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Frontiers in Endocrinology 2023Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.
METHODS
A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).
RESULTS
With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).
CONCLUSION
Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Sodium-Glucose Transporter 2 Inhibitors; Acarbose; Dipeptidyl-Peptidase IV Inhibitors; Insulin; Glucagon-Like Peptide 1
PubMed: 38239984
DOI: 10.3389/fendo.2023.1303238 -
Acta Gastro-enterologica Belgica 2022Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus... (Review)
Review
Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far ?
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.
Topics: Carcinoma, Hepatocellular; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glucose; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Prospective Studies; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35709779
DOI: 10.51821/85.2.9775 -
Cardiovascular Diabetology Feb 2024The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) use. Since then, additional trials of relevance for SGLT2i have been published. This update re-evaluates the clinical recommendations for using SGLTi and their indirect comparison with existing evidence on GLP-1RA as compared to the standard of care to reduce cardiorenal morbidity and mortality.
METHODS
We updated our existing search and screening of the literature from September 2021 to April 2023 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. We conducted risk of bias assessment, data extraction and updated our meta-analysis of studies with similar interventions and components. The certainty of the evidence was determined using GRADE.
RESULTS
Evidence from three new trials and additional results from an updated existing trial on SGLT2i met our inclusion criteria after an updated search. Across all the included studies, the total sample size was 151,023 adults, with 90,943 in SGLT2i trials and 60,080 in GLP-1 RA trials. The mean age ranged from 59.9 to 68.4 years. Compared with standard care, the use of SGLT2i and GLP-1 RA showed significant reductions in the outcomes of cardiovascular (CV) mortality (14% & 13%), any-cause mortality (12% & 12%), major adverse CV events (MACE) (11% & 14%), heart failure (HF) hospitalization (30% & 9%), CV death or HF hospitalization (23% & 11%), and kidney composite outcome (32% & 22%). In participants with T2D, both classes demonstrated significant cardiorenal protection. But, only GLP-1RA showed a reduction in non-fatal stroke (16%) and only SGLT2i showed a reduction in HF hospitalization (30%) in this population of people living with T2D.
CONCLUSIONS
This updated and comprehensive meta-analysis substantiates and strengthens the clinical recommendations of the CCS cardiorenal guidelines.
Topics: Adult; Aged; Humans; Middle Aged; Canada; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Heart Failure; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38360604
DOI: 10.1186/s12933-024-02154-w -
International Journal of Molecular... Apr 2023As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered... (Review)
Review
As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment's pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Liraglutide; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Cardiovascular Diseases; Microbiota; Glucagon-Like Peptide-1 Receptor
PubMed: 37108347
DOI: 10.3390/ijms24087184 -
Toxins Apr 2020Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of...
Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of low-molecular-weight peptide toxins that have evolved to target voltage-gated ion channels to interfere with the central system of prey and produce pain or paralysis for efficient hunting. Peptide toxins usually contain several intramolecular disulfide bonds, which confer chemical, thermal and biological stability. In addition, centipede peptides generally have novel structures and high potency and specificity and therefore hold great promise both as diagnostic tools and in the treatment of human disease. Here, we review the centipede peptide toxins with reported effects on ion channels, including Nav, Kv, Cav and the nonselective cation channel polymodal transient receptor potential vanilloid 1 (TRPV1).
Topics: Animals; Arthropod Proteins; Arthropod Venoms; Bites and Stings; Chilopoda; Drug Discovery; Humans; Ion Channels; Membrane Transport Modulators; Protein Conformation; Signal Transduction; Structure-Activity Relationship
PubMed: 32260499
DOI: 10.3390/toxins12040230 -
Annals of Medicine and Surgery (2012) May 2022We aim to evaluate the impacts of sodium-glucose co-transporter 2 inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4)... (Review)
Review
AIM
We aim to evaluate the impacts of sodium-glucose co-transporter 2 inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4) inhibitors on the levels of high-density lipoprotein, low-density lipoprotein, triglyceride and total cholesterol.
METHODS
The MEDLINE database was searched from inception till October 2021, for randomized controlled trials assessing the effects of sodium-glucose co-transporter two inhibitors (SGLT-2), glucagon-like peptide 1 agonist (GLP-1RAs), and dipeptidyl peptidase-four (DPP4) inhibitors on lipid levels.
RESULTS
A total of 57 trials were included in the analysis. Our pooled analysis demonstrates that SGLT-2 inhibitors significantly increase the levels of HDL (WMD = 0.07 mg/dL [0.06 to 0.08], P < 0.00001). SGLT-2 inhibitors were also found to be significantly associated with an increase in the levels of LDL (WMD = 0.11 mg/dL, [0.09-0.13 mg/dL, P < 0.00001). Pooled analysis also demonstrates that SGLT-2 inhibitors significantly reduce the levels of triglyceride (WMD = -0.10 mg/dL, [-0.13 to -0.06], P < 0.00001). Our pooled analysis demonstrates that SGLT-2 inhibitors significantly increased the levels of total cholesterol (WMD = 0.10 mg/dL, [0.06 to 0.15], P < 0.0001), whereas, GLP-1RAs significantly reduced the levels of total cholestrol (WMD = -0.18 mg/dL, [-0.34 to -0.02], P = 0.03).
CONCLUSION
This is the first head-to-head study comparing the effects of 3-novel glucose-lowering agents to lipid parameters. However, more trials are crucial to better understand the impact of glucose-lowering drugs on lipid parameters.
PubMed: 35637990
DOI: 10.1016/j.amsu.2022.103633 -
BMC Endocrine Disorders Nov 2023The low-grade chronic inflammation in diabetes plays an important role in development of cardiovascular and renal complications. Sodium-glucose co-transporter-2 (SGLT2)... (Meta-Analysis)
Meta-Analysis
The effect of sodium-glucose co-transporter-2 (SGLT2) inhibitors on blood interleukin-6 concentration: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The low-grade chronic inflammation in diabetes plays an important role in development of cardiovascular and renal complications. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recognized as protective agents for cardio-renal complications. Interleukin-6 (IL-6) is positively associated with the pathophysiology of metabolic-related pathologies. The aim of this meta-analysis is to investigate the effect of SGLT2 inhibitors on blood IL-6 concentration in randomized controlled trials (RCTs).
METHODS
Embase, PubMed, and Scopus were systematically searched up to 1 of November 2023. The eligible studies were RCTs with adult population that had provided blood IL-6 for both control and intervention groups. Cochrane risk-of-bias tool were for study quality assessment. Data were analyzed using random effect model via Stata statistical software.
RESULTS
Eighteen studies with a total of 5311 patients were included. Of which 3222 and 2052 patients were in intervention and control arm, respectively. Of the total population, 49.7% were men. The study durations ranged from 8 to 52 weeks. The pooled analysis showed a significant association between the use of SGLT2 inhibitors and lower IL-6 levels (standardized mean difference (SMD) = -1.04, Confidence Interval (CI): -1.48; -0.60, I = 96.93%). Dapagliflozin was observed to have a higher IL-6-lowering effect (SMD = -1.30, CI: -1.89; -0.71, I = 92.52) than empagliflozin or canagliflozin. Sub-group analysis of control groups (SMD = -0.58 (-1.01, -0.15) and -1.35 (-2.00, -0.70 for the placebo and active control sub-groups, respectively) and duration of interventions (SMD = -0.78 (-1.28, -0.28) and -1.20 (-1.86, -0.55) for study duration of ≤ 12 and > 12 weeks, respectively) did not change the results. Meta-regression analysis showed a significant correlation between the level of HbA and IL-6-lowering efficacy of SGLT2 inhibitors.
CONCLUSION
IL-6 levels are significantly reduced with the use of SGLT2 inhibitors with HbA as the only marker influencing such reductions, and dapagliflozin had the highest potency. The anti-inflammatory effect of SGLT2 inhibitors supports their broader use to address diabetic complications related to inflammatory responses.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Interleukin-6; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2; Randomized Controlled Trials as Topic; Glucose; Sodium
PubMed: 37996879
DOI: 10.1186/s12902-023-01512-1 -
Diabetes Research and Clinical Practice Feb 2021This systematic review and meta-analysis aims to evaluate the safety and efficacy of the newer glucose lowering treatments on glycemic control, weight, blood pressure... (Meta-Analysis)
Meta-Analysis
AIMS
This systematic review and meta-analysis aims to evaluate the safety and efficacy of the newer glucose lowering treatments on glycemic control, weight, blood pressure and hypoglycemia in patients with T2DM during Ramadan.
METHODS
A literature search was done in PubMed, Embase, and the Cochrane Library. Quality assessment was done using the ROBINS-I and Cochrane tools for risk of bias and analyses were performed using RevMan version 5.3.
RESULTS
A total of 20 studies were included in the meta-analysis. Dipeptidyl peptidase-4 inhibitors (DPP-4i) led to a significant reduction in Hb (%) (SMD -0.25) and a non-significant decrease in weight (kg) (SMD -1.06) during Ramadan. Glucagon-like peptide (GLP-1) agonist therapy was associated with a significant decrease in Hb (%) (SMD -0.68) and a non-significant decrease in weight (kg) (SMD -2.57) and systolic blood pressure (SBP) (mmHg) (SMD -3.50) after Ramadan. Sodium-glucose co-transporter 2 inhibitor (SGLT-2i) therapy was associated with a significant decrease in Hb (%) (SMD -0.51) and a non-significant decrease in weight (kg) (SMD -1.41), SBP (SMD -1.10) and diastolic blood pressure (DBP) (mmHg) (SMD -2.08) after Ramadan.
CONCLUSIONS
This systematic review and meta-analysis shows clinical benefits with the newer glucose lowering medications in patients with T2DM who fast during Ramadan.
Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Humans; Hypoglycemia; Hypoglycemic Agents; Islam
PubMed: 33271228
DOI: 10.1016/j.diabres.2020.108562 -
Frontiers in Endocrinology 2024The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes... (Meta-Analysis)
Meta-Analysis
First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis.
BACKGROUND
The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) with low risk of cardiovascular diseases are not clear.
METHODS
PubMed, EMBASE and Cochrane Library databases were searched to identify eligible randomized controlled trials. We used the odds ratio (OR) and mean difference (MD) and the corresponding 95% confidence interval (CI) to assess the dichotomous and continuous variable, respectively.
RESULTS
Thirteen studies involving 2,885 T2DM at low risk of cardiovascular diseases were included. Compared to placebo, first line use of SGLT2i significantly reduced glycosylated hemoglobin type A1C (HbA1c) (MD: -0.72), weight (MD: -1.32) and fasting plasma glucose (FPG) (MD: -27.05) levels. Compared with metformin, SGLT2i reduced body weight (MD: -1.50) and FPG (MD: -10.13) more effectively, with similar reduction for HbA1c (MD: -0.05). No significant increased safety adverse was found for SGLT2i, including nasopharyngitis (OR: 1.07), urinary tract infection (OR: 2.31), diarrhea (OR: 1.18) and hypoglycemia (OR: 1.06). GLP-1RAs significantly reduced HbA1c (MD: -1.13), weight (MD: -2.12) and FPG (MD: -31.44) levels as first-line therapy compared to placebo. GLP-1RAs significantly increased occurrence of diarrhea (OR: 2.18), hypoglycemia (OR: 3.10), vomiting (OR: 8.22), and nausea (OR: 4.41).
CONCLUSION
First line use of SGLT2i and GLP-1RAs is effective in reducing HbA1c, weight, and FPG levels in T2DM patients at low risk for cardiovascular disease. SGLT2i may be superior to metformin in controlling body weight and FPG. GLP-1RAs may increase the occurrence of diarrhea, hypoglycemia, vomiting, and nausea.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (International Prospective Register of Systematic Reviews. https://www.york.ac.uk/inst/crd, CRD42022347233).
Topics: Humans; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diarrhea; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Hypoglycemia; Hypoglycemic Agents; Metformin; Nausea; Sodium; Systematic Reviews as Topic; Vomiting
PubMed: 38348420
DOI: 10.3389/fendo.2024.1289643 -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in...
BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.
OBJECTIVE
A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.
METHODS
Searches were conducted via three different databases (PubMed, Embase, and Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: 'glucagon-like peptide 1 receptor agonist' and 'Alzheimer's disease', as well as entry terms 'GLP-1 RA', 'AD', and three types of GLP-1 RA: 'liraglutide', 'exenatide', and 'lixisenatide'.
RESULTS
A total of 1,444 studies were screened. Six articles that met criteria were included (four randomized control trials [RCTs] and two protocol studies). Two RCTs with amyloid-β and tau biomarker endpoints did not observe an end of treatment difference between the placebo and treated groups. In three RCTs with cognitive endpoints, there was no end of treatment difference between placebo and treated groups. GLP-1 RA showed metabolic benefits, such as lower body mass index and improved glucose levels on oral glucose tolerance tests in treated groups. GLP-1 RA may mitigate the decline in cerebral glucose metabolism and show enhanced blood-brain glucose transport capacity using F-FDG PET, however, more data is needed.
CONCLUSIONS
GLP-1 RA therapy did not alter amyloid-β and tau biomarkers nor show improvements in cognition but showed potential metabolic and neuroprotective benefits.
PubMed: 38746639
DOI: 10.3233/ADR-230181