Efficacy and safety of thiazolidinediones in diabetes patients with renal impairment: a systematic review and meta-analysis.
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SUBMITTER: Wang W
PROVIDER: S-EPMC5431943 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo perform a systematic review and meta-analysis regarding the efficacy and safety of dipeptidyl peptidase-4 (DDP-4) inhibitors ("gliptins") for the treatment of type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment.MethodsAll available randomized-controlled trials (RCTs) that assessed the efficacy and safety of DDP-4 inhibitors compared with placebo, no treatment, or active drugs were identified using PubMed, EMBASE, Cochrane CENTRAL, conference abstracts, clinical trials.gov, pharmaceutical company websites, the FDA, and the EMA (up to June 2014). Two independent reviewers extracted the data, and a random-effects model was applied to estimate summary effects.ResultsThirteen reports of ten studies with a total of 1,915 participants were included in the final analysis. Compared with placebo or no treatment, DPP-4 inhibitors reduced HbA1c significantly (-0.52%, 95%CI -0.64 to -0.39) and had no increased risk of hypoglycemia (RR 1.10, 95%CI 0.92 to 1.32) or weight gain. In contrast to glipizide monotherapy, DPP-4 inhibitors showed no difference in HbA1c lowering effect (-0.08%, 95% CI -0.40 to 0.25) but had a lower incidence of hypoglycemia (RR 0.40, 95%CI 0.23 to 0.69). Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events. However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.ConclusionsDPP-4 inhibitors are effective at lowering HbA1c in T2DM patients with moderate to severe renal impairment. DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events. Regarding the low quality of the evidence according to GRADE, additional well-designed randomized trials that focus on the safety and efficacy of DPP-4 inhibitors in various CKD stages are needed urgently.
| S-EPMC4216116 | biostudies-literature
Project description:AimsThis post hoc assessment evaluated the efficacy and safety of once-daily, prandial glucagon-like peptide-1 receptor agonist lixisenatide in patients with type 2 diabetes (T2D) and normal renal function (estimated glomerular filtration rate ≥90 mL/min), or mild (60-89 mL/min) or moderate (30-59 mL/min) renal impairment.MethodsPatients from 9 lixisenatide trials in the GetGoal clinical trial programme were categorized by baseline creatinine clearance: normal renal function (lixisenatide n = 2094, placebo n = 1150); renal impairment (mild: lixisenatide n = 637, placebo n = 414; moderate: lixisenatide n = 122, placebo n = 68). Meta-analyses of placebo-adjusted mean differences between baseline renal categories were performed for efficacy and safety outcomes.ResultsHbA1c, 2-hour postprandial plasma glucose and fasting plasma glucose were comparably reduced in lixisenatide-treated patients with normal renal function, and mild and moderate renal impairment. The most common adverse events (AEs) in all renal function categories were gastrointestinal (GI), predominantly nausea and vomiting. A 14% higher incidence of GI AEs and a 10% higher incidence of nausea and vomiting were seen with mild impairment vs normal function (P = .003 for both), but no significant differences were observed between the mild and moderate impairment categories (P = .99 and P = .57, respectively), or between the moderate impairment and normal categories (P = .16 and P = .65, respectively). Additionally, the incidence of hypoglycaemia was similar in all categories.ConclusionsThis study demonstrates that baseline renal status does not affect efficacy outcomes in lixisenatide- vs placebo-treated patients, and that no lixisenatide dose adjustment is required for patients with T2D with mild or moderate renal impairment.
| S-EPMC5655920 | biostudies-literature
Project description:IntroductionType 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). The recommended dose of the dipeptidyl peptidase-4 inhibitor saxagliptin is 2.5 mg in patients with moderate or severe renal impairment (creatinine clearance ≤50 mL/min). In this post hoc analysis, we assessed the effect of saxagliptin 2.5 and 5 mg/day versus placebo on glycemic measures in patients with T2D and estimated glomerular filtration rate 45-60 mL/min/1.73 m(2).MethodsEfficacy and safety data were pooled from nine 24-week, randomized, placebo-controlled clinical trials.ResultsThe majority (56-61%) of patients were women aged <65 years with glycated hemoglobin (A1C) 8.1-8.2%; half of the patients had a T2D duration ≥5 years. Mean change from baseline in A1C was significantly greater with saxagliptin 2.5 (-0.6%, P = 0.036 vs placebo) and 5 mg/day (-0.9%, P < 0.001 vs placebo) compared with placebo (-0.2%). There were numerically greater reductions in fasting plasma glucose and 2-h postprandial glucose, and a significantly greater proportion of patients achieved A1C <7% with saxagliptin 5 mg/day (44.8%) compared with placebo (20.0%, P = 0.004 vs placebo). The incidence of hypoglycemia was not significantly different across groups (16.2% in the saxagliptin 5-mg/day, 12.2% in the saxagliptin 2.5-mg/day, and 11.3% in the placebo groups).ConclusionThese results suggest that saxagliptin 2.5 and 5 mg/day improve glycemic control and are generally well tolerated in patients with T2D and moderate CKD.Trial registrationClinicalTrials.gov identifier, NCT00121641, NCT00316082, NCT00698932, NCT00918879, NCT00121667, NCT00661362, NCT00313313, NCT00295633, NCT00757588.FundingAstraZeneca, Gaithersburg, MD, USA.
| S-EPMC5014790 | biostudies-literature
Project description:BackgroundCognitive enhancers, including cholinesterase inhibitors and memantine, are used to treat dementia, but their effectiveness for mild cognitive impairment is unclear. We conducted a systematic review to examine the efficacy and safety of cognitive enhancers for mild cognitive impairment.MethodsOur eligibility criteria were studies of the effects of donepezil, rivastigmine, galantamine or memantine on mild cognitive impairment reporting cognition, function, behaviour, global status, and mortality or harms. We identified relevant material by searching electronic databases (e.g., MEDLINE, Embase), the references of included studies, trial registries and conference proceedings, and by contacting experts. Two reviewers independently screened the results of the literature search, abstracted data and appraised risk of bias using the Cochrane risk-of-bias tool.ResultsWe screened 15,554 titles and abstracts and 1384 full-text articles. Eight randomized clinical trials and 3 companion reports met our inclusion criteria. We found no significant effects of cognitive enhancers on cognition (Mini-Mental State Examination: 3 randomized clinical trials [RCTs], mean difference [MD] 0.14, 95% confidence interval [CI] -0.22 to 0.50; Alzheimer's Disease Assessment Scale - cognition subscale: 3 RCTs, standardized MD -0.07, 95% CI-0.16 to 0.01]) or function (Alzheimer's Disease Cooperative Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI -0.26 to 0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea and vomiting than placebo.InterpretationCognitive enhancers did not improve cognition or function among patients with mild cognitive impairment and were associated with a greater risk of gastrointestinal harms. Our findings do not support the use of cognitive enhancers for mild cognitive impairment.
| S-EPMC3826344 | biostudies-literature
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.
| S-EPMC5963790 | biostudies-literature
Project description: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.
| S-EPMC4705511 | biostudies-literature
Project description:BACKGROUND: Peroral endoscopic esophageal myotomy (POEM) represents a less invasive alternative, as compared with conventional laparoscopic Heller myotomy for treating achalasia patients. In the last years, a number of prospective and retrospective experiences with POEM use for achalasia have been published. METHODS: Relevant publications in which patients affected by achalasia underwent POEM treatment were identified by PubMed databases for the period 2010 - 2013. From each study, we extracted the number and type of major complications (defined as those requiring any additional medical or surgical intervention). Data were pooled, using random-effects models. Heterogeneity among studies was assessed by using Cochran's Q and the I (2) statistic. RESULTS: We found 16 studies that provided data on 551 patients. The median surveillance period was 6 months (range: 3-12). The median of mean POEM duration was 156 minutes (range: 42-112). Median myotomy length was 10?cm (range: 6-14). Technical and clinical success were reported in 97% (95% CI: 94-98%) and 93% (407/428; 95% CI: 90-95%). No heterogeneity (I (2?)=?0%) or publication bias was present in both estimates. When limiting the analysis only to adverse events that require medical or surgical interventions, major adverse events occurred in 14% (95% CI: 11-17%); however, only one patient needed post-POEM surgery (0.2%; 95% CI: 0-0.5%). CONCLUSIONS: POEM appeared to be a highly feasible and effective endoscopic treatment for achalasia. Despite POEM being apparently associated with relatively high morbidity, most patients are successfully managed conservatively, so that POEM appears as a very safe procedure; however, POEM should only be performed in centers able to treat POEM complications, such as pneumothorax or pneumoperitoneum.
| S-EPMC4528214 | biostudies-other
Project description:To analyze the efficacy and safety of auricular acupuncture (AA) in patients with cognitive impairment and dementia.Twelve electronic databases were searched for randomized controlled trials evaluating effects of AA in patients with cognitive impairment and/or dementia, from their inception to August 2017. The primary outcome was cognitive function, and secondary outcomes were self-care ability, quality of life, clinical efficacy rate, and incidences of adverse events.Nine studies were included, and five involving 677 participants were analyzed quantitatively. Compared with Western medications (WM), AA had mixed effects on cognitive functions (Mini-Mental State Examination [MMSE], mean difference [MD] 0.73, 95% confidence interval [CI] -0.02 to 1.48; Hierarchic Dementia Scale [HDS], MD 2.21, 95% CI 1.09 to 3.33); there was no significant improvement in the activities of daily living (ADL) score (MD 0.20, 95% CI -3.51 to 3.91) in patients with vascular dementia (VD). Compared to WM, AA combined with WM showed better clinical efficacy rate (risk ratio [RR] 1.42, 95% CI 1.06 to 1.91) in patients with VD; there was no significant improvement in cognitive functions (MMSE, MD 0.97, 95% CI -0.44 to 2.38; Montreal Cognitive Assessment [MoCA], MD 0.22, 95% CI -1.83 to 2.27) in patients with mild cognitive impairment (MCI). Compared to herbal medicine (HM), AA plus HM showed significant improvements in cognitive function (MMSE, MD 1.31, 95% CI 0.13 to 2.49) in patients with MCI and patients with vascular cognitive impairment, no dementia (VCIND) and in ADL score (MD -6.70, 95% CI -8.78 to -4.62) in patients with MCI. No adverse event associated with AA was reported.The evidence reveals mixed efficacy of AA in patients with cognitive impairment and/or dementia. However, the results were inconclusive because of the small number and poor methodological quality of the included studies.
| S-EPMC6000857 | biostudies-other
Project description:BackgroundThe results of a meta-analysis of retrospective studies suggest that the use of metformin in cancer patients may prolong progression-free disease survival and overall survival. However, the studies included in the meta-analysis did not strictly distinguish between patients with or without type 2 diabetes mellitus. Therefore, further studies are needed to assess whether the use of adjuvant chemotherapy with metformin in cancer patients without diabetes improves prognosis.MethodSystematic searches of Embase, Pubmed, and The Cochrane library were performed for the subject terms metformin and neoplasm and for free words. Data related to PFS, OS were extracted according to inclusion exclusion criteria. The data were combined and meta-analysis was performed using Review Manager 5.4 to confirm the efficacy and safety of metformin administration.ResultsThere were 3228 publications retrieved from the database and a total of 13 publications with 955 patients were included in the meta-analysis after screening. All included studies were randomised controlled trials. Metformin combined with adjuvant chemotherapy did not improve progression-free survival (HR=1,95CI 0.79-1.25), overall survival (HR=0.91,95% CI 0.69-1.20) and did not improve objective disease response rates in patients. There was no significant difference in grade 3-4 adverse reactions compared to placebo.ConclusionIn this meta-analysis of randomised controlled trial studies, we found that chemotherapy in combination with metformin in cancer patients without diabetes did not prolong progression-free survival and overall survival and improved disease control in patients, although there was no significant difference in terms of safety. More high-quality randomised controlled trials are needed in the future to confirm the in vivo anti-tumour activity and survival benefit of metformin.
| S-EPMC10402741 | biostudies-literature
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.
| S-EPMC6592598 | biostudies-literature