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Frontiers in Endocrinology 2024The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear... (Meta-Analysis)
Meta-Analysis
AIM
The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation.
METHODS
A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach.
RESULTS
Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses.
CONCLUSION
The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.
Topics: Humans; Insulin Glargine; Insulin, Long-Acting; Glycated Hemoglobin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Hypoglycemia; Insulin; Weight Gain; Protamines
PubMed: 38586456
DOI: 10.3389/fendo.2024.1286827 -
International Journal of Cardiology Oct 2023To determine the safety and efficacy of protamine in the reversal of heparin in percutaneous coronary intervention (PCI). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the safety and efficacy of protamine in the reversal of heparin in percutaneous coronary intervention (PCI).
BACKGROUND
Heparin is routinely used for anticoagulation in PCI. Protamine is not used routinely to reverse heparin's effects in PCI, partly due to the perceived risk of stent thrombosis.
METHODS
Relevant studies published in English were searched for in PubMed, Embase, and Cochrane databases from inception to April 26th, 2023. Our primary outcome of interest was stent thrombosis in patients receiving PCI for all indications. Secondary outcomes included mortality, major bleeding complications, and hospitalization length. Dichotomous outcomes were analyzed using a Mantel-Haenszel random-effects model and expressed as odds ratios (OR) with their 95% confidence intervals (CI), while continuous outcomes were analyzed using an inverse variance random-effects model expressed as mean differences (MD) with their 95% CI.
RESULTS
11 studies were included in our analysis. Protamine use was not associated with stent thrombosis: OR 0.58, 95% CI: 0.33, 1.01 (p = 0.05) nor with mortality (p = 0.89). Protamine administration was associated with a decreased incidence of major bleeding complications: OR 0.48; 95% CI: 0.25, 0.95 (p = 0.03) and decreased length of hospitalization (p < 0.0001).
CONCLUSIONS
In patients pre-treated with dual antiplatelet therapy (DAPT), protamine may be a safe and efficacious option to facilitate earlier sheath removal, reduce major bleeding complications, and reduce length of hospitalization without increased risk of stent thrombosis.
Topics: Humans; Heparin; Percutaneous Coronary Intervention; Protamines; Hemorrhage; Thrombosis; Platelet Aggregation Inhibitors; Treatment Outcome
PubMed: 37429445
DOI: 10.1016/j.ijcard.2023.131168 -
Cureus Feb 2024The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the... (Review)
Review
BACKGROUND
The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes.
METHODS
We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding.
RESULTS
Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression.
CONCLUSIONS
There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future.
PubMed: 38357407
DOI: 10.7759/cureus.54144 -
Minerva Obstetrics and Gynecology Oct 2023The relative efficacy and safety of insulin neutral protamine Hagedorn (NPH) and detemir (IDet), in the management of diabetes in pregnancy remains unclear. We sought to...
INTRODUCTION
The relative efficacy and safety of insulin neutral protamine Hagedorn (NPH) and detemir (IDet), in the management of diabetes in pregnancy remains unclear. We sought to conduct an updated systematic review and meta-analysis to study the effect of NPH versus IDet during pregnancy on clinically relevant maternal and fetal outcomes.
EVIDENCE ACQUISITION
MEDLINE and Google Scholar were queried from inception till September 2022 for original studies comparing NPH with IDet for management of diabetes during pregnancy. Data was pooled using a random-effects model, to generate risk ratios (RR) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes, along with 95% confidence intervals (CIs). I test was used to assess the magnitude of heterogeneity. Sensitivity analysis was conducted to explore the potential source of heterogeneity. As less than ten studies were included in our analysis, funnel plots were not made to evaluate publication bias. A P value of ≤0.05 was considered significant in all cases.
EVIDENCE SYNTHESIS
Our search of the literature yielded 1087 articles initially, of which seven articles comprising 1396 patients, were included in our analysis. All included articles were of reasonably high methodological quality. Our pooled analysis demonstrates no statistically significant difference between the efficacy of insulin Detemir and insulin NPH as assessed by the HbA1c values from baseline. For safety outcomes, insulin detemir was significantly associated with a greater gestational age at delivery (WMD=0.39, 95%CI: 0.07 to 0.71, P=0.02) and lower incidence of hypoglycemic events (RR=0.64, 95%CI: 0.48 to 0.86, P=0.003) in-contrast to insulin NPH.
CONCLUSIONS
Our findings demonstrate that both, insulin IDet and insulin NPH have a similar efficacy in reducing HbA1c from baseline. However, insulin detemir was associated with lesser incidence of maternal hypoglycemic events and greater gestational age at delivery, compared to NPH.
PubMed: 37877940
DOI: 10.23736/S2724-606X.23.05318-6 -
Human Fertility (Cambridge, England) Jul 2023Genetic association studies (GAS) may have the capability to probe the genetic susceptibility alleles in many disorders. This systemic review aimed to assess whether an... (Review)
Review
Genetic association studies (GAS) may have the capability to probe the genetic susceptibility alleles in many disorders. This systemic review aimed to assess whether an association exists between gene(s)/allelic variant(s), and varicocele-related male infertility (VRMI). This review included 19 GAS that investigated 26 genes in 1,826 men with varicocele compared to 2,070 healthy men, and 263 infertile men without varicocele. These studies focussed on candidate genes and relevant variants, with glutathione S-transferase gene being the most frequently studied ( = 5) followed by the nitric oxide synthase 3 (NOS3) gene ( = 3) and the phosphoprotein tyrosine phosphatase 1 gene ( = 2). In one study the genes for NAD(P)H quinone oxidoreductase 1, sperm protamine, human 8-oxoguanine DNA glycosylase 1, methylenetetrahydrofolate reductase, polymerase gamma, heat shock protein 90, mitochondrial DNA, superoxide dismutase 2, transition nuclear protein 1, and transition nuclear protein 2, were assessed. There is no clear indication that any of these polymorphisms are sturdily associated with VRMI. However, three studies established that the polymorphic genotype (GT + TT) for polymorphism of the gene is more frequent in varicocele patients. Further endeavours such as standardising reporting, exploring complementary designs, and the use of GWAS technology are justified to help replicate these early findings.
PubMed: 34587863
DOI: 10.1080/14647273.2021.1983214 -
Annals of Internal Medicine May 2024In the United States, costs of antidiabetes medications exceed $327 billion. (Review)
Review
Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.
BACKGROUND
In the United States, costs of antidiabetes medications exceed $327 billion.
PURPOSE
To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes.
DATA SOURCES
Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English.
STUDY SELECTION
Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer.
DATA EXTRACTION
Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative.
DATA SYNTHESIS
Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE).
LIMITATIONS
Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established.
CONCLUSION
Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42022382315).
Topics: Diabetes Mellitus, Type 2; Humans; Cost-Benefit Analysis; Hypoglycemic Agents; Quality-Adjusted Life Years; United States; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38639547
DOI: 10.7326/M23-1492