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Diabetologia Jul 2024We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for... (Meta-Analysis)
Meta-Analysis Review
AIMS/HYPOTHESIS
We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus.
METHODS
We searched PubMed and Cochrane up to 11 November 2023 for RCTs with an intervention duration of at least 12 weeks assessing s.c. tirzepatide at maintenance doses of 5 mg, 10 mg or 15 mg once weekly, or s.c. semaglutide at maintenance doses of 0.5 mg, 1.0 mg or 2.0 mg once weekly, in adults with type 2 diabetes, regardless of background glucose-lowering treatment. Eligible trials compared any of the specified doses of tirzepatide and semaglutide against each other, placebo or other glucose-lowering drugs. Primary outcomes were changes in HbA and body weight from baseline. Secondary outcomes were achievement of HbA target of ≤48 mmol/mol (≤6.5%) or <53 mmol/mol (<7.0%), body weight loss of at least 10%, and safety outcomes including gastrointestinal adverse events and severe hypoglycaemia. We used version 2 of the Cochrane risk-of-bias tool (ROB 2) to assess the risk of bias, conducted frequentist random-effects network meta-analyses and evaluated confidence in effect estimates utilising the Confidence In Network Meta-Analysis (CINeMA) framework.
RESULTS
A total of 28 trials with 23,622 participants (44.2% female) were included. Compared with placebo, tirzepatide 15 mg was the most efficacious treatment in reducing HbA (mean difference -21.61 mmol/mol [-1.96%]) followed by tirzepatide 10 mg (-20.19 mmol/mol [-1.84%]), semaglutide 2.0 mg (-17.74 mmol/mol [-1.59%]), tirzepatide 5 mg (-17.60 mmol/mol [-1.60%]), semaglutide 1.0 mg (-15.25 mmol/mol [-1.39%]) and semaglutide 0.5 mg (-12.00 mmol/mol [-1.09%]). In between-drug comparisons, all tirzepatide doses were comparable with semaglutide 2.0 mg and superior to semaglutide 1.0 mg and 0.5 mg. Compared with placebo, tirzepatide was more efficacious than semaglutide for reducing body weight, with reductions ranging from 9.57 kg (tirzepatide 15 mg) to 5.27 kg (tirzepatide 5 mg). Semaglutide had a less pronounced effect, with reductions ranging from 4.97 kg (semaglutide 2.0 mg) to 2.52 kg (semaglutide 0.5 mg). In between-drug comparisons, tirzepatide 15 mg, 10 mg and 5 mg demonstrated greater efficacy than semaglutide 2.0 mg, 1.0 mg and 0.5 mg, respectively. Both drugs increased incidence of gastrointestinal adverse events compared with placebo, while neither tirzepatide nor semaglutide increased the risk of serious adverse events or severe hypoglycaemia.
CONCLUSIONS/INTERPRETATION
Our data show that s.c. tirzepatide had a more pronounced effect on HbA and weight reduction compared with s.c. semaglutide in people with type 2 diabetes. Both drugs, particularly higher doses of tirzepatide, increased gastrointestinal adverse events.
REGISTRATION
PROSPERO registration no. CRD42022382594.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Glucagon-Like Peptides; Randomized Controlled Trials as Topic; Network Meta-Analysis; Glycated Hemoglobin; Adult; Blood Glucose; Female; Male; Injections, Subcutaneous; Glucagon-Like Peptide-2 Receptor; Gastric Inhibitory Polypeptide
PubMed: 38613667
DOI: 10.1007/s00125-024-06144-1 -
Diabetes Technology & Therapeutics May 2024Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects... (Meta-Analysis)
Meta-Analysis Review
Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.
Topics: Humans; Insulin; Hypoglycemic Agents; Glycemic Control; Blood Glucose; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Hypoglycemia
PubMed: 38215209
DOI: 10.1089/dia.2023.0491 -
Current Diabetes Reports Sep 2023Despite the crucial role that prediction models play in guiding early risk stratification and timely intervention to prevent type 2 diabetes after gestational diabetes... (Review)
Review
PURPOSE OF REVIEW
Despite the crucial role that prediction models play in guiding early risk stratification and timely intervention to prevent type 2 diabetes after gestational diabetes mellitus (GDM), their use is not widespread in clinical practice. The purpose of this review is to examine the methodological characteristics and quality of existing prognostic models predicting postpartum glucose intolerance following GDM.
RECENT FINDINGS
A systematic review was conducted on relevant risk prediction models, resulting in 15 eligible publications from research groups in various countries. Our review found that traditional statistical models were more common than machine learning models, and only two were assessed to have a low risk of bias. Seven were internally validated, but none were externally validated. Model discrimination and calibration were done in 13 and four studies, respectively. Various predictors were identified, including body mass index, fasting glucose concentration during pregnancy, maternal age, family history of diabetes, biochemical variables, oral glucose tolerance test, use of insulin in pregnancy, postnatal fasting glucose level, genetic risk factors, hemoglobin A1c, and weight. The existing prognostic models for glucose intolerance following GDM have various methodological shortcomings, with only a few models being assessed to have low risk of bias and validated internally. Future research should prioritize the development of robust, high-quality risk prediction models that follow appropriate guidelines, in order to advance this area and improve early risk stratification and intervention for glucose intolerance and type 2 diabetes among women who have had GDM.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Glucose Intolerance; Diabetes Mellitus, Type 2; Postpartum Period; Glucose; Blood Glucose
PubMed: 37294513
DOI: 10.1007/s11892-023-01516-0 -
Nutrition Journal Oct 2023It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings have yet to be evaluated. This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) assessed the impact of MP supplementation on the glycemic parameters in adults.
METHODS
A systematic search was carried out among online databases to determine eligible RCTs published up to November 2022. A random-effects model was performed for the meta-analysis.
RESULTS
A total of 36 RCTs with 1851 participants were included in the pooled analysis. It was displayed that supplementation with MP effectively reduced levels of fasting blood glucose (FBG) (weighted mean difference (WMD): -1.83 mg/dL, 95% CI: -3.28, -0.38; P = 0.013), fasting insulin (WMD: -1.06 uU/mL, 95% CI: -1.76, -0.36; P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -0.27, 95% CI: -0.40, -0.14; P < 0.001) while making no remarkable changes in serum hemoglobin A1c (HbA1c) values (WMD: 0.01%, 95% CI: -0.14, 0.16; P = 0.891). However, there was a significant decline in serum levels of HbA1c among participants with normal baseline body mass index (BMI) based on sub-group analyses. In addition, HOMA-IR values were significantly lower in the MP supplement-treated group than their untreated counterparts in short- and long-term supplementation (≤ 8 and > 8 weeks) with high or moderate doses (≥ 60 or 30-60 g/d) of MP or whey protein (WP). Serum FBG levels were considerably reduced upon short-term administration of a low daily dose of WP (< 30 g). Furthermore, the levels of serum fasting insulin were remarkably decreased during long-term supplementation with high or moderate daily doses of WP.
CONCLUSION
The findings of this study suggest that supplementation with MP may improve glycemic control in adults by reducing the values of fasting insulin, FBG, and HOMA-IR. Additional trials with longer durations are required to confirm these findings.
Topics: Adult; Humans; Glycated Hemoglobin; Blood Glucose; Milk Proteins; Diabetes Mellitus, Type 2; Dietary Supplements; Insulin; Insulin Resistance; Whey Proteins
PubMed: 37798798
DOI: 10.1186/s12937-023-00878-1 -
Scientific Reports Jan 2024This systematic review and meta-analysis aimed to determine the magnitude of the effect of combined exercise training on glucose metabolism markers, adipokines, and... (Meta-Analysis)
Meta-Analysis
This systematic review and meta-analysis aimed to determine the magnitude of the effect of combined exercise training on glucose metabolism markers, adipokines, and inflammatory cytokines in non-diabetic sedentary adults. PubMed, Web of Science, Scopus, Cochrane Library electronic databases and reference lists of included studies were explored for randomized controlled trials (RCTs) that included physically inactive adults and provided combined training interventions (aerobic plus resistance exercise). Effects on fasting glucose and insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), HbA1c, adiponectin, leptin, IL-6, TNF-α, and C-reactive protein (CRP) in exercise vs control groups were analyzed using random effects meta-analysis. The Cochrane Risk of Bias Tool for Randomized Trials 2.0 (RoB 2) was used to assess the risk of bias. A total of 24 RCTs were included in the quantitative analysis. Combined exercise training significantly decrease fasting glucose (standardized mean difference, SMD: - 0.474, 95% CI [- 0.829, - 0.120], p = 0.009, 35 study arms), fasting insulin (SMD: - 1.024, 95% CI [- 1.502, - 0.545], p < 0.001, 27 study arms), HOMA-IR (SMD: - 0.946, 95% CI [- 1.450, - 0.442], p < 0.001, 23 study arms), TNF-α (SMD: - 0.972, 95% CI [- 1.361, - 0.582], p < 0.001, 10 study arms), and CRP (SMD: - 0.507, 95% CI [- 0.818, - 0.196], p = 0.001, 14 study arms). No significant effects were observed for HbA1c, adiponectin, leptin, and IL-6 levels. Random effects meta-regression models by age, sex, and intervention length were not able to explain any of the variation in the effect size of HOMA-IR. Findings from this systematic review and meta-analysis suggest that combined exercise training improves some glucose metabolism markers and inflammatory parameters in sedentary adults without diabetes.
Topics: Adult; Humans; Adiponectin; Glycated Hemoglobin; Interleukin-6; Leptin; Tumor Necrosis Factor-alpha; Insulin; C-Reactive Protein; Exercise; Glucose
PubMed: 38253590
DOI: 10.1038/s41598-024-51832-y -
Medicine Oct 2023To systematically evaluate the effects of vitamin D supplementation in patients with nonalcoholic fatty liver disease (NAFLD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically evaluate the effects of vitamin D supplementation in patients with nonalcoholic fatty liver disease (NAFLD).
METHODS
National Library of Medicine, Cochrane Library, Elsevier, China National Knowledge Infrastructure, Web of Science, WANFANG databases, and Google Scholar were retrieved to collect relevant randomized controlled trials, which are published from the earliest records the time the database was created to April 2023. Meta-analysis was conducted by using Review Manager 5.4 software after evaluating in terms of inclusion and exclusion criteria. The outcome indicators include 25-hydroxyvitamin D [25(OH)D] levels, insulin resistance index (homeostasis model assessment of insulin resistance), fasting blood glucose, and fasting insulin levels (FINS).
RESULTS
Eight randomized controlled trials with a total of 657 patients are included. Vitamin D supplementation increased 25(OH)D levels significantly (mean difference [MD] = 2.01, 95% confidence intervals [CI]: 0.94 to 3.08, P < .05) and vitamin D supplementation had a significant effect on insulin resistance index (MD = -0.54, 95% CI: -1.28 to 0.20, P = .16), fasting glucose (MD = -0.59, 95% CI: -1.50 to 0.32, P = .20), and FINS levels (MD = -0.30, 95% CI: -0.77 to 0.17, P = .21) had no significant effect.
CONCLUSION
Vitamin D supplementation improves 25(OH)D levels in patients with nonalcoholic fatty liver disease, but there is no effect on homeostasis model assessment of insulin resistance, fasting blood glucose, or FINS.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Insulin Resistance; Blood Glucose; Dietary Supplements; Vitamin D; Insulin; Randomized Controlled Trials as Topic
PubMed: 37861495
DOI: 10.1097/MD.0000000000035717 -
Hormones (Athens, Greece) Dec 2023To assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D. (Meta-Analysis)
Meta-Analysis
Comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging in patients with type 2 diabetes mellitus: systematic review and network meta-analysis.
PURPOSE
To assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D.
METHODS
We searched several databases and grey literature sources. Eligible trials had at least 12 weeks of intervention, included patients with T2D, and assessed the efficacy of glucose-lowering drugs as monotherapies. The primary outcome of interest was absolute reduction in liver fat content (LFC), assessed by means of MRI. Secondary efficacy outcomes were reduction in visceral and subcutaneous adipose tissue. We performed random effects frequentist network meta-analyses to estimate mean differences (MDs) with 95% confidence intervals (CIs). We ranked treatments based on P-scores.
RESULTS
We included 29 trials with 1906 patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (P-score 0.84) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (0.71) were the most efficacious in terms of liver fat content reduction. Among individual agents, empagliflozin was the most efficacious (0.86) and superior to pioglitazone (MD -5.7, 95% CI -11.2 to -0.3) (very low confidence). GLP-1 RAs had also the most favorable effects on visceral and subcutaneous adipose tissue.
CONCLUSIONS
GLP-1 RAs and SGLT-2 inhibitors seem to be the most efficacious glucose-lowering drugs for liver steatosis in patients with T2D. Assessment of their efficacy on NAFLD in patients irrespective of presence of T2D is encouraged.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Network Meta-Analysis; Glucose; Non-alcoholic Fatty Liver Disease; Glucagon-Like Peptide 1
PubMed: 37770761
DOI: 10.1007/s42000-023-00493-z -
Diabetes Research and Clinical Practice Jan 2024This systematic review aims to provide evidence on effectiveness of interventions used in emergency care of hypoglycaemia and diabetic ketoacidosis (DKA). (Review)
Review
AIM
This systematic review aims to provide evidence on effectiveness of interventions used in emergency care of hypoglycaemia and diabetic ketoacidosis (DKA).
METHODOLOGY
This is a systematic review of randomized controlled trials and analytical studies. We selected studies based on eligibility criteria. The databases Medline, Cochrane library and Embase were searched from their inception till November 2, 2022, using search strategy. We used the term such as "diabetes mellitus", "treatment", "hypoglycaemia", "diabetic ketoacidosis", "low blood sugar", "high blood sugar" and Mesh terms like "disease management", "hypoglycaemia", "diabetic ketoacidosis", and "diabetes mellitus" to form search strategy.
RESULTS
Hypoglycemia: Both 10 % dextrose (D10) and 50 % dextrose (D50) are effective options with similar hospital mortality D10 (4.7 %) and D50 (6.2 %). DKA: Low dose insulin is non-inferior to standard dose with time till resolution of DKA 16.5 (7.2) hours and 17.2 (7.7) hours (p value = 0.73) respectively. In children, subcutaneous insulin was associated with reduced ICU admissions and hospital readmissions (67.8 % to 27.9 %). Plasmalyte (PL) is noninferior to sodium chloride (SC), with ICU length of stay 49 h (IQR 23-72) and 55 h (IQR 41-80) respectively, hyperchloremia was associated with longer in-hospital length of stay and longer time to resolution of DKA. And potassium replacement at < 10 mmol/L was associated with higher mortality (n = 72).
CONCLUSION
We conclude either of the 10 % or 50 % dextrose is effective for management of hypoglycaemia. For DKA subcutaneous insulin and intravenous insulin, chloride levels ≤ 109 mEq/L, potassium above 10 mmol/l, IV fluids like Plasmalyte and normal saline are effective.
Topics: Child; Humans; Diabetic Ketoacidosis; Blood Glucose; Hypoglycemia; Insulin; Emergency Medical Services; Insulin, Regular, Human; Potassium; Diabetes Mellitus
PubMed: 38154537
DOI: 10.1016/j.diabres.2023.111078 -
Clinical Oral Investigations May 2024There are 500 million patients living with diabetes mellitus worldwide and 50% of them remain undiagnosed. Routine periodontal probing provides gingival crevicular... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
There are 500 million patients living with diabetes mellitus worldwide and 50% of them remain undiagnosed. Routine periodontal probing provides gingival crevicular blood in patients with gingivitis. Gingival blood may be useful for diabetes screening without the need for any expensive, painful or time-consuming method by using convenient glucometers. Therefore, the objective of this systematic review and meta-analysis is to answer the question to "is there a difference in glucose or HbA1c levels (O) in patients with positive gingival bleeding (P) measured on gingival crevicular blood (GCB) (I) compared to finger prick capillary blood (CB) (C).
MATERIALS AND METHODS
The authors performed an electronic search of six databases using identical MeSH phrases. Only human clinical studies without limitations on the year of publication were considered. Data extraction was done by using standardized data collection sheets. Risk of bias assessment were conducted using QUADAS-2 and QUADAS-C. Meta-analyses were carried out with the random effects model to aggregate the correlation coefficients and the difference between the means between gingival and capillary blood reading, using 95% confidence intervals.
RESULTS
The database and manual search yielded 268 articles, from which the selection procedure provided 36 articles for full-text screening, and the final pool of eligible articles composed of 23 studies with 1680 patients. Meta-analysis results on glycemic levels showed differences between the GCB and CB procedures in patients with and without diabetes with values of -6.80 [-17.35; 3.76] and - 4.36 [-9.89; 1.18], respectively. Statistically significant correlations were found (p = 0.001) between GCB and CB measurements in patients with (0.97 [0.927; 0.987]) and without diabetes (0.927 [0.873; 0.958]).
CONCLUSION
Gingival blood could prove to be useful to identify patients with undiagnosed diabetes when the necessary amount of uncontaminated blood is present. However, this technique is limited by the possibility of contamination, prandial status and inaccuracies, so it is unsuited to address the patient's glycemic control accurately.
Topics: Humans; Glycated Hemoglobin; Blood Glucose; Gingival Crevicular Fluid; Reproducibility of Results; Diabetes Mellitus
PubMed: 38702475
DOI: 10.1007/s00784-024-05685-4 -
Nutrients Oct 2023(1) Background: Participation in ultra-endurance sports, particularly ultra-running, has increased over the previous three decades. These are accompanied by high... (Review)
Review
(1) Background: Participation in ultra-endurance sports, particularly ultra-running, has increased over the previous three decades. These are accompanied by high energetic demands, which may be further exacerbated by extreme environmental conditions. Preparation is long-term, comprising of sufficient exercise management, supportive dietary habits, and nutritional intakes for optimal adaptations. Gastrointestinal symptoms are often cited as causing underperformance and incompletion of events. Though the majority do not pose serious long-term health risks, they may still arise. It has been suggested that the nutritional interventions employed by such athletes prior to, during, and after exercise have the potential to alter symptom incidence, severity, and duration. A summary of such interventions does not yet exist, making it difficult for relevant personnel to develop recommendations that simultaneously improve athletic performance by attenuating gastrointestinal symptoms. The aim of this research is to systematically review the literature investigating the effects of a nutrition intervention on ultra-endurance athletes exercise-induced gastrointestinal symptom incidence, severity, or duration. (2) Methods: A systematic review of the literature was conducted (PubMed, CINAHL, Web of Science, and Sports Discus) in January 2023 to investigate the effects of various nutrition interventions on ultra-endurance athletes' (regardless of irritable bowel syndrome diagnosis) exercise-induced gastrointestinal symptoms. Variations of key words such as "ultra-endurance", "gastrointestinal", and "nutrition" were searched. The risk of bias in each paper was assessed using the ADA quality criteria checklist. (3) Results: Of the seven eligible studies, one was a single field-based case study, while the majority employed a crossover intervention design. A total of = 105 participants ( = 50 male; = 55 female) were included in this review. Practicing a diet low in short-chain, poorly absorbed carbohydrates, known as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs), as well as employing repetitive gut challenges of carbohydrates, remain the most promising of strategies for exercise-induced gastrointestinal symptom management. (4) Conclusion: Avoiding high-FODMAP foods and practicing repetitive gut challenges are promising methods to manage gastrointestinal symptoms. However, sample sizes are often small and lack supportive power calculations.
Topics: Humans; Male; Female; Gastrointestinal Diseases; Diet; Oligosaccharides; Disaccharides; Monosaccharides; Irritable Bowel Syndrome; Running; Athletes; Fermentation
PubMed: 37892406
DOI: 10.3390/nu15204330