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Frontiers in Endocrinology 2021Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients.
METHODS
Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas.
RESULTS
One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and sex distribution (0.63; 0.15-1.56).
CONCLUSIONS
We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients.
SYSTEMATIC REVIEW REGISTRATION
This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
Topics: Diabetes Mellitus, Type 2; Fractures, Bone; Humans; Hypoglycemic Agents; Network Meta-Analysis; Risk Factors
PubMed: 34721294
DOI: 10.3389/fendo.2021.735824 -
Brain Sciences Nov 2022cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving... (Review)
Review
BACKGROUND
cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials.
OBJECTIVES
we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes.
RESULTS
Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes.
LIMITATIONS
Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy.
CONCLUSIONS
There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.
PubMed: 36421870
DOI: 10.3390/brainsci12111546 -
Cureus Aug 2023Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM),... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Weight loss and dietary modifications are established first-line treatments for NAFLD. Currently, there is no approved drug for NAFLD; however, pioglitazone and vitamin E have shown some beneficial effects. This systematic review covers the comparative efficacies of vitamin E, pioglitazone, and vitamin E plus pioglitazone. As of December 2022, the sources for prior literature review included PubMed, PubMed Central, and Medline. We included studies assessing the efficacy of pioglitazone, vitamin E, and vitamin E plus pioglitazone in improving liver histology, liver markers, and lipid profile when compared to other interventions in patients with NAFLD/non-alcoholic steatohepatitis (NASH). Review materials include randomized control trials (RCTs), traditional reviews, systematic reviews, meta-analyses, and observational studies on human participants published within the last five years in the English language. Studies on animals, pediatric populations, and with insufficient data were excluded from the review. Two authors scanned and filtered articles independently and later performed quality checks. A third reviewer resolved any conflicts. The risk of bias was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systematic reviews, the Cochrane Risk of Bias Tool for RCTs, and the Scale for the Assessment of Narrative Review Articles for Traditional Reviews. A total of 21 articles were shortlisted. The results showed that pioglitazone and vitamin E are effective in reducing steatosis, inflammation, and ballooning, reducing liver markers, but there seem to be conflicting data on fibrosis resolution. Pioglitazone decreases triglycerides and increases high-density lipoproteins. One study has suggested that pioglitazone has superior efficacy to vitamin E in fibrosis reduction and vitamin E plus pioglitazone has superior efficacy than pioglitazone alone for NASH resolution. However, these conclusions require further validation through extensive analysis and additional research. In conclusion, diabetic patients with NAFLD can be given pioglitazone, and non-diabetic patients with NAFLD can be given vitamin E.
PubMed: 37719477
DOI: 10.7759/cureus.43635 -
Journal of Clinical and Experimental... 2022Due to lack of targeted treatment options and inconsistent utilization of histologic endpoints among clinical trials, identifying efficacious pharmacotherapies for...
BACKGROUND
Due to lack of targeted treatment options and inconsistent utilization of histologic endpoints among clinical trials, identifying efficacious pharmacotherapies for nonalcoholic steatohepatitis [NASH] has proven challenging.
METHODS
A thorough systematic review and frequentist random-effects network meta-analysis was performed across all randomized clinical trials reporting a pharmacotherapeutic intervention on biopsy-proven NASH. Primary outcomes were based on the most current, up-to-date recommended histologic endpoints.
RESULTS
A total of 40 RCTs were identified including 6593 total patients. The most effective and statistically significant treatment interventions for minimum two-point improvement in NAFLD Activity Score were aldafermin 1 mg [RR 7.69, 95% CI 2.00; 29.57], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 3.38, 95% CI 1.88; 6.07], pioglitazone 45 mg [RR 3.29, 95% CI 1.74; 6.22], vitamin E 800 IU [RR 2.06, 95% CI 1.33; 3.18], resmetirom 80 mg [RR 1.74, 95% CI 1.03; 2.94], obeticholic acid 25 mg [RR 1.63, 95% CI 1.32; 2.01], and obeticholic acid 10 mg [RR 1.31, 95% CI 1.02; 1.67]). The most robust pharmacotherapies for NASH resolution without worsening fibrosis were found to be aldafermin 1 mg [RR 5.77, 95% CI 1.48; 22.51], pioglitazone 45 mg [RR 2.65, 95% CI 1.43; 4.91], vitamin E 800 IU in combination with pioglitazone 45 mg [RR 2.64, 95% CI 1.36; 5.12], pioglitazone 30 mg [RR 2.46, 95% CI 1.56; 3.88], vitamin E 800 IU [RR 1.90, 95% CI 1.20; 3.00], and obeticholic acid 25 mg [RR 1.52, 95% CI 1.03; 2.23]). Obeticholic acid had a significant improvement on fibrosis. Multiple interventions were found to improve individual histologic scores across secondary outcome analyses and are detailed below.
CONCLUSION
This novel systematic review and network meta-analysis represents the most comprehensive investigation to date regarding the pharmacotherapeutic options for biopsy-proven NASH using current recommended histologic endpoints.
PubMed: 35814516
DOI: 10.1016/j.jceh.2022.01.011 -
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 -
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 -
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 -
Cureus Sep 2023Non-alcoholic fatty liver disease (NAFLD) is a complication related to obesity and metabolic syndrome. There are increased incidences of NAFLD/non-alcoholic... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is a complication related to obesity and metabolic syndrome. There are increased incidences of NAFLD/non-alcoholic steatohepatitis (NASH) due to rising obesity and type 2 diabetes mellitus (T2DM). This has resulted in significant morbidity and mortality. The two promising therapeutic agents for treating NAFLD/NASH are sodium-glucose cotransporter 2 (SGLT2) inhibitors and pioglitazone. The reason is their potential to target underlying pathophysiological mechanisms. SGLT2 inhibitors may help treat NAFLD/NASH by reducing insulin resistance and improving glucose control, thereby lowering hepatic fat accumulation and inflammation, although their exact mechanism in this context is still being studied. This systematic review aims to compare the efficacy of SGLT2 inhibitors and pioglitazone in treating NAFLD/NASH. Major research literature databases were searched, and appropriate keywords were used to find relevant articles published in the last three years. Eighteen studies were critically evaluated using standardized quality assessment tools. Among those, nine studies qualified as medium or high quality and were included in the review. Both SGLT2 inhibitors and pioglitazone showed promising results in improving NAFLD/NASH. The efficacy outcomes assessed liver fat content, liver enzyme levels, histological improvement, and metabolic parameters. The safety outcomes considered adverse events and cardiovascular events. The conducted review suggests that SGLT2 inhibitors and pioglitazone are potential treatment options for NAFLD/NASH. Having said that, individualized considerations are essential. It includes patient comorbidities, preferences, and overall safety profiles. Further research is needed to assess long-term effects and outcomes. It would provide more definitive evidence of these treatment options' comparative efficacy and safety for NAFLD/NASH.
PubMed: 37745748
DOI: 10.7759/cureus.45789 -
Frontiers in Endocrinology 2023This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD).
MATERIALS AND METHODS
PubMed and Scopus were searched from inception to 27 March 2022 to identify all randomized controlled trials (RCTs) in NAFLD patients. Outcomes included reductions in intrahepatic steatosis (IHS) and liver enzyme levels. The efficacy and safety of DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and other therapies were indirectly compared using a NMA approach. Unstandardized mean difference (USMD) with 95% confidence intervals (CI) were calculated.
RESULTS
2,252 patients from 31 RCTs were included. "Add-on" GLP-1 agonists with standard of care (SoC) treatment showed significantly reduced IHS compared to SoC alone [USMD (95%CI) -3.93% (-6.54%, -1.33%)]. Surface under the cumulative ranking curve (SUCRA) identified GLP-1 receptor agonists with the highest probability to reduce IHS (SUCRA 88.5%), followed by DPP-4 inhibitors (SUCRA 69.6%) and pioglitazone (SUCRA 62.2%). "Add-on" GLP-1 receptor agonists were also the most effective treatment for reducing liver enzyme levels; AST [USMD of -5.04 (-8.46, -1.62)], ALT [USMD of -9.84 (-16.84, -2.85)] and GGT [USMD of -15.53 (-22.09, -8.97)] compared to SoC alone. However, GLP-1 agonists were most likely to be associated with an adverse event compared to other interventions.
CONCLUSION
GLP-1 agonists may represent the most promising anti-diabetic treatment to reduce hepatic steatosis and liver enzyme activity in T2DM and NAFLD patients. Nevertheless, longer-term studies are required to determine whether this delays progression of liver cirrhosis in patients with NAFLD and T2DM.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021259336.1.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Dipeptidyl-Peptidase IV Inhibitors; Network Meta-Analysis; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1
PubMed: 37441498
DOI: 10.3389/fendo.2023.1182037