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PloS One 2023Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.
METHODS
We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.
CONCLUSIONS
As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.
Topics: Adult; Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Angiotensin Receptor Antagonists; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Kidney Failure, Chronic; Angiotensins; Diabetes Mellitus
PubMed: 37917640
DOI: 10.1371/journal.pone.0293183 -
Journal of Inherited Metabolic Disease Mar 2023In patients with ATP7A-related disorders, counseling is challenging due to clinical overlap between the entities, the absence of predictive biomarkers and a clear... (Review)
Review
In patients with ATP7A-related disorders, counseling is challenging due to clinical overlap between the entities, the absence of predictive biomarkers and a clear genotype-phenotype correlation. We performed a systematic literature review by querying the MEDLINE and Embase databases identifying 143 relevant papers. We recorded data on the phenotype and genotype in 162 individuals with a molecularly confirmed ATP7A-related disorder in order to identify differentiating clinical criteria, evaluate genotype-phenotype correlations and propose management guidelines. Early seizures are specific for classical Menkes disease (CMD), that is characterized by early-onset neurodegenerative disease with high mortality rates. Ataxia is an independent indicator for atypical Menkes disease, that shows better survival rates than CMD. Bony exostoses, radial head dislocations, herniations and dental abnormalities are specific for occipital horn syndrome (OHS) that may further present with developmental delay and connective tissue manifestations. Intracranial tortuosity and bladder diverticula, both with high risk of complications, are common among all subtypes. Low ceruloplasmin is a more sensitive and discriminating biomarker for ATP7A-related disorders than serum copper. Truncating mutations are frequently associated with CMD, in contrast with splice site and intronic mutations which are more prevalent in OHS.
Topics: Humans; Menkes Kinky Hair Syndrome; Copper; Neurodegenerative Diseases; Copper-Transporting ATPases; Cutis Laxa; Mutation; Peptide Fragments
PubMed: 36692329
DOI: 10.1002/jimd.12590 -
The Cochrane Database of Systematic... Oct 2021Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists... (Meta-Analysis)
Meta-Analysis
Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.
BACKGROUND
Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) were approved for treating people with type 2 diabetes mellitus. Although metformin remains the first-line pharmacotherapy for people with type 2 diabetes mellitus, a body of evidence has recently emerged indicating that DPP4i, GLP-1RA and SGLT2i may exert positive effects on patients with known CVD.
OBJECTIVES
To systematically review the available evidence on the benefits and harms of DPP4i, GLP-1RA, and SGLT2i in people with established CVD, using network meta-analysis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and the Conference Proceedings Citation Index on 16 July 2020. We also searched clinical trials registers on 22 August 2020. We did not restrict by language or publication status.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) investigating DPP4i, GLP-1RA, or SGLT2i that included participants with established CVD. Outcome measures of interest were CVD mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, all-cause mortality, hospitalisation for heart failure (HF), and safety outcomes.
DATA COLLECTION AND ANALYSIS
Three review authors independently screened the results of searches to identify eligible studies and extracted study data. We used the GRADE approach to assess the certainty of the evidence. We conducted standard pairwise meta-analyses and network meta-analyses by pooling studies that we assessed to be of substantial homogeneity; subgroup and sensitivity analyses were also pursued to explore how study characteristics and potential effect modifiers could affect the robustness of our review findings. We analysed study data using the odds ratios (ORs) and log odds ratios (LORs) with their respective 95% confidence intervals (CIs) and credible intervals (Crls), where appropriate. We also performed narrative synthesis for included studies that were of substantial heterogeneity and that did not report quantitative data in a usable format, in order to discuss their individual findings and relevance to our review scope.
MAIN RESULTS
We included 31 studies (287 records), of which we pooled data from 20 studies (129,465 participants) for our meta-analysis. The majority of the included studies were at low risk of bias, using Cochrane's tool for assessing risk of bias. Among the 20 pooled studies, six investigated DPP4i, seven studied GLP-1RA, and the remaining seven trials evaluated SGLT2i. All outcome data described below were reported at the longest follow-up duration. 1. DPP4i versus placebo Our review suggests that DPP4i do not reduce any risk of efficacy outcomes: CVD mortality (OR 1.00, 95% CI 0.91 to 1.09; high-certainty evidence), myocardial infarction (OR 0.97, 95% CI 0.88 to 1.08; high-certainty evidence), stroke (OR 1.00, 95% CI 0.87 to 1.14; high-certainty evidence), and all-cause mortality (OR 1.03, 95% CI 0.96 to 1.11; high-certainty evidence). DPP4i probably do not reduce hospitalisation for HF (OR 0.99, 95% CI 0.80 to 1.23; moderate-certainty evidence). DPP4i may not increase the likelihood of worsening renal function (OR 1.08, 95% CI 0.88 to 1.33; low-certainty evidence) and probably do not increase the risk of bone fracture (OR 1.00, 95% CI 0.83 to 1.19; moderate-certainty evidence) or hypoglycaemia (OR 1.11, 95% CI 0.95 to 1.29; moderate-certainty evidence). They are likely to increase the risk of pancreatitis (OR 1.63, 95% CI 1.12 to 2.37; moderate-certainty evidence). 2. GLP-1RA versus placebo Our findings indicate that GLP-1RA reduce the risk of CV mortality (OR 0.87, 95% CI 0.79 to 0.95; high-certainty evidence), all-cause mortality (OR 0.88, 95% CI 0.82 to 0.95; high-certainty evidence), and stroke (OR 0.87, 95% CI 0.77 to 0.98; high-certainty evidence). GLP-1RA probably do not reduce the risk of myocardial infarction (OR 0.89, 95% CI 0.78 to 1.01; moderate-certainty evidence), and hospitalisation for HF (OR 0.95, 95% CI 0.85 to 1.06; high-certainty evidence). GLP-1RA may reduce the risk of worsening renal function (OR 0.61, 95% CI 0.44 to 0.84; low-certainty evidence), but may have no impact on pancreatitis (OR 0.96, 95% CI 0.68 to 1.35; low-certainty evidence). We are uncertain about the effect of GLP-1RA on hypoglycaemia and bone fractures. 3. SGLT2i versus placebo This review shows that SGLT2i probably reduce the risk of CV mortality (OR 0.82, 95% CI 0.70 to 0.95; moderate-certainty evidence), all-cause mortality (OR 0.84, 95% CI 0.74 to 0.96; moderate-certainty evidence), and reduce the risk of HF hospitalisation (OR 0.65, 95% CI 0.59 to 0.71; high-certainty evidence); they do not reduce the risk of myocardial infarction (OR 0.97, 95% CI 0.84 to 1.12; high-certainty evidence) and probably do not reduce the risk of stroke (OR 1.12, 95% CI 0.92 to 1.36; moderate-certainty evidence). In terms of treatment safety, SGLT2i probably reduce the incidence of worsening renal function (OR 0.59, 95% CI 0.43 to 0.82; moderate-certainty evidence), and probably have no effect on hypoglycaemia (OR 0.90, 95% CI 0.75 to 1.07; moderate-certainty evidence) or bone fracture (OR 1.02, 95% CI 0.88 to 1.18; high-certainty evidence), and may have no impact on pancreatitis (OR 0.85, 95% CI 0.39 to 1.86; low-certainty evidence). 4. Network meta-analysis Because we failed to identify direct comparisons between each class of the agents, findings from our network meta-analysis provided limited novel insights. Almost all findings from our network meta-analysis agree with those from the standard meta-analysis. GLP-1RA may not reduce the risk of stroke compared with placebo (OR 0.87, 95% CrI 0.75 to 1.0; moderate-certainty evidence), which showed similar odds estimates and wider 95% Crl compared with standard pairwise meta-analysis. Indirect estimates also supported comparison across all three classes. SGLT2i was ranked the best for CVD and all-cause mortality.
AUTHORS' CONCLUSIONS
Findings from both standard and network meta-analyses of moderate- to high-certainty evidence suggest that GLP-1RA and SGLT2i are likely to reduce the risk of CVD mortality and all-cause mortality in people with established CVD; high-certainty evidence demonstrates that treatment with SGLT2i reduce the risk of hospitalisation for HF, while moderate-certainty evidence likely supports the use of GLP-1RA to reduce fatal and non-fatal stroke. Future studies conducted in the non-diabetic CVD population will reveal the mechanisms behind how these agents improve clinical outcomes irrespective of their glucose-lowering effects.
Topics: Cardiovascular Diseases; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Glucagon-Like Peptide 1; Glucose; Humans; Network Meta-Analysis; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 34693515
DOI: 10.1002/14651858.CD013650.pub2 -
Journal of Affective Disorders Apr 2023Growing evidence suggests that epigenetic modification is vital in biological processes of depression. Findings from studies exploring the associations between DNA... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Growing evidence suggests that epigenetic modification is vital in biological processes of depression. Findings from studies exploring the associations between DNA methylation and depression have been inconsistent.
METHODS
A systematical search of EMBASE, PubMed, Web of Science, and PsycINFO databases was conducted to include studies focusing on the associations between DNA methylation and depression (up to November 1st 2021) according to PRISMA guidelines with registration in PROSPERO (CRD42021288664).
RESULTS
A total of 47 studies met inclusion criteria and 31 studies were included in the meta-analysis. This meta-analysis found that genes hypermethylation, including BDNF (OR: 1.15, 95%CI: 1.01-1.32, I = 90 %), and NR3C1 (OR: 1.43, 95%CI: 1.09-1.87, I = 88 %) was associated with increased risk of depression. Significant association of SLC6A4 hypermethylation with depression was only found in the subgroup of using original data (OR: 1.09, 95%CI: 1.01-1.19, I = 52 %). BDNF hypermethylation could increase the risk of depression only in the Asian population (OR: 1.18, 95%CI: 1.01-1.40, I = 91 %), and significant associations of NR3C1 hypermethylation with depression were found in the group for depressive symptoms (OR: 1.34, 95%CI: 1.08-1.67, I = 85 %), but not for depressive disorder (OR: 1.89, 95%CI: 0.54-6.55, I = 94 %).
LIMITATIONS
More studies are needed to explore the factors that might influence the estimates owing to the contextual heterogeneity of the pooling of included studies.
CONCLUSIONS
It is noted that DNA hypermethylation, namely BDNF and NR3C1, is associated with increased risk of depression. The findings in this study could provide some material evidence for preventing and diagnosing of depression.
Topics: Humans; Brain-Derived Neurotrophic Factor; Depression; DNA Methylation; Epigenesis, Genetic; Serotonin Plasma Membrane Transport Proteins
PubMed: 36717033
DOI: 10.1016/j.jad.2023.01.079 -
Acta Diabetologica Dec 2023To investigate the lowering BP effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on the risk of... (Meta-Analysis)
Meta-Analysis
Blood pressure-lowering effects of SGLT2 inhibitors and GLP-1 receptor agonists for preventing of cardiovascular events and death in type 2 diabetes: a systematic review and meta-analysis.
AIMS
To investigate the lowering BP effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on the risk of major cardiovascular event stratified by glucose-lowering drugs, baseline BP, glycated hemoglobin (HbA), and history of cardiovascular disease in patients with type 2 diabetes.
METHODS
We performed a systematic review of the MEDLINE and EMBASE databases search up to December 31, 2022, (PROSPERO, CRD42023400899) to identify all large-scale cardiovascular outcomes (CVO) trials of SGLT2i and GLP-1 RAs in which more than 1,000 patient-years of follow-up in each randomized group. Outcomes included all-cause mortality, major adverse cardiovascular event (MACE) and its component (cardiovascular death, myocardial infarction [MI], and stroke), heart failure, and renal failure. A random-effects meta-analyses were used to pool the estimates.
RESULTS
Eighteen CVOTs (ten for SGLT2i and eight for GLP-1 RAs) with 127,606 patients with type 2 diabetes were included. Over 2.5 years median follow-up, the average reduction of systolic BP was 2.2 mmHg (mean difference [MD] - 2.2; 95% CI - 2.7 to - 1.7) with more important reduction (P = 0.001) with SGLT2 inhibitors (- 2.9; - 3.4 to - 2.5) than with GLP-1 RAs (- 1.4; - 1.8 to - 1). With SGLT2i, every 5-mmHg reduction in systolic BP was associated with a significantly lower risk of mortality (hazard ratio[HR], 0.77; 95% CI 0.65-0.90), MACE (HR 0.81 [0.74-0.89]), cardiovascular death (HR 0.72 [0.59-0.88]), MI (HR 0.82 [0.71-0.95]), heart failure (HR 0.49 [0.42-0.57]), and renal failure (HR 0.46 [0.38-0.55]), while the association was not significant for stroke (HR 0.91 [0.69-1.19]). The corresponding effects for every 5-mmHg reduction in SBP with GLP-1 RAs were 0.65 (0.51-0.84) for all-cause mortality, 0.65 (0.56-0.76) for MACE, 0.62 (0.45-0.85) for CV death, 0.71 (0.52-0.76) for MI, 0.49 (0.35-0.69) for stroke, and 0.49 (0.35-0.66) for renal failure, while the association was not significant for heart failure (HR 0.82 [0.63-1.08]).
CONCLUSION
In patients with type 2 diabetes, the hypotensive effects of SGLT2i and GLP-1 RAs were significantly associated with a reduction in mortality and cardiorenal events. These findings suggest that the lowering BP effect could be seen as an additive indicator of cardiovascular protection by SGLT2i and GLP-1 RAs drugs.
Topics: Humans; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glucagon-Like Peptide-1 Receptor; Blood Pressure; Cardiovascular Diseases; Heart Failure; Myocardial Infarction; Glucagon-Like Peptide 1; Stroke; Renal Insufficiency; Hypoglycemic Agents
PubMed: 37439858
DOI: 10.1007/s00592-023-02154-4 -
Diabetes, Obesity & Metabolism Jun 2023To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy of sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta-analysis.
AIM
To compare the relative efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in improving the cardiovascular and renal outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).
MATERIALS AND METHODS
We searched PubMed, Embase and Cochrane Library from inception through 25 November 2022. We selected randomized controlled trials that studied patients with CKD and T2D with a follow-up of at least 24 weeks and compared SGLT-2is, GLP-1RAs and nsMRAs with each other and with placebo. Primary outcomes were major adverse cardiovascular events (MACE) and composite renal outcomes (CRO). Secondary outcomes were cardiovascular death, all-cause death, stroke, myocardial infarction and heart failure hospitalization (HFH). A frequentist approach was used to pool risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
Twenty-nine studies with 50 938 participants for MACE and 49 965 participants for CRO were included. SGLT-2is did not significantly reduce MACE but were associated with significantly lower risks of CRO compared with GLP-1RAs (RR, 0.77; 95% CI, 0.64-0.91; P = .003) and nsMRAs (RR, 0.78; 95% CI, 0.68-0.90; P = .001). Compared with GLP-1RAs and nsMRAs, SGLT-2is significantly reduced risks of HFH by 31% (RR, 0.69; 95% CI, 0.55-0.88; P = .002) and 22% (RR, 0.78; 95% CI, 0.63-0.95; P = .016), respectively, but did not significantly reduce other secondary outcomes. There were no significant differences between GLP-1RAs and nsMRAs in lowering all outcomes.
CONCLUSIONS
SGLT-2is were associated with better cardiorenal protection than GLP-1RAs and nsMRAs in patients with CKD and T2D.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucose; Hypoglycemic Agents; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Renal Insufficiency, Chronic; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 36751968
DOI: 10.1111/dom.15009 -
Neuroscience and Biobehavioral Reviews Sep 2023Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction,... (Review)
Review
Recent lifestyle changes have resulted in tremendous peer pressure and mental stress, and increased the incidences of chronic psychological disorders; like addiction, depression and anxiety (ADA). In this context, the stress-tolerance levels vary amongst individuals and genetic factors play prominent roles. Vulnerable individuals may often be drawn towards drug-addiction to combat stress. This systematic review critically appraises the relationship of various genetic factors linked with the incidences of ADA development. For coherence, we focused solely on cocaine as a substance of abuse in this study. Online scholarly databases were used to screen pertinent literature using apt keywords; and the final retrieval included 42 primary-research articles. The major conclusion drawn from this systematic analysis states that there are 51 genes linked with the development of ADA; and 3 (BDNF, PERIOD2 and SLC6A4) of them are common to all the three aspects of ADA. Further, inter-connectivity analyses of the 51 genes further endorsed the central presence of BDNF and SLC6A4 genes in the development of ADA disorders. The conclusions derived from this systematic study pave the way for future studies for the identification of diagnostic biomarkers and drug targets; and for the development of novel and effective therapeutic regimens against ADA.
Topics: Humans; Cocaine-Related Disorders; Depression; Brain-Derived Neurotrophic Factor; Anxiety; Anxiety Disorders; Cocaine; Serotonin Plasma Membrane Transport Proteins
PubMed: 37271299
DOI: 10.1016/j.neubiorev.2023.105270 -
Frontiers in Endocrinology 2023To assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM).
METHODS
A systemic review and meta-analysis were designed by reviewing articles published between 2000 January 1 and 2022 December 31 using PubMed system and Web of Science system based on the PRISMA 2020 guidelines. The end point of interest was gout (including gout flares, gout events, starting uric-acid lowering therapy and starting anti-gout drugs use) among patients with T2DM using SGLT2i versus not using SGLT2i. A random-effects model was utilized to measure the pooled hazard ratio (HR) with 95% confidence interval (CI) for the risk of gout associated with SGLT2i use.
RESULTS
Two prospective post-hoc analyses of randomized controlled trials and 5 retrospective electronic medical record-linkage cohort studies met the inclusion criteria. The meta-analysis demonstrated that there was a decreased risk of developing gout for SGLT2i use as comparing with non-use of SGLT2i among patients with T2DM (pooled HR=0.66 and 95%CI=0.57-0.76).
CONCLUSIONS
This meta-analysis demonstrates that SGLT2i use is associated with a 34% decreased risk of developing gout among patients with T2DM. SGLT2i may be the treatment options for patients with T2DM who are at high risk of gout. More randomized controlled trials and real-world data are needed to confirm whether there is a class effect of SGLT2i for the risk reduction of gout among patients with T2DM.
Topics: Sodium-Glucose Transporter 2 Inhibitors; Gout; Diabetes Mellitus, Type 2; Humans; Male; Female; Middle Aged; Placebos; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor
PubMed: 37288295
DOI: 10.3389/fendo.2023.1158153 -
BMC Endocrine Disorders Oct 2022Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes.
METHODS
Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES
MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs.
STUDY SELECTION
Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.
OUTCOMES
The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia.
SYNTHESIS OF RESULTS
Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780).
RESULTS
Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules.
CONCLUSION
Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.
Topics: Adult; Humans; Adolescent; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glipizide; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemia; Glucagon-Like Peptide 1; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Symporters; Glucose; Sodium
PubMed: 36261824
DOI: 10.1186/s12902-022-01158-5 -
Journal of Controlled Release :... Dec 2020For the past two decades, biomimetic high-density lipoproteins (b-HDL) have been used for various drug delivery applications. The b-HDL mimic the endogenous HDL, and... (Meta-Analysis)
Meta-Analysis Review
For the past two decades, biomimetic high-density lipoproteins (b-HDL) have been used for various drug delivery applications. The b-HDL mimic the endogenous HDL, and therefore possess many attractive features for drug delivery, including high biocompatibility, biodegradability, and ability to transport and deliver their cargo (e.g. drugs and/or imaging agents) to specific cells and tissues that are recognized by HDL. The b-HDL designs reported in the literature often differ in size, shape, composition, and type of incorporated cargo. However, there exists only limited insight into how the b-HDL design dictates their biodistribution. To fill this gap, we conducted a comprehensive systematic literature search of biodistribution studies using various designs of apolipoprotein A-I (apoA-I)-based b-HDL (i.e. b-HDL with apoA-I, apoA-I mutants, or apoA-I mimicking peptides). We carefully screened 679 papers (search hits) for b-HDL biodistribution studies in mice, and ended up with 24 relevant biodistribution profiles that we compared according to b-HDL design. We show similarities between b-HDL biodistribution studies irrespectively of the b-HDL design, whereas the biodistribution of the b-HDL components (lipids and scaffold) differ significantly. The b-HDL lipids primarily accumulate in liver, while the b-HDL scaffold primarily accumulates in the kidney. Furthermore, both b-HDL lipids and scaffold accumulate well in the tumor tissue in tumor-bearing mice. Finally, we present essential considerations and strategies for b-HDL labeling, and discuss how the b-HDL biodistribution can be tuned through particle design and administration route. Our meta-analysis and discussions provide a detailed overview of the fate of b-HDL in mice that is highly relevant when applying b-HDL for drug delivery or in vivo imaging applications.
Topics: Animals; Apolipoprotein A-I; Biomimetics; Drug Delivery Systems; Lipids; Lipoproteins, HDL; Mice; Tissue Distribution
PubMed: 32971201
DOI: 10.1016/j.jconrel.2020.09.038