Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial

Context  Most antidiabetic agents target only 1 of several underlying causes of diabetes. The complementary actions of the antidiabetic agents metformin hydrochloride and rosiglitazone maleate may maintain optimal glycemic control in patients with type 2 diabetes; therefore, their combined use may be indicated for patients whose diabetes is poorly controlled by metformin alone. Objective  To evaluate the efficacy of metformin-rosiglitazone therapy in patients whose type 2 diabetes is inadequately controlled with metformin alone. Design  Randomized, double-blind, placebo-controlled trial from April 1997 and March 1998. Setting  Thirty-six outpatient centers in the United States. Patients  Three hundred forty-eight patients aged 40 to 80 years with a mean fasting plasma glucose level of 12.0 mmol/L (216 mg/dL), a mean glycosylated hemoglobin level of 8.8%, and a mean body mass index of 30.1 kg/m² were randomized. Interventions  Patients were assigned to receive 2.5 g/d of metformin plus placebo (n = 116); 2.5 g/d of metformin plus 4 mg/d of rosiglitazone (n = 119); or 2.5 g/d of metformin and 8 mg/d of rosiglitazone (n = 113) for 26 weeks. Main Outcome Measures  Glycosylated hemoglobin levels, fasting plasma glucose levels, insulin sensitivity, and -cell function, compared between baseline and week 26, by treatment group. Results  Glycosylated hemoglobin levels, fasting plasma glucose levels, insulin sensitivity, and -cell function improved significantly with metformin-rosiglitazone therapy in a dose-dependent manner. The mean levels of glycosylated hemoglobin decreased by 1.0% in the 4 mg/d metformin-rosiglitazone group and by 1.2% in the 8 mg/d metformin-rosiglitazone group and fasting plasma glucose levels by 2.2 mmol/L (39.8 mg/dL) and 2.9 mmol/L (52.9 mg/dL) compared with the metformin-placebo group (P<.001 for all). Of patients receiving 8 mg/d of metformin-rosiglitazone, 28.1% achieved a glycosylated hemoglobin level of 7% or less. Dose-dependent increases in body weight and total and low-density lipoprotein cholesterol levels were observed (P<.001 for both rosiglitazone groups vs placebo). The proportion of patients reporting adverse experiences was comparable across all groups. Conclusions  Our data suggest that combination treatment with once-daily metformin-rosiglitazone improves glycemic control, insulin sensitivity, and -cell function more effectively than treatment with metformin alone.      

Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial

Context  -Blockers have been shown to decrease cardiovascular risk in patients with hypertension and type 2 diabetes mellitus (DM); however, some components of the metabolic syndrome are worsened by some -blockers. Objective  To compare the effects of -blockers with different pharmacological profiles on glycemic and metabolic control in participants with DM and hypertension receiving renin-angiotensin system (RAS) blockade, in the context of cardiovascular risk factors. Design, Setting, and Participants  A randomized, double-blind, parallel-group trial (The Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives [GEMINI]) conducted between June 1, 2001, and April 6, 2004, at 205 US sites that compared the effects of carvedilol and metoprolol tartrate on glycemic control. The 1235 participants were aged 36 to 85 years with hypertension (>130/80 mm Hg) and type 2 DM (glycosylated hemoglobin [HbA_1c], 6.5%-8.5%) and were receiving RAS blockers. Participants were followed up for 35 weeks. Interventions  Participants were randomized to receive a 6.25- to 25-mg dose of carvedilol (n = 498) or 50- to 200-mg dose of metoprolol tartrate (n = 737), each twice daily. Open-label hydrochlorothiazide and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure target. Main Outcome Measures  Difference between groups in mean change from baseline HbA_1c following 5 months of maintenance therapy. Additional prespecified comparisons included change from baseline HbA_1c in individual treatment groups, treatment effect on insulin sensitivity, and microalbuminuria. Results  The 2 groups differed in mean change in HbA_1c from baseline (0.13%; 95% confidence interval [CI], –0.22% to –0.04%; P = .004; modified intention-to-treat analysis). The mean (SD) HbA_1c increased with metoprolol (0.15% [0.04%]; P<.001) but not carvedilol (0.02% [0.04%]; P = .65). Insulin sensitivity improved with carvedilol (–9.1%; P = .004) but not metoprolol (–2.0%; P = .48); the between-group difference was –7.2% (95% CI, –13.8% to –0.2%; P = .004). Blood pressure was similar between groups. Progression to microalbuminuria was less frequent with carvedilol than with metoprolol (6.4% vs 10.3%; odds ratio, 0.60; 95% CI, 0.36-0.97; P = .04). Conclusions  Both -blockers were well tolerated; use of carvedilol in the presence of RAS blockade did not affect glycemic control and improved some components of the metabolic syndrome relative to metoprolol in participants with DM and hypertension. The effects of the 2 -blockers on clinical outcomes need to be compared in long-term clinical trials.      

Long-term beta-carotene supplementation and risk of type 2 diabetes mellitus: a randomized controlled trial.

CONTEXT: Recent data suggest a protective role of carotenoids in the development of type 2 diabetes mellitus (DM), possibly via an antioxidant effect, but no randomized trial has directly assessed the efficacy of beta-carotene to prevent DM. OBJECTIVE: To determine whether long-term beta-carotene supplementation reduces the risk of developing type 2 DM. DESIGN, SETTING, AND PARTICIPANTS: A total of 22, 071 healthy US male physicians aged 40 to 84 years in a randomized, double- blind, placebo-controlled trial, from 1982 to 1995. More than 99% of the participants had complete follow-up (median duration, 12 years). INTERVENTION: Subjects were randomly assigned to receive beta-carotene (50 mg on alternate days) or placebo. MAIN OUTCOME MEASURE: Incidence of type 2 DM. RESULTS: A total of 10, 756 subjects were assigned to beta-carotene and 10, 712 to placebo. Incidence of type 2 DM did not differ between groups: 396 men in the beta-carotene group and 402 men in the placebo group developed type 2 DM (relative risk, 0.98; 95% confidence interval, 0.85-1.12). The lack of association between beta-carotene supplementation and incidence of type 2 DM persisted despite multivariate adjustment. There was no evidence of benefit when the period of risk was subdivided into years of follow-up or increasing duration of treatment. CONCLUSION: In this trial of apparently healthy men, supplementation with beta-carotene for an average of 12 years had no effect on the risk of subsequent type 2 DM.     

Effect of short term intensive multitherapy on carotid intima- media thickness in patients with newly diagnosed type 2 diabetes mellitus

Background Controlling plasma glucose levels, blood pressure and lipid levels is proven to reduce the risk of vascular complications in patients with type 2 diabetes mellitus. This has prompted intensive multitherapy targeted at several macrovascular risk factors. Carotid intima-media thickness （cIMT） is a reliable measure of early atherosclerosis. We sought to determine whether a 6-month intensive mutiltherapy program resulted in better goal attainment than usual care and its effect on the development of cIMT among patients with newly diagnosed type 2 diabetes mellitus.
Methods The study randomly assigned 220 patients with newly diagnosed type 2 diabetes mellitus to intensive or traditional therapy groups. The clinical parameters, such as fasting plasma glucose, total cholesterol, triglyceride, blood pressure, body weight and insulin were assessed at the baseline and after the 6-month therapy, cIMT of the patients was also obtained.
Results The average levels of fasting plasma glucose, hemoglobin Alc, total cholesterol （TC） and low-density lipoprotein cholesterol （LDL-C） in the intensive group were significantly lower than those in the control group at the end of 6-month treatment. By 6 months, a higher proportion of patients in the intensive therapy group than in the control group attained goals for fasting plasma glucose （FPG）, TC, LDL-C and hemoglobin Alc. With intensive multherapy the level of carotid intima-media thickness in the intensive therapy group was lower than that in the control group （（0.88±0.26） mm vs （0.96±0.22） mm, P 〈0.01）.
Conclusions The evidence from this clinical trial demonstrates that intensive glucose, lipid and blood pressure control in patients with newly diagnosed type 2 diabetes is associated with diabetic macrovascular benefits. Intensive multitherapy allows more patients to achieve aims of control and may reduce macrovascular complications and delay disease progression.     

Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial

Context  Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes. Objective  To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control. Design, Setting, and Participants  Unblinded randomized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia, with general community recruitment to established treatment programs. Participants were 60 obese patients (BMI >30 and <40) with recently diagnosed (<2 years) type 2 diabetes. Interventions  Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric banding with conventional diabetes care. Main Outcome Measures  Remission of type 2 diabetes (fasting glucose level <126 mg/dL [7.0 mmol/L] and glycated hemoglobin [HbA_1c] value <6.2% while taking no glycemic therapy). Secondary measures included weight and components of the metabolic syndrome. Analysis was by intention-to-treat. Results  Of the 60 patients enrolled, 55 (92%) completed the 2-year follow-up. Remission of type 2 diabetes was achieved by 22 (73%) in the surgical group and 4 (13%) in the conventional-therapy group. Relative risk of remission for the surgical group was 5.5 (95% confidence interval, 2.2-14.0). Surgical and conventional-therapy groups lost a mean (SD) of 20.7% (8.6%) and 1.7% (5.2%) of weight, respectively, at 2 years (P < .001). Remission of type 2 diabetes was related to weight loss (R² = 0.46, P < .001) and lower baseline HbA_1c levels (combined R² = 0.52, P < .001). There were no serious complications in either group. Conclusions  Participants randomized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss. These results need to be confirmed in a larger, more diverse population and have long-term efficacy assessed. Trial Registration  actr.org Identifier: ACTRN012605000159651      

血脂康治疗2型糖尿病合并高脂血症临床随机对照试验的Meta分析*

目的：运用Meta分析评价血脂康对2型糖尿病合并高脂血症患者的临床疗效。方法：检索Pubmed、Web of Knowledge、The Cochrane library、中国学术期刊数据库(China National Knowledge Infrastructure, CNKI)、维普中文科技期刊数据库(Chinese Scientifc Journal Database, VIP)、万方数据库中的文献,检索年限为2000年1月—2019年9月,筛选所有血脂康治疗2型糖尿病合并高脂血症临床随机对照试验(randomized controlled trial, RCT)。应用改良Jadad评分法进行质量评价,应用RevMan 5.2软件进行Meta分析。结果：共纳入13个RCT,均为低质量研究。血脂康试验组总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、空腹血糖,餐后2 h血糖及糖化血红蛋白等指标的改善均较常规治疗对照组明显(P<0.05)。结论：在常规降糖治疗基础上加用血脂康对于改善2型糖尿病合并高脂血症患者的血脂及血糖均优于常规降糖治疗。     

Red ginseng for type 2 diabetes mellitus: A systematic review of randomized controlled trials

Objective:Red ginseng（RG,Panax ginseng C.A.Meyer） is one of the widely used herbs for treating type 2 diabetes mellitus（DM）.However,no systematic review of the effectiveness of RG for type 2 DM is available.This systematic review aimed to evaluate the current evidence for the effectiveness of RG in patients with type 2 DM.Methods:Electronic searches of 14 electronic databases were conducted without language restrictions.All randomized clinical trials（RCTs） with RG as a treatment for type 2 DM were considered for inclusion.Their methodological quality was assessed using the Cochrane criteria.Results:Four RCTs met our inclusion criteria.Their methodological quality was variable.Three of the RCTs compared the effectiveness of RG with placebo.The meta-analysis of these data failed to favor RG over placebo for fasting plasma glucose （FPG）[n=76,weighted mean difference（WMD）:-0.43 mmol/L;95%confidence interval（CI）:-1.16 to 0.30, P=0.25]and fasting plasma insulin（FPI）（n=76,WMD:-8.43 pmol/L;95%CI:-19.54 to 2.68,P=0.14） for 12 weeks of treatment.One RCT compared the effects of RG with no treatment.The results did not suggest favorable effects of RG on FPG,hemoglobin A_1c(HbA_1c) or 2-h blood glucose after a meal（PP2h）.Conclusions: The evidence for the effectiveness of RG in controlling glucose in type 2 DM is not convincing.Few included studies with various treatment regimens prohibit definitive conclusions.More rigorous studies are needed to clarify the effects of RG on this condition.     

2型糖尿病强化治疗患者低血糖发生情况的调查分析

目的 探讨2型糖尿病患者低血糖的发生的时间、临床症状及相关的危险因素,为临床糖尿病护理过程中预防低血糖的发生提供参考.方法 回顾性分析2010年10月～2012年10月于解放军总医院内分泌科住院的2型糖尿病患者640例资料.按住院期间有无发生低血糖分为两组,A组为发生低血糖,B组为未发生低血糖.观察低血糖发生时间、临床症状,比较两组年龄、住院时间、病程及体重指数（BMI）.结果 ①2型糖尿病患者共640例,其中发生低血糖的患者190例,男97例,女93例.②发生低血糖最多的时间为午餐前、早餐前和凌晨.③低血糖的主要症状为心慌、手抖、出汗.④A组BMI小于B组,住院时间以及糖尿病病程均大于B组,差异有统计学意义（P＜0.05）.结论 糖尿病病程较长、肾功能不全、老年、BMI过低的2型糖尿病患者会增加低血糖发生风险,护理人员应积极管理有高危因素的人群,有效地预防低血糖的发生.     

胰岛素泵强化治疗2型糖尿病患者的观察

目的:观察胰岛素泵强化治疗2型糖尿病患者的疗效。方法:将135例糖尿病患者随机分为胰岛素泵组和胰岛素法组。胰岛素泵组患者68例,给予胰岛素泵皮下注射法(CSII)强化治疗;胰岛素法组患者67例,应用多次皮下注射胰岛素法(MSII)强化治疗。两组患者均同时给予饮食、运动和心理等多方面的综合护理。观察两组患者治疗前后的效果。结果:两组患者经过14 d的强化治疗,胰岛素泵组与胰岛素法组患者相比能更好地控制血糖(P<0.05)。结论:在综合护理的基础上,胰岛素泵强化治疗2型糖尿病效果优于多次皮下注射胰岛素法(MSII)强化治疗。     

Acupuncture for patients with migraine: a randomized controlled trial

Context  Acupuncture is widely used to prevent migraine attacks, but the available evidence of its benefit is scarce. Objective  To investigate the effectiveness of acupuncture compared with sham acupuncture and with no acupuncture in patients with migraine. Design, Setting, and Patients  Three-group, randomized, controlled trial (April 2002-January 2003) involving 302 patients (88% women), mean (SD) age of 43 (11) years, with migraine headaches, based on International Headache Society criteria. Patients were treated at 18 outpatient centers in Germany. Interventions  Acupuncture, sham acupuncture, or waiting list control. Acupuncture and sham acupuncture were administered by specialized physicians and consisted of 12 sessions per patient over 8 weeks. Patients completed headache diaries from 4 weeks before to 12 weeks after randomization and from week 21 to 24 after randomization. Main Outcome Measures  Difference in headache days of moderate or severe intensity between the 4 weeks before and weeks 9 to 12 after randomization. Results  Between baseline and weeks 9 to 12, the mean (SD) number of days with headache of moderate or severe intensity decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline of 5.0 (2.4) days in the sham acupuncture group, and by 0.8 (2.0) days from a baseline if 5.4 (3.0) days in the waiting list group. No difference was detected between the acupuncture and the sham acupuncture groups (0.0 days, 95% confidence interval, –0.7 to 0.7 days; P = .96) while there was a difference between the acupuncture group compared with the waiting list group (1.4 days; 95% confidence interval; 0.8-2.1 days; P<.001). The proportion of responders (reduction in headache days by at least 50%) was 51% in the acupuncture group, 53% in the sham acupuncture group, and 15% in the waiting list group. Conclusion  Acupuncture was no more effective than sham acupuncture in reducing migraine headaches although both interventions were more effective than a waiting list control.      

阿仑膦酸钠联合胰岛素强化治疗2型糖尿病性骨质疏松症的临床研究

目的 观察阿仑膦酸钠联合胰岛素强化治疗对2型糖尿病性骨质疏松症的影响.方法 将入选病例随机分为阿仑膦酸钠联合胰岛素强化治疗组、阿仑膦酸钠联合磺脲类药物组及对照组,于治疗前后检测同部位骨密度,观察比较各组骨密度值变化的差别.结果 阿仑膦酸钠联合胰岛素强化治疗组骨密度较磺脲类药物组及对照组明显升高,二者比较有显著性差异(P＜0.05).结论 阿仑膦酸钠联合胰岛素强化治疗可明显改善2型糖尿病患者骨密度.     

2型糖尿病患者不同胰岛素治疗方案的对比观察

目的 探讨2型糖尿病患者理想的胰岛素治疗方案.方法 103例2型糖尿病患者,给予不同胰岛素治疗.治疗方案:用人胰岛素类似物预混制剂优泌乐25多次皮下注射(A组)32例,人胰岛素类似物预混制剂诺和锐30多次皮下注射(B组)47例,甘精胰岛素每天注射1次(C组)24例,比较3种方法治疗前后平均空腹血糖、早餐后2 h血糖、平均胰岛素用量、日均胰岛素花费及低血糖发生率的情况.结果 3组均可使血糖显著下降(P<0.01),3组每日胰岛素用量差别有统计学意义(F=46.904,P<0.05),3组每日胰岛素花费差别有统计学意义(F=3.992,P<0.05),3组低血糖发生率差别有统计学意义(χ2=6.766,P<0.05).结论 采用甘精胰岛素治疗方法日均花费最高,胰岛素用量最少,低血糖发生率最低.     

二甲双胍单药疗效不佳的2型糖尿病患者联合达格列净或格列美脲治疗的效果及安全性观察

目的探讨二甲双胍单药疗效不佳的2型糖尿病患者联合达格列净或格列美脲的效果及安全性,为临床治疗提供依据。方法选取2017年1月至2019年6月期间暨南大学附属顺德医院收治的90例经二甲双胍单药治疗疗效不佳的2型糖尿病患者作为研究对象,采用随机数表法将患者分为观察组和对照组各45例。对照组在二甲双胍治疗的基础上采用格列美脲治疗,观察组在二甲双胍治疗的基础上采用达格列净治疗,两组患者的治疗时间均为24周。比较两组患者治疗前、治疗后的血糖[糖化血红蛋白(HbAlc)、空腹血糖(FBG)、餐后2 h血糖(2 hPG)]、血脂[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、平均血糖波动(MAGE)、C反应蛋白(CRP)和体质量(BMI)变化,并记录不良事件发生情况。结果治疗后,两组患者的血糖Hb Alc、FBG、2 h PG水平明显低于治疗前,差异均有统计学意义(P<0.05),但两组间比较差异无统计学意义(P>0.05);治疗后,两组患者的血脂TC、TG、LDL-C及BMI指数均明显下降,且观察组[(2.88±0.42) m...     

Intensive glycemic control and macrovascular events in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

Background There is no agreement as to whether intensive glucose control in type 2 diabetes can reduce the incidence of macrovascular events in these patients. We performed a meta-analysis comparing intensive glucose control or conventional glucose control in randomized controlled trials.Methods Databases including MEDLINE, EMBASE, and Cochrane controlled trials register, the Cochrane Library, and Science Citation Index were searched to find relevant trials. Outcome measures were the incidence of major macrovascular events.Results Six trials involving 28 065 patients were included. Analysis suggested that there was an obviously decreased incidence of major macrovascular events in patients having intensive glucose treatment vs. Controls （RR 0.92; 95% Cl 0.87, 0.98; P=0.005）. However, intensive glycemia control strategies in type 2 diabetes showed no significant impact on the incidence of death from any cause compared with conventional glycemia control strategies, intensive 14.7%, controls 12.0% （RR 0.95; 95% Cl 0.80, 1.12; P=0.55）, as well as on the incidence of cardiovascular death, intensive 3.7%,controls 3.6% （RR 1.10, 95% Cl 0.79, 1.53; P=0.57）.Conclusions Control of glycemia to normal （or near normal levels） in type 2 diabetes appears to be effective in reducing the incidence of major macrovascular events, but there were no significant differences of either the mortality from any cause or from cardiovascular death between the two glycemia-control strategies.     

替米沙坦治疗2型糖尿病合并高血压患者效果分析

目的 评价替米沙坦治疗2型糖尿病伴高血压患者的疗效.方法 68例2型糖尿病合并高血压患者随机分为替米沙坦组和对照组（氨氯地平）,分析两组的疗效.结果 替米沙坦组和对照组患者治疗后收缩压和舒张压均低于治疗前,差异有统计学意义（P〈0.05）.替米沙坦组空腹血糖、空腹胰岛素和胰岛素抵抗指数较其试验前及与对照组治疗后差异有统计学意义（P〈0.05）,而对照组患者治疗前后差异无统计学意义（P〉0.05）.结论 替米沙坦治疗2型糖尿病合并高血压患者具有较好的临床效果.     

Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial

Context  No antidiabetic regimen has demonstrated the ability to reduce progression of coronary atherosclerosis. Commonly used oral glucose-lowering agents include sulfonylureas, which are insulin secretagogues, and thiazolidinediones, which are insulin sensitizers. Objective  To compare the effects of an insulin sensitizer, pioglitazone, with an insulin secretagogue, glimepiride, on the progression of coronary atherosclerosis in patients with type 2 diabetes. Design, Setting, and Participants  Double-blind, randomized, multicenter trial at 97 academic and community hospitals in North and South America (enrollment August 2003-March 2006) in 543 patients with coronary disease and type 2 diabetes. Interventions  A total of 543 patients underwent coronary intravascular ultrasonography and were randomized to receive glimepiride, 1 to 4 mg, or pioglitazone, 15 to 45 mg, for 18 months with titration to maximum dosage, if tolerated. Atherosclerosis progression was measured by repeat intravascular ultrasonography examination in 360 patients at study completion. Main Outcome Measure  Change in percent atheroma volume (PAV) from baseline to study completion. Results  Least squares mean PAV increased 0.73% (95% CI, 0.33% to 1.12%) with glimepiride and decreased 0.16% (95% CI, –0.57% to 0.25%) with pioglitazone(P = .002). An alternative analysis imputing values for noncompleters based on baseline characteristics showed an increase in PAV of 0.64% (95% CI, 0.23% to 1.05%) for glimepiride and a decrease of 0.06% (–0.47% to 0.35%) for pioglitazone (between-group P = .02). Mean (SD) baseline HbA_1c levels were 7.4% (1.0%) in both groups and declined during treatment an average 0.55% (95% CI, –0.68% to –0.42%) with pioglitazone and 0.36% (95% CI, –0.48% to –0.24%) with glimepiride (between-group P = .03). In the pioglitazone group, compared with glimepiride, high-density lipoprotein levels increased 5.7 mg/dL (95% CI, 4.4 to 7.0 mg/dL; 16.0%) vs 0.9 mg/dL (95% CI, –0.3 to 2.1 mg/dL; 4.1%), and median triglyceride levels decreased 16.3 mg/dL (95% CI, –27.7 to –11.0 mg/dL; 15.3%) vs an increase of 3.3 mg/dL (95% CI, –10.7 to 11.7 mg/dL; 0.6%) (P < .001 for both comparisons). Median fasting insulin levels decreased with pioglitazone and increased with glimepiride (P < .001). Hypoglycemia was more common in the glimepiride group and edema, fractures, and decreased hemoglobin levels occurred more frequently in the pioglitazone group. Conclusion  In patients with type 2 diabetes and coronary artery disease, treatment with pioglitazone resulted in a significantly lower rate of progression of coronary atherosclerosis compared with glimepiride. Trial Registration  clinicaltrials.gov Identifier: NCT00225277      

Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial

Context  Anemia is common in critically ill patients and results in a large number of red blood cell (RBC) transfusions. Recent data have raised the concern that RBC transfusions may be associated with worse clinical outcomes in some patients. Objective  To assess the efficacy in critically ill patients of a weekly dosing schedule of recombinant human erythropoietin (rHuEPO) to decrease the occurrence of RBC transfusion. Design  A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted between December 1998 and June 2001. Setting  A medical, surgical, or a medical/surgical intensive care unit (ICU) in each of 65 participating institutions in the United States. Patients  A total of 1302 patients who had been in the ICU for 2 days and were expected to be in the ICU at least 2 more days and who met eligibility criteria were enrolled in the study; 650 patients were randomized to rHuEPO and 652 to placebo. Intervention  Study drug (40 000 units of rHuEPO) or placebo was administered by subcutaneous injection on ICU day 3 and continued weekly for patients who remained in the hospital, for a total of 3 doses. Patients in the ICU on study day 21 received a fourth dose. Main Outcome Measures  The primary efficacy end point was transfusion independence, assessed by comparing the percentage of patients in each treatment group who received any RBC transfusion between study days 1 and 28. Secondary efficacy end points identified prospectively included cumulative RBC units transfused per patient through study day 28; cumulative mortality through study day 28; change in hemoglobin from baseline; and time to first transfusion or death. Results  Patients receiving rHuEPO were less likely to undergo transfusion (60.4% placebo vs 50.5% rHuEPO; P<.001; odds ratio, 0.67; 95% confidence interval [CI], 0.54-0.83). There was a 19% reduction in the total units of RBCs transfused in the rHuEPO group (1963 units for placebo vs 1590 units for rHuEPO) and reduction in RBC units transfused per day alive (ratio of transfusion rates, 0.81; 95% CI, 0.79-0.83; P = .04). Increase in hemoglobin from baseline to study end was greater in the rHuEPO group (mean [SD], 1.32 [2] g/dL vs 0.94 [1.9] g/dL; P<.001). Mortality (14% for rHuEPO and 15% for placebo) and adverse clinical events were not significantly different. Conclusions  In critically ill patients, weekly administration of 40 000 units of rHuEPO reduces allogeneic RBC transfusion and increases hemoglobin. Further study is needed to determine whether this reduction in RBC transfusion results in improved clinical outcomes.