% in the sitagliptin and glinide groups, respectively, with a significant improvement with sitagliptin. The differences in fasting plasma glucose (FPG), glycoalbumin and 1,5‐anhydroglucitol between the two groups were 14.2 mg/dL, 0.7% and 1.7 μg/mL, respectively, showing significant improvements with sitagliptin. In the meal tolerance test, glucose at 0 min was lower in the sitagliptin group; however, there were no differences in glucose elevation at 30 and 60 min compared with 0 min. Plasma insulin and glucagon secretion at week 12 were significantly lower than at baseline in the sitagliptin group. Adverse events including hypoglycemia did not differ between the groups.

Conclusions

FPG decreased and glucose control improved in patients who switched from glinides to sitagliptin. Sitagliptin decreased secretion of insulin and glucagon in a meal tolerance test compared with glinides, whereas the agents showed similar inhibition of postprandial hyperglycemia. This trial was registered with UMIN (UMIN‐CTR no. 000003479).     

Addition of sitagliptin to ongoing metformin monotherapy improves glycemic control in Japanese patients with type 2 diabetes over 52 weeks

Aims/Introduction

The efficacy and safety of sitagliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, when added to metformin monotherapy was examined in Japanese patients with type 2 diabetes.

Materials and Methods

In this 52‐week, add‐on to metformin study, 149 patients were randomly assigned to receive sitagliptin 50 mg or placebo once daily in a double‐blind fashion for 12 weeks. Thereafter, all patients who completed the double‐blind period of the study received open‐label sitagliptin 50 mg once daily for 40 weeks, with the investigator option of increasing sitagliptin to 100 mg once daily for patients who met predefined glycemic thresholds.

Results

After 12 weeks of treatment, the mean change from baseline in glycated hemoglobin (HbA1c) significantly decreased with sitagliptin relative to placebo (between‐group difference [95% confidence interval] = −0.7% [−0.9 to −0.5] P < 0.001). At week 12, the mean changes in 2‐h post‐meal glucose (−2.6 mmol/L [−3.5 to −1.7]) and fasting plasma glucose (−1.0 mmol/L [−1.3 to −0.6]) also decreased significantly with sitagliptin relative to placebo (P < 0.001 for both). Significant improvements from baseline in glycemic control were also observed in the open‐label period through to week 52. There were no differences between treatment groups in the incidence of adverse events (AEs), including hypoglycemia and predefined gastrointestinal AEs (nausea, vomiting and diarrhea) during the double‐blind period, with similar findings in the open‐label period.

Conclusions

Over a period of 52 weeks, the addition of sitagliptin once‐daily to ongoing metformin therapy was efficacious and generally well tolerated in Japanese patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT00363948).     

Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus

Introduction

The aim of the present study was to determine the effect of sitagliptin on microalbuminuria in patients with type 2 diabetes mellitus.

Materials and Methods

A total of 85 patients with type 2 diabetes mellitus (age >20 years, <80 years, hemoglobin A1c [HbA1c] <8.4%) were randomized to patients taking sitagliptin 50 mg or other oral glucose‐lowering agents. The following parameters were evaluated at 0, 3 and 6 months after the treatment: bodyweight, blood pressure, HbA1c, fasting plasma glucose, fasting plasma insulin, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate and urinary albumin excretion. The primary outcome was changes in urinary albumin excretion at 6 months.

Results

Significant and comparable falls in HbA1c and fasting plasma glucose were found in both groups. However, sitagliptin significantly reduced urinary albumin excretion within 6 months, especially in patients with high urinary albumin at baseline. A total of 27 patients with normoalbuminuria showed a reduction in urinary albumin excretion, suggesting that sitagliptin prevents the development of albuminuria. A total of 15 patients with albuminuria showed a reduction in urinary albumin excretion, suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy. There was a significant correlation between improvement of proteinuria and that of diastolic blood pressure.

Conclusions

The results suggested that sitagliptin improved albuminuria, in addition to improving glucose. The mechanism of the reduction of albuminuria by sitagliptin could be a direct effect, as well as an increase in active glucagon‐like peptide‐1, independently affecting blood pressure, bodyweight and glucose metabolism. This trial was registered with the University Hospital Medical Information Network (UMIN no. #000010871).     

西格列汀联合津力达颗粒治疗老年2型糖尿病疗效及安全性

目的 探讨西格列汀联合津力达颗粒治疗老年2型糖尿病的疗效和安全性。方法 选取我院2019年5月至2020年1月期间收治的90例老年2型糖尿病患者为研究对象,按随机数字表法分为对照组和观察组,各45例。对照组患者给予口服西格列汀片治疗,100 mg/次,1次/d,观察组患者在对照组治疗方案的基础上联用津力达颗粒治疗,9g/次,3次/d。统计两组患者治疗效果、血糖指标和胰岛功能指标变化以及不良反应发生情况。结果 观察组临床总有效率为93.3%,显著高于对照组;两组患者血糖指标和胰岛功能指标均显著改善,但观察组水平显著优于对照组;观察组总不良反应发生率为8.9%,显著低于对照组,差异均具有统计学意义(P<0.05)。结论 西格列汀联合津力达颗粒治疗老年2型糖尿病,作用机制互补,疗效确切,安全性高,值得临床推广。     

西格列汀联合预混胰岛素治疗脆性糖尿病伴高脂血症疗效

目的分析西格列汀联合预混胰岛素治疗脆性糖尿病伴高脂血症的疗效。方法按照随机抽样的方式,从该院2018年3月—2019年3月的脆性糖尿病伴高脂血症患者中,选取110例作为研究对象。对患者的临床资料进行整理,确定其完备性后,按照双色球分组的方式将其划分为两组——对照组(n=55)和观察组(n=55),前者采取单纯的预混胰岛素治疗,后者采取西格列汀联合预混胰岛素治疗。对两组患者治疗前、持续用药12周以后的血糖指标与血脂指标进行观察。结果两组患者治疗前的血糖指标与血脂指标比较,差异无统计学意义(P>0.05);在治疗后,观察组患者与对照组患者的血糖指标与血脂指标相比较,差异有统计学意义(P<0.05)。结论西格列汀联合预混胰岛素治疗脆性糖尿病伴高脂血症的临床效果较好,能够对患者的血糖与血脂水平进行调整,且安全性较高,值得推广。     

Safety and efficacy of adding sitagliptin to insulin in patients with type 2 diabetes: The ASSIST-K study

We retrospectively studied more than 1000 patients with type 2 diabetes attending 36 Japanese clinics to investigate the efficacy and safety of adding sitagliptin to various insulin regimens. We found that the treatment with add-on sitagliptin for 6-months was effective, irrespective of the type or dose of concomitant insulin.     

Effects of concomitant drugs on sitagliptin-mediated improvement in glycemic control in Japanese patients with type 2 diabetes

AimsWe investigated to clarify factors associated with the efficacy of sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor, for glycemic control including the confounding effect of concomitant drugs in patients with type 2 diabetes.MethodsWe included type 2 diabetes patients with HbA1c levels of ≥7% who were not under insulin treatment and were administered sitagliptin (50 mg/day for 6 months). Reduction or discontinuation of insulin sensitizers was not permitted during the study period. Outcomes included HbA1c level variations and attaining a target HbA1c level of <7%. Associated factors with each outcome were examined using multivariate analysis.ResultsOf the 313 patients enrolled in this study, 147 (47.0%) attained HbA1c levels of <7%. High baseline HbA1c levels were associated with HbA1c level variations but inversely associated with attaining the target HbA1c level of <7%. Concomitant use of an insulin sensitizer and a α-glucosidase inhibitor and maintenance of the baseline dose of concomitant drugs were significantly associated with each outcome.ConclusionsOur results suggest that concomitant sitagliptin administration (50 mg/day) will improve glycemic control if treatment is initiated before HbA1c levels deteriorate. Other medication should be continued at initiation of sitagliptin administration.     

Sitagliptin added to voglibose monotherapy improves glycemic control in patients with type 2 diabetes

Aims/Introduction

Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control. The present multicenter, randomized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy (0.2–0.3 mg three times daily) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control (glycated hemoglobin ≥6.9% and <10.5%).

Materials and Methods

The present study had an initial 12‐week, double‐blind treatment period in which patients were randomized (1:1) to sitagliptin 50 mg/day (n = 70) or placebo (n = 63), followed by a 40‐week, open‐label treatment period during which all patients received sitagliptin 50 mg/day, that could have been increased to 100 mg/day for patients meeting predefined glycemic criteria.

Results

After 12 weeks, treatment with sitagliptin resulted in placebo‐subtracted mean changes from baseline in glycated hemoglobin (the primary end‐point), fasting plasma glucose and 2‐h postmeal glucose of –0.9%, –22.5 mg/dL and –51.3 mg/dL, respectively (all, P < 0.001). During the double‐blind period, adverse experiences were reported with similar frequency in both treatment groups, and the occurrences of hypoglycemia and gastrointestinal adverse experiences were low. In the open‐label period, sustained improvements in glycemic parameters were observed with sitagliptin treatment, and sitagliptin was generally well tolerated.

Conclusions

Sitagliptin added on to ongoing voglibose monotherapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control. This trial was registered with ClinicalTrails.gov (no. NCT00837577).     

Sitagliptin attenuates methionine/choline-deficient diet-induced steatohepatitis

Aims

Accumulating evidence suggests that inhibitors of dipeptidyl peptidase-4 (DPP-4), such as sitagliptin, may play an important role in the prevention of non-alcoholic steatohepatitis (NASH). This study was conducted to elucidate whether sitagliptin could prevent steatohepatitis by inhibiting pathways involved in hepatic steatosis, inflammation, and fibrosis.

Methods

C57BL/6 mice were fed a methionine/choline-deficient (MCD) diet with or without supplement with sitagliptin for 5 weeks. Liver and adipose tissue from mice were examined histologically and immunohistochemically to estimate the effect of sitagliptin on the development of NASH.

Results

Supplementation with sitagliptin resulted in significant improvement of MCD diet-induced fat accumulation in the liver. In addition, sitagliptin treatment lowered fatty acid uptake, expression of VLDL receptor and hepatic triglyceride content. Sitagliptin also effectively attenuated MCD diet-induced hepatic inflammation, endoplasmic reticulum (ER) stress, and liver injury, as evidenced by reduced proinflammatory cytokine levels, ER stress markers, and TUNEL staining. Expression of CYP2E1 and 4NHE were strongly increased by the MCD diet, but this effect was successfully prevented by sitagliptin treatment. Furthermore, sitagliptin significantly decreased levels of MCD diet-induced fibrosis-associated proteins such as fibronectin and α-SMA in the liver. Inflammatory and atrophic changes of adipose tissue by MCD diet were restored by sitagliptin treatment.

Conclusions

Sitagliptin attenuated MCD diet-induced hepatic steatosis, inflammation, and fibrosis in mice through amelioration of mechanisms responsible for the development of NASH, including CD36 expression, NF-κB activation, ER stress, CYP2E1 expression, and lipid peroxidation. Treatment with sitagliptin may represent an effective approach for the prevention and treatment of NASH.     

西格列汀与阿卡波糖对初发2型糖尿病的疗效比较和胃肠道相关激素的影响研究

目的探讨西格列汀与阿卡波糖对初发2型糖尿病的治疗效果及胃肠道相关激素的影响。方法选取该院2012年5月—2013年12月收治的58例初发2型糖尿病患者为研究对象,随机将其分为两组,各29例,A组患者给予西格列汀治疗,B组患者给予阿卡波糖治疗,对两组患者血糖控制情况（空腹血糖、餐后2 h血糖及糖化血红蛋白）及胃肠道相关激素（胃饥饿素及胃泌素）变化进行比较。结果治疗后两组间血糖、血脂及体重质量指数变化比较,差异无统计学意义（P〉0.05）。A组患者治疗后空腹、餐后2 h胃饥饿素及胃泌素较治疗前明显下降,差异有统计学意义（P〈0.05）,B组患者上述指标则无显著变化,差异无统计学意义（P〉0.05）。结论西格列汀与阿卡波糖治疗初发2型糖尿病疗效均良好,但西格列汀可显著降低患者空腹及餐后胃饥饿素,更安全。     

Sitagliptin added to treatment with ongoing pioglitazone for up to 52 weeks improves glycemic control in Japanese patients with type 2 diabetes

Aims/Introduction:  Patients with type 2 diabetes mellitus often require treatment with more than one oral antihyperglycemic agent to achieve their glycemic goal. The present study was carried out to assess the efficacy and safety of sitagliptin as add‐on therapy in Japanese patients with type 2 diabetes mellitus inadequately controlled (HbA1c ≥ 6.9% and <10.4%) on pioglitazone monotherapy (15–45 mg/day).Materials and Methods:  In the initial 12‐week, double‐blind treatment period, patients were randomized (1:1) to sitagliptin 50 mg/day (n = 66) or placebo (n = 68), followed by a 40‐week open‐label treatment period in which all patients received sitagliptin 50 mg/day that could have been increased to 100 mg/day for patients meeting predefined glycemic parameters.Results:  After 12 weeks, mean changes from baseline in HbA1c (the primary end‐point), fasting plasma glucose and 2‐h post‐meal glucose were −0.8%, −0.9 mmol/L and −2.7 mmol/L, respectively, in the sitagliptin group compared with placebo (all P < 0.001). The incidence of adverse experiences during the double‐blind treatment period was similar in both treatment groups, and the incidences of hypoglycemia and gastrointestinal adverse experiences were low. In the open‐label period, improvements in glycemic parameters with sitagliptin treatment were maintained and sitagliptin was generally well tolerated.Conclusions:  Sitagliptin as add‐on therapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus inadequately controlled on pioglitazone monotherapy. This trial was registered with ClinicalTrials.gov (no. {"type":"clinical-trial","attrs":{"text":"NCT00372060","term_id":"NCT00372060"}}NCT00372060). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00120.x, 2011)     

Sitagliptin: Anti-platelet effect in diabetes and healthy volunteers

Sitagliptin, a selective dipeptidyl peptidase-4 inhibitor drug is used to treat type-2 diabetes (T2DM). We investigated the anti-platelet activity of sitagliptin in patients with T2DM and in in vitro samples obtained from healthy humans. Patients with T2DM (27 male + 23 female) were selected and followed up before (control) and after treatment with sitagliptin for up to 3 months. Platelets were isolated from the blood of sitagliptin treated patients and controls. Patients with T2DM treated with sitagliptin for 1and 3 months, showed 10?±?2% and 30?±?5% inhibition of platelet aggregation, respectively. For the in vitro study, platelets from 10 normal humans (n?=?10) were isolated. Platelet aggregation, intracellular free calcium and tyrosine phosphorylation of multiple proteins were measured by aggregometer, spectrofluorometer and western blotting, respectively. Platelets pre-treated with 5 and 10?µg/ml of sitagliptin, showed 25?±?4% and 40?±?6% inhibition of thrombin-induced platelet aggregation, respectively. Sitagliptin decreased intracellular free calcium (2.5-fold) and tyrosine phosphorylation of multiple proteins in thrombin-induced platelet activation. Sitagliptin inhibited platelet aggregation in T2DM as well as in healthy humans. Sitagliptin has significant concentration-dependent anti-platelet activity. This activity was due to its inhibitory effect on intracellular free calcium and tyrosine phosphorylation.     

西格列汀联合地特胰岛素治疗老年2型糖尿病的疗效研究

目的格列汀联合地特胰岛素治疗老年2型糖尿病的疗效研究。方法择在该院进行2型糖尿病治疗的68例老年患者进行调查,选取时间为2018年2月-2019年1月。将患者分为两组,每组34例。对比组采用常规治疗方式,实验组采用了西格列汀联合地特胰岛素治疗方式。分析两组最终的治疗结果。结果对比组患者胰岛素使用剂量和实验组相比较高,差异有统计学意义(P<0.05);对比组HbAlc水平、2 hPG水平、FBG水平和实验组相比较高,差异有统计学意义(P<0.05)。结论老年2型糖尿病治疗中,可采取西格列汀联合地特胰岛素治疗方式,效果优异。