2型糖尿病的药物治疗进展

糖尿病(DM)是一种与遗传因素有关又与多种环境因素相关的慢性全身性疾病,是由于体内胰岛素的绝对或相对分泌不足而引起的糖、脂肪、蛋白质的代谢紊乱.随着经济的发展、人类生活水平的提高和环境污染的加剧,DM的患病率呈上升趋势,DM的各种并发症已经成为DM患者致残和早亡的主要原因[1].近20年来,DM发病率迅速上升,DM正成为全球流行的慢性非传染性疾病,其中1型DM的发病情况变化不大,以2型DM急剧上升为主.     

2型糖尿病药物治疗进展

糖尿病是一种因胰岛素绝对或相对不足或靶细胞对胰岛素敏感性减低引起的以糖代谢紊乱为主的慢性综合性疾病,其严重影响患者的健康和生活质量.随着人民生活水平的日益提高,2型糖尿病的发病率日渐升高,糖尿病的降糖药物治疗方面目前已取得较大进展.充分认识各种类型的治疗2型糖尿病的药物的机理及适应范围,可有效控制血糖及减少并延缓糖尿病并发症的出现,减少不良反应的发生.     

罗格列酮治疗2型糖尿病疗效观察

自2002年7月～2003年7月 ,我们采用罗格列酮治疗2型糖尿病32例 ,效果显著 ,报道如下。1临床资料1 1一般资料 :本组共32例 ,年龄37～48岁 ,平均病程2 2年。曾服用二甲双胍17例 ,美吡达11例 ,其它降糖药4例。全部病例均符合1997年ADA诊断标准 ,并且没有心、肝功能异常。1 2治疗方     

糖化血红蛋白监测在2型糖尿病患者并发症控制中的意义

目的 对糖化血红蛋白监测在2型糖尿病患者并发症控制中的重要意义进行探讨.方法 选取本院2年内收治的140例2型糖尿病患者作为研究对象,根据患者糖化血红蛋白水平将其分为A、B、C、D共四组,每组35例,对四组患者并发症发生率进行比较.结果 本次研究结果表明,A组患者并发症发生率为2.86％,B组为17.14％,C组为34.29％,D组为54.29％,各组间比较差异有统计学意义(P＜0.05).结论 糖化血红蛋白的有效监测,能够降低2型糖尿病患者的并发症发生率,对其并发症进行良好的控制,具有重要积极意义,值得临床应用并推广.     

2型糖尿病胰岛素治疗进展

胰岛素疗法已不是2型糖尿病(T2 DM)患者晚期所采用的迫不得已的治疗方法,它已成为该病患者严格控制血糖,有效地延缓或减慢各种晚期并发症的发生与发展、改善预后的重要措施,本文对T2 DM胰岛素治疗的进展作一综述。1　T2 DM患者应更早期开始胰岛素治疗T2 DM是一种缓慢进展性疾病     

糖化血红蛋白检测在2型糖尿病患者治疗中的意义研究

糖化血红蛋白(HbA1c)于1958年被使用色谱法首次从其他类型的血红蛋白中分离出来,并于1968年被分类为一种糖蛋白。1969年,人们发现HbA1c在糖尿病患者中的数量增加。现在HbA1c监测广泛应用于糖尿病的诊断和病情检测     

2型糖尿病治疗药物TAK-875

GPR40受体为一种表达于胰岛细胞的G-蛋白偶联受体（GPCR）,研究显示,该受体与多种疾病尤其是糖尿病密切相关。游离脂肪酸作为胰岛素分泌过程中一种重要的信号分子,其促胰岛素分泌作用依赖于葡萄糖且由GPR40受体介导,故而GPR40可成为糖尿病治疗的新型潜在靶点。由日本武田制药公司开发的2型糖尿病治疗药TAK-875为一种口服有效的选择性GPR40受体激动剂,具有介导游离脂肪酸对β细胞胰岛素分泌调节功能的作用;     

2型糖尿病合并高血压病的抗高血压药物治疗

糖尿病慢性并发症是糖尿病患者致死、致残的主要原因。在占临床糖尿病病例90％～95％以上的2型糖尿病患者中，最常见且危害最大的慢性并发症是心血管疾病，尤其是高血压病。因此，针对2型糖尿病患者合并的高血压病，早期、及时和达标治疗非常必要。由于糖尿病本身代谢紊乱和病理生理变化的影响，使得糖尿病合并的高血压病具有一些临床特点，临床医生在降压方案的确定和降压药物的选择时，应当注意这些特点。     

钠-葡萄糖共转运蛋白2抑制剂治疗2型糖尿病的临床研究进展

2 型糖尿病是一种以胰岛素分泌缺陷、胰岛素抵抗或者两者并存所致的高血糖为特征的慢性代谢性疾病。早期血糖控制不佳可以促进微血管并发症的进展,以及大血管风险的发生。虽然有众多的降糖药物在临床使用,但只有约50%的患者能实现血糖控制,传统药物仍存在某些不足,因此,需要开发具有新机制的治疗药物。钠-葡萄糖共转运蛋白2（SGLT2）是近年来发现的具有全新作用机制的一个糖尿病治疗靶点。SGLT2 抑制剂通过抑制肾脏近端小管对葡萄糖的重吸收来增加尿中葡萄糖的排泄而达到控制血糖的目的,其独立于葡萄糖依赖的胰岛素途径,能使低血糖发生风险降低。临床试验数据表明,SGLT2 抑制剂单药治疗和与传统降糖药物联合治疗均可以有效地控制血糖,并改善胰岛素抵抗,同时也有降血压和减少体质量作用。尽管后续的研究显示了SGLT2 抑制剂具有良好的耐受性,该类药物在临床上报道的意想不到的风险仍需要大量和长期的临床数据证实。     

2型糖尿病糖化血红蛋白与全天7点血糖水平的关系

目的探讨2型糖尿病患者糖化血红蛋白（HbA1c）与全天7点血糖水平的关系。方法 162例2型糖尿病患者检测三餐前、三餐后2 h及睡前共7次血糖值,并计算平均血糖水平（MBG）,同时测定HbA1c。按HbA1c水平不同将患者分为两组：血糖控制尚可组（HbA1c≤7.5%,A组）和控制差组（HbA1c〉7.5%,B组）。直线回归相关分析总体及各组HbA1c与MBG、全天7点血糖的相关性。结果 162例患者中,MBG与HbA1c显著正相关（r=0.849,P〈0.01）,MBG=-0.72＋1.31×HbA1c;HbA1c与全天7点血糖水平均呈正相关,逐步多元线性回归分析显示HbA1c与空腹、晚餐后、中餐后及早餐后血糖相关。A组的HbA1c与晚餐后、中餐后及中餐前血糖相关,而B组HbA1c与空腹、晚餐后、中餐后及早餐后血糖相关。结论 HbA1c受全天平均血糖水平的影响,血糖控制尚可组晚餐后、中餐后及中餐前的血糖对HbA1c影响明显,而血糖控制差组空腹、晚餐后、中餐后及早餐后的血糖对HbA1c影响明显。     

Emerging treatment options for type 2 diabetes

Type 2 diabetes mellitus (T2DM) is rapidly increasing in prevalence and is a major public health problem. It is a progressive disease which commonly requires multiple pharmacotherapy. Current options for treatment may have undesirable side effects (particularly weight gain and hypoglycaemia) and contraindications, and little effect on disease progression. Incretin based therapy is one of several newer therapies to improve glycaemia and is available in two different forms, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. Use of these agents results in a ‘glucose-dependant’ increase in insulin secretion and glucagon suppression resulting in improved glycaemia with low incidence of hypoglycaemia. DPP-4 inhibitors are oral drugs which are weight neutral, while GLP-1 agonists are injected subcutaneously and help promote weight loss while improving glycaemia. GLP-1 agonists have also been shown to increase beta cell mass in rat models. Bariatric surgery is another option for the obese patient with T2DM, with blood glucose normalizing in over half of the patients following surgery. Other therapies in development for the treatment of T2DM include sodium-glucose transporter 2 (SGLT-2) inhibitors, glucagon receptor antagonists, glucokinase activators and sirtuins. In this article, we will review the various existing and emerging treatment options for T2DM.     

Efficacy and safety of ertugliflozin across racial groups in patients with type 2 diabetes mellitus

Abstract

Objective: To assess the efficacy and safety of the sodium–glucose cotransporter 2 inhibitor ertugliflozin across racial groups in patients with type 2 diabetes mellitus (T2DM).

Methods: Pooled analysis of data from randomized, double-blind studies in the ertugliflozin phase III development program. Seven placebo- and comparator-controlled studies were used to assess safety (N?=?4859) and three placebo-controlled studies were used to assess efficacy (N?=?1544). Least-squares (LS) mean change from baseline was calculated for glycated hemoglobin (HbA1c), body weight and systolic blood pressure (SBP). Safety evaluation included overall and prespecified adverse events (AEs).

Results: At Week 26, ertugliflozin provided a greater reduction in HbA1c, body weight and SBP versus placebo in all racial subgroups. The placebo-adjusted LS mean change (95% confidence interval) from baseline in HbA1c was ?0.8% (?1.0, ?0.7) and ?1.0% (?1.1, ?0.8) with ertugliflozin 5?mg and 15?mg, respectively, in the White subgroup, ?0.7% (?1.2, ?0.2) and ?0.8% (?1.3, ?0.3) in the Black subgroup, and ?0.8% (?1.1, ?0.5) and ?1.0% (?1.3, ?0.8) in the Asian subgroup. The incidences of overall AEs, serious AEs and AEs leading to discontinuation from study medication were similar between the ertugliflozin 5?mg, 15?mg and non-ertugliflozin groups within each racial subgroup. The incidence of female genital mycotic infection (GMI) was higher with ertugliflozin than non-ertugliflozin across all racial subgroups. The incidence of male GMI was higher with ertugliflozin than non-ertugliflozin in the White sub-group; however, there were few male GMI events in the non-White subgroups.

Conclusions: In patients with T2DM, treatment with ertugliflozin improved HbA1c, body weight and SBP across all racial subgroups. Ertugliflozin had a generally similar safety profile across racial subgroups and was generally well tolerated.

Clinicaltrials.gov identifiers: NCT01986855, NCT01999218, NCT01958671, NCT02099110, NCT02036515, NCT02033889, and NCT02226003.     

Sociodemographic disparities in the management of type 2 diabetes in the United States

Abstract

Objective: To examine the potential sociodemographic disparities in type 2 diabetes (T2D) management and care among US adult individuals, after controlling for clinical and behavioral factors.

Methods: This was a retrospective cohort study of individuals with T2D (N?=?4552) from a linked database of the National Health and Wellness Survey and a large US ambulatory electronic health record (EHR) database. This study period was between 1 January 2015 and 31 December 2018 and individuals were followed up for at least 6?months through EHR after the completion of the survey. The sociodemographic characteristics included gender, race, ethnicity, marital status, education, employment status, household income, insurance status, and geographic region. The independent variables included testing and control of HbA1c, blood pressure (BP), and low-density lipoprotein-cholesterol (LDL-C); hypoglycemia, emergency room (ER) visits, and all-cause hospitalization. Multivariable analyses were conducted using generalized linear models.

Results: The percentage of uncontrolled HbA1c was 38.6%. With clinical and behavioral characteristics adjusted, individuals living in the Northeast region had 30% higher odds of having HbA1c testing than those who lived in the South. Blacks and Asians were less likely to have HbA1c control than Whites. Uninsured individuals had a lower likelihood of receiving HbA1c, BP, or LDL-C testing compared with commercial insurers. Individuals with low income were more likely to have higher ER visits and hospitalizations.

Conclusion: Potential sociodemographic disparities exist in T2D management and care in the US, indicating the needs for improvement in healthcare access, educational and behavioral programs, as well as disease and treatment management in these subgroups.     

Efficacy of hypoglycemic treatment in type 2 diabetes stratified by age or diagnosed age: a meta-analysis

Aim: To compare the effects of blood glucose lowering regimens in groups of patients categorized by baseline age and diagnosed age.

Methods: Placebo-controlled randomized trials in type 2 diabetes patients with a study length ≥12 weeks were included.

Results: A total of 246 trials were included. HbA1c changes from baseline corrected by placebo were comparable in sulfonylurea treatment between older and younger patients’ groups (weighted mean difference (WMD), –1.28% vs –0.92%, p > 0.05). Treatment with metformin between groups resulted in a comparable change in HbA1c levels (WMD, –0.97% vs –1.23%, p > 0.05). Treatment with α–glucosidase inhibitor (WMD, –0.68% vs –0.67%, p > 0.05), treatment with thiazolidinedione (WMD, –0.74% vs –1.01%, p > 0.05), treatment with DPP-4 inhibitors (WMD, –0.67% vs –0.67%, p > 0.05), and treatment with SGLT2 inhibitors (WMD, –0.54% vs –0.67%, p > 0.05) between groups also resulted in comparable HbA1c changes. Treatment with GLP-1 analogs between groups in HbA1c changes were also comparable (p > 0.05). Regression analysis indicated that the baseline age or diagnosed age was not associated with the HbA1c changes from baseline.

Conclusion: In each hypoglycemic treatment, the baseline age or diagnosed age was not associated with the HbA1c changes from baseline.     

米格列醇联合格列吡嗪治疗2型糖尿病的疗效分析

目的 研究米格列醇联合格列吡嗪对2型糖尿病的疗效。方法 选择2016年1月—2019年1月荣县人民医院的98例2型糖尿病患者作为研究对象,用抽签法随机将患者分为对照组和观察组,每组各49例。对照组口服格列吡嗪片,起始的剂量为5 mg/d,最大的给药剂量为5～10 mg/次,2次/d。观察组在对照组的基础上服用米格列醇片,50 mg/次,3次/d。两组均治疗12周。观察两组患者的临床疗效,同时比较两组患者的血糖水平和不良反应发生情况。结果 治疗后,观察组治疗的总有效率为91.84%,明显高于对照组的73.47%（P<0.05）。两组治疗后的空腹血糖（FBG）、糖化血红蛋白（HbA1c）和餐后2 h血糖（2 h PG）均明显降低（P<0.05）,且治疗后观察组血糖指标水平明显更低（P<0.05）。两组治疗期间不良反应的发生情况对比无统计学差异。结论 米格列醇联合格列吡嗪对2型糖尿病的疗效确切,能有效降低患者的血糖水平,安全有效,值得临床上应用。     

绝经后女性2型糖尿病患者骨代谢研究

目的探讨绝经后女性2型糖尿病患者骨代谢及生化指标的特征。方法对我院内分泌科住院44例中老年女性2型糖尿病患者(均为绝经后)的骨代谢及相关指标进行检测。糖尿病患者根据病程分为糖尿病1组(糖尿病病程10年以下)及糖尿病2组(糖尿病病程10年以上,含10年);根据糖化血红蛋白水平(HbA1c)分为糖尿病3组(HbA1c<8%)及糖尿病4组(HbA1c≥8%)。同时选取我院50例体检健康女性作为对照组。结果①糖尿病组25-羟维生素D3、I型前胶原氨基末端(C端)前肽(PICP)及估计肾小球滤过率(eGFR)明显低于正常对照组,而抗酒石酸碱性磷酸酶(TrACP-5b)明显较正常对照组升高,且有统计学差异(P<0.05)。②糖尿病2组患者血I型前胶原氨基末端(N端)前肽(PINP)、PICP和eGFR水平明显低于糖尿病1组患者(P<0.05),而TrACP-5b水平高于糖尿病1组,雌二醇(estradiol,E)、25-羟维生素D3则无明显统计学差异。③糖尿病3组血PINP、PICP和eGFR明显高于糖尿病4组,TrACP-5b低于糖尿病4组,差异存在统计学意义(P<0.05)。④HbA1c和eGFR与PINP、PICP和TrACP-5b存在显著相关性(相关系数>0.3),而雌二醇与PINP、PICP、25-羟维生素D3、TrACP-5b无明显相关性。结论①2型糖尿病患者的骨形成降低,而骨吸收增加,肾脏出现较重的损害,这提示糖尿病患者的骨质形成减弱、骨质破坏增加。②随着糖尿病病程的延长,患者的骨质形成速率减慢,骨吸收增加,肾脏损害加重。③血糖控制不佳会对骨的形成及骨质的吸收产生影响,而肾脏损害亦是加重发生骨质疏松的重要因素,因而严格的血糖控制可有效延缓骨质疏松进展。     

Association between hypoglycemia risk and hemoglobin A1C in patients with type 2 diabetes mellitus

Objective: To better manage type 2 diabetes mellitus (T2DM), the tradeoff between improved glycemic control and hypoglycemia should be evaluated. The purpose of this study was to assess the relationship between hypoglycemia and hemoglobin A1c (HbA1c) in a real-world population.

Research design and methods: Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) was a multi-center, observational study. Patients ≥30 years old using any oral anti-hyperglycemic agent were recruited from seven European and five Asian countries between 2006 and 2007. Hypoglycemia events were collected through patient-reported questionnaires. HbA1c data was collected through chart review. Logistic regression was performed to assess the relationship between hypoglycemia and the most proximate HbA1c levels adjusting for potential confounders (demographics, clinical variables, other medication use, and comorbid conditions).

Results: A total of 4399 patients were recruited and analyzed. Mean age was 60 years, 52% were male, and 75% were on sulfonylureas (S.U.s). Respectively, 37% or 42% of patients reported hypoglycemia in the past 6 (Asia) or 12 months (Europe) before recruitment. Prevalence of hypoglycemia increased significantly (33% to 40%) as HbA1c decreased (p?=?0.035). The same trend was also observed among S.U.-treated patients (p?<?0.01). After adjusting for confounders, hypoglycemia prevalence was significantly higher for HbA1c <7.0% (odds ratio [O.R.]?=?1.66 [95% C.I. 1.21, 2.28]; p?=?0.002) vs. HbA1c ≥10.0%.

Limitations: Our analyses pooled data from Asia and Europe, which differed in terms of the recall period for ascertaining hypoglycemia symptoms and the timing of latest HbA1c measure.

Conclusions: Lower HbA1c level was associated with higher hypoglycemia prevalence among S.U.-treated patients. HbA1c level should be taken into consideration when reporting hypoglycemia prevalence.     

Clinical outcomes after insulin initiation in patients with type 2 diabetes: 6-month data from the INSTIGATE observational study in five European countries

Abstract

Objectives:

To examine insulin regimens and factors that affect glycaemic control at 6 months after initiation of insulin therapy in patients with type 2 diabetes mellitus.