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Expert Opinion on Biological Therapy Jun 2024We evaluated a potential move from one rapid-acting insulin analog to another, or their biosimilars, to aid better and faster decisions for diabetes management. (Comparative Study)
Comparative Study Review
Comparison of the efficacy and safety of rapid-acting insulin analogs, lispro versus aspart, in the treatment of diabetes: a systematic review of randomized controlled trials.
INTRODUCTION
We evaluated a potential move from one rapid-acting insulin analog to another, or their biosimilars, to aid better and faster decisions for diabetes management.
METHODS
A systematic literature review was performed according to PRISMA reporting guidelines. The MEDLINE/EMBASE/COCHRANE databases were searched for randomized control trials (RCTs) comparing aspart/lispro in type-1 (T1D) and type-2 (T2D) diabetes. The methodological quality of the included studies was assessed using the Cochrane Collaboration's risk of bias assessment criteria.
RESULTS
Of the 753 records retrieved, the six selected efficacy/safety RCTs and the additional three hand-searched pharmacokinetics/pharmacodynamics RCTs showed some heterogeneity in the presentation of the continuous variables; however, collectively, the outcomes demonstrated that lispro and aspart had comparable efficacy and safety in adult patients with T1D and T2D. Both treatments yielded a similar decrease in glycated hemoglobin (HbA1c) and had similar dosing and weight changes, with similar treatment-emergent adverse events (TEAE) and serious adverse event (SAE) reporting, similar hypoglycemic episodes in both T1D and T2D populations, and no clinically significant differences for hyperglycemia, occlusions or other infusion site/set complications.
CONCLUSIONS
Aspart and lispro demonstrate comparative safety and efficacy in patients with T1D/T2D. Since both are deemed equally suitable for controlling prandial glycemic excursions and both have similar safety attributes, they may be used interchangeably in clinical practice.
PROSPERO REGISTRATION NUMBER
CRD42023376793.
Topics: Humans; Insulin Lispro; Randomized Controlled Trials as Topic; Insulin Aspart; Hypoglycemic Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Treatment Outcome; Glycated Hemoglobin; Blood Glucose
PubMed: 38934226
DOI: 10.1080/14712598.2024.2371046 -
Frontiers in Endocrinology 2024There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM)...
There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies.
Topics: Humans; Hypoglycemia; Child; Adolescent; Blood Glucose Self-Monitoring; Insulin; Hypoglycemic Agents; Blood Glucose; Diabetes Mellitus, Type 1; Insulin Infusion Systems; Risk Assessment; Practice Guidelines as Topic; Disease Management
PubMed: 38894740
DOI: 10.3389/fendo.2024.1387537 -
Journal of the ASEAN Federation of... 2024Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is... (Review)
Review
BACKGROUND
Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is a 72-hour fasting test which is inconvenient and inefficient as it requires hospitalization. Research has found that measurement of insulin and C-peptide during OGTT may help diagnose insulinoma. We aimed to assess the diagnostic value of OGTT in diagnosing insulinoma.
METHODOLOGY
The literature search was conducted on 19 August 2022 using several databases (MEDLINE, Scopus, Embase, and ScienceDirect). All studies that measured OGTT as diagnostic tools in diagnosing insulinoma and 72-hour fasting test as reference standard were included. The quality assessment of the selected studies was based on the Centre of Evidence-Based Medicine University of Oxford and the Quality Assessment of Diagnostic Accuracy-2 tool (QUADAS-2). Analysis of the included studies was performed qualitatively. This study was registered on PROSPERO (CRD42022360205).
RESULTS
A total of two case-control studies (106 patients) were included, which were at risk of bias and low concern of applicability. Both studies demonstrated that the combination of insulin and C-peptide levels measured during OGTT had high specificity, sensitivity, positive predictive value, and negative predictive value in diagnosing insulinoma compared to the reference standard. A logistic regression model of 8.305 - (0.441 × insulin 2-h/0-h) - (1.679 × C-peptide 1-h/0-h) >0.351 has the highest diagnostic value in one study (AUC 0.97, Sensitivity 86.5%, Specificity 95.2%, PPV 94.1, NPV 88.9).
CONCLUSION
The measurement of 0-h and 2-h insulin and C-peptide levels during 2-h OGTT was found in two small case-control studies with a total of 106 patients to have good sensitivity and specificity. However, due to these limitations, future research is still needed to validate the potential use of OGTT for the diagnosis of insulinoma.
Topics: Humans; C-Peptide; Insulinoma; Glucose Tolerance Test; Pancreatic Neoplasms; Insulin; Sensitivity and Specificity; Insulin Secretion
PubMed: 38863915
DOI: 10.15605/jafes.039.01.16 -
Journal of Evidence-based Medicine Jun 2024This study aimed to evaluate the safety and efficacy of the fixed-ratio combination (FRC) and free combination of basal insulin and glucagon-like peptide-1 receptor... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparation of fixed-ratio (IDegLira and iGlarLixi) versus free combination of basal insulin and glucagon-like peptide-1 receptor agonist for uncontrolled type 2 diabetes: A systematic review and network meta-analysis.
OBJECTIVE
This study aimed to evaluate the safety and efficacy of the fixed-ratio combination (FRC) and free combination of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with type 2 diabetes mellitus (T2DM).
METHODS
PubMed, Web of Science, Embase, The Cochrane Library, and four Chinese databases were searched for relevant studies from inception to April 13, 2023. Phase III clinical trials involving FRC or free combination in patients with uncontrolled T2DM were included. A network meta-analysis (NMA) was used to evaluate the effects of FRC and free combination. The Cochrane Collaboration's tool was used to evaluate the risk-of-bias. The primary outcomes were changes in hemoglobin A1c (HbA1c), body weight, and incident hypoglycemia. Secondary outcomes included changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). This study was registered with PROSPERO (CRD42023409585).
RESULTS
Forty-two trials with 23,619 patients were included in the NMA, and treatments were categorized as FRC, free combination and NOINSGLP (neither FRC nor free combination). The forest plots revealed comparable HbA1c control (mean difference (MD) = 0.07%, 95% confidence interval (CI): -0.17 to -0.30) between free combination and FRC. However, there were significant differences in the body weight (MD = -2.06 kg; 95% CI: -3.34 to -0.77), SBP (MD = -1.22 mmHg; 95% CI: -2.41 to -0.04), and DBP (MD = -1.09 mmHg; 95% CI: -1.94 to -0.24) between the two groups.
CONCLUSIONS
In patients with uncontrolled T2DM, the safety and efficacy of FRC and free combination therapy were comparable. The use of FRC is justifiable in patients requiring free combination.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Network Meta-Analysis; Glucagon-Like Peptide-1 Receptor; Drug Combinations; Glycated Hemoglobin; Insulin, Long-Acting; Liraglutide
PubMed: 38858300
DOI: 10.1111/jebm.12620 -
Endocrinologia, Diabetes Y Nutricion May 2024To determine the risk factors for hypoglycaemia in patients with diabetes on general hospital wards based on a systematic review of the literature since 2013 and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the risk factors for hypoglycaemia in patients with diabetes on general hospital wards based on a systematic review of the literature since 2013 and meta-analysis.
METHODS
Systematic review of the literature focused on the conceptual and methodological aspects of the PRISMA Declaration. The search carried out in Pub Med, Web of Science, Medline, Scielo, Lilacs, OVID, grey literature and Google Academic focused on risk factors for hypoglycaemia in patients with diabetes on general hospital wards. The CASPe (Critical Appraisal Skills Programme Spanish) tool was applied for quality control.
RESULTS
From 805 references, 70 potentially eligible articles were identified for review of abstracts and full text. Finally, according to inclusion and exclusion criteria, seven studies with 554,601 patients of Asian, European and North American ethnicity were selected. A meta-analysis performed using the random effects model found an association between the presence of hypoglycaemia and: the use of insulin (OR 2.89 [95% CI: 1.8-4.5]); the use of long-acting insulin (OR 2.27 [95% CI: 1.8-2.8]) or fast-acting insulin (OR 1.4 [95% CI: 1.18-1.85]); nasogastric tube feeding (OR 1.75 [95% CI: 1.33-2.3]); chronic kidney disease (OR 1.65 [95% CI: 1.14-2.38]); congestive heart failure (OR 1.36 [95% CI: 1.10-1.68]); and elevated levels of glycosylated haemoglobin (OR 1.59 [95% CI: 1.32-1.91]).
CONCLUSION
The factors associated with the risk of hypoglycaemia in non-critically ill hospitalised patients with type 2 diabetes were: use of any insulin; nasogastric tube feeding; elevated glycosylated haemoglobin levels; history of congestive heart failure; and chronic kidney disease.
Topics: Humans; Hypoglycemia; Risk Factors; Hospitalization; Hypoglycemic Agents; Insulin; Diabetes Mellitus; Diabetes Mellitus, Type 2
PubMed: 38852007
DOI: 10.1016/j.endien.2024.02.006 -
BMC Endocrine Disorders Jun 2024There is equivocal evidence that psyllium can prevent or attenuate increases in fasting blood sugar. Therefore, this systematic review and meta-analysis sought to... (Meta-Analysis)
Meta-Analysis
There is equivocal evidence that psyllium can prevent or attenuate increases in fasting blood sugar. Therefore, this systematic review and meta-analysis sought to investigate the influence of psyllium on hemoglobin A1C (HbA1c), fasting blood sugar (FBS), insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA IR). We searched PubMed, ISI Web of Science (WOS), and Scopus for eligible publications, up to 15 July 2022, including randomized controlled trials (RCT) assessing the effect of psyllium on HbA1c, FBS, insulin, and HOMA IR levels in adults. Using a random effects model, we report the weighted mean differences (WMD) with 95% confidence intervals (CI). In this article, 19 RCT studies, consisting of 962 participants, were included. Psyllium significantly decreased FBS, HbA1c, and HOMA IR levels, but not insulin levels, as compared to placebo (FBS: WMD): -6.89; 95% CI: -10.62, -3.16; p < .001), HbA1c: (WMD: -0.75; 95% CI: -1.21, -0.29; p < .001), HOMA IR: (WMD: -1.17; 95% CI: -2.11, -0.23; p < .05), and insulin: (WMD: -2.08; 95% CI: -4.21, -0.035; p > .05)). Subgroup analyses illustrated differences in the effects of psyllium on FBS: dosages less than and more than 10 g/d showed significant differences (p value < 0.05). However, it was not significant in intervention durations less than 50 days (p value > 0.05). For HbA1c: psyllium consumption less than 10 g/d (p value > 0.05) was non-significant. For HOMA IR and insulin: no significant changes were noted with psyllium consumption less than vs. more than 10 g/d. In conclusion, we found that psyllium could significantly decrease FBS, HbA1c, and HOMA IR levels, but not insulin levels, as compared to placebo.
Topics: Humans; Psyllium; Insulin Resistance; Glycated Hemoglobin; Randomized Controlled Trials as Topic; Insulin; Blood Glucose; Fasting
PubMed: 38844885
DOI: 10.1186/s12902-024-01608-2 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024To conduct a randomized controlled trial meta-analysis and provide concise and specific recommendations for clinical practice optimization of gestational diabetes for... (Meta-Analysis)
Meta-Analysis
AIMS
To conduct a randomized controlled trial meta-analysis and provide concise and specific recommendations for clinical practice optimization of gestational diabetes for probiotics.
METHODS
Up until May 2023, we conducted a thorough, systematic search of PubMed, Cochrane Central Controlled Trials, and Embase. Stata software was used to merge the resulting data from the original studies. Cochran's Q and the I statistics were used to evaluate and quantify heterogeneity. The GRADE method was used to evaluate the overall quality of the evidence. Sources of heterogeneity were analyzed through a leave-one-out meta-analysis, a Galbraith plot, and a subgroup analysis.
RESULTS
A meta-analysis of 11 randomized controlled trials with a total of 713 participants was finally conducted. Our findings indicated the administration of probiotics at a median dosage of 6 × 10 CFU/day led to a substantial improvement in fasting glucose levels (MD: -4.16 mg/dL [95% CI: -6.78, -1.54]; P < 0.001), fasting insulin levels (MD: -3.33 μIU/ml [95% CI: -4.92, -1.74]; P < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (MD: -0.71 [95% CI: -0.97, -0.45]; P < 0.001), and quantitative insulin sensitivity check index (QUICKI) (MD: 0.01 [95% CI: 0.01, 0.02]; P < 0.001). Subgroup analysis indicated that probiotic intervention exerted a more significant reduction in fasting blood glucose in patients with higher baseline BMI and glucose levels, and reduced fasting insulin more markedly in those with elevated baseline insulin. According to the GRADE assessment, the quality of evidence for fasting blood glucose and QUICKI was rated as "high", while the quality for fasting insulin and HOMA-IR was rated as "moderate".
CONCLUSIONS
Probiotic intervention has been shown to significantly decrease levels of fasting blood glucose, fasting insulin, and HOMA-IR, while elevating QUICKI levels in patients with GDM, underscoring the potential utility of probiotics in the adjunctive management of GDM.
Topics: Probiotics; Humans; Diabetes, Gestational; Pregnancy; Female; Randomized Controlled Trials as Topic; Blood Glucose; Insulin Resistance; Insulin; Adult
PubMed: 38815494
DOI: 10.1016/j.clnu.2024.05.020 -
Journal of Ovarian Research May 2024The incidence of infertility caused by diminished ovarian reserve has become a significant problem worldwide. The beneficial effect of PRP treatment of the ovaries has... (Meta-Analysis)
Meta-Analysis
Platelet-rich plasma (PRP) treatment of the ovaries significantly improves fertility parameters and reproductive outcomes in diminished ovarian reserve patients: a systematic review and meta-analysis.
INTRODUCTION
The incidence of infertility caused by diminished ovarian reserve has become a significant problem worldwide. The beneficial effect of PRP treatment of the ovaries has already been described, but the high-level evidence of its effectiveness has not yet been proven.
MATERIALS AND METHODS
A systematic search was performed in five databases, until March 12th, 2024. Both randomized and non-randomized studies that compared PRP treatment of the ovaries to self-control among women with diminished ovarian reserve were eligible for inclusion. Hormonal levels (Anti-Müllerian hormone (AMH), Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Estradiol (E2), In-vitro fertilization parameters (Antral follicle count, oocyte, and embryo count), biochemical and spontaneous pregnancy and livebirth were measured.
RESULTS
38 eligible studies were identified reporting on 2256 women. The level of AMH rised, the level of FSH decreased significantly after the PRP treatment. AMH 1 month MD 0.20 (n = 856, p > 0.001, 95% CI: [0.12;0.28]), 2 months MD 0.26 (n = 910, p = 0.013, 95% CI: [0.07;0.44]), 3 months MD 0.36 (n = 881, p = 0.002,95% CI: [0.20;0.52]). FSH 1 month MD -10.20 (n = 796, p > 0.039, 95% CI: [-19.80;-0.61]), 2 months MD -7.02 (n = 910, p = 0.017, 95% CI: [-12.48; -1.57]), 3 months MD -8.87 (n = 809, p = 0.010, 95% CI: [-14.19; -3.55]). The antral follicle count elevated significantly MD 1.60 (n = 1418, p = < 0.001, 95% CI: [0.92; 2.27]). Significant improvement was observed in the number of retrieved oocytes MD 0.81 (n = 802, p = 0.002, 95% CI: [0.36; 1.26]), and embryos created MD 0.91 (n = 616, p = 0.001, 95% CI: [0.45;1.36]). The incidence of spontaneous pregnancy following PRP treatment showed a rate with a proportion of 0.07 (n = 1370, 95% CI: 0.04-0.12), the rate of biochemical pregnancy was 0.18 (n = 1800, 95% CI: 0.15-0.22), livebirth was 0.11 (n = 1482, 95% CI: 0.07-0.15).
CONCLUSIONS
Our meta-analysis showed that based on protocolized analysis of the widest scientific literature search to date, containing predominantly observational studies, PRP treatment resulted in a statistically significant improvement in the main fertility parameters of diminished ovarian reserve women. Further multicenter, randomized trials, with large patient numbers and a longer follow-up period are needed to certify our results and develop the most effective treatment protocol.
Topics: Humans; Female; Ovarian Reserve; Platelet-Rich Plasma; Pregnancy; Ovary; Fertility; Anti-Mullerian Hormone; Fertilization in Vitro; Infertility, Female; Treatment Outcome; Follicle Stimulating Hormone
PubMed: 38760869
DOI: 10.1186/s13048-024-01423-2 -
Diabetes/metabolism Research and Reviews May 2024The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in patients with T1DM, using a systematic review and meta-analysis approach.
METHODS
We systematically searched multiple databases including Medline, Scopus, and others up to 10 January 2024, without language or regional restrictions. We included randomized controlled trials (RCTs) comparing teplizumab with placebo in T1DM patients.
RESULTS
Our analysis incorporated 8 RCTs, predominantly involving participants aged 7-35 years, diagnosed with T1DM and treated with 14-day courses of teplizumab. The primary outcomes included insulin use, C-peptide levels, and HbA1c levels. We observed a significant reduction in insulin use in the teplizumab group standardised mean difference of -0.50 (95% Confidence Interval [CI]: -0.76 to -0.23, p < 0.001; I2 = 49%). C-peptide levels were consistently higher in the teplizumab group, indicating improved endogenous insulin production. However, no significant change was noted in HbA1c levels between the groups. Quality assessment indicated a low risk of bias in most studies.
CONCLUSIONS
Teplizumab has a significant impact on reducing insulin dependence and enhancing endogenous insulin production in T1DM patients. However, its effect on long-term glycaemic control, as indicated by HbA1c levels, remains inconclusive.
Topics: Adolescent; Humans; Antibodies, Monoclonal, Humanized; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Hypoglycemic Agents; Insulin; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Child; Young Adult; Adult
PubMed: 38757421
DOI: 10.1002/dmrr.3806 -
Nutrition, Metabolism, and... Jun 2024The impact of the loss-of-function (LOF) genetic variant PCSK9 R46L on glucose homeostasis and cardiovascular disease (CVD) remains uncertain, despite its established... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
The impact of the loss-of-function (LOF) genetic variant PCSK9 R46L on glucose homeostasis and cardiovascular disease (CVD) remains uncertain, despite its established correlation with diminished blood cholesterol levels. This meta-analysis aimed at exploring the effect of the PCSK9 R46L genetic variant on plasma insulin and glucose levels, risk of diabetes mellitus and CVD.
METHODS AND RESULTS
PubMed, Embase, and the Cochrane Library were searched for cohort and case-control studies published until October 1, 2023. The studies should report the association of the PCSK9 R46L genetic variant with one of the following: fasting plasma insulin, blood glucose levels, diabetes mellitus, and CVD risk. A dominant model of the PCSK9 R46L genetic variant was employed to statistical analysis. The meta-analyses were performed for continuous variables with standard mean difference (SMD), categorical variables with odds ratio (OR) using a random-effects model. A total of 17 articles with 20 studies engaging 1,186,861 population were identified and mobilized for these analyses. The overall results indicated that, compared with non-carriers of the PCSK9 R46L genetic variant, carriers of the PCSK9 R46L genetic variant did not increase or decrease the levels of fasting plasma insulin (3 studies with 7277 population; SMD, 0.08; 95% CI, -0.04 to 0.19; P = 0.270), and the levels of fasting plasma glucose (7 studies with 9331 population; SMD, 0.03; 95% CI, -0.08 to 0.13; P = 0.610). However, carriers of the PCSK9 R46L genetic variant indeed had 17% reduction in the risk of CVD (11 studies with 558,263 population; OR, 0.83; 95% CI, 0.71 to 0.98; P = 0.030), and 9% increase in the risk of diabetes mellitus (10 studies with 744,466 population; OR, 1.09; 95% CI, 1.04 to 1.14; P < 0.01). Meta-regression analyses indicated that the increased risk of diabetes mellitus and the reduced risk of CVD were positively correlated with reduction in LDL-C (P = 0.004 and 0.033, respectively).
CONCLUSIONS
PCSK9 R46L genetic variant exhibited an elevated susceptibility to diabetes mellitus alongside a reduced vulnerability to CVD.
Topics: Humans; Proprotein Convertase 9; Cardiovascular Diseases; Blood Glucose; Genetic Predisposition to Disease; Insulin; Risk Assessment; Biomarkers; Diabetes Mellitus; Female; Male; Middle Aged; Phenotype; Adult; Aged; Loss of Function Mutation; Risk Factors; Young Adult; Heart Disease Risk Factors
PubMed: 38734541
DOI: 10.1016/j.numecd.2024.04.007