利格列汀联合二甲双胍治疗初诊2型糖尿病的效果研究

目的 探究初诊2型糖尿病患者应用利格列汀联合二甲双胍治疗的临床效果.方法 80例初诊2型糖尿病患者,随机分为对照组和观察组,各40例.对照组患者应用二甲双胍治疗,观察组在对照组基础上联合利格列汀治疗.对比两组患者血糖水平及不良反应发生情况.结果 治疗后,观察组空腹血糖(6.5±0.7)mmol/L和餐后2 h血糖(8....     

利格列汀联合二甲双胍治疗2型糖尿病的临床疗效观察

目的分析利格列汀与二甲双胍联合方案在2型糖尿病治疗中的有效性。方法回顾性比较我院应用联合药物治疗的97例2型糖尿病患者(即观察组,利格列汀+二甲双胍治疗)和单独应用二甲双胍治疗(即对照组)的94例2型糖尿病患者在空腹血糖、餐后血糖(即2h PG)、糖化血红蛋白(HbA1c)、药物不良反应等方面的差异性。结果规范治疗12周之后,两组患者的空腹血糖、2h PG、HbA1c均有明显改善,组内治疗前后数据具有显著差异(P<0.05);治疗后,观察组各项指标的改善效果均优于对照组,组间比较,P<0.05,具有显著性差异;组间不良反应相近(P>0.05)。结论利格列汀联合二甲双胍具有良好的降糖作用,且药物不良反应少,是2型糖尿病安全有效的治疗方案。     

利格列汀联合二甲双胍治疗2型糖尿病疗效与安全性初步研究

目的 探讨利格列汀与安慰剂作为二甲双胍的添加治疗对血糖控制不良的2型糖尿病患者的有效性、安全性。方法 15例2型糖尿病患者随机分为2组：5 mg利格列汀联合二甲双胍组(n=10)、安慰剂联合二甲双胍组(n=5),治疗24周,观察治疗前后2组糖化血红蛋白(HbAlc)、空腹血糖(FPG)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、血清肌酐(Scr)、尿白蛋白肌酐比(UACR)、肌酸激酶(CK)、体质指数(BMI)、腰围、收缩压(SBP)、舒张压(DBP),记录不良事件及低血糖事件。结果 2组HbA1c改变幅度分别为-14.9%,-7.3%(P<0.05);FPG改变幅度分别为-4.7%,-8.0%(P>0.05);SBP改变幅度分别为-1.6%,+9.0%(P<0.05);DBP改变幅度分别为+0.2%,+13.7%(P<0.05),UACR改变幅度分别为-33.3%,+91.1%(P<0.01)。2组间ALT、AST、ALP、Scr、BMI、腰围改变、不良事件差异均无统计学意义。2组均无低血糖事件。结论 利格列汀联合二甲双胍治疗较二甲双胍单药治疗,降低HbA1c更优,有相似的降低FPG疗效,能适当降低SBP,显著降低UACR。无体质量增加和低血糖风险,是一种安全有效的治疗方法。     

利格列汀联合二甲双胍治疗糖尿病的临床疗效研究

目的:探讨糖尿病患者采用二甲双胍联合利格列汀治疗的临床疗效。方法:将2017年6月~2018年6月治疗糖尿病的86例患者随机分为两组,A组采用格列齐特联合二甲双胍治疗,B组采用二甲双胍联合利格列汀治疗,比较两组的治疗效果。结果:两组患者治疗前HbAlc、2hPG、FPG水平比较差异不明显(P>0.05);B组患者治疗后以上血糖指标明显低于A组,治疗总有效率明显高于A组,对比差异有统计学意义(P<0.05)。结论:糖尿病患者采用利格列汀联合二甲双胍治疗,能有效降低患者的血糖水平,提高其治疗效果,适合在临床上应用。     

二甲双胍治疗老年2型糖尿病患者中联合利格列汀的临床观察

目的探讨二甲双胍治疗老年2型糖尿病(T2DM)患者中联合利格列汀的效果。方法 34例老年T2DM患者口服二甲双胍联合利格列汀5 mg,治疗3个月。观察治疗前后空腹血糖(FBG)、餐后血糖(PBG)、糖化血红蛋白(Hb A1c)、总胆固醇(TC)、三酰甘油(TG)、体质量指数(BMI)、空腹C肽(FCP)、餐后2 h C肽(PCP)及胰岛素抵抗指数(HOMA-IR)的差异。结果治疗后FBG、PBG、Hb A1c及TG下降,PCP较治疗前上升,HOMA-IR较前下降(P均<0.05)。结论二甲双胍联合利格列汀可有效降低老年T2DM患者血糖,改善胰岛素抵抗和血脂水平。     

利格列汀在单用二甲双胍效果不佳2型糖尿病患者中的治疗效果观察

目的观察在单用二甲双胍效果不佳的2型糖尿病患者治疗中应用利格列汀的临床效果。方法择取2017年1月至2018年1月人民医院收治的108例单用二甲双胍治疗效果不佳的2型糖尿病患者,随机将所选患者分成对照组和研究组,对照组54例患者行以安慰剂治疗,研究组54例患者行以利格列汀治疗,对两组临床效果进行分析和比较。结果治疗后,研究组空腹血糖水平、餐后2 h血糖水平、糖化血红蛋白水平均低于对照组(P<0.05)。结论在单用二甲双胍效果不佳的2型糖尿病患者治疗中应用利格列汀的效果良好,可以有效控制患者血糖水平。     

利格列汀联合二甲双胍治疗2型糖尿病有效性和安全性的Meta分析

目的评价利格列汀联合二甲双胍治疗2型糖尿病的疗效和安全性。方法计算机检索中国期刊全文数据库、万方数据库、维普数据库、Pubmed、ISI Web of Science和Embase数据库,筛选出利格列汀治疗2型糖尿病的所有随机对照试验(RCTs),采用Rev Man5.1软件包进行Meta分析,比较利格列汀联合二甲双胍(试验组)或安慰剂联用及单用二甲双胍(对照组)治疗对2型糖尿病患者糖化血红蛋白(Hb A1c)和空腹血糖(FPG)水平的影响,并比较低血糖发生率。结果共检出中英文文献725篇,经筛选最终纳入4项RCTs研究,共2 036例患者。在降低患者Hb A1c水平方面,试验组(利格列汀2.5 mg,bid)明显优于对照组[标准化平均差(SMD)=-7.47,95%置信区间(CI):-10.37~-4.58,P<0.000 01],而试验组(利格列汀5 mg,qd)与对照组相比无显著意义[SMD=-9.13,95%CI:-18.86~0.60,P=0.007]。在降低患者FPG水平方面,试验组的治疗效果明显优于对照组(SMD=-6.00,95%CI:-8.82~-3.91,P<0.001)。在安全性方面,试验组(利格列汀2.5 mg,bid)与对照组患者的低血糖发生率差异无显著意义[相对危险系数(RR)=0.94,95%CI:0.16~5.50,P=0.94],而试验组(利格列汀5 mg,qd)与对照组患者的低血糖发生率差异有显著意义(RR=0.24,95%CI:0.07~0.80,P=0.02)。结论利格列汀联合二甲双胍治疗能有效降低2型糖尿病患者的Hb A1c和FPG水平,且安全性较好,因本研究异质性高,需进一步研究证实。但是长期用药的有效性和安全性仍缺乏足够证据。     

利格列汀联合银杏叶提取物对早期二甲双胍单药治疗不佳的2型糖尿病患者肺功能的影响

目的观察利格列汀联合银杏叶提取物对早期二甲双胍单药治疗不佳的2型糖尿病(T_2DM)患者肺功能的影响,并评估其有效性与安全性。方法收集早期(不合并微血管病变)经二甲双胍单药治疗效果不佳的T_2DM患者,将其随机分为干预组(44例)和对照组(42例),并选择40例健康人作对照。对照组患者给予二甲双胍降糖、羟苯磺酸钙胶囊改善循环、甲钴胺片营养神经等治疗,干预组给予二甲双胍+利格列汀降糖、羟苯磺酸钙胶囊+银杏叶提取物片改善循环、甲钴胺片营养神经。治疗前记录三组观察对象的血糖及肺功能等。T_2DM患者连续治疗24周后,记录空腹血糖(FBG)、餐后2 h血糖(2hPG)、体重指数(BMI)与肺功能的变化情况,观察治疗过程中的不良反应。结果治疗前,T_2DM患者的FBG、PBG、BMI均高于健康人(P<0.05),肺功能各项指标低于健康人(P<0.05);治疗后,T_2DM患者的FBG、PBG均降低(P<0.01),且两组FBG、PBG、BMI比较差异无统计学意义(P>0.05);治疗后,两组患者的肺功能均改善(P<0.01),且干预组优于对照组(P<0.05)。治疗过程中两组均未发生严重不良反应(AEs),仅出现轻度胃肠道反应(恶心不伴呕吐)与皮肤瘙痒感,且两组不良反应发生率比较差异无统计学意义(P>0.05)。结论T_2DM患者早期即出现肺功能低下,控制血糖的同时加用银杏叶提取物可改善患者的肺功能,方法安全可靠,且对体重无影响。     

二甲双胍联合维格列汀治疗2型糖尿病临床疗效分析

目的 讨论二甲双胍联合维格列汀治疗2型糖尿病的临床疗效。方法 73例2型糖尿病患者,随机分为二甲双胍组(34例)和二甲双胍联合维格列汀组(39例),测定两组患者治疗前后空腹血糖(FBG)、口服葡萄糖耐量试验餐后2 h血糖(2 h FPG)、糖化血红蛋白(Hb A1c)、血脂、肾功、体质量指数(BMI)等生化指标。结果 组内比较二甲双胍组FBG、OGTT2 h、Hb A1c治疗后明显低于治疗前,差异有统计学意义(P<0.05),二甲双胍联合维格列汀组FBG、OGTT2 h、Hb A1c、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)治疗后明显低于治疗前,差异有统计学意义(P<0.05)。组间比较,治疗前二甲双胍组和二甲双胍联合维格列汀组各指标差异无统计学意义(P>0.05),治疗后二甲双胍联合维格列汀组BMI、LDL-C、TC明显低于二甲双胍组,差异有统计学意义(P<0.05)。结论 二甲双胍联合维格列汀具有良好降糖降血脂疗效。     

磷酸西格列汀联合二甲双胍治疗2型糖尿病的临床疗效研究

目的分析对2型糖尿病患者予以二甲双胍、磷酸西格列汀联合治疗的具体效果。方法选择2016年1月至2018年1月于我院接受治疗的2型糖尿病患者74例,采用奇偶法将其分为观察组(37例患者行磷酸西格列汀联合二甲双胍治疗)与对照组(37例患者行二甲双胍治疗),对比2组患者治疗后生化指标、体质量指数和临床治疗效果。结果观察组患者的空腹血糖、餐后2 h血糖、糖化血红蛋白、体质量指数、血脂总胆固醇均优于对照组,存在统计学意义(P <0.05)。与对照组治疗的总有效率对比(83.78%),观察组患者的治疗有效率(97.29%)更高,存在统计学意义(P <0.05)。结论二甲双胍、磷酸西格列汀联合治疗模式在2型糖尿病患者治疗方面效果显著,可以有效控制患者空腹血糖、餐后2 h血糖及糖化血红蛋白情况,安全性高,值得予以临床推广。     

Combination therapy in type 2 diabetes mellitus: adding linagliptin to a stable regimen of metformin and a sulfonylurea

Linagliptin, the most recently approved drug of the dipeptidyl peptidase-4 (DPP-4) inhibitor class, is an oral agent used to improve glycemic control in type 2 diabetes mellitus (T2DM). By inhibiting the DPP-4 enzyme, these drugs slow the inactivation of the endogenous incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), in turn reducing blood glucose levels in a glucose-dependent manner. As well as significantly reducing glycosylated hemoglobin, the class has a good safety profile, with a low incidence of hypoglycemia, and is not associated with weight gain. From a practical point of view, they also have simple regimens, generally with once-daily oral administration, and can be used as monotherapy or in combination with other anti-diabetic drugs. Owens and colleagues have reported a 6-month study of linagliptin add-on therapy in patients who were receiving a stable regimen of metformin and a sulfonylurea, but needed additional glycemic control. Linagliptin was associated with significant improvement in glycemic control and was well-tolerated by patients, indicating that it provides a valuable option for a large number of patients with T2DM, especially for those who would prefer to add an oral therapy to a current regimen.     

转运体介导的二甲双胍药物相互作用研究进展

二甲双胍作为治疗2型糖尿病的一线药物广泛应用于临床。多种转运体参与二甲双胍的体内处置过程,对药物的吸收、分布及排泄行为有重要影响。某些药物可影响转运体的功能,当其与二甲双胍联用时,有可能引起后者药动学和药效学的改变,从而导致不良的临床治疗结局。本文通过查阅和分析相关文献,将转运体介导的与二甲双胍相关的药物相互作用作一综述,旨在为二甲双胍的合理应用提供依据。     

利格列汀治疗2型糖尿病重度肾脏损伤患者有效性和安全性的临床应用

目的：观察DPP-4抑制剂利格列汀治疗2型糖尿病重度肾脏损伤患者的有效性和安全性。方法：84例2型糖尿病（HbA1c 7.0%~10.0%）合并严重肾脏损伤（eGFR < 30 mL·min^-1·1.73 m^-2）患者,在原有降糖药物基础上,按1：1比例随机分为利格列汀组（5 mg每日一次口服）（n=41）和安慰剂组（n=43）。主要有效终点是12周后HbA1c自基线的变化。结果：12周后,利格列汀组HbA1c下降0.71%,而安慰剂组下降0.12%（P < 0.000 1）。利格列汀组与安慰剂相比,1,5脱水葡萄糖醇明显升高（36.4±12.3）ng·mL^-1 vs.（10.4±5.2）ng·mL^-1,P<0.05）。两组总的不良反应类似（35% vs. 32.5%）,严重低血糖反应率都较低（每组2例）。利格列汀和安慰剂对肾功能影响较小（eGFR下降,0.8 mL·min^-1·1.73 m^-2 vs.2 mL·min^-1·1.73 m^-2）,没有药物相关的肾衰竭发生。结论：利格列汀治疗2型糖尿病严重肾脏损伤患者,有效地降低血糖,严重低血糖发生少,且没有影响肾功能、引起药物相关的肾衰,是可以用于治疗2型糖尿病重度肾脏损伤患者的降糖药物。     

Pharmacokinetics of linagliptin in subjects with hepatic impairment

AIM

To investigate whether hepatic impairment affects linagliptin pharmacokinetics, pharmacodynamics and tolerability.

METHOD

This open label, parallel group, single centre study enrolled patients with mild (n = 8), moderate (n = 9) or severe (n = 8) hepatic impairment and healthy subjects (n = 8). Groups were matched with regard to age, weight and gender. Primary endpoints were linagliptin exposure following 5 mg linagliptin once daily for 7 days in patients with mild and moderate hepatic impairment vs. healthy subjects or after a single 5 mg dose for patients with severe hepatic impairment vs. healthy subjects.

RESULTS

In mild hepatic impairment, steady-state linagliptin exposure was slightly lower than in healthy subjects [AUC_τ,ss geometric mean ratio (GMR) 75.5%, 90% confidence interval (CI) 61.6%, 92.5%, and C_max,ss GMR 64.4%, 90% CI 43.2%, 96.0%]. Exposure also tended to be lower in moderate hepatic impairment (AUC_τ,ss GMR 85.5%, 90% CI 70.2%, 104.2% and C_max,ss GMR 92.3%, 90% CI 62.8%, 135.6%). After a single dose, AUC(0,24 h) in patients with severe hepatic impairment was similar to that in healthy subjects (GMR 100.4%, 90% CI 75.0%, 134.3%) and C_max was lower (GMR 77.0%, 90% CI 44.9%, 132.3%). Accumulation based on AUC or C_max and renal excretion of unchanged linagliptin (≤7%) were comparable across groups. Median plasma DPP-4 inhibition was similar in healthy subjects (91%), and patients with mild (90%) and moderate (89%) hepatic impairment at steady-state trough concentrations, and in patients with severe hepatic impairment 24 h after a single dose (84%). Linagliptin was well tolerated.

CONCLUSION

Mild, moderate or severe hepatic impairment did not result in an increase in linagliptin exposure after single and multiple dosing compared with normal hepatic function. Dose adjustment with linagliptin is not required in patients with hepatic impairment.     

Empagliflozin/linagliptin single-pill combination therapy for patients with type 2 diabetes mellitus

Introduction: Type 2 diabetes mellitus (T2DM) is typically progressive, with sequential addition of therapies often needed to address increasing hyperglycemia over the disease course. Using treatments in combination may be preferred to sequential addition, as a means of providing a more rapid clinical response and potentially avoiding clinical inertia. In such cases, a single-pill combination can help to reduce pill burden. Although various single-pill combinations of oral glucose-lowering agents are available, empagliflozin/linagliptin was the first approved combination of a sodium glucose co-transporter 2 (SGLT2) inhibitor with a dipeptidyl peptidase 4 (DPP-4) inhibitor in the United States.

Areas covered: Two publications of the clinical trial investigating the efficacy and safety of single-pill combinations of empagliflozin/linagliptin in treatment-naive or metformin-treated patients with T2DM (NCT01422876) are reviewed, and their potential impact on clinical practice is discussed.

Expert opinion: The study discussed provides evidence for the efficacy and safety of empagliflozin/linagliptin single pills. Addition of an empagliflozin/linagliptin single pill may be considered in patients with inadequate glycemic control on metformin, or as an alternative to first-line treatment with empagliflozin or linagliptin when metformin is not suitable, particularly in patients with very poor glycemic control, or those who need to achieve target more quickly.     

Use of the dipeptidyl peptidase-4 inhibitor linagliptin in combination therapy for type 2 diabetes

Introduction: Most patients with type 2 diabetes mellitus (T2DM) are prescribed multiple medications – typically more than one for glycemic control alone, and others for the management of lipids and hypertension. Within a few years following diagnosis, many patients progress beyond an initial starting regimen of metformin and/or sulfonylurea in order to maintain glycemic control. With the broad selection of antidiabetes medications available today, the choice of which agents to add when progressing from monotherapy to combination therapy has led to much discussion on how to best tailor a treatment regimen to the individual patient's needs.

Areas covered: The aim of this paper is to review the literature describing the use of linagliptin as a component of combination therapy for the treatment of T2DM. Literature searches were conducted to retrieve articles reporting on linagliptin clinical trial data. For comparison of safety and efficacy, studies of linagliptin as monotherapy were included.

Expert opinion: Dipeptidyl peptidase-4 inhibitors are used across all stages of treatment, from monotherapy to dual or triple therapy regimens for glycemic control. Linagliptin has been studied in combination with the most commonly used classes of antihyperglycemic medications, with demonstrated efficacy and a safety profile comparable to placebo.     

Pharmacokinetic and pharmacodynamic evaluation of linagliptin in African American patients with type 2 diabetes mellitus

Aim

This was an open label, multicentre phase I trial to study the pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin in African American patients with type 2 diabetes mellitus (T2DM).

Methods

Forty-one African American patients with T2DM were included in this study. Patients were admitted to a study clinic and administered 5 mg linagliptin once daily for 7 days, followed by 7 days of outpatient evaluation.

Results

Primary endpoints were area under the plasma concentration–time curve (AUC), maximum plasma concentration (C_max) and plasma DPP-4 trough inhibition at steady-state. Linagliptin geometric mean AUC was 194 nmol l⁻¹ h (geometric coefficient of variation, 26%), with a C_max of 16.4 nmol l⁻¹ (41%). Urinary excretion was low (0.5% and 4.4% of the dose excreted over 24 h, days 1 and 7). The geometric mean DPP-4 inhibition at steady-state was 84.2% at trough and 91.9% at maximum. The exposure range and overall pharmacokinetic/pharmacodynamic profile of linagliptin in this study of African Americans with T2DM was comparable with that in other populations. Laboratory data, vital signs and physical examinations did not show any relevant findings. No safety concerns were identified.

Conclusions

The results of this study in African American patients with T2DM support the use of the standard 5 mg dose recommended in all populations.     

A safety evaluation of empagliflozin plus linagliptin for treating type 2 diabetes

Introduction: Dipeptidyl-peptidase-IV inhibitors (DPP-4i) and sodium-glucose-transporter-2 inhibitors (SGLT-2i) are oral antidiabetic drugs that improve glycemic parameters and possess a very low intrinsic hypoglycemia risk and favorable cardiovascular data.

Areas covered: An overview on the clinical studies investigating the combination therapy with the DPP-4i linagliptin and the SGLT-2i empagliflozin is given. The clinical evidence for the efficacy and safety of free combinations as well as for their fixed dose combinations is presented. Empagliflozin has recently proved to reduce cardiovascular risk in type 2 diabetes and cardiovascular high risk situations. A fixed dose combination (FDC) of empagliflozin and linagliptin as add on therapy to metformin or as initial treatment lowered the HbA1c by approximately 1.1% and reduced the body weight by 2.0–3.0 kg. The hypoglycemia risk was not significantly increased. The relevant studies were identified by a search in Medline and in clinicaltrials.gov.

Expert opinion/commentary: A DPP-4i/SGLT-2i FDC may be especially useful to simplify treatment, to reduce the tablet burden and to increase medication adherence. This FDC may be particularly beneficial for patients where the reduction of body weight, blood pressure and cardiovascular risk are important and in whom hypoglycemia should be avoided.     

格列吡嗪盐酸二甲双胍片治疗2型糖尿病的多中心、随机、双盲双模拟临床研究

目的评价格列吡嗪盐酸二甲双胍片(降血糖药)的疗效及安全性。方法用多中心、随机、双盲双模拟临床研究,试验组120例,二甲双胍组、格列吡嗪片组各60例,治疗12周。结果治疗前后试验组较二甲双胍组HbAlc多降低了0.78%,较格列吡嗪组多降低了0.41%(P<0.001);治疗前后试验组较二甲双胍组空腹血糖多降低了0.97 mmol·L~(-1),较格列吡嗪组多降低了1.36 mmol·L~(-1)(P<0.001);低血糖发生率3组相似。结论格列吡嗪盐酸二甲双胍与单药治疗相比,降低HbAlc、空腹及餐后2 h血糖均更为明显,且耐受性很好。