Abstract<br/><h3 class="a-plus-plus">Introduction</h3><p class="a-plus-plus">Use of dipeptidyl peptidase-4 (DPP-4) inhibitors is prevalent for the treatment of type 2 diabetes since they have fewer adverse effects compared with other non-insulin medications currently available; however, as monotherapy, the glycosylated hemoglobin (HbA1c)-lowering power of these agents is moderate. The aim of this article is to evaluate the current literature regarding the safety and efficacy of DPP-4 inhibitors in combination with metformin.</p><h3 class="a-plus-plus">Methods</h3><p class="a-plus-plus">A literature search was conducted through MEDLINE (from 1950 to October 2012), PubMed (from 1966 to October 2012), EMBASE (from 1966 to October 2012), and International Pharmaceutical Abstracts (from 1970 to October 2012) using the search terms “sitagliptin,” “linagliptin,” “alogliptin,” “vildagliptin,” “saxagliptin,” and “metformin.” Studies that did not evaluate the DPP-4 inhibitors in combination with metformin and those that were not phase 3, were excluded.</p><h3 class="a-plus-plus">Results</h3><p class="a-plus-plus">Many of the studies evaluated DPP-4 inhibitors in combination with metformin versus glucagon-like peptide-1 (GLP-1) agonists, placebo, DPP-4 inhibitors as monotherapy, thiazolidinediones, and sulfonylureas. The results of these noninferiority trials were that DPP-4 inhibitors as a whole are noninferior to either each other or other agents except for GLP-1 agonists. Also, in superiority studies, GLP-1 agonists proved to have greater HbA1c lowering.</p><h3 class="a-plus-plus">Conclusion</h3><p class="a-plus-plus">In summary, DPP-4 inhibitors play a vital role in the treatment of diabetes. They have relatively limited adverse effects, especially regarding hypoglycemia. DPP-4 inhibitors in combination with metformin are generally well tolerated and are available as combination products to reduce pill burden and enhance compliance. The limitations to DPP-4 inhibitors are the lack of outcomes data and more limited HbA1c lowering than other medications currently approved for the treatment of type 2 diabetes. However, as previously stated, thiazolidinediones, glinides, sulfonylureas, pramlinitide, and GLP-1 agonists are all quite beneficial in HbA1c lowering but are not without major adverse effects. Therefore, DPP-4 inhibitors have a vital role as an oral add-on agent for the treatment of type 2 diabetes.</p><br/>

This study aimed to compare the effects of sitagliptin on glycemic change and 24-h blood glucose variability with those of the sulfonylurea glimepiride.A 4-week randomized double blind-labeled prospective design was used. We recruited 33 patients who had been treated with metformin for at least 2 months. Each participant prescribed with metformin was randomly assigned to either the sitagliptin (100 mg) or the glimepiride (2 mg) group. Continuous glucose monitoring (CGM) was used to monitor glycemic changes for 3 successive days in both groups at baseline and at the 4-week follow-up. Glycemic changes and glucose variability were obtained using CGM, and these data were averaged over all subjects. Results: The comparison of glycated hemoglobin (HbA1c) between baseline and the 4-week follow-up showed that HbA1c was significantly reduced in the sitagliptin group (7.0 ± 0.5% to 6.6 ± 0.4%, P<0.001) and the glimepiride group (7.3 ± 0.4% to 6.9 ± 0.4%, P<0.001). The sitagliptin and glimepiride groups had similar HbA1c levels after 4 weeks, and there were no significant differences between the two groups. The mean amplitude of glycemic excursions (MAGE) decreased significantly in the sitagliptin group (4.9 ± 1.0 to 3.7 ± 0.9 mmol/L, P<0.001), but no significant difference was observed in the glimepiride group (5.7 ± 1.5 to 5.0 ± 1.4 mmol/L, P=0.175). The SD and oxidative stress markers did not differ significantly between the two groups. Conclusions: When sitagliptin was combined with metformin, the patients showed much more efficient blood glucose controlling effects, not only the three indexes of fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, but also MAGE.

糖尿病肾病是糖尿病微血管主要并发症之一，早期表现为肾小球肥大、基底膜增厚、系膜扩张，逐渐发展为肾小球、肾小管间质纤维化，最终导致肾衰竭［1］。糖尿病肾病的发病机制尚未完全阐明。目前认为其主要机制有高血糖、肾脏血流动力学改变、氧化应激和炎性反应等。临床上用于治疗糖尿病肾病的药物如 ACEⅠ类及 ARB 类对其虽有一定疗效，但对延缓糖尿病肾病的进展却不十分理想。GLP-1受体激动剂作为一种新型降糖药物，因其特殊的生理作用引起了广泛关注，GLP-1受体激动剂能通过多种机制延缓糖尿病肾病的发生、发展，为糖尿病肾病的治疗提供了全新的选择方案。本文就近年来 GLP-1受体激动剂改善糖尿病肾病的研究进展综述如下。

胰高血糖素样肽-1（GLP-1）是一种肠源性激素，具有促进胰岛素分泌、抑制胰高血糖素释放，改善胰岛β细胞功能，促进胰岛β细胞增殖并抑制其凋亡、延缓胃排空以及保护心血管等重要作用。天然的GLP-1在体内被二肽基肽酶-4（DPP-4）迅速降解，因此很难在临床中直接应用。 GLP-1类似物可以抵抗DPP-4的降解，增强与GLP-1受体的结合，有效延长作用时间，具有很好地应用前景。该文就GLP-1及其类似物的作用特点、临床应用、潜在风险和不良反应等最新研究进展作一综述。

目的：二肽基肽酶-4（Dipeptidyl Peptidase-4，DPP-4）可以裂解包括胰高血糖素样肽一1（glucagon—like peptide 1，GLP-1）和抑胃肽（glucose—dependent insulinotropic polypeptide，GIP）在内的多种肽类激素，而前两者与2型糖尿病有着密切联系，是近年来2型糖尿病治疗领域研究的热点。本文就DDP4抑制剂的作用特点、临床应用以及安全性和耐受性做一综述。方法：通过对国内外近期文献进行分析。结果与结论：DDP一4抑制剂不仅具有良好的降糖效果及保护β细胞功能，并且在糖尿病并发症进展中也起着一定的保护作用。

Dipeptidyl peptidase-4 (DPP-4) inhibitors offer new options for the management of type 2 diabetes. Direct comparisons with active glucose-lowering comparators in drug-naive patients have demonstrated that DPP-4 inhibitors exert slightly less pronounced HbA(1c) reduction than metformin (with the advantage of better gastrointestinal tolerability) and similar glucose-lowering effects as with a thiazolidinedione (TZD; with the advantage of no weight gain). In metformin-treated patients, gliptins were associated with similar HbA(1c) reductions compared with a sulphonylurea (SU; with the advantage of no weight gain, considerably fewer hypoglycaemic episodes and no need for titration) and a TZD (with the advantage of no weight gain and better overall tolerability). DPP-4 inhibitors also exert clinically relevant glucose-lowering effects compared with a placebo in patients treated with SU or TZD (of potential interest when metformin is either not tolerated or contraindicated), and as oral triple therapy with a good tolerability profile when added to a metformin SU or pioglitazone SU combination. Several clinical trials also showed a consistent reduction in HbA(1c) when DPP-4 inhibitors were added to basal insulin therapy, with no increased risk of hypoglycaemia. Because of the complex pathophysiology of type 2 diabetes and the complementary actions of glucose-lowering agents, initial combination of a DPP-4 inhibitor with either metformin or a glitazone may be applied in drug-naive patients, resulting in greater efficacy and similar safety compared with either drug as monotherapy. However, DPP-4 inhibitors were less effective than GLP-1 receptor agonists for reducing HbA(1c) and body weight, but offer the advantage of being easier to use (oral instead of injected administration) and lower in cost. Only one head-to-head trial demonstrated the non-inferiority of saxagfiptin vs sitagliptin. Clearly, more trials of direct comparisons between different incretin-based therapies are needed. Because of their pharmacokinetic characteristics, pharmacodynamic properties (glucose-dependent glucose-lowering effect) and good overall tolerability profile, DPP-4 inhibitors may have a key role to play in patients with renal impairment and in the elderly. The role of DPP-4 inhibitors in the therapeutic armamentarium of type 2 diabetes is rapidly evolving as their potential strengths and weaknesses become better defined mainly through controlled clinical trials. (C) 2011 Elsevier Masson SAS. All rights reserved.

Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of the incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The first available DPP-4 inhibitors are sitagliptin and vildagliptin. These compounds are orally active and have been shown to be efficacious and well tolerated. Two additional DPP-4 inhibitors are under review, and there are several others in clinical development. This article gives an overview on the mechanism of action of DPP-4 inhibitors and focuses on their development and their important physiological actions with regard to the treatment of type 2 diabetes.

二甲双胍的降糖效应主要通过改善胰岛素抵抗，二肽基肽酶4(DPP-4)抑制剂主要通过延长内源性胰升糖素样肽1(GLP-1)的生物活性进而改善胰岛功能异常。此外，二甲双胍可通过不同机制增强GLP-1的生物学效应，而DPP-4抑制剂则可提高胰岛素敏感性。因此，DPP-4抑制剂与二甲双胍的联合治疗可针对2型糖尿病不同的病理生理缺陷，发挥机制互补、协同增效的作用。【关键词】 二肽基肽酶4抑制剂； 二甲双胍； 胰升糖素样肽1； 联合治疗； 机制

目的 探讨西格列汀联合二甲双胍缓释片治疗2型糖尿病的疗效.方法 选取近9月内诊断为2型糖尿病的患者45例,随机分为三组:二甲双胍缓释片组、西格列汀组和联合用药组,每组各15例.二甲双胍缓释片组给予二甲双胍缓释 片0.5 bid 治疗;西格列汀组给予西格列汀100mg qd 治疗;联合用药组给予二甲双胍缓释片0.5bid+ 西格列汀100mg qd 治疗.治疗8 周后检测每个受试者空腹血糖、餐后2h 血糖、糖化血红蛋白,比较三组间各项指标的变化.结果 治疗8 周后,二甲双胍缓释片组空腹血糖、餐后2h 血糖、糖化血红蛋白较治疗前均下降(P ＜ 0.05);西格列汀组空腹血糖、餐后2h 血糖及糖化血红蛋白均较治疗前下降(P ＜ 0.05);联合用药组空腹血糖、餐后2h 血糖及糖化血红蛋白均较治疗前下降(P ＜ 0.05).治疗后,三组空腹血糖、餐后2h 血糖及糖化血红蛋白间差异有统计学意义(P ＜ 0.05).与二甲双胍缓释片组相比,西格列汀组三项指标差异无显著性,联合用药组三项指标均降低(P ＜ 0.05).与西格列汀组相比,联合用药组三项指标均降低(P ＜ 0.05).结论 西格列汀联合二甲双胍缓释片治疗2型糖尿病,疗效优于单用二甲双胍缓释片或西格列汀.

Used together, sitagliptin (Januvia) and metformin (Glucophage) help to improve glycemic levels in diabetic patients, suggesting a synergy between the agents. However, the cost of sitagliptin and the need for more data may restrict its use. More studies are needed to assess the effects of long-term sitagliptin and to determine its role in combination therapy.

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(HbA1c)、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、HbA1c治疗后明显低于治疗前，差异有统计学意义(P0.05)，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。

Abstract<br/><h3 class="a-plus-plus">Introduction</h3><p class="a-plus-plus">Type 2 diabetes mellitus (T2DM) is associated not only with high direct healthcare costs, but also with indirect costs, as diabetic complications and the disease itself result in loss of productivity. Vildagliptin is a novel dipeptidyl peptidase-4 inhibitor that is given either alone or in combination with oral hypoglycemic drugs, including metformin. The study was designed to assess the hypothesis that fixed-combination vildagliptin/metformin improves work productivity measured as Work Productivity and Activity Impairment (WPAI) scores. Secondary objectives were the assessment of patient satisfaction by means of the Diabetes Treatment Satisfaction Questionnaire (DTSQs), the change in anthropometric measurements and in glucose control (glycated hemoglobin [HbA1c]), and the evaluation of resource utilization (Resources Utilization Questionnaire).</p><h3 class="a-plus-plus">Methods</h3><p class="a-plus-plus">This study was an addendum to a mandatory, prospective, observational study carried out by the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]) in 49 diabetes centers in Italy. The addendum included 1,046 adult outpatients with a diagnosis of T2DM, who were no longer responding to metformin monotherapy. Patients were observed for up to 1 year.</p><h3 class="a-plus-plus">Results</h3><p class="a-plus-plus">Mean activity impairment improved by 40.6% (15.4 ± 17.4 vs. 26.1 ± 24.4; <em class="a-plus-plus">P</em> &lt; 0.0001), absenteeism by 49.9% (2.0 ± 9.4 vs. 3.8 ± 13.3; <em class="a-plus-plus">P</em> = 0.0076), and total work productivity by 37.6% (14.9 ± 15.9 vs. 21.5 ± 24.6; <em class="a-plus-plus">P</em> &lt; 0.0001). This resulted in a reduction of the annual indirect cost due to impaired productivity of yy400 per working patient and yy135 per patient in general. The DTSQ score increased by 30.2% (29.6 ± 5.6 vs. 22.8 ± 6.9; <em class="a-plus-plus">P</em> &lt; 0.0001). The satisfaction rate increased from baseline by 44.7%; the hyperglycemia-free or almost hyperglycemia-free perception rate by 37.9%; and the hypoglycemia-free or almost hypoglycemia-free rate by 15.2%. Mean healthcare costs per patients diminished by 19.2% in the second semester of treatment.</p><h3 class="a-plus-plus">Conclusion</h3><p class="a-plus-plus">This observational study suggests that the fixed combination of vildagliptin/ metformin increases work productivity, reducing indirect costs, and improves quality of life, especially in terms of perception of blood glucose variability, in patients with T2DM.</p><br/>

Metformin is considered as the first-line drug therapy for the management of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors, by promoting insulin secretion and reducing glucagon secretion in a glucose-dependent manner, offer new opportunities for oral therapy after failure of metformin.An updated review of the literature demonstrates that saxagliptin, a DPP-4 inhibitor, and metformin may be administered together, separately or in fixed-dose combination (FDC), either as saxagliptin added to metformin or as initial combination in drug-naive patients. Both compounds exert complementary pharmacodynamic actions leading to better improvement in blood glucose control (fasting plasma glucose, postprandial glucose, HbA1c) than either compound separately. Adding saxagliptin to metformin monthotherapy results in a consistent, sustained and safe reduction in HbA1c levels. Tolerance is excellent without hypoglycemia or weight gain.The combination saxaglitpin plus metformin may be used as first-line or second-line therapy in the management of type 2 diabetes, especially as a valuable alternative to the classical metformin-sulfonylurea combination.

<FONT face=Verdana>目的评价沙格列汀联合二甲双胍治疗 2 型糖尿病的疗效和安全性。方法以“saxagliptin” 和“metformin”为关键词检索PubMed和EMbase数据库，筛选出沙格列汀治疗2 型糖尿病的所有随机对照试验(RCTs)，根据纳入标准对文献进行筛选和评估，采用RevMan 5.1软件进行meta分析，比较沙格列汀联合二甲双胍(沙格列汀组)与安慰剂(安慰剂对照组)或其他降糖药物联合二甲双胍(阳性药物对照组)治疗对2 型糖尿病患者糖化血红蛋白(HbA1c)和空腹血糖(FPG)水平的影响，并比较低血糖发生率，结果以平均差(MD)、相对危险系数(RR)及其95%置信区间(CI)表示。结果共纳入5项RCTs研究。meta分析结果显示，在降低患者HbA1c水平方面，沙格列汀组明显优于安慰剂对照组(MD=-0.59, 95%CI为-0.87～-032，P=0.00)，也优于阳性药物对照组(MD=-0.36, 95%CI为-0.73～-0.54, P=0.00)。在降低患者FPG水平方面，沙格列汀组的治疗效果明显优于安慰剂对照组(MD=-16.27, 95%CI为-21.64～-10.91, P=0.00)，而与阳性药物对照组的治疗效果相比，差异无统计学意义(MD=-2.75, 95%CI为-22.52～17.01, P =0.78)。沙格列汀组与安慰剂或阳性药物对照组患者的低血糖发生率差异无统计学意义(RR=0.55, 95%CI 为0.15～2.09, P=0.38)。结论沙格列汀联合二甲双胍治疗能有效降低2 型糖尿病患者的HbA1c和FPG水平，且安全性较好。</FONT>

HIV-1病毒为包膜病毒，其感染靶细胞的第一步是由HIV包膜蛋白表面亚基gp120与靶细胞上的CD4分子和辅助受体（趋化因子受体CCR5或CXCR4等）结合，导致gp41的构型发生改变，启动病毒包膜与靶细胞膜的融合。与gp120相结合的一些抗体、蛋白、多糖、多肽和小分子化合物，都可能影响HIV-1病毒包膜和靶细胞膜融合的过程，从而起到抗HIV-1病毒的作用。该文对近年来以HIV gp120为靶点的HIV进入抑制剂的研究进展进行综述。

利格列汀是一种新一代口服二肽基肽酶-4抑制剂，具有高溶解性、低渗透性特点，与其他列汀类药物相比具有独特的药动学和药效学表征。本文综述利格列汀的药效学、药动学及药物相互作用，以供临床应用参考。

目的观察利格列汀对新诊断的2型糖尿病患者糖代谢和胰岛功能的影响。方法采用随机、双盲、安 慰剂对照研究，新诊断2型糖尿病患者50例，随机分为两组，治疗组27例，安慰剂组23例。在饮食控制、运动治疗基础上，治疗组和安慰剂组分别给予利格列 汀5mg和安慰剂，口服，每日1次，疗程24周。检测治疗前后两组糖化血红蛋白（HbA1c）、空腹血糖（FBG）、餐后2h血糖（2hPBG）、空腹胰 岛素、体重、血脂、肝功能和血淀粉酶等指标，并计算稳态模型胰岛素抵抗指数（HOMA·IR）和p细胞功能指数（HOMA．p）。结果治疗后，两组 HbA1c和2hPBG均有所下降，治疗组下降幅度大于安慰剂组（P〈0．05）。治疗组FBG下降（1．25±1．50）mmol·^L- 1，HOMA．B上升12．73±19．76，安慰剂组FBG和HOMA-β无显著变化，两组差异显著（P〈0．05）。两组血脂、肝功能、肾功能、血淀 粉酶等均无明显变化．组间亦无显著差异（P〉0．05）。治疗组发生低血糖1例，两组均无严重不良事件发生。结论利格列汀能有效降低新诊断2型糖尿病患者 的血糖水平，并改善胰岛β细胞分泌功能。

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。

Making appropriate treatment decisions for patients newly diagnosed with type 2 diabetes mellitus (T2DM) and severe hyperglycemia (glycated hemoglobin [HbA1c] > 10% or fasting plasma glucose a parts per thousand yen250 mg/dL) presents a formidable challenge to primary care physicians. Extreme defects in insulin secretion make it unlikely that these patients will achieve glycemic targets with metformin monotherapy. Additionally, uncontrolled hyperglycemia is associated with an increased risk of short-term acute complications, such as hyperosmolar coma, and long-term complications affecting the micro- and macrovasculature. Thus, severely hyperglycemic patients require prompt, intensive treatment to re-establish glycemic control. Current guidelines indicate that either initial insulin therapy or initial combination therapy with metformin plus non-insulin drug(s) are the treatments of choice for these challenging-to-treat patients. This mini-review examines the clinical evidence supporting these two treatment options, with particular reference to the findings of a phase 3 study of treatment with an initial combination of metformin plus the dipeptidyl peptidase-4 inhibitor, linagliptin. Intensive insulin therapy can induce sustained euglycemia and improve beta-cell function in newly diagnosed patients. However, insulin use is associated with an increased risk of adverse events, such as hypoglycemia and weight gain. These potentially serious side effects cause concern among patients and physicians, and are a major barrier to initiating and maintaining adherence to insulin treatment. In the phase 3 study, open-label treatment of severely hyperglycemic patients (HbA1c a parts per thousand yen11.0%) with linagliptin plus metformin resulted in a mean change in HbA1c of -3.7% +/- 1.7%. This combination therapy was generally well tolerated with most adverse events being of mild or moderate intensity; asymptomatic hypoglycemia was reported by just 1 of 66 (1.5%) patients. These findings provide evidence in support of linagliptin plus metformin as a well-tolerated and effective treatment alternative to insulin for new-onset patients with T2DM and severe hyperglycemia.

Combination therapies are a widely accepted approach to type 2 diabetes treatment, considering that monotherapies fail to provide adequate glycemic control in the majority of cases. The combination of oral antidiabetic agents into a single tablet would significantly simplify the therapeutic regimen and maximize patients' adherence to treatment. Recently, a fixed-dose, single-tablet, combined formulation of linagliptin (a dipeptidyl peptidase-4 inhibitor) and metformin has been approved for use in type 2 diabetic patients, and is indicated as an adjunct to diet and exercise for those patients who remain inadequately controlled despite maximal tolerated doses of metformin, metformin and sulfonylurea, or linagliptin and metformin monotherapies. The combination tablet is administered twice daily and can be used either alone or combined with sulfonylureas. Clinical trials suggest that this fixed-dose combination provides significantly superior glycemic control compared to linagliptin and metformin monotherapy, in terms of improving key parameters of glucose homeostasis such as glycosylated hemoglobin, fasting and postprandial glucose levels. It also exhibits an excellent tolerability profile, without promoting weight gain and hypoglycemic episodes. The compounds of this formulation do not display clinically relevant pharmacokinetic interactions with each other, and exert synergistic (complementary) pharmacodynamic effects, including an enhanced incretin effect, suppressed hepatic glucose production, and improved peripheral insulin sensitivity. As a result, a linagliptin/metformin fixeddose combination offers the potential to address multiple defects of type 2 diabetes pathophysiology (pancreatic islet dysfunction, insulin resistance, increased hepatic glucose output), and most importantly, in the context of a safe, efficacious, flexible, and convenient therapeutic regimen.

Alogliptin is a selective dipeptidyl peptidase-4 inhibitor recently marketed for once-daily administration in the treatment of type 2 diabetes mellitus (T2DM). Fixed-dose combinations of alogliptin with both metformin and pioglitazone are also commercially available, providing a measure of convenience in addition to an effective mode of delivering combination therapy to improve glycemic control. Alogliptin has been studied clinically as initial therapy in treatment-na茂ve patients with T2DM and as initial therapy or add-on in combination with other antidiabetic agents. Clinical trial data with alogliptin demonstrate clinical efficacy in terms of glycosylated hemoglobin A1c and fasting plasma glucose reductions when used both as monotherapy and as a component of two- or three-drug combination regimens for the treatment of T2DM. Extensive Phase II and Phase III clinical trial data support the use of alogliptin in combination with metformin and pioglitazone. Glycemic reduction with both combinations is similar to the sum of the respective monotherapies, with adverse event rates similar - or more moderate - than those observed with up-titration of monotherapy or the addition of other antihyperglycemic agents.