-
BMJ Open Mar 2023To compare the efficacy and safety between and within glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis.
OBJECTIVE
To compare the efficacy and safety between and within glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2is) in overweight or obese adults with or without diabetes mellitus.
METHODS
PubMed, ISI Web of Science, Embase and Cochrane Central Register of Controlled Trials database were comprehensively searched to identify randomised controlled trials (RCTs) of effects of GLP-1RAs and SGLT-2is in overweight or obese participants from inception to 16 January 2022. The efficacy outcomes were the changes of body weight, glucose level and blood pressure. The safety outcomes were serious adverse events and discontinuation due to adverse events. The mean differences, ORs, 95% credible intervals (95% CI), the surface under the cumulative ranking were evaluated for each outcome by network meta-analysis.
RESULTS
Sixty-one RCTs were included in our analysis. Both GLP-1RAs and SGLT-2is conferred greater extents in body weight reduction, achieving at least 5% wt loss, HbA1c and fasting plasma glucose decrease compared with placebo. GLP-1RAs was superior to SGLT-2is in HbA1c reduction (MD: -0.39%, 95% CI -0.70 to -0.08). GLP-1RAs had high risk of adverse events, while SGLT-2is were relatively safe. Based on intraclass comparison, semaglutide 2.4 mg was among the most effective interventions in losing body weight (MD: -11.51 kg, 95% CI -12.83 to -10.21), decreasing HbA1c (MD: -1.49%, 95% CI -2.07 to -0.92) and fasting plasma glucose (MD: -2.15 mmol/L, 95% CI -2.83 to -1.59), reducing systolic blood pressure (MD: -4.89 mm Hg, 95% CI -6.04 to -3.71) and diastolic blood pressure (MD: -1.59 mm Hg, 95% CI -2.37 to -0.86) with moderate certainty evidences, while it was associated with high risk of adverse events.
CONCLUSIONS
Semaglutide 2.4 mg showed the greatest effects on losing body weight, controlling glycaemic level and reducing blood pressure while it was associated with high risk of adverse events.PROSPERO registration numberCRD42021258103.
Topics: Adult; Humans; Blood Glucose; Body Weight; Diabetes Mellitus; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Network Meta-Analysis; Obesity; Overweight; Sodium-Glucose Transporter 2 Inhibitors; Weight Loss
PubMed: 36882248
DOI: 10.1136/bmjopen-2022-061807 -
Diabetes Research and Clinical Practice Apr 2023To evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of drugs for people with type 2 diabetes mellitus and chronic kidney disease on kidney and cardiovascular outcomes: A systematic review and network meta-analysis of randomized controlled trials.
AIM
To evaluate the comparative efficacy and safety of promising kidney protection drugs, including sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), aldosterone receptor agonists (MRAs), endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), on cardiovascular and kidney outcomes in type 2 diabetes (T2DM) and chronic kidney disease (CKD) population.
METHODS
PubMed, Embase, and Cochrane Library were searched from inception to August 12, 2022. We used the Bayesian model for network meta-analyses, registered in the PROSPERO (CRD42022343601).
RESULTS
This network meta-analysis identified 2589 citations, and included 27 eligible trials, enrolling 50,237 patients. All results presented below were moderate to high quality. For kidney outcomes, SGLT-2Is were optimal in terms of reducing composite kidney events (RR 0.69, 95%CI 0.61-0.79), and slowing eGFR slope (MD1.34, 95%CI 1.06-1.62). Then MRAs (RR 0.77, 95%CI 0.68-0.88; MD 1.31, 95%CI 0.89-1.74), GLP-1RAs (RR 0.78, 95%CI 0.62-0.97; MD 0.75, 95%CI 0.46-1.05), and ERAs (RR 0.75, 95%CI 0.57-0.99; MD 0.7, 95%CI 0.3-1.1) were followed in parallel. For cardiovascular outcomes, SGLT-2 inhibitors were also among the best for lowing the risk of heart failure hospitalization (RR 0.67, 95%CI 0.57-0.78), followed by GLP-1RAs (RR 0.73, 95%CI 0.55-0.97) and MRAs (RR 0.79, 95%CI 0.67-0.92). SGLT-2Is (RR 0.8, 95%CI 0.71-0.89) and GLP-1RAs (RR 0.72, 95%CI 0.6-0.86) had comparable effects to reduce the risk of major adverse cardiovascular events. MRAs were possibly associated with increased drug discontinuation due to adverse events (RR 1.21, 95%CI 1.05-1.38). For the hyperkalemia outcome, MRAs (RR 2.08, 95%CI 1.86-2.33) were linked to the risk of hyperkalemia, whereas SGLT-2Is (RR 0.78, 95%CI 0.65-0.93) were in contrast.
CONCLUSIONS
SGLT-2Is significantly reduced kidney and cardiovascular risk in T2DM and CKD, subsequently GLP-1RAs and MRAs. SGLT-2Is-MRAs combination might be a recommended treatment regimen for maximizing kidney and cardiovascular protection but with a low risk of hyperkalemia in T2DM and CKD.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; Network Meta-Analysis; Bayes Theorem; Hyperkalemia; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Kidney; Glucagon-Like Peptide-1 Receptor
PubMed: 36842477
DOI: 10.1016/j.diabres.2023.110592 -
Cells Feb 2023Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple... (Review)
Review
Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple steatosis to non-alcoholic steatohepatitis (NASH), with or without fibrosis. Multiple factors are involved in the development of NAFLD. However, details about its pathogenesis and factors that promote the progression to NASH are still missing. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) regulate metabolic, immune, and hepatic stellate cell functions. Increasing evidence suggests they may have roles in the progression from NAFLD to NASH. Following the PRISMA reporting guidelines, we conducted a systematic review to evaluate all clinical and experimental studies published in the literature correlating GH and IGF-1 to inflammation and fibrosis in NAFLD and NASH. Our results showed that GH and IGF-1 have a fundamental role in the pathogenesis of NASH, acting in slightly different ways to produce a synergic effect. Indeed, GH may mediate its protective effect in the pathogenesis of NASH by regulating lipogenesis pathways, while IGF-1 has the same effect by regulating cholesterol transport. Therefore, they could be used as therapeutic strategies in preventing NAFLD progression to NASH.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Growth Hormone; Insulin-Like Growth Factor I; Insulin; Liver Cirrhosis; Human Growth Hormone; Insulin, Regular, Human; Hepatitis
PubMed: 36831184
DOI: 10.3390/cells12040517 -
Journal of the American Geriatrics... Jul 2023Preclinical studies have suggested potential beneficial effects of newer glucose-lowering drugs (GLDs) including dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preclinical studies have suggested potential beneficial effects of newer glucose-lowering drugs (GLDs) including dipeptidyl peptidase (DPP)-4 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors, in protecting humans against cognitive decline and dementia. However, population studies aiming to demonstrate such cognitive benefits from newer GLDs have produced mixed findings. This meta-analysis aimed to evaluate the association between newer GLDs and risk of dementia in adults with type 2 diabetes (T2D).
METHODS
Electronic databases were searched up to March 11, 2022 to include observational studies that examined the association between DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors and risk of dementia (including all-cause dementia, Alzheimer's disease [AD], and vascular dementia [VD]) in people with T2D. We conducted a random-effects meta-analysis to calculate the relative risk (RR) with 95% confidence interval (CI) for each class of newer GLD.
RESULTS
Ten studies (from nine articles) involving 819,511 individuals with T2D were included. Three studies found that SGLT2 inhibitor users had a lower risk of all-cause dementia than non-SGLT2 inhibitor users (RR, 0.62; 95% CI, 0.39-0.97). Five studies found that users versus nonusers of GLP-1RAs were associated with a significant reduction in the risk of all-cause dementia (RR, 0.72; 95% CI, 0.54-0.97). However, a meta-analysis for AD and VD was unavailable for SGLT2 inhibitors and GLP-1RAs because only one study was included for each drug. In seven studies, users vs. nonusers of DPP-4 inhibitors were significantly associated with a decreased risk of all-cause dementia (RR, 0.84; 95% CI, 0.74-0.94) and VD (RR, 0.59; 95% CI, 0.47-0.75) but not AD (RR, 0.82; 95% CI, 0.63-1.08).
CONCLUSION
Newer GLDs were associated with a decreased risk of all-cause dementia in people with T2D. Because of the observational nature and significant heterogeneity between studies, the results should be interpreted with caution. Further research is warranted to confirm our findings.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Dipeptidyl-Peptidase IV Inhibitors; Glucose; Sodium-Glucose Transporter 2 Inhibitors; Dementia
PubMed: 36821780
DOI: 10.1111/jgs.18306 -
Archives of Suicide Research : Official... 2024Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a...
Suicide is defined as the action of harming oneself with the intention of dying. It is estimated that worldwide, one person dies by suicide every 40 s, making it a major health problem. Studies in families have suggested that suicide has a genetic component, so the search for genetic variants associated with suicidal behavior could be useful as potential biomarkers to identify people at risk of suicide. In Mexico, some studies of gene variants related to neurotransmission and other important pathways have been carried out and potential association of variants located in the following genes has been suggested: , , , , , , , , , and This systematic review shows the genetic studies conducted on the Mexican population. This article contributes by compiling the existing information on genetic variants and genes associated with suicidal behavior, in the future could be used as potential biomarkers to identify people at risk of suicide.
Topics: Humans; Mexico; Suicide; Suicidal Ideation; Biomarkers; RGS Proteins; Serotonin Plasma Membrane Transport Proteins; Protein Serine-Threonine Kinases
PubMed: 36772904
DOI: 10.1080/13811118.2023.2176269 -
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 -
Cardiovascular Diabetology Jan 2023Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction.
METHODS
A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses.
RESULTS
All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively).
CONCLUSIONS
Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.
Topics: Humans; Cardiovascular Diseases; Glucagon-Like Peptide 1; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Obesity; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36721184
DOI: 10.1186/s12933-023-01738-2 -
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 -
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 -
Journal of Diabetes Feb 2023Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19.
METHODS
We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission.
RESULTS
The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).
CONCLUSIONS
AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; COVID-19; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Glucagon-Like Peptide-1 Receptor
PubMed: 36690377
DOI: 10.1111/1753-0407.13359