钠-葡萄糖转运蛋白2抑制剂相关胃肠道反应风险的网状meta分析CSCD

目的系统评价钠-葡萄糖转运蛋白2(SGLT2)抑制剂致2型糖尿病患者胃肠道反应的风险。方法检索国内外有关数据库(截至2022年12月30日),收集SGLT2抑制剂治疗2型糖尿病且结局指标包含胃肠道反应的随机对照试验。采用Cochrane偏倚风险评估工具对纳入的研究进行质量评价。采用Stata 15.1软件贝叶斯方法进行网状meta分析,绘制SGLT2抑制剂不同干预措施胃肠道反应风险的网状证据图、两两比较的联赛图和累积概率排序曲线下面积图(SUCRA),并对SGLT2抑制剂不同干预措施胃肠道反应风险的大小进行排序。胃肠道反应的效应量以相对危险度(RR)及其95%置信区间(CI)表示。结果最终纳入15项研究进行分析,共包括5540例患者。SGLT2抑制剂治疗组3949例,干预药物包括达格列净(1872例)、卡格列净(1100例)、恩格列净(649例)、艾托格列净(219例)、伊格列净(61例)、利格列净(48例);对照组1591例,均给予安慰剂。网状meta分析结果显示,与卡格列净50 mg和卡格列净100 mg相比,艾托格列净10 mg治疗发生胃肠道反应的风险更高(RR=1.37,95%CI:1.02~3.48;RR=2.98,95%CI:1.19~4.09;均P<0.05);SGLT2抑制剂其他干预措施之间的比较差异均无统计学意义。按SUCRA对SGLT2抑制剂不同干预措施胃肠道反应发生风险的排序结果显示,胃肠道反应发生风险从大到小依次为利格列净50 mg、艾托格列净25 mg、艾托格列净10 mg、恩格列净25 mg、伊格列净100 mg、伊格列净300 mg、伊格列净200 mg、艾托格列净5 mg、利格列净10 mg、伊格列净50 mg、恩格列净10 mg、利格列净2.5 mg、达格列净20 mg、达格列净10 mg、恩格列净5 mg、艾托格列净1 mg、达格列净5 mg、安慰剂、卡格列净300 mg、卡格列净200 mg、达格列净2.5 mg、达格列净1 mg、卡格列净100 mg、卡格列净50 mg。结论不同SGLT2抑制剂治疗方案导致2型糖尿病患者发生胃肠道反应的风险不同。卡格列净导致胃肠道反应的风险较小,尤其是卡格列净50 mg方案;而利格列净和艾托格列净容易引起胃肠道反应,尤其在较高剂量治疗时。     

SGLT-2抑制剂治疗2型糖尿病的研究进展

钠-葡萄糖协同转运蛋白2抑制剂(SGLT-2i)类药物为近年来出现的一种新型口服糖尿病药物,由于其不依赖于胰岛素的独特降糖机制而日益受到关注。该类药物通过抑制肾脏肾小管中负责从尿液中重吸收葡萄糖的SGLT-2来降低肾糖阈,排出多余的葡萄糖,从而降低血液循环中葡萄糖水平。此外,该类药物还具有降压、减重、减轻尿蛋白等额外获益,在中国2型糖尿病治疗指南(2017版)中被推荐作为单一口服降糖药物效果不佳而采用的二联或三联治疗用药之一。目前,我国临床常见的SGLT-2i抑制剂类药物包括国内批准上市的恩格列净、达格列净和卡格列净。本文对SGLT-2抑制剂类药物的作用机制、降糖效果、降糖外获益等方面进行综述,为临床医师和药师合理用药提供参考。     

SGLT2抑制剂不良反应信号的挖掘与评价

目的:挖掘和评价钠-葡萄糖共转运蛋白2(SGLT2)抑制剂卡格列净、达格列净、恩格列净上市后的不良反应(ADR)信号,为临床合理用药提供参考。方法:采用比例报告比法(PRR)和报告比值比法(ROR)对2013年第2季度至2020年第3季度美国FDA不良事件报告系统自发呈报系统中接收的卡格列净、达格列净、恩格列净等3种SGLT2抑制剂的ADR进行信号挖掘,分析ADR报告中对应患者的基本信息(包括性别、年龄、上报年份、上报国家、严重ADR)和安全警告信号。结果:收集到的6029375份ADR报告中,SGLT2抑制剂为伴随和怀疑药物的ADR报告有43807份,其中卡格列净ADR报告19301份、达格列净ADR报告10960份、恩格列净ADR报告13546份。除性别未知和年龄缺失的ADR报告外,纳入报告患者的性别分布均衡,主要集中在50~75岁范围内,上报年份主要在2018年,主要上报国家为美国,以“住院或住院时间延长”为主要的严重ADR。共挖掘得到ADR信号573个,累及系统26个,主要集中在代谢与营养类疾病、内分泌失调、肾脏及泌尿系统疾病、感染及侵扰类疾病等方面。卡格列净、达格列净、恩格列净ADR频数排序前10位的主要ADR信号共14个,达格列净、恩格列净的ADR信号中强度最强的信号都依次为酮症酸中毒(PRR值分别为119.64、140.11,ROR值的95%CI下限分别为148.28、178.78)和真菌感染(PRR值分别为47.76、34.77,ROR值的95%CI下限分别为50.69、36.28);而卡格列净除上述2个信号较强外,截趾(PRR值为489.79,ROR值的95%CI下限为520.15)和骨髓炎(PRR值为61.42,ROR值的95%CI下限为65.38)的信号也较强。结论:SGLT2抑制剂在代谢与营养类疾病、内分泌失调、肾脏及泌尿系统疾病、感染及侵扰类疾病方面的安全风险较高。达格列净、卡格列净、恩格列净易引起酮症酸中毒、真菌感染等ADR,卡格列净还易引起截趾、骨髓炎等ADR。     

胰高血糖素样肽-1受体激动剂与钠-葡萄糖协同转运蛋白-2抑制剂治疗2型糖尿病疗效及安全性的系统评价

目的：系统评价胰高血糖素样肽-1受体激动剂（GLP-1RA）与钠-葡萄糖协同转运蛋白-2抑制剂（SGLT-2i）治疗2型糖尿病（T2DM）的疗效及安全性,为临床治疗提供循证参考。方法：计算机检索相关的随机对照试验。采用Stata 14.0软件进行Meta分析,并运用成本-效果分析方法进行短期经济学评价。结果：共纳入6项RCT,合计2 248例患者,纳入药物包括利拉鲁肽、艾塞那肽、司美格鲁肽、卡格列净、达格列净和恩格列净。Meta分析结果显示：GLP-1RA能更有效地降低糖化血红蛋白（HbA1c）水平[SMD=-0.28,95% CI （-0.40,-0.16）,P<0.01],且HbA1c<7%的达标率更高,而SGLT-2i能更有效地控制患者的收缩压、舒张压和脉搏;GLP-1RA治疗组导致停药、腹泻、恶心、呕吐等不良反应的发生率均显著高于SGLT-2i治疗组,而SGLT-2i治疗组患者出现生殖器感染的发生率更高,差异均有统计学意义。SGLT-2i的成本-效果比更低。结论：GLP-1RA降低T2DM患者HbA1c水平的疗效更好,但SGLT-2i控制患者血压和脉搏的效果更优、耐受性更佳且具有较高的经济学优势,临床治疗中应根据患者的具体情况选择合适的药物。     

钠-葡萄糖共转运蛋白2抑制剂相关的药物相互作用

钠-葡萄糖共转运蛋白2(sodium-glucose cotransporter 2,SGLT-2)抑制剂是治疗2型糖尿病的新型口服药物。SGLT-2抑制剂通过降低肾糖阈,增加尿葡萄糖排泄,同时排出部分能量;由于SGLT-2抑制剂的降糖机制依赖于血液和尿液中葡萄糖的浓度差,因此,在血糖较低的时候其效用就大大减弱,从而降低了低血糖发生风险。在降血糖外,SGLT-2抑制剂还有诸多获益,包括降低收缩压、舒张压,改变血液动力学,提高血细胞比容;降低体质量,减少内脏脂肪和皮下脂肪;降低尿酸;对心脏、肾脏还有保护作用。本文就我国批准使用的SGLT-2抑制剂恩格列净、达格列净和卡格列净的药物相互作用进行综述,以期为临床医师和药师合理用药提供参考。     

胰高血糖素样肽1受体激动剂类降糖药致2型糖尿病患者头疼和眩晕的网状Meta分析

摘 要 目的：使用网状Meta分析系统评价胰高血糖素样肽1受体激动剂（GLP-1 RAs）类降糖药对2型糖尿病（T2DM）患者头疼和眩晕的影响。方法：系统检索Medline、Embase、Clinical trials和Cochrane数据库中（截止2017年6月23日）比较GLP-1 RAs与传统降糖药或安慰剂对头疼和眩晕发生风险影响的随机对照试验（RCT）,采用贝叶斯网状Meta分析对纳入的研究进行分析。结果：共纳入100项RCTs,包括15种干预措施：8种GLP-1 RAs类降糖药（艾塞那肽、艾塞那肽缓释剂、利拉鲁肽、利西拉来、他司鲁肽、阿必鲁肽、杜拉鲁肽、索玛鲁肽）、安慰剂、2种二肽基肽酶-4（DPP-4）抑制剂（西格列汀和维格列汀）和4种传统降糖药（胰岛素、二甲双胍、磺脲类、噻唑烷二酮类）。网状Meta分析结果显示：与胰岛素相比,艾塞那肽（OR=1.35,95%CI：1.13~1.60）、利拉鲁肽（OR=1.35,95%CI：1.12~1.62）、利西拉来（OR=1.59,95%CI：1.22~2.06）和他司鲁肽（OR=1.78,95%CI：1.33~2.37）致T2DM患者发生头疼的风险增加;与安慰剂、胰岛素及噻唑烷二酮相比,艾塞那肽和利拉鲁肽显著增加了眩晕发生的风险（OR的取值范围为1.56~2.56）。此外,后验概率显示,致T2DM患者发生头疼风险最高的前三位为艾塞那肽缓释剂、二甲双胍、他司鲁肽;致T2DM患者发生眩晕风险最高的前三位为利拉鲁肽、利西拉来和艾塞那肽。结论：艾塞那肽缓释剂和他司鲁肽显著增加了头疼的发生风险,利拉鲁肽显著增加了眩晕的发生风险,但仍建议开展相应的大型前瞻性研究加以验证。     

SGLT-2抑制剂与其他降糖药物对比治疗2型糖尿病有效性与安全性的网状Meta分析

目的：采用网状Meta分析研究评价钠-葡萄糖共转运蛋白-2抑制剂（sodium-glucose cotransporter-2 inhibitors,SGLT-2抑制剂）与其他降糖药物对比治疗2型糖尿病（type 2 diabetes,T2DM）的有效性和安全性。方法：计算机检索Embase、PubMed、OVID、clinicaltrials.gov网站、万方、知网和维普数据库。检索时间从建库至2019年5月30日,并筛选研究SGLT-2抑制剂与其他降糖药物治疗T2DM的有效性和安全性的临床随机对照试验（clinicalrandomized trials,RCT）。结果：共纳入12项RCTs,总计8 845名患者。网状Meta分析结果显示,卡格列净、恩格列净、达格列净、埃格列净与二甲双胍、格列美脲、西他列汀、利格列汀相比：（1）恩格列净以及达格列净与二甲双胍相比,未能明显降低患者的HbA1c （P<0.05）;卡格列净300 mg以及埃格列净15 mg对比格列美脲及西他列汀能明显降低患者的HbA1c （P<0.05）;与利格列汀相比,SGLT-2抑制剂均无显著性差异（P>0.05）。（2）仅达格列净在降低患者FPG上与其他降糖药物无显著性差异（P>0.05）。（3）卡格列净及恩格列净能显著降低患者的体质量（P<0.05）。（4） SGLT-2抑制剂均不会增加不良反应发生率,无显著性差异（P>0.05）。（5）与格列美脲相比,SGLT-2抑制剂均不会增加患者低血糖的发生率（P<0.05）,但与另外3个降糖药物相比,无显著性差异（P>0.05）。结论：卡格列净、恩格列净、达格列净、埃格列净治疗2型糖尿病有效,且均不会增加患者不良反应及低血糖的发生率。根据4种药物的等级概率排序,其中埃格列净疗效最好,但由于该药物的纳入文献较少,仍需高质量、大样本的RCT再进行更进一步的评估;此外,4种药物的安全性均较高。     

恩格列净治疗2型糖尿病有效性和安全性的Meta分析

摘 要 目的：采用Meta分析方法评价恩格列净治疗2型糖尿病的有效性和安全性,为其临床应用提供依据。方法：计算机检索 PubMed、EMbase、MEDLINE、Cochrane 图书馆、CNKI、WanFang Data、VIP、SinoMed 数据库有关恩格列净治疗2型糖尿病的随机临床对照试验,检索时间为建库至2017年6月。按Cochrane系统评价的方法评价纳入研究的方法学质量并提取相应数据,采用 RevMan 5.3软件进行 Meta分析。结果：纳入符合标准的随机对照试验14个,2型糖尿病患者共计5 003例。Meta分析结果显示,与安慰剂相比,使用恩格列净治疗后糖化血红蛋白（HbA1c）水平改善较好[MD=-0.66,95%CI（-0.73,-0.58）,P＜0.000 01],空腹血糖水平改善较好[MD=-1.50,95%CI（-1.63,-1.37）,P＜0.000 01]。安全性分析结果显示恩格列净组与安慰剂组不良反应发生率差异无统计学意义（P=0.05）。结论：与安慰剂相比,恩格列净治疗能更加有效地降低糖化血红蛋白以及空腹血糖水平。受纳入研究方法学限制,该结论尚长期RCT进一步验证。     

恩格列净治疗2型糖尿病不良反应的Meta-分析

目的 评价恩格列净治疗2型糖尿病的安全性。方法 检索PubMed、Embase、CENTRAL,中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和万方等数据库,检索时限从建库至2018年3月,纳入有关的随机对照试验（RCTs）,用Stata 14软件完成Meta-分析。结果 共纳入10篇文献,6 618例患者。Meta-分析结果发现：治疗末期,恩格列净生殖器感染发生人数明显多于对照组,差异有统计学意义[OR=3.65,95% CI（2.55,5.23）];恩格列净组尿路感染发生人数与对照组相当,差异无统计学意义[OR=0.95,95% CI（0.82,1.11）];恩格列净组与对照组低血糖发生人数相当,差异无统计学意义[OR=1.05,95% CI（0.82,1.36）];恩格列净组与对照组骨折发生人数相当,差异无统计学意义[OR=1.143,95% CI（0.59,2.216）]。结论 恩格列净治疗2型糖尿病仅增加生殖器感染风险,不会增加尿路感染、低血糖、骨折发生率,安全性较好。     

2型糖尿病的克星——SGLT-2抑制剂

SGLT-2抑制剂为非胰岛素依赖型药物,可选择性抑制SGLT-2,抑制肾小管对葡萄糖重吸收,增加尿糖排泄以降低血糖,且不易引起低血糖.SGLT-2抑制剂包括糖苷类及非糖苷类.本文重点介绍已上市药物卡格列净、达格列净、伊格列净、鲁格列净的药动学、药效学、不良反应与药物联用.     

The effect of SGLT2 inhibitors on cardiovascular events and renal function

Introduction: Sodium-glucose co-transporters-2inhibitors have emerged as a very promising antidiabetic drug class, with data from the two available cardiovascular trials of this class suggesting remarkable benefits in terms of cardiovascular events, total mortality and renal outcomes.

Areas covered: Data point toward clinically meaningful benefits from SGLT-2inhibition on a variety of cardiovascular risk factors. Empagliflozin, and to a lesser extent canagliflozin, resulted in significant reductions of an abundance of cardiovascular mortality and morbidity endpoints. SGLT-2inhibitors were also found to reduce the incidence of heart failure events and ameliorate the progression of diabetic kidney disease. However, empagliflozin was associated with a trend for stroke risk increase, that could be partially attributed to the drug-induced hematrocrit increases, while canagliflozin was related with higher amputations risk.

Expert commentary: The beneficial impact of SGLT-2inhibitors on cardiovascular risk factors seem to be manifested in significant morbidity and mortality benefits. The bright future of SGLT-2inhibitors in diabetes therapeutics is overshadowed by the higher amputations risk and the potential harms in terms of stroke incidence. Further analyses of the data and future studies could unveil patients subgroups that might be more prone to such events or put to rest the concerns for this otherwise promising class of drugs.     

基于模型荟萃分析5个SGLT2抑制剂在单用和 联合用药治疗2型糖尿病的临床疗效

目的：采用基于模型的荟萃分析（MBMA）方法,建立钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）的药物效应模型,定量分析不同SGLT2i单用、或SGLT2i联合二甲双胍、联合二肽基肽酶-4抑制剂（DPP4i）、联合DPP4i和二甲双胍,共四种治疗方式对于2型糖尿病（T2DM）的临床疗效。方法：通过ClinicalTrials.gov和Web of Science（MEDLINE）进行文献检索,纳入5个SGLT2i（卡格列净、达格列净、恩格列净、埃格列净、依格列净）临床研究,选择糖化血红蛋白（HbA1c）的相对基线变化值作为药效学指标,建立药物效应模型。结果：最终纳入54篇文献,涵盖167组研究的24802名受试者,最终建立以时间、剂量描述的SGLT2i药物效应模型。SGLT2i按疗效顺序为依格列净>卡格列净>埃格列净>恩格列净>达格列净。相比单药治疗,72周各药联合二甲双胍使得HbA1c变化值再降0.13%,联合DPP4i可再降0.09%。SGLT2i联合二甲双胍和DPP4i可分为两个亚组：因DPP4i和二甲双胍控制不足而联用的人群比单药组可再降0.02%,而因二甲双胍控制不足而联用的人群可再降0.75%。目前各药推荐剂量几乎已达到最大降糖效果。未来同类药物的开发可以卡格列净和依格列净作为对照药物,衡量新化合物开发是否具有良好的临床优势性。结论：采用MBMA方法量化SGLT2i在单用、二联、三联不同治疗方式的降糖作用,按药物疗效高低排序依次为依格列净、卡格列净、埃格列净、恩格列净、达格列净。     

Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis

Objective: Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin.

Methods: Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL. Primary efficacy outcomes were: change from baseline in HbA_1c, weight, systolic blood pressure (SBP), post-prandial blood glucose (PPG), and fasting blood glucose (FPG). Treatment effects at 26 (±4) weeks were compared using Bayesian NMAs. Meta-regression and sensitivity analysis were used to address the trial heterogeneity.

Results: Eight trials were found eligible for this NMA. Statistically significant reductions in HbA1c were observed with both 1.0?mg and 0.5?mg doses of once-weekly semaglutide when compared to SGLT-2is. The mean differences in change from baseline in HbA_1c for once-weekly semaglutide 1.0?mg vs SGLT-2is ranged from ?0.66% for canagliflozin 300?mg (95% Credible Intervals [CrI]: ?0.82, ?0.50%) to ?1.11% for dapagliflozin 5?mg (95% CrI: ?1.37, ?0.85%). Once-weekly semaglutide 1.0?mg performed significantly better than all SGLT-2is of interest in reducing weight and improving FPG levels: however, SBP reduction was not statistically differentiable. Results of sensitivity analysis and meta-regressions aligned with base-case results. NMAs were not possible for PPG and safety outcomes, due to lack of data.

Conclusion: Once-weekly semaglutide treatment is significantly better compared to SGLT-2is in achieving adequate glycemic control in T2D patients inadequately controlled with metformin monotherapy.     

Evaluating the costs of glycemic response with canagliflozin versus dapagliflozin and empagliflozin as add-on to metformin in patients with type 2 diabetes mellitus in the United Arab Emirates

Objective: This study evaluates the cost of achieving glycemic control with three sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE).

Methods: A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26?±?4 weeks in duration, published by 10 September 2014. A Bayesian network-meta analysis (NMA) compared HbA1c changes with canagliflozin 100 and 300?mg versus dapagliflozin 10?mg and empagliflozin 10 and 25?mg. The cost associated with a 1% placebo-adjusted HbA1c reduction with each SGLT2 inhibitor as add-on to metformin was calculated based on NMA results and UAE drug costs.

Results: In the NMA, canagliflozin 100 and 300?mg were associated with HbA1c reductions (?0.67% and ?0.79%) compared with dapagliflozin 10?mg (?0.41%) and empagliflozin 10 and 25?mg (?0.57% and ?0.64%). Probabilities of canagliflozin 100?mg performing better were 79%, 60%, and 53% versus dapagliflozin 10?mg and empagliflozin 10 and 25?mg, respectively; probabilities for canagliflozin 300?mg performing better were 88%, 72%, and 65%, respectively. The cost per 1%-point reduction in HbA1c was projected to be lower with canagliflozin 100 and 300?mg ($448 and $422) compared with dapagliflozin 10?mg ($785) and empagliflozin 10 and 25?mg ($527 and $563).

Conclusions: Canagliflozin may provide a greater glycemic response at a lower effective cost than dapagliflozin or empagliflozin for patients with T2DM inadequately controlled with metformin from the payer perspective in the UAE.     

A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials.

Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile.

Area Covered: adverse events and the safety concerns most often emerged in trials with GLP-1RA namely, exenatide long acting release (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at comparing the safety profiles of molecules of these two classes.

Expert opinion: GLP-1RA and SGLT2i, although each associated with different specific side effects, share a ‘similar’ safety profile and are both drugs relatively easy to handle. The potentially complementary mechanisms of action, the cardio and nephroprotective effects demonstrated by molecules of both classes, make these drugs potentially useful even in add on to each other.     

钠-葡萄糖共转运蛋白2抑制剂致急性胰腺炎文献分析

目的:探讨钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂致急性胰腺炎发生的规律和特点,为临床合理用药提供参考.方法:检索2013—2020年中国学术期刊全文数据库(CNKI),维普中文科技期刊数据库(VIP)、Pubmed、Wiley、EBSCO等数据库,收集SGLT-2抑制剂致急性胰腺炎的个案报道,进行统计分析.结果:...     

Economic analysis of glucagon like peptide-1 receptor agonists from the Saudi Arabia payer perspective

ObjectivesTo perform a cost of control analysis of glucagon like peptide-1 receptor agonists (GLP1RA) in Saudi Arabia (SA) and determine the economic impact of adopting GLP1RAs.MethodsA budget impact model that captures the cost of control model was constructed to simulate hypothetical patient on six treatment options: a current mix of 60% liraglutide and 40% dulaglutide, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide. We estimated the relative amounts of SAR spend to achieve HbA1c targets (≤6.5% or < 7.0%). For each treatment option, annual treatment cost, proportion of patients achieving HbA1c targets, and cost to treat major adverse cardiovascular events (MACE) were aggregated to estimate the cost of control per patient per year (CCPPPY) over 5-year horizon (2021–2025). Probabilistic sensitivity analysis (PSA) was performed as a confirmatory analysis.ResultsThe CCPPPY to achieve HbA1c ≤ 6.5%/<7.0% using current mix, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 17,097/SAR 14,113, SAR 12,889/SAR 11,123, SAR 15,594/SAR 12,892, SAR 19,184/SAR 15,940, SAR 580,211/SAR 380,936, and SAR 246,570/SAR 143,759, respectively. The relative amounts of SAR spend to achieve HbA1c ≤ 6.5%/<7.0% relative to 1 SAR on semaglutide in case of adopting current mix, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 1.42/SAR 1.18, SAR 1.30/SAR 1.07, SAR 1.60/SAR 1.33, SAR 48.33/SAR 31.73, and SAR 20.54/SAR 11.97, respectively. These results were confirmed in the PSA.ConclusionsSemaglutide 1 mg once weekly was the most economically favorable GLP1RA; associated with the least CCPPPY, and amount of SAR spent to achieve HbA1c of ≤6.50%/<7.00% versus all other GLP1RAs.     

Pharmacological management of type 2 diabetes: what’s new in 2017?

Introduction: Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications.

Areas covered: Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients. The recent data regarding DPP-4 inhibitors (gliptins) focused on the safety profile of this pharmacological class, including in patients with impaired renal function. The highlight concerns the cardiovascular (and renal) protection by some GLP-1 receptor agonists (liraglutide, semaglutide) and SGLT2 inhibitors (empagliflozin, canagliflozin) in patients with high cardiovascular risk. Finally, efficacy and safety of new combinations and advances in insulin therapy will be briefly discussed.

Expert commentary: The recent data from randomized controlled trials, meta-analyses and observational real-life studies should trigger a revision of the algorithm for the treatment of hyperglycemia in type 2 diabetes, especially in patients with high cardiovascular and/or renal risk.