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Epilepsia Apr 2011Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose-response relationship.
METHODS
We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose-response relationships of pregabalin AEs.
KEY FINDINGS
Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose-response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others.
SIGNIFICANCE
Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions.
Topics: Analgesics; Anticonvulsants; Epilepsy; Humans; Neuralgia; Outcome Assessment, Health Care; Pregabalin; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 21320112
DOI: 10.1111/j.1528-1167.2010.02966.x -
The Cochrane Database of Systematic... Apr 2013Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected... (Review)
Review
BACKGROUND
Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome.
OBJECTIVES
To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication.
SEARCH METHODS
The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies.
SELECTION CRITERIA
We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion and intended to extract information from the trials.
MAIN RESULTS
No studies were identified comparing rutosides versus any alternative in the prevention of PTS.
AUTHORS' CONCLUSIONS
As there were no studies identified in this review it is not possible to support the use of rutosides in the prevention of PTS. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.
Topics: Aesculus; Humans; Phytotherapy; Plant Extracts; Postthrombotic Syndrome; Rutin; Venous Thrombosis
PubMed: 23633331
DOI: 10.1002/14651858.CD005626.pub2 -
Critical Care Medicine Mar 2022Sepsis is a life-threatening organ dysfunction caused by a host's unregulated immune response to eliminate the infection. After hospitalization, sepsis survivors often...
OBJECTIVES
Sepsis is a life-threatening organ dysfunction caused by a host's unregulated immune response to eliminate the infection. After hospitalization, sepsis survivors often suffer from long-term impairments in memory, attention, verbal fluency, and executive functioning. To understand the effects of sepsis and the exacerbated peripheral inflammatory response in the brain, we asked the question: What are the findings and inflammatory markers in the brains of deceased sepsis patients? To answer this question, we conducted this systematic review by the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
DATA SOURCES
Relevant studies were identified by searching the PubMed/National Library of Medicine, PsycINFO, EMBASE, Bibliographical Index in Spanish in Health Sciences, Latin American and Caribbean Health Sciences Literature, and Web of Science databases for peer-reviewed journal articles published on April 05, 2021.
STUDY SELECTION
A total of 3,745 articles were included in the primary screening; after omitting duplicate articles, animal models, and reviews, 2,896 articles were selected for the study. These studies were selected based on the title and abstract, and 2,772 articles were still omitted based on the exclusion criteria.
DATA EXTRACTION
The complete texts of the remaining 124 articles were obtained and thoroughly evaluated for the final screening, and 104 articles were included.
DATA SYNTHESIS
The postmortem brain had edema, abscess, hemorrhagic and ischemic injuries, infarction, hypoxia, atrophy, hypoplasia, neuronal loss, axonal injuries, demyelination, and necrosis.
CONCLUSIONS
The mechanisms by which sepsis induces brain dysfunction are likely to include vascular and neuronal lesions, followed by the activation of glial cells and the presence of peripheral immune cells in the brain.
Topics: Atrophy; Autopsy; Biomarkers; Brain; Humans; Inflammation; Magnetic Resonance Imaging; Sepsis
PubMed: 34402457
DOI: 10.1097/CCM.0000000000005307 -
International Journal of Molecular... Aug 2022In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its... (Review)
Review
BACKGROUND
In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its similarity to the lymphatic system in peripheral tissue and the relevant role of the AQP4 glial channels and described for the first time in 2012. Consequently, numerous studies focused on its role in organ damage in cases of neuropathologies, including TBI.
METHODS
To evaluate the role that the glymphatic system has in the pathogenesis of TBI, on 23 March 2022, a systematic review of the literature according to PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, resulting in 12 articles after the selection process.
DISCUSSION AND CONCLUSION
The present review demonstrated that an alteration of AQP4 is associated with the accumulation of substances S100b, GFAP, and NSE, known markers of TBI in the forensic field. In addition, the alteration of the functionality of AQP4 favors edema, which, as already described, constitutes alterations of secondary brain injuries. Moreover, specific areas of the brain were demonstrated to be prone to alterations of the glymphatic pathway, suggesting their involvement in post-TBI damage. Therefore, further studies are mandatory. In this regard, a study protocol on cadavers is also proposed, based on the analyzed evidence.
Topics: Brain; Brain Injuries; Glymphatic System; Humans; Lymphatic System; Neuroglia
PubMed: 36012401
DOI: 10.3390/ijms23169138 -
BMC Pharmacology & Toxicology Oct 2017Vildagliptin and pioglitazone/rosiglitazone are emerging Oral Hypoglycemic Agents (OHAs) which are used to treat patients suffering from Type 2 Diabetes Mellitus (T2DM).... (Meta-Analysis)
Meta-Analysis Review
Adverse drug effects observed with vildagliptin versus pioglitazone or rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Vildagliptin and pioglitazone/rosiglitazone are emerging Oral Hypoglycemic Agents (OHAs) which are used to treat patients suffering from Type 2 Diabetes Mellitus (T2DM). In this analysis, we aimed to systematically compare the adverse drug events which were observed with the use of vildagliptin versus pioglitazone or rosiglitazone respectively.
METHODS
Online databases were searched for studies comparing vildagliptin with pioglitazone/rosiglitazone. Adverse drug events were considered as the clinical endpoints in this analysis. We calculated Odds Ratios (OR) with 95% Confidence Intervals (CIs) using the RevMan 5.3 software. All the authors had full access to the data which were used and approved the final version of the manuscript.
RESULTS
A total number of 2396 patients were analyzed (1486 and 910 patients were treated with vildagliptin and pioglitazone/rosiglitazone respectively). Vildagliptin and pioglitazone/rosiglitazone were both associated with similar overall adverse drug events (OR: 1.00, 95% CI: 0.81-1.24; P = 1.00). Headache (OR: 0.88, 95% CI: 0.60-1.27; P = 0.49) and upper respiratory tract infection (OR: 0.95, 95% CI: 0.71-1.27; P = 0.75) were similarly observed. However, dizziness was significantly lower with pioglitazone/rosiglitazone (OR: 0.63, 95% CI: 0.43-0.92; P = 0.02). Back pain, diarrhea and nausea were insignificantly lower with pioglitazone/rosiglitazone (OR: 0.81, 95% CI: 0.49-1.33; P = 0.40), (OR: 0.83, 95% CI: 0.48-1.44; P = 0.52) and (OR: 0.52, 95% CI: 0.25-1.05; P = 0.07) respectively, whereas peripheral edema and weight gain were insignificantly higher (OR: 1.21, 95% CI: 0.56-2.62; P = 0.63) and (OR: 2.29, 95% CI: 0.51-10.34; P = 0.28) respectively. Nevertheless, when pioglitazone and rosiglitazone were separately compared with vildagliptin, peripheral edema and weight gain were significantly higher with rosiglitazone (OR: 2.36, 95% CI: 1.40-3.99; P = 0.001) and (OR: 5.20, 95% CI: 2.47-10.92; P = 0.0001) respectively.
CONCLUSION
Both vildagliptin and pioglitazone/rosiglitazone are acceptable for the treatment of patients with T2DM on the basis that they are not significantly different in terms of overall adverse drug events. However, weight gain and peripheral edema would have to be re-assessed in further larger randomized controlled trials.
Topics: Adamantane; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Nitriles; Pioglitazone; Pyrrolidines; Randomized Controlled Trials as Topic; Rosiglitazone; Thiazolidinediones; Vildagliptin
PubMed: 29058622
DOI: 10.1186/s40360-017-0175-0 -
The Cochrane Database of Systematic... Apr 2008Many palliative care patients have reduced oral intake during their illness. The management of this can include the provision of medically assisted hydration with the... (Review)
Review
BACKGROUND
Many palliative care patients have reduced oral intake during their illness. The management of this can include the provision of medically assisted hydration with the aim of prolonging the length of life of a patient, improving their quality of life, or both.
OBJECTIVES
To determine the effect of medically assisted hydration in palliative care patients on their quality and length of life.
SEARCH STRATEGY
Studies were identified from searching CENTRAL, MEDLINE (1966 to 2008), EMBASE (1980 to 2008), CINAHL, CANCERLIT, Caresearch, Dissertation abstracts, SCIENCE CITATION INDEX and the reference lists of all eligible studies, key textbooks, and previous systematic reviews. The date of the latest search was February 2008.
SELECTION CRITERIA
All relevant randomised controlled trials (RCTs) or prospective controlled studies of medically assisted hydration in palliative care patients.
DATA COLLECTION AND ANALYSIS
Five relevant studies were identified. These included two RCTs (93 participants), and three prospective controlled trials (360 participants). These were assessed independently by two review authors for quality and validity. The small number of studies and the heterogeneity of the data meant that a quantitative analysis was not possible, so a description of the main findings was included only.
MAIN RESULTS
One study found that sedation and myoclonus (involuntary contractions of muscles) were improved more in the intervention group (28 - hydration, 23 - placebo). Another study found that dehydration was significantly higher in the non-hydration group, but that some fluid retention symptoms (pleural effusion, peripheral oedema and ascites) were significantly higher in the hydration group (59 - hydration group, 167 - non -hydration group). The other three studies did not show significant differences in outcomes between the two groups.
AUTHORS' CONCLUSIONS
There are insufficient good quality studies to make any recommendations for practice with regard to the use of medically assisted hydration in palliative care patients.
Topics: Clinical Trials as Topic; Dehydration; Fluid Therapy; Humans; Longevity; Palliative Care; Quality of Life; Terminally Ill
PubMed: 18425944
DOI: 10.1002/14651858.CD006273.pub2 -
Annales de Cardiologie Et D'angeiologie Oct 2020Cardiovascular disease is the leading cause of death worldwide. Conceptually, endothelial dysfunction, inflammatory conditions and oxidative stress are at the forefront...
Cardiovascular disease is the leading cause of death worldwide. Conceptually, endothelial dysfunction, inflammatory conditions and oxidative stress are at the forefront of the onset and development of most cardiovascular diseases, particularly coronary artery disease and heart failure. Serum albumin has many physiological properties, including in particular antioxidant, anti-inflammatory, anticoagulant and anti-platelet aggregation activity. It also plays an essential role in the exchange of fluids across the capillary membrane. Hypoalbuminemia is a powerful prognostic marker in the general population as well as in many disease states. In the more specific context of cardiovascular disease, low serum albumin is independently associated with the development of various deleterious conditions such as coronary artery disease, heart failure, atrial fibrillation, stroke and venous thromboembolism. Low serum albumin has also emerged as a potent prognostic parameter in patients with cardiovascular disease regardless of usual prognostic markers. Remarkably, its potent prognostic value persists after adjusting for causative confounders such as malnutrition and inflammation. This prognostic value probably refers primarily to the syndrome of malnutrition-inflammation and the severity of comorbidities. Nevertheless, several recent meta-analyses strongly support the hypothesis that hypoalbuminemia may act as an unrecognized, potentially modifiable risk factor contributing to the emergence and progression of cardiovascular disease, primarily by exacerbating oxidative stress, inflammation and platelet aggregation, and by favouring peripheral congestion and pulmonary edema. Currently, it is unknown whether prevention and correction of low serum albumin offers a benefit to patients with or at risk for cardiovascular disease, and further studies are critically needed in this setting.
Topics: Atrial Fibrillation; Cardiac Surgical Procedures; Cardiovascular Diseases; Coronary Artery Disease; Disease Progression; Heart Defects, Congenital; Heart Failure; Humans; Hypoalbuminemia; Prognosis; Risk Factors; Serum Albumin; Stroke; Venous Thromboembolism
PubMed: 32797938
DOI: 10.1016/j.ancard.2020.07.012 -
The Cochrane Database of Systematic... Mar 2023Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the... (Review)
Review
BACKGROUND
Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process. OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 1), Ovid MEDLINE, Ovid MEDLINE E-pub Ahead of Print, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to 10 January 2022), Embase (January 1947 to 10 January 2022), PubMed (1946 to 10 January 2022), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 10 January 2022), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 10 January 2022.
SELECTION CRITERIA
We included randomized controlled clinical trials comparing lens extraction against LPI in adult participants ( ≥ 35 years) with APAC in one or both eyes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach.
MAIN RESULTS
We included two studies conducted in Hong Kong and Singapore, comprising 99 eyes (99 participants) of predominantly Chinese origin. The two studies compared LPI with phacoemulsification performed by experienced surgeons. We assessed that both studies were at high risk of bias. There were no studies evaluating other types of lens extraction procedures. Phacoemulsification may result in an increased proportion of participants with intraocular pressure (IOP) control compared with LPI at 18 to 24 months (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.28 to 2.15; 2 studies, n = 97; low certainty evidence) and may reduce the need for further IOP-lowering surgery within 24 months (RR 0.07, 96% CI 0.01 to 0.51; 2 studies, n = 99; very low certainty evidence). Phacoemulsification may result in a lower mean IOP at 12 months compared to LPI (mean difference (MD) -3.20, 95% CI -4.79 to -1.61; 1 study, n = 62; low certainty evidence) and a slightly lower mean number of IOP-lowering medications at 18 months (MD -0.87, 95% CI -1.28 to -0.46; 1 study, n = 60; low certainty evidence), but this may not be clinically significant. Phacoemulsification may have little to no effect on the proportion of participants with one or more recurrent APAC episodes in the same eye (RR 0.32, 95% CI 0.01 to 7.30; 1 study, n = 37; very low certainty evidence). Phacoemulsification may result in a wider iridocorneal angle assessed by Shaffer grading at six months (MD 1.15, 95% CI 0.83 to 1.47; 1 study, n = 62; very low certainty evidence). Phacoemulsification may have little to no effect on logMAR best-corrected visual acuity (BCVA) at six months (MD -0.09, 95% CI -0.20 to 0.02; 2 studies, n = 94; very low certainty evidence). There was no evidence of a difference in the extent of peripheral anterior synechiae (PAS) (clock hours) between intervention arms at 6 months (MD -1.86, 95% CI -7.03 to 3.32; 2 studies, n = 94; very low certainty evidence), although the phacoemulsification group may have less PAS (degrees) at 12 months (MD -94.20, 95% CI -140.37 to -48.03; 1 study, n = 62) and 18 months (MD -127.30, 95% CI -168.91 to -85.69; 1 study, n = 60). In one study, there were 26 adverse events in the phacoemulsification group: intraoperative corneal edema (n = 12), posterior capsular rupture (n = 1), intraoperative bleeding from iris root (n = 1), postoperative fibrinous anterior chamber reaction (n = 7), and visually significant posterior capsular opacification (n = 5), and no cases of suprachoroidal hemorrhage or endophthalmitis. There were four adverse events in the LPI group: closed iridotomy (n = 1) and small iridotomies that required supplementary laser (n = 3). In the other study, there was one adverse event in the phacoemulsification group (IOP > 30 mmHg on day 1 postoperatively (n = 1)), and no intraoperative complications. There were five adverse events in the LPI group: transient hemorrhage (n = 1), corneal burn (n = 1), and repeated LPI because of non-patency (n = 3). Neither study reported health- or vision-related quality of life measures.
AUTHORS' CONCLUSIONS
Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.
Topics: Adult; Humans; Cataract Extraction; Glaucoma; Intraocular Pressure; Phacoemulsification; Quality of Life
PubMed: 36884304
DOI: 10.1002/14651858.CD015116.pub2 -
The Cochrane Database of Systematic... Jul 2005Chronic venous insufficiency (CVI) is a common condition caused by inadequate blood flow through the veins, usually in the lower limbs. It can result in considerable... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic venous insufficiency (CVI) is a common condition caused by inadequate blood flow through the veins, usually in the lower limbs. It can result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Sufferers may also experience swelling and ulcers. Phlebotonics are a class of drugs that are often used to treat CVI.
OBJECTIVES
To assess the efficacy of oral or topical phlebotonics.
SEARCH STRATEGY
We searched the Cochrane Peripheral Vascular Diseases Group trials register (April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2005), MEDLINE (January 1966 to April 2005), EMBASE (January 1980 to April 2005) and reference lists of articles. We also contacted pharmaceutical companies.
SELECTION CRITERIA
Randomised, double blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and aminaftone in CVI patients at any stage of the disease.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed trial quality. The effects of treatment were estimated by relative risk (RR) or by standardised mean differences (SMD) by applying a random effects statistical model. Sensitivity analyses were also performed.
MAIN RESULTS
Fifty-nine RCTs of oral phlebotonics were included, but only 44 trials involving 4413 participants contained quantifiable data for the efficacy analysis: 23 of rutosides, ten of hidrosmine and diosmine, six of calcium dobesilate, two of centella asiatica, one of french maritime pine bark extract, one of aminaftone and one of grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Outcomes included oedema, venous ulcers, trophic disorders, subjective symptoms (pain, cramps, restless legs, itching, heaviness, swelling and paraesthesias), global assessment measures and side effects. The results of many variables were heterogeneous. Phlebotonics showed some global benefit (i.e. oedema reduction) (relative risk 0.72, 95% confidence interval 0.65 to 0.81). The benefit for the remaining CVI signs and symptoms must be evaluated by phlebotonic group. There were no quantifiable data on quality of life.
AUTHORS' CONCLUSIONS
There is not enough evidence to globally support the efficacy of phlebotonics for chronic venous insufficiency. There is a suggestion of some efficacy of phlebotonics on oedema but this is of uncertain clinical relevance. Due to the limitations of current evidence, there is a need for further randomised, controlled clinical trials with greater attention paid to methodological quality.
Topics: 4-Aminobenzoic Acid; Calcium Dobesilate; Centella; Chronic Disease; Diosmin; Hematologic Agents; Humans; Phytotherapy; Randomized Controlled Trials as Topic; Venous Insufficiency; para-Aminobenzoates
PubMed: 16034893
DOI: 10.1002/14651858.CD003229.pub2 -
PloS One Jul 2009Type 2 diabetes is treated in a stepwise manner, progressing from diet and physical activity to oral antidiabetic agents and insulin. The oral agent pioglitazone is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Type 2 diabetes is treated in a stepwise manner, progressing from diet and physical activity to oral antidiabetic agents and insulin. The oral agent pioglitazone is licensed for use with insulin when metformin is contraindicated or not tolerated. This systematic review and meta-analysis investigates the extent to which adding pioglitazone to insulin-containing regimens produces benefits in terms of patient-relevant outcomes.
METHODOLOGY/PRINCIPAL FINDINGS
Medline, Embase, and the Cochrane Library were searched for randomised controlled trials comparing pioglitazone in combination with any insulin-containing regimen in comparison with the same insulin regimen alone in patients with type 2 diabetes. Outcomes investigated included HbA1c, hypoglycaemia, weight, and adverse events. Studies were selected, assessed and summarised according to standard systematic review methodology and in a meta-analysis. We included eight trials that examined the benefits of adding pioglitazone to an insulin regimen and studied a total of 3092 patients with type 2 diabetes. All studies included patients with previously inadequate glucose control. Trial duration was between 12 weeks and 34.5 months. The trials used pioglitazone doses of up to 45 mg/day. In our meta-analysis, the mean reduction in HbA1c was 0.58% (95% CI: -0.70, -0.46, p<0.00001). Hypoglycaemic episodes were slightly more frequent in the pioglitazone arms (relative risk 1.27; 95% CI: 0.99, 1.63, p = 0.06). Where reported, HDL-cholesterol tended to be increased with pioglitazone. Patients on pioglitazone tended to gain more weight than those who were not, with an average difference of almost 3 kg. Peripheral oedema was more frequent in the pioglitazone groups. None of the studies reported on fractures in women, and data on cardiovascular events were inconclusive, with most studies being too short or too small to assess these long-term outcomes.
CONCLUSIONS/SIGNIFICANCE
When added to insulin regimens, pioglitazone confers a small advantage in terms of HbA1c in type 2 diabetes patients with previous inadequate glucose control, but at the cost of increased hypoglycaemia and weight gain. Other considerations include the risk of heart failure, fractures in women, a reduced insulin dose, and the net financial cost.
Topics: Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Lipids; Pioglitazone; Thiazolidinediones
PubMed: 19568428
DOI: 10.1371/journal.pone.0006112