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Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review.

ABSTRACT: A meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane Library and www. clinicaltrials. gov (up to February 15(th), 2015) were searched. Randomized controlled trials comparing dulaglutide to other drugs for T2DM were collected. Twelve RCTs were included, and the overall bias was low. As the monotherapy, compared with control (placebo, metformin and liraglutide), dulaglutide resulted in a significant reduction in HbA1c (WMD, -0.68%; 95% CI, -0.95 to -0.40), FPG (WMD, -0.90 mmol/L; 95% CI, -1.28 to -0.52), a similar risk of hypoglycemia (7.8% vs. 10.6%), less body weight loss (WMD, 0.51 kg; 95% CI, 0.27 to 0.75). As an add-on intervention with oral antihyperglycemic medication (OAM) and insulin, compared with control (placebo, sitagliptin, exenatide, liraglutide and glargine), dulaglutide lowered HbA1c (WMD, -0.51%; 95% CI, -0.68 to -0.35) and body weight significantly (WMD, -1.30 kg, 95% CI, -1.85 to -1.02) notably, and elicited a similar reduction in FPG (WMD, -0.19 mmol/L; 95% CI, -1.20 to 0.82), an similar incidence of hypoglycemia (24.5% vs. 24.5%). This meta-analysis revealed the use of dulaglutide as a monotherapy or an add-on to OAM and lispro appeared to be effective and safe for adults with T2DM.

SUBMITTER: Zhang L

PROVIDER: S-EPMC4705511 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review.

Zhang Lin L Zhang Mei M Zhang Yuwei Y Tong Nanwei N

Scientific reports 20160108

A meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane Library and www. clinicaltrials. gov (up to February 15(th), 2015) were searched. Randomized controlled trials comparing dulaglutide to other drugs for T2DM were collected. Twelve RCTs were included, and the overall bias was low. As the monotherapy, compared with control (placebo, metformin and liraglutide), dulaglutide resulted in a ...[more]

PMID: 26742577

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Project description:OBJECTIVE:To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D). METHODS:A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs). Dichotomous data were presented as Mantel-Haenzel risk ratios (RRs). RESULTS:Thirty-nine references of 30 RCTs involving 29,938 patients were analyzed. Compared with placebo, saxagliptin significantly reduced glycated hemoglobin (HbA1c, WMD -0.52%, 95% CI -0.60 to -0.44) and fasting plasma glucose (WMD -13.78 mg/dL, 95% CI -15.31 to -12.25), and increased the proportion of patients achieving HbA1c <7% (RR 1.64, 95% CI 1.53 to 1.75). When combined with submaximal-dose metformin, saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose (RR 2.38, 95% CI 1.17 to 4.83) and uptitrated metformin (RR 1.30, 95% CI 1.04 to 1.63). Saxagliptin was similar to other DPP-4 inhibitors but inferior to liraglutide and dapagliflozin on glycemic control. Saxagliptin significantly decreased the incidences of overall adverse events compared with acarbose (RR 0.71, 95% CI 0.57 to 0.89) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71) when added to metformin. Weight gain and hypoglycemia with saxagliptin was slightly but significantly higher than placebo and lower than sulfonylureas. Saxagliptin did not increase the risk of arthralgia, heart failure, pancreatitis and other adverse events. CONCLUSIONS:Generally, saxagliptin has similar efficacy compared with most oral antidiabetic drugs and may be more effective than acarbose, while having a better safety profile than both acarbose and sulfonylureas.

Project description:BackgroundThe last international consensus on the management of type 2 diabetes (T2D) recommends SGLT-2 inhibitors or GLP-1 agonists for patients with clinical cardiovascular (CV) disease; metformin remains the first-line glucose lowering medication. Last studies suggested beneficial effects of SGLT-2 inhibitors or GLP-1 agonists compared to DPP-4 inhibitors, in secondary CV prevention. Recently, a potential benefit of SGLT-2 inhibitors in primary CV prevention also has been suggested. However, no comparison of all the new and the old hypoglycemic drugs is available on CV outcomes. We aimed to compare the effects of old and new hypoglycemic drugs in T2D, on major adverse cardiovascular events (MACE) and mortality.Methods and findingsWe conducted a systematic review and network meta-analysis of clinical trials. Randomized trials, blinded or not, assessing contemporary hypoglycemic drugs on mortality or MACE in patients with T2D, were searched for in Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. References screening and data extraction were done by multiple observers. Each drug was analyzed according to its therapeutic class. A random Bayesian network meta-analysis model was used. The primary outcomes were overall mortality, cardiovascular mortality, and MACE. Severe adverse events and severe hypoglycemia were also recorded. 175,966 patients in 34 trials from 1970 to 2018 were included. No trials evaluating glinides or alpha glucosidase inhibitors were found. 17 trials included a majority of patients with previous cardiovascular history, 16 trials a majority of patients without. Compared to control, SGLT-2 inhibitors were associated with a decreased risk of overall mortality (OR = 0.84 [95% CrI: 0.74; 0.95]), SGLT-2 inhibitors and GLP-1 agonists with a decreased risk of MACE (OR = 0.89 [95% CrI: 0.81; 0.98] and OR = 0.88 [95% CrI: 0.81; 0.95], respectively). Compared to DPP-4 inhibitors, SGLT-2 inhibitors were associated with a decreased risk of overall mortality (OR = 0.82 [95% CrI: 0.69; 0.98]), GLP-1 agonists with a decreased risk of MACE (OR = 0.88 [95% CrI: 0.79; 0.99]). Insulin was also associated with an increased risk of MACE compared to GLP-1 agonists (OR = 1.19 [95% CrI: 1.01; 1.42]). Insulin and sulfonylureas were associated with an increased risk of severe hypoglycemia. In the trials including a majority of patients without previous CV history, the comparisons of SGLT-2 inhibitors, metformin and control did not showed significant differences on primary outcomes. We limited our analysis at the therapeutic class level.ConclusionsSGLT-2 inhibitors and GLP-1 agonists have the most beneficial effects, especially in T2D patients with previous CV diseases. Direct comparisons of SGLT-2 inhibitors, GLP-1 agonists and metformin are needed, notably in primary CV prevention.Trial registrationPROSPERO CRD42016043823.

Project description:Objective: To evaluate the efficacy and safety of ertugliflozin in patients with type 2 diabetes. Methods: MEDLINE, EMBASE, and Cochrane Library were searched (July 31, 2021) for phase II/III randomized clinical trials, which reported the efficacy and safety of ertugliflozin. Continuous variables were calculated as weighted mean difference (WMD) and associated 95% confidence intervals (CIs); dichotomous data were expressed as risk ratios (RRs) with 95% CIs. Results: Nine randomized clinical trials including 5638 type 2 diabetes patients were included. For efficacy, ertugliflozin significantly reduced HbA1c (%) (WMD -0.452%; 95% CI -0.774 to -0.129), fasting plasma glucose (FPG) (WMD -0.870 mmol/L; 95% CI -1.418 to -0.322), body weight (WMD -1.774 kg; 95% CI -2.601 to -0.946), and blood pressure levels (systolic blood pressure: WMD -2.572 mmHg; 95% CI -3.573 to -1.571 and diastolic blood pressure: WMD -1.152 mmHg; 95% CI -2.002 to -0.303) compared with placebo and other hypoglycaemic agents. Compared with placebo, ertugliflozin was superior in reducing HbA1c (%) (WMD -0.641%) and FPG (WMD -1.249 mmol/L). And compared with active agents, ertugliflozin also could decrease HbA1c by 0.215% and FPG by 0.266 mmol/L. The interactive effect between different controls was significant (P interaction of 0.039). For safety, similar to other sodium-glucose cotransporter type-2 inhibitors, ertugliflozin mainly increased the risk of genital mycotic infection (RR: 4.004; 95% CI 2.504-6.402). There was no significant difference in the incidence of any adverse events (AEs), AEs related to study drug, serious AEs, deaths, and discontinuations due to AEs. Results were consistent with the most primary outcomes in subgroups analysis and sensitivity analysis. Conclusion: Ertugliflozin was relatively effective and tolerated in patients with type 2 diabetes compared with placebo or other hypoglycaemic agents, except for a high risk of genital mycotic infection. Systematic Review Registration: (ClinicalTrials.gov), identifier (CRD42020206356).

Project description:IntroductionThe aim of this study was to evaluate the efficacy and safety of initial combination therapy compared with monotherapy in drug-naïve type 2 diabetes patients.MethodsMEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials of initial combination therapy with hypoglycemic agents compared with monotherapy. Those which satisfied the search criteria were included in the meta-analysis. Weighted mean difference and relative risks were calculated.ResultsA total of 36 studies were included in the meta-analysis. Compared with metformin monotherapy, initial combination therapy with metformin plus another anti-diabetes drug exhibited significant reductions in glycated hemoglobin (HbA1c) (p < 0.001). Most of the combination therapies had a similar risk of hypoglycemia (p > 0.05), with the exception of combinations of sulfonylurea/glinide and metformin or combinations of thiazolidinedione and metformin. Compared with dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy, initial combination therapy with DPP-4 inhibitor plus another anti-diabetes drug showed a significant decrease in HbA1c (p < 0.001) and a similar risk of hypoglycemia (p > 0.05). Compared with monotherapy with other anti-diabetes drugs, initial combination therapies also resulted in significant HbA1c reductions, a similar risk of hypoglycemia and similar risks of other adverse events.ConclusionCompared with monotherapy, all initial combination therapies resulted in significant HbA1c reductions. Compared with metformin monotherapy, initial combination therapies with DPP-4 inhibitors plus metformin, sodium/glucose cotransporter 2 inhibitors and metformin, respectively, were associated with similar risks of hypoglycemia, but initial combination therapies with sulfonylurea plus metformin, thiazolidinedione and metformin, respectively, were associated with higher risks of hypoglycemia.FundingAstraZeneca Ltd. (China).Trial registrationRegistration number CRD42017060717 in PROSPERO.

Project description:BackgroundMomordica charantia Linnaeus (Cucurbitaceae) has been used traditionally as a nutritious food and as a herbal medicine for type 2 diabetes mellitus. However, human studies that investigated its glycemic control have generated inconsistent findings. Therefore, this systematic review and meta-analysis is aimed at evaluating the safety and efficacy of M. charantia L. preparations in human studies that have investigated its role in glycemic control.MethodsThis protocol has been prepared according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The review will include randomized clinical trials and non-randomized clinical trials. The included studies will have assessed glycemic control of M. charantia preparations with placebo or standard oral anti-hyperglycemic agents in adult pre-diabetes and/or type 2 diabetes mellitus patients and have at least 4 weeks of follow-up. The primary outcomes of review are fasting blood glucose levels, glycosylated hemoglobin A1c, and post-prandial blood glucose level. Electronic database search for published literatures will be conducted without language restriction in EMBASE, MEDLINE/PubMed, the Cochrane Library, SCOPUS, Web of Sciences, and CINAHL databases. Search for gray literatures and references of the retrieved full-text articles will be conducted in Google, Google Scholar, OpenGrey, ProQuest dissertations & Theses, British Library EThos, and university digital library systems. Two independent reviewers will later evaluate full texts, extract data, and assess risk of bias of eligible articles. Publication biases will be assessed by testing asymmetry of funnel plot using Egger's or Begg's tests while heterogeneity will be assessed using Cochran Q test, P value, and I2. Revman software version 5.3 will be used for meta-analysis including subgroup and sensitivity analysis.DiscussionThis systematic review and meta-analysis will investigate both safety and efficacy of M. charantia preparations in type 2 diabetes mellitus. The review results will be published in a peer-reviewed journal. The results will bring better understanding of clinical outcomes in treatment of type 2 diabetes mellitus patients and highlight gaps for future research.Systematic review registrationPROSPERO CRD42018083653 .

Project description:INTRODUCTION:To evaluate the efficacy and safety of dulaglutide 0.75 and 1.5 mg in patients with type 2 diabetes mellitus (T2DM) by baseline glycated hemoglobin (HbA1c)?<?8.5% or???8.5% after 26 weeks of treatment. METHODS:Assessment of the Weekly AdministRation of dulaglutide in Diabetes (AWARD) China 1 (CHN1) study (NCT01644500, n?=?556) included patients on dulaglutide vs. glimepiride who were treatment naïve or on monotherapy but discontinued therapy. AWARD-CHN2 (NCT01648582, n?=?591) patients were on dulaglutide vs. insulin glargine and continued on metformin and/or sulfonylurea. Mean daily dose of glimepiride and insulin glargine was 2.51 mg and 21.0 IU, respectively. Post hoc analyses were conducted based on mixed-model repeated measures using a modified intent-to-treat analysis set with only the Chinese population. Change from baseline in HbA1c and body weight was analyzed by individual study. RESULTS:In the two studies, 70.1% of patients in AWARD-CHN1 and 59.7% in AWARD-CHN2 had baseline HbA1c?<?8.5% (mean HbA1c 7.4% and 7.6%, respectively) and 29.9% in AWARD-CHN1 and 40.3% in AWARD-CHN2 had baseline HbA1c???8.5% (mean HbA1c 9.2% and 9.4%, respectively). In AWARD-CHN1, the HbA1c reductions at 26 weeks with baseline HbA1c?<?8.5% and???8.5%, respectively, were dulaglutide 1.5 mg: -?1.1% and -?2.2%; dulaglutide 0.75 mg: -?0.9% and -?2.0%; glimepiride: -?0.7% and -?1.4%. In AWARD-CHN2, the HbA1c reductions at 26 weeks with baseline HbA1c?<?8.5% and???8.5%, respectively, were dulaglutide 1.5 mg: -?1.2% and -?2.3%; dulaglutide 0.75 mg: -?1.0% and -?1.7%; and insulin glargine: -?0.6% and -?1.7%. Irrespective of baseline HbA1c, body weight decreased with both dulaglutide doses and increased with either glimepiride or insulin glargine at 26 weeks. Dulaglutide demonstrated low incidence of hypoglycemia in both doses in the two trials. Hypoglycemia incidence was generally lower in patients with baseline HbA1c???8.5%. CONCLUSIONS:Dulaglutide demonstrated significantly greater HbA1c reduction with weight loss and lower risk of hypoglycemia compared with active comparators in Chinese patients with T2DM irrespective of baseline HbA1c, with much greater HbA1c reductions in patients with a higher baseline HbA1c. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT01644500 and NCT01648582.

Project description:PURPOSE:In East Asian patients, type 2 diabetes mellitus (T2DM) is characterized primarily by β-cell dysfunction, with lower insulin secretion than in Caucasian individuals. Therefore, bolus insulin and premixed insulin containing a bolus insulin component are important therapeutic tools in Japan, in addition to basal insulin. This subgroup analysis is stratified by insulin regimen and uses data from a phase 4, randomized, placebo-controlled, double-blind and subsequent open-label study in Japan to assess the efficacy and safety of once-weekly dulaglutide combined with various insulin therapies. METHODS:This multicenter study enrolled Japanese patients with T2DM and inadequate glycemic control [glycated hemoglobin A1c (HbA1c) ≥ 7.5% to ≤ 10.5%] on insulin therapy [basal (B), premixed (PM), or basal bolus (BB)] in combination with or without one or two oral antidiabetic agents. Randomized participants received once-weekly dulaglutide 0.75 mg (n = 120) or placebo (n = 39) during a 16-week double-blind treatment period, and dulaglutide during a 36-week open-label extension. In this subgroup analysis, efficacy measures were changes from baseline in HbA1c, 7-point self-monitored blood glucose profiles, and body weight. Safety measures were incidence of adverse events and hypoglycemia during the first 16 weeks. RESULTS:At week 16, least squares mean differences (95% CI) regarding changes from baseline in HbA1c for each insulin regimen versus placebo were: B: - 1.62% (- 1.96, - 1.28), PM: - 1.78% (- 2.25, - 1.30), and BB: - 1.15% (- 1.54, - 0.77); p < 0.001 dulaglutide vs. placebo for each subgroup. No significant differences in body weight changes were observed between dulaglutide and placebo for any insulin regimen. Gastrointestinal symptoms were the most commonly observed adverse events in dulaglutide-treated patients. Hypoglycemia incidence rates were: B: dulaglutide 38.5% vs. placebo 23.5%; PM: dulaglutide 38.5% vs. placebo 44.4%; BB: dulaglutide 50.0% vs. placebo 30.8%. CONCLUSIONS:Overall, dulaglutide was generally well tolerated and improved glycemic control significantly versus placebo, regardless of insulin regimen. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02750410.

Dataset Information

Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review.

Publications

Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review.

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