-
The Cochrane Database of Systematic... Sep 2018Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose-lowering agents in CKD to guide treatment.
OBJECTIVES
To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs looking at head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m) were eligible.
DATA COLLECTION AND ANALYSIS
Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Forty-four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co-transporter-2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; 2 studies compared glucagon-like peptide-1 (GLP-1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due to funding and attrition bias, and an unclear risk of detection bias.Compared to placebo, SGLT2 inhibitors probably reduce HbA1c (7 studies, 1092 participants: MD -0.29%, -0.38 to -0.19 (-3.2 mmol/mol, -4.2 to -2.2); I = 0%), fasting blood glucose (FBG) (5 studies, 855 participants: MD -0.48 mmol/L, -0.78 to -0.19; I = 0%), systolic blood pressure (BP) (7 studies, 1198 participants: MD -4.68 mmHg, -6.69 to -2.68; I = 40%), diastolic BP (6 studies, 1142 participants: MD -1.72 mmHg, -2.77 to -0.66; I = 0%), heart failure (3 studies, 2519 participants: RR 0.59, 0.41 to 0.87; I = 0%), and hyperkalaemia (4 studies, 2788 participants: RR 0.58, 0.42 to 0.81; I = 0%); but probably increase genital infections (7 studies, 3086 participants: RR 2.50, 1.52 to 4.11; I = 0%), and creatinine (4 studies, 848 participants: MD 3.82 μmol/L, 1.45 to 6.19; I = 16%) (all effects of moderate certainty evidence). SGLT2 inhibitors may reduce weight (5 studies, 1029 participants: MD -1.41 kg, -1.8 to -1.02; I = 28%) and albuminuria (MD -8.14 mg/mmol creatinine, -14.51 to -1.77; I = 11%; low certainty evidence). SGLT2 inhibitors may have little or no effect on the risk of cardiovascular death, hypoglycaemia, acute kidney injury (AKI), and urinary tract infection (low certainty evidence). It is uncertain whether SGLT2 inhibitors have any effect on death, end-stage kidney disease (ESKD), hypovolaemia, fractures, diabetic ketoacidosis, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, DPP-4 inhibitors may reduce HbA1c (7 studies, 867 participants: MD -0.62%, -0.85 to -0.39 (-6.8 mmol/mol, -9.3 to -4.3); I = 59%) but may have little or no effect on FBG (low certainty evidence). DPP-4 inhibitors probably have little or no effect on cardiovascular death (2 studies, 5897 participants: RR 0.93, 0.77 to 1.11; I = 0%) and weight (2 studies, 210 participants: MD 0.16 kg, -0.58 to 0.90; I = 29%; moderate certainty evidence). Compared to placebo, DPP-4 inhibitors may have little or no effect on heart failure, upper respiratory tract infections, and liver impairment (low certainty evidence). Compared to placebo, it is uncertain whether DPP-4 inhibitors have any effect on eGFR, hypoglycaemia, pancreatitis, pancreatic cancer, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, GLP-1 agonists probably reduce HbA1c (7 studies, 867 participants: MD -0.53%, -1.01 to -0.06 (-5.8 mmol/mol, -11.0 to -0.7); I = 41%; moderate certainty evidence) and may reduce weight (low certainty evidence). GLP-1 agonists may have little or no effect on eGFR, hypoglycaemia, or discontinuation due to adverse effects (low certainty evidence). It is uncertain whether GLP-1 agonists reduce FBG, increase gastrointestinal symptoms, or affect the risk of pancreatitis (very low certainty evidence).Compared to placebo, it is uncertain whether glitazones have any effect on HbA1c, FBG, death, weight, and risk of hypoglycaemia (very low certainty evidence).Compared to glipizide, sitagliptin probably reduces hypoglycaemia (2 studies, 551 participants: RR 0.40, 0.23 to 0.69; I = 0%; moderate certainty evidence). Compared to glipizide, sitagliptin may have had little or no effect on HbA1c, FBG, weight, and eGFR (low certainty evidence). Compared to glipizide, it is uncertain if sitagliptin has any effect on death or discontinuation due to adverse effects (very low certainty).For types, dosages or modes of administration of insulin and other head-to-head comparisons only individual studies were available so no conclusions could be made.
AUTHORS' CONCLUSIONS
Evidence concerning the efficacy and safety of glucose-lowering agents in diabetes and CKD is limited. SGLT2 inhibitors and GLP-1 agonists are probably efficacious for glucose-lowering and DPP-4 inhibitors may be efficacious for glucose-lowering. Additionally, SGLT2 inhibitors probably reduce BP, heart failure, and hyperkalaemia but increase genital infections, and slightly increase creatinine. The safety profile for GLP-1 agonists is uncertain. No further conclusions could be made for the other classes of glucose-lowering agents including insulin. More high quality studies are required to help guide therapeutic choice for glucose-lowering in diabetes and CKD.
Topics: Cause of Death; Diabetes Mellitus; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Glipizide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sitagliptin Phosphate; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones
PubMed: 30246878
DOI: 10.1002/14651858.CD011798.pub2 -
Frontiers in Medicine 2022To evaluate the effects of vitamin E, pioglitazone, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists in patients...
Efficacy of Off-Label Therapy for Non-alcoholic Fatty Liver Disease in Improving Non-invasive and Invasive Biomarkers: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
OBJECTIVE
To evaluate the effects of vitamin E, pioglitazone, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with non-alcoholic fatty liver disease (NAFLD).
DESIGN
A network meta-analysis.
DATA SOURCES
PubMed, Embase, Cochrane Library, and Web of Science databases from their inception until September 1, 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomized controlled trials (RCTs) comparing the effects of four different drugs in patients with NAFLD were included. All superiority, non-inferiority, phase II and III, non-blinded, single-blinded, and double-blinded trials were included. Interventions of interest included vitamin E (α-tocopherol and δ-tocotrienol), pioglitazone, three kinds of GLP-1 receptor agonists (liraglutide, semaglutide, and dulaglutide), four SGLT2 inhibitors (dapagliflozin, empagliflozin, ipragliflozin, and tofogliflozin), and comparisons of these different drugs, and placebos.
MAIN OUTCOME MEASURES
The outcome measures included changes in non-invasive tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), controlled attenuation parameter (CAP), enhanced liver fibrosis (ELF) score, liver fat content (LFC), and keratin-18 (K-18)] and invasive tests [fibrosis score and resolution of non-alcoholic steatohepatitis (NASH)].
RESULTS
Twenty-seven trials including 3,416 patients were eligible for inclusion in the study. Results refer to vitamin E, pioglitazone, GLP-1 receptor agonists, and SGLT2 inhibitors. First, placebos were used as a reference. δ-Tocotrienol was superior to placebo in decreasing the GGT level. Semaglutide, ipragliflozin, and pioglitazone induced a significantly higher decrease in the ALT level than a placebo. Semaglutide, pioglitazone, and dapagliflozin were superior to placebo in decreasing the AST level. Tofogliflozin and pioglitazone induced a significantly higher decrease in the K-18 level than a placebo. Liraglutide was superior to placebo in decreasing CAP. Liraglutide, pioglitazone, and vitamin E induced a significantly higher increase in resolution of NASH than a placebo. As for pairwise comparisons, semaglutide and pioglitazone were superior to liraglutide in decreasing the ALT level. Semaglutide induced a significantly higher decrease in the ALT level than dulaglutide. Semaglutide was obviously superior to empagliflozin, liraglutide, dulaglutide, and tofogliflozin in decreasing the AST level. Pioglitazone induced a significantly higher decrease in the GGT level than ipragliflozin. δ-Tocotrienol was superior to liraglutide in decreasing the GGT level. Tofogliflozin and pioglitazone induced a significantly higher decrease in the K-18 level than dulaglutide. Pioglitazone was superior to vitamin E in increasing the resolution of NASH. Furthermore, liraglutide treatment had the highest SUCRA ranking in decreasing CAP and ELF scores and increasing the resolution of NASH. Pioglitazone treatment had the highest SUCRA ranking in decreasing LFC and fibrosis scores. Tofogliflozin treatment had the highest SUCRA ranking in decreasing K-18, while dapagliflozin treatment had the highest SUCRA ranking in decreasing the GGT level. Semaglutide treatment had the highest SUCRA ranking in decreasing the levels of ALT and AST.
CONCLUSION
The network meta-analysis provided evidence for the efficacy of vitamin E, pioglitazone, SGLT2 inhibitors, and GLP-1 receptor agonists in treating patients with NAFLD. To find the best guide-level drugs, it is necessary to include more RCTs with these off-label drugs, so that patients and clinicians can make optimal decisions together.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier: CRD42021283129.
PubMed: 35280867
DOI: 10.3389/fmed.2022.793203 -
Alimentary Pharmacology & Therapeutics Oct 2021Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for the treatment of NASH.
AIM
To assess the relative rank-order of different pharmacological interventions in fibrosis improvement and NASH resolution.
METHODS
A comprehensive search of several databases was conducted by an experienced librarian. We included randomised controlled-trials (RCTs) comparing pharmacological interventions in patients with biopsy-proven NASH. The primary outcome was ≥1 stage improvement in fibrosis. The secondary outcome was NASH resolution.
RESULTS
A total of 26 RCTs with 23 interventions met the eligibility criteria. Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively. For NASH resolution, semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively. Lanifibranor, obeticholic acid, pioglitazone and vitamin E were significantly better than placebo in achieving ≥1 stage of fibrosis improvement. Conversely, semaglutide, liraglutide, vitamine E plus pioglitazone, pioglitazone, lanifibranor and obeticholic acid were significantly better than placebo in achieving NASH resolution.
CONCLUSION
These data provide relative rank-order efficacy of various NASH therapies in terms of their improvements in liver fibrosis and NASH resolution. Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.
Topics: Biopsy; Humans; Liver Cirrhosis; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Pioglitazone; Vitamin E
PubMed: 34435378
DOI: 10.1111/apt.16583 -
Neurology India 2023Disease-modifying agents like Pioglitazone have shown promising effects on neuroinflammation and homeostasis of amyloid plaques, but there is a lack of research papers... (Meta-Analysis)
Meta-Analysis Review
Drug Repositioning of Pioglitazone in Management and Improving the Cognitive Function among the Patients With Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-Analysis.
BACKGROUND
Disease-modifying agents like Pioglitazone have shown promising effects on neuroinflammation and homeostasis of amyloid plaques, but there is a lack of research papers providing conclusive evidence.
OBJECTIVES
This study is aimed to determine the safety and efficacy of Pioglitazone in improving cognitive function in patients with mild-moderate Alzheimer's disease (AD).
MATERIALS AND METHODS
Trials published in the last 12 years were identified from PubMed, Scopus, Cochrane Central, and other trial registries. Five hundred twenty-five records were obtained, from which five studies were included for quantitative analysis. Studies comparing Pioglitazone with a suitable placebo or other oral hypoglycemic agent were considered for review. Data was extracted using a pretested form, which was followed by a risk of bias assessment (ROB) with Cochrane's ROB assessment tool.
RESULTS
This meta-analysis included studies where Pioglitazone (15-30 mg) was compared to other oral hypoglycemic agents, placebo, or diabetic diet for a minimum duration of 6 months. Pioglitazone did not show a statistically significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores [mean difference (MD): -1.16; 95% confidence interval (CI): -4.14-1.81]. By conducting sensitivity analysis with the removal of one study, significant efficacy was obtained [MD: -2.75; 95% CI: -4.84--0.66]. The Wechsler Memory Scale-Revised logical memory I (WMS-R) scores had a significant improvement in the Pioglitazone group [MD: 2.02; 95% CI: 0.09-3.95].
CONCLUSION
Pioglitazone is a safe medication that has a promising effect in slowing the advancement of AD.
Topics: Humans; Alzheimer Disease; Pioglitazone; Drug Repositioning; Cognition
PubMed: 38174446
DOI: 10.4103/0028-3886.391397 -
Reproductive Biology and Endocrinology... Mar 2023Polycystic ovarian syndrome (PCOS) is one of the most common causes of infertility in reproductive-age women. However, the efficacy and optimal therapeutic strategy for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovarian syndrome (PCOS) is one of the most common causes of infertility in reproductive-age women. However, the efficacy and optimal therapeutic strategy for reproductive outcomes are still under debate. We conducted a systematic review and network meta-analysis to compare the efficacy of different first-line pharmacological therapies in terms of reproductive outcomes for women with PCOS and infertility.
METHODS
A systematic retrieval of databases was conducted, and randomized clinical trials (RCTs) of pharmacological interventions for infertile PCOS women were included. The primary outcomes were clinical pregnancy and live birth, and the secondary outcomes were miscarriage, ectopic pregnancy and multiple pregnancy. A network meta-analysis based on a Bayesian model was performed to compare the effects of the pharmacological strategies.
RESULTS
A total of 27 RCTs with 12 interventions were included, and all therapies tended to increase clinical pregnancy, especially pioglitazone (PIO) (log OR 3.14, 95% CI 1.56 ~ 4.70, moderate confidence), clomiphene citrate (CC) + exenatide (EXE) (2.96, 1.07 ~ 4.82, moderate confidence) and CC + metformin (MET) + PIO (2.82, 0.99 ~ 4.60, moderate confidence). Moreover, CC + MET + PIO (2.8, -0.25 ~ 6.06, very low confidence) could increase live birth most when compared to placebo, even without a significant difference. For secondary outcomes, PIO showed a tendency to increase miscarriage (1.44, -1.69 ~ 5.28, very low confidence). MET (-11.25, -33.7 ~ 0.57, low confidence) and LZ + MET (-10.44, -59.56 ~ 42.11, very low confidence) were beneficial for decreasing ectopic pregnancy. MET (0.07, -4.26 ~ 4.34, low confidence) showed a neutral effect in multiple pregnancy. Subgroup analysis demonstrated no significant difference between these medications and placebo in obese participants.
CONCLUSIONS
Most first-line pharmacological treatments were effective in improving clinical pregnancy. CC + MET + PIO should be recommended as the optimal therapeutic strategy to improve pregnancy outcomes. However, none of the above treatments had a beneficial effect on clinical pregnancy in obese PCOS.
TRIAL REGISTRATION
CRD42020183541; 05 July 2020.
Topics: Female; Pregnancy; Humans; Network Meta-Analysis; Abortion, Spontaneous; Polycystic Ovary Syndrome; Infertility, Female; Clomiphene; Live Birth; Metformin; Obesity; Pioglitazone; Randomized Controlled Trials as Topic
PubMed: 36869381
DOI: 10.1186/s12958-023-01075-9 -
BMJ Open Jan 2017To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes.
DESIGN AND SETTING
Systematic review and meta-analysis of randomised, controlled trials.
DATA SOURCES
Literature searches were performed across PubMed, EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials from 1966 to May 2016 to identify randomised, controlled trials with more than 1 year follow-up.
OUTCOME MEASURES
Relative risk (RR) with 95% CI was used to evaluate the association between pioglitazone and the risk of major adverse cardiovascular events (MACE: composite of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and safety outcomes, after pooling data across trials in a fixed-effects model.
RESULTS
Nine trials with 12 026 participants were enrolled in the current meta-analysis. Pioglitazone therapy was associated with a lower risk of MACE in patients with pre-diabetes or insulin resistance (RR 0.77, 95% CI 0.64 to 0.93), and diabetes (RR 0.83, 95% CI 0.72 to 0.97). Risks of heart failure (RR 1.32; CI 1.14 to 1.54), bone fracture (RR 1.52, 95% CI 1.17 to 1.99), oedema (RR, 1.63; CI 1.52 to 1.75) and weight gain (RR 1.60; CI 1.50 to 1.72) increased in pioglitazone group.
CONCLUSIONS
Pioglitazone was associated with reduced risk of MACE in people with insulin resistance, pre-diabetes and diabetes mellitus. However, the risks of heart failure, bone fracture, oedema and weight gain were increased.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Edema; Fractures, Bone; Humans; Hypoglycemic Agents; Insulin Resistance; Pioglitazone; Prediabetic State; Protective Factors; Randomized Controlled Trials as Topic; Thiazolidinediones; Weight Gain
PubMed: 28057658
DOI: 10.1136/bmjopen-2016-013927 -
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 -
Expert Review of Gastroenterology &... Mar 2023There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials.
INTRODUCTION
There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for nonalcoholic fatty liver disease (NAFLD). Therefore, we aim to compare the effects of GLP-1 receptor agonists, pioglitazone and vitamin E in patients with NAFLD.
METHODS
We searched PubMed, Embase, Web of Science and Cochrane Library up to 11 April 2022. Randomized clinical trials (RCTs) comparing GLP-1 receptor agonists, pioglitazone and vitamin E against placebo or other active controls in patients with NAFLD were included.
RESULTS
Nine RCTs including 1482 patients proved eligible. GLP-1 receptor agonists ranked first in steatosis, ballooning necrosis, γ-glutamyl transferase, body weight, body mass index, and triglycerides. Administration of GLP-1 receptor agonists, as compared with placebo, was associated with improvement in liver histology [steatosis (OR = 4.11, 95% CI: 2.83, 5.96), ballooning necrosis (OR = 3.07, 95% CI: 2.14, 4.41), lobular inflammation (OR = 1.86, 95% CI: 1.29, 2.68), fibrosis (OR = 1.52, 95% CI: 1.06, 2.20)].
CONCLUSIONS
GLP-1 receptor agonists were as effective as pioglitazone and vitamin E for liver histology among patients with NAFLD. GLP-1 receptor agonists might be considered as an alternative or complementary treatment in the future clinical practice. [Figure: see text].
Topics: Humans; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Necrosis; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Pioglitazone; Randomized Controlled Trials as Topic; Vitamin E; Pilot Projects
PubMed: 36689199
DOI: 10.1080/17474124.2023.2172397 -
BMC Medicine Nov 2023Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials.
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM.
METHODS
This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373.
RESULTS
Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA, with standard-treatment (STA-TRE) as reference (MD - 0.17, 95%CI - 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD - 11.72, 95%CI - 17.82 to - 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence.
CONCLUSIONS
The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.
Topics: Humans; Diabetes Mellitus, Type 2; Exenatide; Hypoglycemic Agents; Liraglutide; Non-alcoholic Fatty Liver Disease; Network Meta-Analysis; Pioglitazone; Insulin Resistance; Bayes Theorem
PubMed: 37974258
DOI: 10.1186/s12916-023-03129-6 -
Diabetic Medicine : a Journal of the... Sep 2013Pioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an... (Meta-Analysis)
Meta-Analysis Review
AIMS
Pioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an increased risk of bladder cancer in patients with diabetes. Therefore, we sought to perform a systematic review and meta-analysis to evaluate the magnitude of this association and the quality of the supporting evidence.
METHODS
Electronic databases were queried to identify controlled studies of pioglitazone that measured the risk of bladder cancer.
RESULTS
Six studies involving 215 142 patients using pioglitazone were included, with a median period of follow-up of 44 months. The hazard of developing bladder cancer was significantly higher in patients using pioglitazone (hazard ratio 1.23; 95% CI 1.09-1.39; I² = 0%) compared with control groups. The risk of bias was moderate across the six studies. Considering an incidence rate of 20.8 per 100 000 person years, the number needed to harm was five additional cases of bladder cancer per 100 000 person years.
CONCLUSIONS
Patients treated with pioglitazone have a slight increased risk of bladder cancer compared to general population. Patient involvement and weighing treatment benefits versus risks should be discussed with patient toward shared decision. Patients with type 2 diabetes with risk factors, such as family history, smoking, or exposure to certain forms of chemotherapy may need to consider other anti-hyperglycemic agents. Also, pioglitazone should be discontinued in type 2 diabetes patients with newly diagnosed bladder cancer.
Topics: Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Hypoglycemic Agents; Pioglitazone; Risk; Thiazolidinediones; Urinary Bladder Neoplasms
PubMed: 23350856
DOI: 10.1111/dme.12144