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BMJ (Clinical Research Ed.) Jan 2024To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults... (Meta-Analysis)
Meta-Analysis
Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis.
OBJECTIVE
To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible.
RESULTS
76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration.
CONCLUSIONS
GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022342845.
Topics: Adult; Humans; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Glycemic Control; Hypoglycemic Agents; Network Meta-Analysis; Weight Loss; Lipid Metabolism
PubMed: 38286487
DOI: 10.1136/bmj-2023-076410 -
Osteoporosis International : a Journal... Jul 2023The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the... (Meta-Analysis)
Meta-Analysis Review
Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators.
The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I = 20%, TH BMD) to substantial (I = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur.
Topics: Female; Humans; Bone Density; Postmenopause; Osteoporosis, Postmenopausal; Exercise; Osteoporosis; Femur Neck; Lumbar Vertebrae
PubMed: 36749350
DOI: 10.1007/s00198-023-06682-1 -
European Heart Journal Jul 2023Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular... (Meta-Analysis)
Meta-Analysis
AIMS
Due to growing environmental focus, plant-based diets are increasing steadily in popularity. Uncovering the effect on well-established risk factors for cardiovascular diseases, the leading cause of death worldwide, is thus highly relevant. Therefore, a systematic review and meta-analysis were conducted to estimate the effect of vegetarian and vegan diets on blood levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B.
METHODS AND RESULTS
Studies published between 1980 and October 2022 were searched for using PubMed, Embase, and references of previous reviews. Included studies were randomized controlled trials that quantified the effect of vegetarian or vegan diets vs. an omnivorous diet on blood lipids and lipoprotein levels in adults over 18 years. Estimates were calculated using a random-effects model. Thirty trials were included in the study. Compared with the omnivorous group, the plant-based diets reduced total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels with mean differences of -0.34 mmol/L (95% confidence interval, -0.44, -0.23; P = 1 × 10-9), -0.30 mmol/L (-0.40, -0.19; P = 4 × 10-8), and -12.92 mg/dL (-22.63, -3.20; P = 0.01), respectively. The effect sizes were similar across age, continent, duration of study, health status, intervention diet, intervention program, and study design. No significant difference was observed for triglyceride levels.
CONCLUSION
Vegetarian and vegan diets were associated with reduced concentrations of total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B-effects that were consistent across various study and participant characteristics. Plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease.
Topics: Adult; Humans; Diet, Vegan; Diet, Vegetarian; Randomized Controlled Trials as Topic; Lipids; Vegetarians; Cholesterol, LDL; Lipoproteins; Cardiovascular Diseases; Atherosclerosis; Apolipoproteins
PubMed: 37226630
DOI: 10.1093/eurheartj/ehad211 -
Aging Clinical and Experimental Research Sep 2023The objective of this systematic review and meta-analysis is to systematically identify and review the efficacy of pharmacological treatments in men with osteoporosis. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The objective of this systematic review and meta-analysis is to systematically identify and review the efficacy of pharmacological treatments in men with osteoporosis.
METHODS
Medline (via Ovid) and Cochrane CENTRAL were searched up to May 2023 for any randomized controlled trial (RCT) evaluating the efficacy of osteoporotic treatment on the evolution of Bone Mineral Density (BMD) and incidence of fractures of men suffering from primary osteoporosis. If at least two studies used the same pharmacological treatment and evaluated the same outcome, a random effect model meta-analysis was applied to reported pooled mean difference (MD) and 95% confidence interval (CI).
RESULTS
From the 1,061 studies identified through bibliographic search, 21 RCTs fitted the inclusion criteria. Bisphosphonates (k = 10, n = 2992 men with osteoporosis) improved all three BMD sites compared to placebo; lumbar spine: MD + 4.75% (95% CI 3.45, 6.05); total hip: MD + 2.72% (95% CI 2.06; 3.37); femoral neck: MD + 2.26% (95% CI 1.67; 2.85). Denososumab (k = 2, n = 242), Teriparatide (k = 2, n = 309) and Abaloparatide (k = 2, n = 248) also produced significant improvement of all sites BMD compared to placebo. Romosozumab was only identified in one study and was therefore not meta-analysed. In this study, Romosozumab increased significantly BMD compared to placebo. Incident fractures were reported in 16 RCTs but only four reported fractures as the primary outcome. Treatments were associated with a lower incidence of fractures.
CONCLUSIONS
Medications used in the management of osteoporosis in women appear to provide similar benefits in men with osteoporosis. Therefore, the algorithm for the management of osteoporosis in men could be similar to the one previously recommended for the management of osteoporosis in women.
Topics: Male; Female; Humans; Bone Density Conservation Agents; Osteoporosis; Bone Density; Diphosphonates; Fractures, Bone
PubMed: 37400668
DOI: 10.1007/s40520-023-02478-9 -
Osteoporosis International : a Journal... Sep 2023Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone...
Update on the clinical use of trabecular bone score (TBS) in the management of osteoporosis: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), and the International...
PURPOSE
Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone microarchitecture. In 2015, a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) published a review of the TBS literature, concluding that TBS predicts hip and major osteoporotic fracture, at least partly independent of bone mineral density (BMD) and clinical risk factors. It was also concluded that TBS is potentially amenable to change as a result of pharmacological therapy. Further evidence on the utility of TBS has since accumulated in both primary and secondary osteoporosis, and the introduction of FRAX and BMD T-score adjustment for TBS has accelerated adoption. This position paper therefore presents a review of the updated scientific literature and provides expert consensus statements and corresponding operational guidelines for the use of TBS.
METHODS
An Expert Working Group was convened by the ESCEO and a systematic review of the evidence undertaken, with defined search strategies for four key topics with respect to the potential use of TBS: (1) fracture prediction in men and women; (2) initiating and monitoring treatment in postmenopausal osteoporosis; (3) fracture prediction in secondary osteoporosis; and (4) treatment monitoring in secondary osteoporosis. Statements to guide the clinical use of TBS were derived from the review and graded by consensus using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.
RESULTS
A total of 96 articles were reviewed and included data on the use of TBS for fracture prediction in men and women, from over 20 countries. The updated evidence shows that TBS enhances fracture risk prediction in both primary and secondary osteoporosis, and can, when taken with BMD and clinical risk factors, inform treatment initiation and the choice of antiosteoporosis treatment. Evidence also indicates that TBS provides useful adjunctive information in monitoring treatment with long-term denosumab and anabolic agents. All expert consensus statements were voted as strongly recommended.
CONCLUSION
The addition of TBS assessment to FRAX and/or BMD enhances fracture risk prediction in primary and secondary osteoporosis, adding useful information for treatment decision-making and monitoring. The expert consensus statements provided in this paper can be used to guide the integration of TBS in clinical practice for the assessment and management of osteoporosis. An example of an operational approach is provided in the appendix. This position paper presents an up-to-date review of the evidence base, synthesised through expert consensus statements, which informs the implementation of Trabecular Bone Score in clinical practice.
Topics: Male; Female; Humans; Cancellous Bone; Osteoporosis; Osteoporotic Fractures; Bone Density; Absorptiometry, Photon; Lumbar Vertebrae; Osteoarthritis; Aging; Consensus; World Health Organization; Risk Assessment
PubMed: 37393412
DOI: 10.1007/s00198-023-06817-4 -
JAMA Network Open Jul 2023Plant-based diets are known to improve cardiometabolic risk in the general population, but their effects on people at high risk of cardiovascular diseases (CVDs) remain... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Plant-based diets are known to improve cardiometabolic risk in the general population, but their effects on people at high risk of cardiovascular diseases (CVDs) remain inconclusive.
OBJECTIVE
To assess the association of vegetarian diets with major cardiometabolic risk factors, including low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body weight in people with or at high risk of CVDs.
DATA SOURCES
This meta-analysis was registered before the study was conducted. Systematic searches performed included Embase, MEDLINE, CINAHL, and CENTRAL from inception until July 31, 2021.
STUDY SELECTION
Eligible randomized clinical trials (RCTs) that delivered vegetarian diets in adults with or at high risk of CVDs and measured LDL-C, HbA1c or SBP were included. Of the 7871 records screened, 29 (0.4%; 20 studies) met inclusion criteria.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data including demographics, study design, sample size, and diet description, and performed risk of bias assessment. A random-effects model was used to assess mean changes in LDL-C, HbA1c, SBP, and body weight. The overall certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.
MAIN OUTCOMES AND MEASURES
Mean differences between groups in changes (preintervention vs postintervention) of LDL-C, HbA1c, and SBP; secondary outcomes were changes in body weight and energy intake.
RESULTS
Twenty RCTs involving 1878 participants (range of mean age, 28-64 years) were included, and mean duration of intervention was 25.4 weeks (range, 2 to 24 months). Four studies targeted people with CVDs, 7 focused on diabetes, and 9 included people with at least 2 CVD risk factors. Overall, relative to all comparison diets, meta-analyses showed that consuming vegetarian diets for an average of 6 months was associated with decreased LDL-C, HbA1c, and body weight by 6.6 mg/dL (95% CI, -10.1 to -3.1), 0.24% (95% CI, -0.40 to -0.07), and 3.4 kg (95% CI, -4.9 to -2.0), respectively, but the association with SBP was not significant (-0.1 mm Hg; 95% CI, -2.8 to 2.6). The GRADE assessment showed a moderate level of evidence for LDL-C and HbA1c reduction.
CONCLUSIONS AND RELEVANCE
In this study, consuming a vegetarian diet was associated with significant improvements in LDL-C, HbA1c and body weight beyond standard therapy in individuals at high risk of CVDs. Additional high-quality trials are warranted to further elucidate the effects of healthy plant-based diets in people with CVDs.
Topics: Adult; Humans; Middle Aged; Cardiovascular Diseases; Cholesterol, LDL; Glycated Hemoglobin; Vegetarians; Research Design; Body Weight
PubMed: 37490288
DOI: 10.1001/jamanetworkopen.2023.25658 -
Journal of Orthopaedic Surgery and... Aug 2023Osteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae... (Meta-Analysis)
Meta-Analysis
Osteoporosis affects more than 200 million women worldwide, with postmenopausal women being particularly susceptible to this condition and its severe sequelae disproportionately, such as osteoporotic fractures. To date, the current focus has been more on symptomatic treatment, rather than preventive measures. To address this, we performed a meta-analysis aiming to identify potential predictors of osteoporotic fractures in postmenopausal women, with the ultimate goal of identifying high-risk patients and exploring potential therapeutic approaches. We searched Embase, MEDLINE and Cochrane with search terms (postmenopausal AND fracture) AND ("risk factor" OR "predictive factor") in May 2022 for cohort and case-control studies on the predictors of osteoporotic fracture in postmenopausal women. Ten studies with 1,287,021 postmenopausal women were found eligible for analyses, in which the sample size ranged from 311 to 1,272,115. The surveyed date spanned from 1993 to 2021. Our results suggested that age, BMI, senior high school and above, parity ≥ 3, history of hypertension, history of diabetes mellitus, history of alcohol intake, age at menarche ≥ 15, age at menopause < 40, age at menopause > 50, estrogen use and vitamin D supplements were significantly associated with osteoporotic fracture in postmenopausal women. Our findings facilitate the early prediction of osteoporotic fracture in postmenopausal women and may contribute to potential therapeutic approaches. By focusing on preventive strategies and identifying high-risk individuals, we can work toward reducing the burden of osteoporosis-related fractures in this vulnerable population.
Topics: Humans; Female; Osteoporotic Fractures; Osteoporosis, Postmenopausal; Postmenopause; Osteoporosis; Risk Factors; Bone Density
PubMed: 37543616
DOI: 10.1186/s13018-023-04051-6 -
Clinical Medicine (London, England) Sep 2023Hypercalcaemia of malignancy (HCM) is a common metabolic complication of advanced malignancies with a prevalence varying from 2-30%, depending on cancer type and disease... (Meta-Analysis)
Meta-Analysis
Hypercalcaemia of malignancy (HCM) is a common metabolic complication of advanced malignancies with a prevalence varying from 2-30%, depending on cancer type and disease stage. HCM is associated with impaired quality of life, increased risk of hospitalisation and limited survival. Evidence-based guidelines for management of HCM have been lacking to date, despite its prevalence and detrimental impact. This concise guidance highlights key recommendations from the recent Endocrine Society Clinical Practice Guidelines on Treatment of Hypercalcaemia of Malignancy in Adults, published in December 2022. A systematic review and meta-analysis was commissioned to support the guideline development process. Key suggestions include the use of denosumab in preference to intravenous bisphosphonates as first-line treatment for HCM and the use of denosumab in cases of recurrent or refractory HCM in patients previously treated with intravenous bisphosphonates. The guideline also identifies priority areas for future research.
Topics: Humans; Adult; Hypercalcemia; Denosumab; Diphosphonates; Quality of Life; Neoplasms; Bone Density Conservation Agents
PubMed: 37775175
DOI: 10.7861/clinmed.2023-0227 -
Frontiers in Cardiovascular Medicine 2023Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein... (Review)
Review
INTRODUCTION
Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking.
METHODS
We conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI).
RESULTS
We encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (-14.06 mg/dl; 95% CI -18.0 to -10.0; = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group.
CONCLUSIONS
Our study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.
PubMed: 38075958
DOI: 10.3389/fcvm.2023.1269172 -
BMJ Open Nov 2023To report a systematic review and meta-analysis of the association between dry eye disease (DED) and dyslipidaemia. (Meta-Analysis)
Meta-Analysis
PURPOSE
To report a systematic review and meta-analysis of the association between dry eye disease (DED) and dyslipidaemia.
METHODS
PubMed, Embase, Web of Science and Cochrane Library were systematically searched from January 2000 to December 2021. We included observational studies to assess the correlation of DED with meibomian gland dysfunction and dyslipidaemia without any language restrictions. The pooled OR with 95% CI was calculated in Stata V.15.
RESULTS
Of 6727 identified studies, 18 studies (21 databases) with a total of 2 663 126 patients were analysed in our meta-analysis. The results showed that DED risk was associated with dyslipidaemia (OR=1.53, 95% CI: 1.41 to 1.66, p=0.001), especially elevated total cholesterol levels (OR=1.57, 95% CI: 1.25 to 1.99, p<0.001), elevated low-density lipoprotein cholesterol levels (OR=1.13, 95% CI: 1.06 to 1.20, p<0.001) and high-density lipoprotein cholesterol levels (OR=1.06, 95% CI: 1.01 to 1.11, p<0.001), but not with serum triglyceride levels. Moreover, having a history of lipid-lowering drug use (OR=1.41, 95% CI: 1.19 to 1.67, p<0.001) was also found to be positively associated with DED risk.
CONCLUSIONS
The findings suggested that dyslipidaemia and lipid-lowering drug use might be associated with an increased risk of DED. More evidence is needed to confirm the findings by prospective studies.
PROSPERO REGISTRATION NUMBER
CRD42022296664.
Topics: Humans; Prospective Studies; Dyslipidemias; Dry Eye Syndromes; Cholesterol; Lipids
PubMed: 37989379
DOI: 10.1136/bmjopen-2022-069283