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Diabetes & Vascular Disease Research 2022While hemoglobin A1c (HbA1c) is commonly used to monitor therapy response in type 2 diabetes (T2D), GV is emerging as an essential additional metric for optimizing... (Meta-Analysis)
Meta-Analysis
While hemoglobin A1c (HbA1c) is commonly used to monitor therapy response in type 2 diabetes (T2D), GV is emerging as an essential additional metric for optimizing glycemic control. Our goal was to learn more about the impact of hypoglycemic agents on HbA1c levels and GV in patients with T2D. A systematic review and network meta-analysis (NMA) of randomized controlled trials were performed to assess the effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter (SGLT)-2 inhibitors, dipeptidyl peptidase (DPP)-4 inhibitors, sulfonylurea and thiazolidinediones on Mean Amplitude of Glycemic Excursions (MAGE) and HbA1c. Searches were performed using PubMed and EMBASE. A random-effect model was used in the NMA, and the surface under the cumulative ranking was used to rank comparisons. All studies were checked for quality according to their design and also for heterogeneity before inclusion in this NMA. The highest reduction in MAGE was achieved by GLP-1 RAs (SUCRA 0.83), followed by DPP-4 inhibitors (SUCRA: 0.72), and thiazolidinediones (SUCRA: 0.69). In terms of HbA1c reduction, GLP-1 RAs were the most effective (SUCRA 0.81), followed by DPP-4 inhibitors (SUCRA 0.72) and sulfonylurea (SUCRA 0.65). Our findings indicated that GLP-1 RAs have relatively high efficacy in terms of HbA1c and MAGE reduction when compared with other hypoglycemic agents and can thus have clinical application. Future studies with a larger sample size and appropriate subgroup analyses are warranted to completely understand the glycemic effects of these agents in various patients with T2D. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42021256363).
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones
PubMed: 35686694
DOI: 10.1177/14791641221106866 -
Progress in Lipid Research Oct 2016Epigenetic mechanisms, including DNA methylation and histone modifications, might be involved in the regulation of blood lipid concentration variability and may thereby... (Review)
Review
Epigenetic mechanisms, including DNA methylation and histone modifications, might be involved in the regulation of blood lipid concentration variability and may thereby affect cardiovascular health. We aimed to systematically review studies investigating the association between epigenetic marks and plasma concentrations of triacylglycerol, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Six medical databases were searched until September 3rd 2015, reference lists were screened, and experts in the field were contacted. Of the 757 identified references, 31 articles reporting on 23 unique studies met all inclusion criteria. These studies included data on 8027 unique participants. Overall, no consistent associations were observed between global DNA methylation and blood lipids. Candidate gene and epigenome-wide association studies reported epigenetic regulation of several genes to be related with blood lipids, of which results for ABCG1, CPT1A, TNNT1, MIR33B, SREBF1, and TNIP were replicated. To date, no studies have been performed on histone modification in relation to blood lipids. To conclude, promising results have been reported in the field of epigenetics and dyslipidaemia, however, further rigorous studies are needed to expand our understanding on the role of epigenetics in regulating human's blood lipid levels and its effects on health and disease.
Topics: ATP Binding Cassette Transporter 1; Carrier Proteins; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; DNA Methylation; Dyslipidemias; Epigenomics; Humans; Intracellular Signaling Peptides and Proteins; Membrane Glycoproteins; Niemann-Pick C1 Protein; Triglycerides
PubMed: 27746199
DOI: 10.1016/j.plipres.2016.10.002 -
Diabetes Research and Clinical Practice Sep 2022Current guidelines recommend insulin alone for in-hospital management of diabetes, but growing information suggests that new oral or injectable agents may be as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current guidelines recommend insulin alone for in-hospital management of diabetes, but growing information suggests that new oral or injectable agents may be as effective and safe.
METHODS
Systematic review and meta-analysis with evidence from randomized (RCT) and non-randomized (NRS) studies in PubMed, EMBASE and LILACS databases up to February 10, 2022, for studies including hospitalized type 2 diabetes patients, comparing dipeptidyl peptidase 4 inhibitors (DPP4i), sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1Ra) with insulin alone for glycemic control and safety outcomes.
FINDINGS
7 RCT and 3 NRTs were included. There were no differences in mean blood glucose, measurements within range or rate of hypoglycemia between DPP4i and insulin. We found a lower mean glucose for GLP1Ra plus insulin subgroup (-16.36 mg/dL, 95 % CI -27.31, -5.41; I = 0 %) with lower incidence of hypoglycemia < 70 mg/dL with GLP1Ra (RR 0.31, CI 95 % 0.14-0.70, I = 0 %). SGLT2i data was limited. Adverse events rates were similar between treatments.
CONCLUSION
Our review suggests that inpatient management in the general ward with DPP4i and GLP1Ra is as effective and safe as management with insulin. More randomized studies are required to support these findings before they could be recommended as usual practice.
Topics: Blood Glucose; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 35931222
DOI: 10.1016/j.diabres.2022.110019 -
Diabetic Medicine : a Journal of the... Dec 2012Diabetes is a leading cause of morbidity and mortality worldwide. Studies have frequently looked at dietary components beneficial in treatment and prevention. We aim to... (Meta-Analysis)
Meta-Analysis Review
AIMS
Diabetes is a leading cause of morbidity and mortality worldwide. Studies have frequently looked at dietary components beneficial in treatment and prevention. We aim to systematically evaluate the literature on the safety and efficacy of Cinnamomum zeylanicum on diabetes.
METHODS
A comprehensive search of the literature was conducted in the following databases; PubMed, Web of Science, Biological Abstracts, SciVerse Scopus, SciVerse ScienceDierect, CINAHL and The Cochrane Library. A meta-analysis of studies examining the effect of C. zeylanicum extracts on clinical and biochemical parameters was conducted. Data were analysed using RevMan v5.1.2.
RESULTS
The literature search identified 16 studies on C. zeylanicum (five in-vitro, six in-vivo and five in-vivo/in-vitro). However, there were no human studies. In-vitro C. zeylanicum demonstrated a potential for reducing post-prandial intestinal glucose absorption by inhibiting pancreatic α-amylase and α-glucosidase, stimulating cellular glucose uptake by membrane translocation of glucose transporter-4, stimulating glucose metabolism and glycogen synthesis, inhibiting gluconeogenesis and stimulating insulin release and potentiating insulin receptor activity. The beneficial effects of C. zeylanicum in animals include attenuation of diabetes associated weight loss, reduction of fasting blood glucose, LDL and HbA(1c) , increasing HDL cholesterol and increasing circulating insulin levels. Cinnamomum zeylanicum also significantly improved metabolic derangements associated with insulin resistance. It also showed beneficial effects against diabetic neuropathy and nephropathy, with no significant toxic effects on liver and kidney and a significantly high therapeutic window.
CONCLUSION
Cinnamomum zeylanicum demonstrates numerous beneficial effects both in vitro and in vivo as a potential therapeutic agent for diabetes. However, further randomized clinical trials are required to establish therapeutic safety and efficacy.
Topics: Animals; Cinnamomum zeylanicum; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Insulin Resistance; Phytotherapy; Plant Extracts; Rats; Rats, Wistar
PubMed: 22671971
DOI: 10.1111/j.1464-5491.2012.03718.x -
Diabetes Care Aug 2020The pathophysiology of type 2 diabetes differs markedly by ethnicity. (Meta-Analysis)
Meta-Analysis
Efficacy of Modern Diabetes Treatments DPP-4i, SGLT-2i, and GLP-1RA in White and Asian Patients With Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
BACKGROUND
The pathophysiology of type 2 diabetes differs markedly by ethnicity.
PURPOSE
A systematic review and meta-analysis was conducted to assess the impact of ethnicity on the glucose-lowering efficacy of the newer oral agents, sodium-glucose cotransporter 2 inhibitors (SGLT-2i), glucagon-like peptide 1 receptor agonists (GLP-1RA), and dipeptidyl peptidase 4 inhibitors (DPP-4i), using evidence from randomized clinical trials (RCTs).
DATA SOURCES
A literature search was conducted in PubMed of all randomized, placebo-controlled trials of DPP-4i, SGLT-2i, and GLP-1RA. The search strategy was developed based on Medical Subject Headings (MeSH) terms and keywords.
STUDY SELECTION
A total of 64 studies that qualified for meta-analysis after full-text review based on predefined inclusion and exclusion criteria-RCTs with at least 50 patients in each arm, >70% of population from Asian or white group, duration ≥24 weeks, and publication up to March 2019-were selected for systematic review and meta-analysis.
DATA EXTRACTION
Data extraction was done for aggregated study-level data by two independent researchers. Absolute changes in HbA (%) from baseline to 24 weeks between the drug and placebo were considered as the primary end point of the study.
DATA SYNTHESIS
Change in HbA was evaluated by computing mean differences and 95% CIs between treatment and placebo arms.
LIMITATIONS
The study is based on summarized data and could not be separated based on East Asians and South Asians.
CONCLUSIONS
The glucose-lowering efficacy of SGLT-2i, and to a lesser extent DPP-4i, was greater in studies of predominantly Asian ethnicity compared with studies of predominantly white ethnicity. There was no difference seen by ethnicity for GLP-1RA.
Topics: Asian People; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide Receptors; Humans; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; White People
PubMed: 33534728
DOI: 10.2337/dc19-2419 -
Diabetic Medicine : a Journal of the... Apr 2019To compare the cardiovascular efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in... (Meta-Analysis)
Meta-Analysis
Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis.
AIMS
To compare the cardiovascular efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with Type 2 diabetes.
METHODS
Electronic databases were searched from inception to 22 October 2018 for randomized controlled trials designed to assess the cardiovascular efficacy of SGLT2 inhibitors or GLP-1RAs with regard to a three-point composite measure of major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial infarction and cardiovascular mortality). Cardiovascular and safety data were synthesized using Bayesian network meta-analyses.
RESULTS
Eight trials, including 60 082 participants, were deemed eligible for the network meta-analysis. Both SGLT2 inhibitors [hazard ratio 0.86 (95% credible interval 0.74, 1.01]) and GLP-1RAs [hazard ratio 0.88 (95% credible interval 0.78, 0.98)] reduced the three-point composite measure compared to placebo, with no evidence of differences between them [GLP-1RAs vs SGLT2 inhibitors: hazard ratio 1.02 (95% credible interval 0.83, 1.23)]. SGLT2 inhibitors reduced risk of hospital admission for heart failure compared to placebo [hazard ratio 0.67 (95% credible interval 0.53, 0.85)] and GLP-1RAs [hazard ratio 0.71 (95% credible interval 0.53, 0.93)]. No differences were found between the two drug classes in non-fatal stroke, non-fatal myocardial infarction, cardiovascular mortality, all-cause mortality or safety outcomes.
CONCLUSIONS
SGLT2 inhibitors and GLP-1RAs reduced the three-point major adverse cardiovascular event risk compared to placebo, with no differences between them. Compared with GLP-1RAs and placebo, SGLT2 inhibitors led to a larger reduction in hospital admission for heart failure risk.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 30653708
DOI: 10.1111/dme.13898 -
Diabetes, Obesity & Metabolism Jul 2015To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan. (Meta-Analysis)
Meta-Analysis Review
Safety and effectiveness of non-insulin glucose-lowering agents in the treatment of people with type 2 diabetes who observe Ramadan: a systematic review and meta-analysis.
AIM
To determine which non-insulin glucose-lowering treatment regimens are most appropriate in people with type 2 diabetes who choose to fast during Ramadan.
METHODS
Electronic databases were searched for randomized controlled trials (RCTs) and observational studies that compared non-insulin glucose-lowering agents in people with type 2 diabetes fasting during Ramadan. Those studies which reported hypoglycaemia, weight and glycated haemoglobin (HbA1c) change were included. Data were pooled using random effects models.
RESULTS
A total of 16 studies were included: 9 RCTs and 7 observational studies. There was evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors led to fewer hypoglycaemic events compared with sulphonylureas. Sitagliptin significantly reduced the number of patients with ≥1 hypoglycaemic episodes during Ramadan [risk ratio (RR) 0.48, 95% confidence interval (CI) 0.36, 0.64; p > 0.0001]. This was not replicated in the RCTs of vildagliptin, but a significant reduction was found in the observational studies (RR 0.28, 95% CI 0.10, 0.75; p = 0.01) with high heterogeneity (I(2) = 86.7%). Significant reductions in HbA1c and weight were seen in the observational studies of vildagliptin versus sulphonylureas. The use of liraglutide led to significant weight loss (-1.81 kg, 95% CI -2.91, -0.71; p = 0.001) compared with sulphonylureas. Pioglitazone significantly increased weight compared with placebo (3.48 kg, 95% CI 2.82, 4.14; p < 0.0001).
CONCLUSIONS
The analysis supports the use of DPP-4 inhibitors during Ramadan rather than sulphonylureas for reduction in hypoglycaemia without a cost to diabetes control and weight. The glucagon-like peptide (GLP)-1 agonist liraglutide provides clinical benefits, but more studies are required. RCTs of DPP-4 inhibitors compared with GLP-1 agonists and novel therapies including the sodium-glucose co-transporter 2 and α-glucosidase inhibitors are needed to inform evidence-based guidelines.
Topics: Adamantane; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Holidays; Humans; Hypoglycemia; Hypoglycemic Agents; Islam; Liraglutide; Nitriles; Observational Studies as Topic; Pioglitazone; Pyrrolidines; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; Sulfonylurea Compounds; Thiazolidinediones; Vildagliptin; Weight Loss
PubMed: 25777247
DOI: 10.1111/dom.12462 -
Pharmacological Research Mar 2021Formulation of insulin analogs and its delivery are developed in over recent years but glycemic control in most patients with type-1 diabetes mellitus (DM) is not... (Meta-Analysis)
Meta-Analysis Review
Formulation of insulin analogs and its delivery are developed in over recent years but glycemic control in most patients with type-1 diabetes mellitus (DM) is not adequate yet. The aim of this meta-analysis is to evaluate the efficacy of dapagliflozin in patients with type-1 DM. The MEDLINE/PubMed, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched up to Aug 2020 to identify the potential literature. Random-effects model (DerSimonian and Laird method) was used to estimate the pooled effect size as weighted mean difference (WMD) with 95 % confidence interval (CI). Five randomized placebo-controlled trials with 11 arms were included in the quantitative analysis. The pooled results suggested a significant reduction in glycated hemoglobin A1C (HbA1C; WMD: -0.36 %, 95 % CI: -0.55, -0.18), body weight (WMD: -4.02 kg, 95 % CI: -4.78, -3.25), and total daily insulin dose (TDID; WMD: -10.36 %, 95 % CI: -13.42, -7.29), as well as an increase in 24-h urinary glucose excretion (24-h UGE; WMD: 90.02 g/24-h, 95 % CI: 72.96, 107.09) in dapagliflozin group compared to control group. Dose of dapagliflozin had a significant effect on body weight reduction (Coef = -3.7, p = 0.01) and 24-h UGE (coef = 0.85, p = 0.005). Pooled results of this meta-analysis identified a significant reduction in HbA1c levels, body weight, and TDID, and a substantial increase in 24-h UGE in patients who received dapagliflozin versus placebo.
Topics: Animals; Benzhydryl Compounds; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Glucosides; Glycated Hemoglobin; Humans; Insulin; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 33515709
DOI: 10.1016/j.phrs.2021.105456 -
American Journal of Therapeutics 2020Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But...
BACKGROUND
Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available.
AREAS OF UNCERTAINTY
The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines.
DATA SOURCES
When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases.
THERAPEUTIC ADVANCES
Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future.
CONCLUSIONS
Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.
Topics: Administration, Oral; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31567175
DOI: 10.1097/MJT.0000000000001088 -
Sexual Medicine Reviews Oct 2020A growing number of genetic association studies have been performed to investigate the association between the genetic susceptibility alleles and the risk of premature...
INTRODUCTION
A growing number of genetic association studies have been performed to investigate the association between the genetic susceptibility alleles and the risk of premature ejaculation (PE); however, the results remain inconclusive.
OBJECTIVES
This systematic review aimed: (i) to determine whether an association exists between gene(s) or allelic variant(s) and PE; (ii) to assess whether the associations are consistent across studies in magnitude and direction, and (iii) to identify any limitation, gap, or shortcoming in the included studies.
METHODS
The literature search was conducted in PubMed, MEDLINE, Scopus, Cochrane Library, EMBASE, Academic Search Complete, Google Scholar, and CINAHL databases.
RESULTS
Different gene variants associated with PE were assessed. 25 genetic association studies met the inclusion criteria that investigated 11 genes, 2,624 men with PE compared with 9,346 men as controls, twins, and siblings. 19 studies demonstrated a significant association with PE, whereas 4 studies denied such a relationship. SLC6A4 gene polymorphism was investigated in 11 studies (7 studies demonstrated a significant relationship with PE, and 4 studies denied such a relationship). Dopamine transporter gene (DAT1) polymorphism was investigated in 4 studies exhibiting a significant relationship. Androgen receptor gene polymorphisms were investigated in 2 studies, 1 with a significant relationship and the other with a non-significant relationship. Oxytocin gene polymorphisms and tryptophan hydroxylase 2 gene polymorphisms were investigated in 2 studies with a significant relationship.
CONCLUSION
While this review has highlighted several genes that may be potentially associated with PE such as SLC6A4, limitations such as variance in study methods, lack of robust findings, small sample sizes, lack of reproducibility, quality of reporting, and quality of assessment remain a major concern. Further efforts such as standardizing reporting, exploring complementary designs, and the use of genome-wide association studies technology are warranted to test the reproducibility of these early findings. Mostafa T, Abdel-Hamid IA, Taymour M, et al. Gene Variants in Premature Ejaculation: Systematic Review and Future Directions. Sex Med Rev 2020;8:586-602.
Topics: Dopamine Plasma Membrane Transport Proteins; Genetic Association Studies; Humans; Male; Oxytocin; Polymorphism, Genetic; Premature Ejaculation; Receptors, Androgen; Receptors, Serotonin; Reproducibility of Results; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase
PubMed: 32800770
DOI: 10.1016/j.sxmr.2020.07.002