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Diabetes Therapy : Research, Treatment... Jun 2021Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM), and no approved therapies are currently available. A meta-analysis...
INTRODUCTION
Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM), and no approved therapies are currently available. A meta-analysis was performed to investigate the effects of liraglutide on NAFLD in patients with T2DM.
METHODS
Medline (via PubMed), Embase (via Elsevier), and the Cochrane Central Register of Controlled Trials (CENTRAL) (via Cochrane Library) from inception to April 2020 were searched. After screening the literature and extracting data, we assessed the risk of bias of the eligible studies. The Cochrane Collaboration's RevMan software program was used for the statistical analysis.
RESULTS
Eleven trials involving 535 patients were included for the final analysis. Compared to the placebo or control group, liraglutide decreased liver fat (LF) (insulin: mean difference MD - 2.50, 95% confidence interval [CI] - 4.30 to - 0.70), body mass index (BMI) (placebo: MD - 1.13, 95% CI - 2.03 to - 0.23; pioglitazone: MD - 4.10, 95% CI - 6.27 to - 1.93; metformin: MD - 1.07, 95% CI - 2.06 to - 0.08; insulin: MD - 1.01, 95% CI - 1.60 to - 0.43), lipoproteins, including high-density (insulin: MD - 0.10, 95% CI - 0.15 to - 0.05) and low-density lipoproteins (MD - 0.26, 95% CI - 0.43 to - 0.10), glycated hemoglobin A1c (HbA1c) (placebo: MD - 0.86; 95% CI - 1.22 to - 0.51; insulin: MD - 0.22, 95% CI - 0.41 to - 0.04), total cholesterol (placebo: MD - 0.34, 95% CI - 0.65 to - 0.03; metformin: MD 0.09, 95% CI 0.01-0.18), and triglycerides (placebo: MD - 0.29, 95% CI - 0.57 to - 0.01; insulin: MD - 0.80, 95% CI - 1.03 to - 0.57). Liraglutide may be associated with increased gastrointestinal reactions compared to pioglitazone.
CONCLUSION
These findings revealed that liraglutide decreased LF, BMI, lipids, or HbA1c in T2DM patients complicated with NAFLD, indicating its potential therapeutic efficacy.
PubMed: 34002333
DOI: 10.1007/s13300-021-01072-4 -
Frontiers in Endocrinology 2021To systematically evaluate the effects of pioglitazone in the treatment of patients with prediabetes or T2DM combined with NAFLD. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the effects of pioglitazone in the treatment of patients with prediabetes or T2DM combined with NAFLD.
METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and ClinicalTrials databases were searched until August 2020 for publications written in English. Two reviewers independently assessed study eligibility, continuous data extraction, independent assessment of bias risk, and graded the strength of evidence. Our primary outcomes were the individual number of patients with improvement of at least 1 point in each of the histological parameters. Baseline characteristic data, such as BMI, weight, total body fat, fasting plasma glucose and fasting plasma insulin, and liver biological indicators, such as triglyceride level, HDL cholesterol level, plasma AST, and plasma ALT, were used as secondary outcomes.
RESULTS
A total of 4 studies were included. Compared with placebo, pioglitazone significantly improved steatosis grade, inflammation grade and ballooning grade, while in the fibrosis stage, there was no significant improvement in pioglitazone compared with placebo. In addition, pioglitazone can also improve blood glucose and liver function.
CONCLUSION
Pioglitazone can significantly improve the histological performance of the liver and insulin sensitivity. Additionally, it can significantly reduce fasting blood glucose, glycosylated hemoglobin, plasma AST, ALT and other liver biological indicators. Due to the lack of relevant randomized controlled trials and short intervention times, long-term studies are still needed to verify its efficacy and safety.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO], identifier [CRD42020212025].
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Non-alcoholic Fatty Liver Disease; Pioglitazone; Prediabetic State; Treatment Outcome
PubMed: 33995271
DOI: 10.3389/fendo.2021.615409 -
Frontiers in Endocrinology 2021To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To comprehensively evaluate and compare the therapeutic effects of various hypoglycemic agents in NAFLD patients with or without diabetes.
METHODS
All literature from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Clinical Trials was searched, and the language was limited to English. Two reviewers independently assessed study eligibility, continuous data extraction, and independent assessment of bias risk. Our primary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride levels, while our secondary outcomes were high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, body weight, BMI, and fasting glucose and glycosylated hemoglobin (HbA1c) levels.
RESULTS
The review identified 20 eligible trials that met the inclusion criteria. We found that, compared to other drugs, thiazolidinediones, especially pioglitazone, had a greater effect on the levels of ALT (-8.01 (95% CI -14.3 to 2.02)) and AST (-5.0 (95% CI -9.21 to -1,22)) and other biological indicators, but they were also associated with an increased risk of weight gain (3.62 (95% CI 2.25 to 4.99) and increased BMI (0.59 (95% Cl -0.13 to 1.29). GLP1 RAs and metformin also had better therapeutic effects than other drugs as measured by the levels of ALT (liraglutide: -9.36 (95% Cl -18 to -0.34), metformin: -2.84 (95% CI -11.09 to 5.28)) and AST (liraglutide: -5.14 (95% CI -10.69 to 0.37), metformin: -2.39 (95% CI -7.55, 2.49)) and other biological indicators.
CONCLUSION
Despite the significant risk of weight gain, thiazolidinediones, especially pioglitazone, are beneficial in normalizing liver and glucose metabolism in NAFLD patients. In clinical practice, we believe that GLP1 RAs such as liraglutide and exenatide or metformin can be used in combination to offset the risk of weight gain associated with thiazolidinediones. However, long-term studies are still needed to verify the efficacy and safety of individual hypoglycemic agents.
SYSTEMATIC REVIEW REGISTRATION
[PROSPERO], identifier [CRD42020212025].
Topics: Alanine Transaminase; Aspartate Aminotransferases; Bayes Theorem; Blood Glucose; Body Mass Index; Body Weight; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Glycated Hemoglobin; Glycosylation; Humans; Hypoglycemic Agents; Lipoproteins, HDL; Lipoproteins, LDL; Metformin; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Pioglitazone; Reproducibility of Results; Risk; Treatment Outcome
PubMed: 33841337
DOI: 10.3389/fendo.2021.649018 -
Frontiers in Public Health 2020Diabetes is a long-term condition that can be treated and controlled but do not yet have a cure; it could be induced by inflammation and the goal of managing it is to...
Diabetes is a long-term condition that can be treated and controlled but do not yet have a cure; it could be induced by inflammation and the goal of managing it is to prevent additional co-morbidities and reduce glycemic fluctuations. There is a need to examine inflammatory activities in diabetes-related angiopathies and explore interventions that could reduce the risk for future outcome or ameliorate its effects to provide insights for improved care and management strategies. The study was conducted in Embase (1946-2020), Ovid Medline (1950-2020), and PubMed databases (1960-2020) using the PICO framework. Primary studies (randomized controlled trials) on type 2 diabetes mellitus and inflammatory activities in diabetes-related angiopathies were included. Terms for the review were retrieved from the Cochrane library and from PROSPERO using its MeSH thesaurus qualifiers. Nine articles out of 454 total hits met the eligibility criteria. The quality assessment for the selected study was done using the Center for Evidence-Based Medicine Critical Appraisal Sheet. Data analysis showed that elevated CRP, TNF-α, and IL-6 were the most commonly found inflammatory indicator in diabetes-related angiopathies, while increased IL-10 and soluble RAGE was an indicator for better outcome. Use of drugs such as salsalate, pioglitazone, simvastatin, and fenofibrate but not glimepiride or benfotiamine reported a significant decrease in inflammatory events. Regular exercise and consumption of dietary supplements such as ginger, hesperidin which have anti-inflammatory properties, and those containing prebiotic fibers (e.g., raspberries) revealed a consistent significant ( < 0.05) reduction in inflammatory activities. Inflammatory activities are implicated in diabetes-related angiopathies; regular exercise, the intake of healthy dietary supplements, and medications with anti-inflammatory properties could result in improved protective risk outcome for diabetes patients by suppressing inflammatory activities and elevating anti-inflammatory events.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise; Humans; Tumor Necrosis Factor-alpha
PubMed: 33569370
DOI: 10.3389/fpubh.2020.600427 -
Cureus Dec 2020Lichen planus (L.P.) is a long-standing mucocutaneous inflammatory condition. A less familiar but essential illness association is increased arterial stiffness,... (Review)
Review
Can Pioglitazone Safeguard Patients of Lichen Planus Against Homocysteine Induced Accelerated Cardiovascular Aging and Reduced Myocardial Performance: A Systematic Review.
Lichen planus (L.P.) is a long-standing mucocutaneous inflammatory condition. A less familiar but essential illness association is increased arterial stiffness, endothelial dysfunction, and advanced atherosclerosis. Enhanced cardiac reconditioning and reduced performance of the heart have been suggested. Thiazolidinediones were commenced to manage hyperglycemia in diabetes mellitus. Recently, the class attained popularity after its action on vascular physiology was discovered. With this review, we attempted to explore whether an antidiabetic drug, pioglitazone (PIO), a peroxisome proliferator‑activated receptor γ (PPAR gamma) agonist, can defend patients of lichen planus against increased arterial stiffness and cardiac changes. We methodically screened numerous databases using focused words and phrases for relevant articles. After a comprehensive exploration, we applied the inclusion and exclusion criteria and performed a quality appraisal. Items retained were exhaustively studied. High homocysteine (HHcy) levels in lichen planus play a significant role in modifying the arteries and leading to their dysfunction. Not only does homocysteine affect the precursor cells, but it also increases the free radical damage. Arterial damage and upraised resistance encountered by the heart reduce its performance. After an exhaustive analysis, in our opinion, pioglitazone works in various miscellaneous ways to mitigate the homocysteine mediated changes. Early inclusion of the drug in managing patients with lichen planus seems promising in minimizing the harmful effects of high homocysteine. Evaluating the risk-benefit ratio, we believe that a trial of pioglitazone could be given to patients without underlying cardiac conditions.
PubMed: 33527053
DOI: 10.7759/cureus.12372 -
Diabetes, Obesity & Metabolism Apr 2021To compare different treatments for non-alcoholic steatohepatitis (NASH) and to determine an effectiveness hierarchy. (Meta-Analysis)
Meta-Analysis
AIMS
To compare different treatments for non-alcoholic steatohepatitis (NASH) and to determine an effectiveness hierarchy.
MATERIALS AND METHODS
We conducted a systematic review and Bayesian network meta-analysis including randomized controlled trials or prospective trials with at least 6 months' follow-up and histologically proven NASH in adult participants. Monte Carlo simulations were performed, each generating 10 000 data points, and results are reported as medians and 95% credibility intervals (CrIs). A meta-regression was conducted to find the effects of body mass index (BMI) decrement or reduction of homeostatic model assessment of insulin resistance (HOMA-IR) index on non-alcoholic fatty liver disease activity score (NAS) change.
RESULTS
The review identified 48 eligible trials comprising 2356 adults (55.6% men). Data were pooled using a random-effects model. The most effective treatments in terms of NAS reduction per semester were pioglitazone and Roux-en-Y gastric bypass (RYGB; -1.50 [95% CrI -2.08, -1.00] for pioglitazione and -1.00 [95% CrI -1.70, -0.32] for RYGB). Pioglitazone was also the best therapy for steatosis and lobular inflammation reduction. RYGB was the best treatment for hepatocellular ballooning reduction, whereas antioxidants appeared to be best for fibrosis improvement. For each 1% decrement in BMI, NAS was reduced by 1.3% (β = 1.28%, P = 0.01). Conversely, a 1% reduction of HOMA-IR index reduced NAS by 0.3% (β = 0.31%, P < 0.001). Treatments that were regarded as promising, such as elafibranor, simtuzumab, selonsertib, cenicriviroc, obeticholic acid and liraglutide, did not reduce either NAS or liver fibrosis significantly.
CONCLUSIONS
Pioglitazione and RYGB are the most effective therapies for NASH. Antioxidants may be effective in reducing liver fibrosis. Weight loss and improvement of hepatic insulin resistance are promising approaches in the treatment of NASH.
Topics: Adult; Bariatric Surgery; Bayes Theorem; Female; Humans; Liver; Male; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Pioglitazone; Prospective Studies
PubMed: 33368954
DOI: 10.1111/dom.14304 -
The Cochrane Database of Systematic... Nov 2020The term prediabetes is used to describe a population with an elevated risk of developing type 2 diabetes mellitus (T2DM). With projections of an increase in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The term prediabetes is used to describe a population with an elevated risk of developing type 2 diabetes mellitus (T2DM). With projections of an increase in the incidence of T2DM, prevention or delay of the disease and its complications is paramount. It is currently unknown whether pioglitazone is beneficial in the treatment of people with increased risk of developing T2DM.
OBJECTIVES
To assess the effects of pioglitazone for prevention or delay of T2DM and its associated complications in people at risk of developing T2DM.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Chinese databases, ICTRP Search Portal and ClinicalTrials.gov. We did not apply any language restrictions. Further, we investigated the reference lists of all included studies and reviews. We tried to contact all study authors. The date of the last search of databases was November 2019 (March 2020 for Chinese databases).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with a minimum duration of 24 weeks, and participants diagnosed with intermediate hyperglycaemia with no concomitant diseases, comparing pioglitazone as monotherapy or part of dual therapy with other glucose-lowering drugs, behaviour-changing interventions, placebo or no intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened abstracts, read full-text articles and records, assessed risk of bias and extracted data. We performed meta-analyses with a random-effects model and calculated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, with 95% confidence intervals (CIs) for effect estimates. We evaluated the certainty of the evidence with the GRADE.
MAIN RESULTS
We included 27 studies with a total of 4186 randomised participants. The size of individual studies ranged between 43 and 605 participants and the duration varied between 6 and 36 months. We judged none of the included studies as having low risk of bias across all 'Risk of bias' domains. Most studies identified people at increased risk of T2DM by impaired fasting glucose or impaired glucose tolerance (IGT), or both. Our main outcome measures were all-cause mortality, incidence of T2DM, serious adverse events (SAEs), cardiovascular mortality, nonfatal myocardial infarction or stroke (NMI/S), health-related quality of life (QoL) and socioeconomic effects. The following comparisons mostly reported only a fraction of our main outcome set. Three studies compared pioglitazone with metformin. They did not report all-cause and cardiovascular mortality, NMI/S, QoL or socioeconomic effects. Incidence of T2DM was 9/168 participants in the pioglitazone groups versus 9/163 participants in the metformin groups (RR 0.98, 95% CI 0.40 to 2.38; P = 0.96; 3 studies, 331 participants; low-certainty evidence). No SAEs were reported in two studies (201 participants; low-certainty evidence). One study compared pioglitazone with acarbose. Incidence of T2DM was 1/50 participants in the pioglitazone group versus 2/46 participants in the acarbose group (very low-certainty evidence). No participant experienced a SAE (very low-certainty evidence).One study compared pioglitazone with repaglinide. Incidence of T2DM was 2/48 participants in the pioglitazone group versus 1/48 participants in the repaglinide group (low-certainty evidence). No participant experienced a SAE (low-certainty evidence). One study compared pioglitazone with a personalised diet and exercise consultation. All-cause and cardiovascular mortality, NMI/S, QoL or socioeconomic effects were not reported. Incidence of T2DM was 2/48 participants in the pioglitazone group versus 5/48 participants in the diet and exercise consultation group (low-certainty evidence). No participant experienced a SAE (low-certainty evidence). Six studies compared pioglitazone with placebo. No study reported on QoL or socioeconomic effects. All-cause mortality was 5/577 participants the in the pioglitazone groups versus 2/579 participants in the placebo groups (Peto odds ratio 2.38, 95% CI 0.54 to 10.50; P = 0.25; 4 studies, 1156 participants; very low-certainty evidence). Incidence of T2DM was 80/700 participants in the pioglitazone groups versus 131/695 participants in the placebo groups (RR 0.40, 95% CI 0.17 to 0.95; P = 0.04; 6 studies, 1395 participants; low-certainty evidence). There were 3/93 participants with SAEs in the pioglitazone groups versus 1/94 participants in the placebo groups (RR 3.00, 95% CI 0.32 to 28.22; P = 0.34; 2 studies, 187 participants; very low-certainty evidence). However, the largest study for this comparison did not distinguish between serious and non-serious adverse events. This study reported that 121/303 (39.9%) participants in the pioglitazone group versus 151/299 (50.5%) participants in the placebo group experienced an adverse event (P = 0.03). One study observed cardiovascular mortality in 2/181 participants in the pioglitazone group versus 0/186 participants in the placebo group (RR 5.14, 95% CI 0.25 to 106.28; P = 0.29; very low-certainty evidence). One study observed NMI in 2/303 participants in the pioglitazone group versus 1/299 participants in the placebo group (RR 1.97: 95% CI 0.18 to 21.65; P = 0.58; very low-certainty evidence). Twenty-one studies compared pioglitazone with no intervention. No study reported on cardiovascular mortality, NMI/S, QoL or socioeconomic effects. All-cause mortality was 11/441 participants in the pioglitazone groups versus 12/425 participants in the no-intervention groups (RR 0.85, 95% CI 0.38 to 1.91; P = 0.70; 3 studies, 866 participants; very low-certainty evidence). Incidence of T2DM was 60/1034 participants in the pioglitazone groups versus 197/1019 participants in the no-intervention groups (RR 0.31, 95% CI 0.23 to 0.40; P < 0.001; 16 studies, 2053 participants; moderate-certainty evidence). Studies reported SAEs in 16/610 participants in the pioglitazone groups versus 21/601 participants in the no-intervention groups (RR 0.71, 95% CI 0.38 to 1.32; P = 0.28; 7 studies, 1211 participants; low-certainty evidence). We identified two ongoing studies, comparing pioglitazone with placebo and with other glucose-lowering drugs. These studies, with 2694 participants. may contribute evidence to future updates of this review.
AUTHORS' CONCLUSIONS
Pioglitazone reduced or delayed the development of T2DM in people at increased risk of T2DM compared with placebo (low-certainty evidence) and compared with no intervention (moderate-certainty evidence). It is unclear whether the effect of pioglitazone is sustained once discontinued. Pioglitazone compared with metformin neither showed advantage nor disadvantage regarding the development of T2DM in people at increased risk (low-certainty evidence). The data and reporting of all-cause mortality, SAEs, micro- and macrovascular complications were generally sparse. None of the included studies reported on QoL or socioeconomic effects.
Topics: Acarbose; Bias; Carbamates; Cardiovascular Diseases; Confidence Intervals; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Pioglitazone; Piperidines; Placebos; Randomized Controlled Trials as Topic; Risk
PubMed: 33210751
DOI: 10.1002/14651858.CD013516.pub2 -
Dementia and Geriatric Cognitive... 2020Considering that Alzheimer's disease (AD) and diabetes mellitus share pathophysiological features and AD remains with no cure, antidiabetic drugs like intranasal...
INTRODUCTION
Considering that Alzheimer's disease (AD) and diabetes mellitus share pathophysiological features and AD remains with no cure, antidiabetic drugs like intranasal insulin, glitazones, metformin, and liraglutide are being tested as a potential treatment.
OBJECTIVE
The aim of this systematic review was to assess the efficacy of antidiabetic drugs in patients with AD, mild cognitive impairment (MCI), or subjective cognitive complaints (SCCs). Cognition was studied as the primary outcome and modulation of AD biomarkers, and imaging was also assessed as a secondary outcome.
METHODS
We conducted a search in the electronic databases PubMed/MEDLINE, EMBASE, and Scopus seeking clinical trials evaluating the effect on cognition of antidiabetic drugs in patients with AD, MCI, or SCCs.
RESULTS
A total of 23 articles were found eligible. Intranasal regular insulin improved verbal memory in most studies, especially in apoE4- patients, but results in other cognitive domains were unclear. Detemir improved cognition after 2 months of treatment, but it did not after 4 months. Pioglitazone improved cognition in diabetic patients with AD or MCI in 3 clinical trials, but it is controversial as 2 other studies did not show effect. Metformin and liraglutide showed promising results, but further research is needed as just 2 clinical trials involved each of these drugs. Almost all drugs tested were shown to modulate AD biomarkers and imaging.
CONCLUSIONS
Intranasal insulin, pioglitazone, metformin, and liraglutide are promising drugs that could be useful in the treatment of AD. However, many questions remain to be answered in future studies, so no particular antidiabetic drug can currently be recommended to treat AD.
Topics: Alzheimer Disease; Cognition; Diabetes Mellitus; Humans; Hypoglycemic Agents
PubMed: 33080602
DOI: 10.1159/000510677 -
The Cochrane Database of Systematic... Jul 2020Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017.
OBJECTIVES
To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 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), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). 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
Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause).
AUTHORS' CONCLUSIONS
The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.
Topics: Adamantane; Bias; Cause of Death; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Fasting; Glycated Hemoglobin; Graft Survival; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Kidney Transplantation; Nitriles; Pioglitazone; Postoperative Complications; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones; Transplant Recipients; Vildagliptin
PubMed: 32803882
DOI: 10.1002/14651858.CD009966.pub3 -
Systematic Reviews Nov 2019Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of...
BACKGROUND
Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD.
METHODS
We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications.
RESULTS
We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight.
CONCLUSIONS
Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.
Topics: Blood Glucose; Body Weight; Exenatide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Liraglutide; Metformin; Non-alcoholic Fatty Liver Disease; Pioglitazone; Randomized Controlled Trials as Topic; Rosiglitazone
PubMed: 31783920
DOI: 10.1186/s13643-019-1200-8