-
Cardiovascular Diabetology Jan 2021Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with... (Meta-Analysis)
Meta-Analysis
Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis.
BACKGROUND
Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.
METHODS
We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized.
RESULTS
Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]).
CONCLUSIONS
In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.
Topics: Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Progression; Female; Glucagon-Like Peptide-1 Receptor; Humans; Incretins; Male; Network Meta-Analysis; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 33413348
DOI: 10.1186/s12933-020-01197-z -
The Cochrane Database of Systematic... Jul 2020Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for treatment of type 2 diabetes, work by stimulating GLP-1 receptors in the pancreas, which triggers the release of insulin. GLP-1 receptors have been found in the brain. Insulin signalling in the brain plays a key role in neuronal metabolism and repair and in synaptic efficacy, but insulin signalling is desensitised in the brain of people with PD. Researchers are exploring the neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders such as PD.
OBJECTIVES
To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson's disease.
SEARCH METHODS
We searched the Cochrane Movement Disorders Group trials register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; and Ovid MEDLINE and Embase. We also searched clinical trials registries, and we handsearched conference abstracts. The most recent search was run on 25 June 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of adults with PD that compared GLP-1 receptor agonists with conventional PD treatment, placebo, or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We rated the quality of evidence using GRADE. We resolved discrepancies between the two data extractors by consultation with a third review author.
MAIN RESULTS
Through our searches, we retrieved 99 unique records, of which two met our inclusion criteria. One double-blind study of exenatide versus placebo randomised 62 participants, who self-administered exenatide or placebo for 48 weeks and were followed up at 60 weeks after a 12-week washout. One single-blind study of exenatide versus no additional treatment randomised 45 participants; participants in the intervention group self-administered exenatide for 12 months, and all participants were followed up at 14 months and 24 months following absence of exenatide for 2 months and 12 months, respectively. These trials had low risk of bias, except risk of performance bias was high for Aviles-Olmos 2013. Exenatide versus placebo Primary outcomes We found low-certainty evidence suggesting that exenatide improves motor impairment as assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in the off-medication state (mean difference (MD) -3.10, 95% confidence interval (CI) -6.11 to -0.09). The difference in scores was slightly greater when scores were adjusted for baseline severity of the condition (as reported by study authors) (MD -3.5, 95% CI -6.7 to -0.3), exceeding the minimum clinically important difference (MCID). We found low-certainty evidence suggesting that exenatide has little or no effect on health-related quality of life (HRQoL) as assessed by the Parkinson's Disease Questionnaire (PDQ)-39 Summary Index (SI) (MD -1.80, 95% CI -6.95 to 3.35), the EuroQol scale measuring health status in five dimensions (EQ5D) (MD 0.07, 95% CI -0.03 to 0.16), or the EQ5D visual analogue scale (VAS) (MD 5.00, 95% CI -3.42 to 13.42). Eight serious adverse events (SAEs) were recorded, but all were considered unrelated to the intervention. Low-certainty evidence suggests that exenatide has little or no effect on weight loss (risk ratio (RR) 1.25, 95% CI 0.89 to 1.76). Exenatide versus no treatment Primary outcomes at 14 months We found very low-certainty evidence suggesting that exenatide improves motor impairment as assessed by MDS-UPDRS Part III off medication (MD -4.50, 95% CI -8.64 to -0.36), exceeding the MCID. We are uncertain whether exenatide improves HRQoL as assessed by the PDQ-39 SI (MD 3.50, 95% CI -2.75 to 9.75; very low-quality evidence). We found very low-certainty evidence suggesting that exenatide has little or no effect on the number of SAEs (RR 1.60, 95% 0.40 to 6.32). We found very low-certainty evidence suggesting that exenatide may lead to weight loss (MD -2.40 kg, 95% CI -4.56 to -0.24). Primary outcomes at 24 months We found evidence as reported by study authors to suggest that exenatide improves motor impairment as measured by MDS-UPDRS Part III off medication (MD 5.6 points, 95% CI 2.2 to 9.0). Exenatide may not improve HRQoL as assessed by the PDQ-39 SI (P = 0.682) and may not result in weight loss (MD 0.1 kg, 95% CI 3.0 to 2.8).
AUTHORS' CONCLUSIONS
Low- or very low-certainty evidence suggests that exenatide may improve motor impairment for people with PD. The difference in motor impairment observed between groups may persist for some time following cessation of exenatide. This raises the possibility that exenatide may have a disease-modifying effect. SAEs were unlikely to be related to treatment. The effectiveness of exenatide for improving HRQoL, non-motor outcomes, ADLs, and psychological outcomes is unclear. Ongoing studies are assessing other GLP-1 receptor agonists.
Topics: Bias; Double-Blind Method; Exenatide; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Parkinson Disease; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Self Administration; Single-Blind Method
PubMed: 32700772
DOI: 10.1002/14651858.CD012990.pub2 -
Advances in Therapy Jun 2021In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic... (Meta-Analysis)
Meta-Analysis
In patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations or symptoms, despite being prescribed dual long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) or inhaled corticosteroid (ICS)/LABA therapies, triple ICS/LAMA/LABA therapy is recommended. A previous network meta-analysis showed comparable efficacy of the ICS/LAMA/LABA, budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) 320/18/9.6 µg, to other fixed-dose and open combination triple therapies at 24 weeks in COPD. Subsequently, the ETHOS study was published, including data for 8509 patients, assessing the efficacy and safety of BUD/GLY/FOR over 52 weeks. This network meta-analysis (NMA) was conducted to compare the relative efficacy, safety, and tolerability of BUD/GLY/FOR 320/18/9.6 µg with other fixed-dose and open combination triple therapies in COPD over 52 weeks, including data from ETHOS. A systematic literature review was conducted to identify ≥ 10-week randomized controlled trials, including ≥ 1 fixed-dose or open combination triple-therapy arm, in patients with moderate-to-very severe COPD. The methodologic quality and risk of bias of included studies were assessed. Study results were combined using a three-level hierarchical Bayesian NMA model to assess efficacy and safety outcomes at or over 24 and 52 weeks. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies. Nineteen studies (n = 37,741 patients) met the inclusion criteria of the review; 15 contributed to the base case network. LAMA/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes for exacerbations, lung function, symptoms, health-related quality of life, safety, and tolerability, the efficacy and safety of BUD/GLY/FOR were comparable to those of other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium bromide/formoterol fumarate) and open combinations at or over 24 and 52 weeks. Sensitivity analyses and meta-regression results for exacerbation outcomes were broadly in line with the base case NMA. In this NMA, BUD/GLY/FOR 320/18/9.6 μg showed comparable efficacy versus other ICS/LAMA/LABA fixed-dose or open combination therapies in terms of reducing exacerbation rates and improving lung function, symptoms and health-related quality of life in patients with moderate-to-very-severe COPD, in line with previously published meta-analysis results of triple combinations in COPD. The safety and tolerability profile of BUD/GLY/FOR was also found to be comparable to other triple combination therapies.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Bayes Theorem; Bronchodilator Agents; Budesonide; Drug Combinations; Formoterol Fumarate; Fumarates; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 33929661
DOI: 10.1007/s12325-021-01703-z -
Journal of Clinical Oncology : Official... Jul 2018Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and... (Meta-Analysis)
Meta-Analysis
Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data.
Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
Topics: Adult; Breast Neoplasms; Disease-Free Survival; Female; Fertility Preservation; Gonadotropin-Releasing Hormone; Humans; Organ Sparing Treatments; Ovary; Premenopause; Primary Ovarian Insufficiency; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29718793
DOI: 10.1200/JCO.2018.78.0858 -
Obesity (Silver Spring, Md.) Nov 2022Glucagon-like peptide-1 (GLP-1) receptor agonists recently demonstrated 15% to 20% weight loss in adults with obesity, a range which has previously been achieved only... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) receptor agonists recently demonstrated 15% to 20% weight loss in adults with obesity, a range which has previously been achieved only with bariatric surgery. This systematic review and meta-analysis compares weight loss between GLP-1 receptor agonists and bariatric surgery.
METHODS
The databases MEDLINE, MEDLINE In-Process, MEDLINE Epubs Ahead of Print, Embase Classic + Embase (OvidSP), and Cochrane (Wiley) were searched from inception to April 21, 2021, for randomized controlled trials and observational studies. Two independent reviewers extracted data, reported risk of bias, and graded certainty of evidence. Random-effects models were used to pool change in weight, BMI, and glycated hemoglobin.
RESULTS
Six studies, encompassing 332 patients, were included. Among randomized controlled trials, mean difference in weight between all bariatric surgery types and GLP-1 receptor agonists was -22.68 kg (95% CI: -31.41 to -13.96), mean difference in BMI was -8.18 kg/m (95% CI: -11.59 to -4.77), and mean difference in glycated hemoglobin was -1.28% (95% CI: -1.94% to -0.61%). Among observational studies, mean difference in weight was -25.11 kg (95% CI: -40.61 to -9.60), and mean difference in BMI was -10.60 kg/m (95% CI: -17.22 to -3.98). Only one observational study reported glycemic outcomes.
CONCLUSION
In adults with obesity, bariatric surgery still confers the highest reductions in weight and BMI but confers similar effects in glycemic control when compared with GLP-1 receptor agonists.
Topics: Adult; Humans; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Weight Loss; Bariatric Surgery; Obesity; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Observational Studies as Topic
PubMed: 36321278
DOI: 10.1002/oby.23563 -
Diabetes, Obesity & Metabolism Jan 2024To compare the therapeutic effects of glucose-dependent insulinotropic polypeptide (GIP)/ glucagon-like peptide-1 receptor agonists (GLP-1RAs) or GLP-1RAs in Japanese... (Meta-Analysis)
Meta-Analysis
Effect of tirzepatide on glycaemic control and weight loss compared with other glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes mellitus.
AIM
To compare the therapeutic effects of glucose-dependent insulinotropic polypeptide (GIP)/ glucagon-like peptide-1 receptor agonists (GLP-1RAs) or GLP-1RAs in Japanese patients with type 2 diabetes (T2D).
MATERIALS AND METHODS
We systematically searched PubMed, MEDLINE, EMBASE, and the Cochrane Library up to July 2023. Randomized controlled trials (RCTs) that compared GLP-1RAs or GIP/GLP-1RAs in Japanese patients with T2D were selected. A network meta-analysis was conducted to indirectly compare the treatments, focusing on efficacy in reducing glycated haemoglobin (HbA1c) levels and body weight (BW).
RESULTS
A total of 18 RCTs were included in this analysis. Tirzepatide 15 mg showed the most significant reduction in HbA1c levels and BW compared with subcutaneous semaglutide 1.0 mg and oral semaglutide 14 mg (HbA1c: mean difference [95% confidence interval] -0.52 [-0.96; -0.08] and - 1.23 [-1.64; -0.81]; BW: -5.07 [-8.28; -1.86] and -6.84 [-8.97; -4.71], respectively). Subcutaneous semaglutide showed a superior reduction in HbA1c compared with oral semaglutide. Both subcutaneous and oral semaglutide were more effective than conventional GLP-1RAs, such as dulaglutide, liraglutide and lixisenatide.
CONCLUSIONS
Among Japanese patients with T2D, tirzepatide showed the greatest effectiveness in reducing HbA1c levels and inducing weight loss. The study provides evidence to guide GLP-1RA treatment strategies in Japanese patients with T2D.
Topics: Humans; Body Weight; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-1 Receptor Agonists; Glucagon-Like Peptides; Glycated Hemoglobin; Glycemic Control; Hypoglycemic Agents; Japan; Weight Loss; East Asian People
PubMed: 37828829
DOI: 10.1111/dom.15312 -
Frontiers in Pharmacology 2023The relative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and 4 glucagon-like peptide-1 (GLP-1) receptor agonists for non-alcoholic fatty...
Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials.
The relative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and 4 glucagon-like peptide-1 (GLP-1) receptor agonists for non-alcoholic fatty liver disease (NAFLD) therapy has not been sufficiently investigated. Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included. Primary outcomes were improvements in liver enzymes and liver fat parameters, while secondary outcomes included anthropometric measures, blood lipids and glycemic parameters. The frequentist method was used to perform a network meta-analysis. Evidence certainty was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists). Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin. Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment. Semaglutide, liraglutide, and dapagliflozin all have a certain effect on NAFLD (or comorbid with type 2 diabetes) based on high confidence evidence from indirect comparisons, and semaglutide appears to have a therapeutic advantage over the other included medicines. Head-to-head studies are needed to provide more confidence in clinical decision-making.
PubMed: 36992825
DOI: 10.3389/fphar.2023.1102792 -
Frontiers in Endocrinology 2022The association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of various kinds of thyroid disorders remains uncertain. We aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
UNLABELLED
The association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of various kinds of thyroid disorders remains uncertain. We aimed to evaluate the relationship between the use of GLP-1 receptor agonists and the occurrence of 6 kinds of thyroid disorders. We searched PubMed (MEDLINE), EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science from database inception to 31 October 2021 to identify eligible randomized controlled trials (RCTs). We performed meta-analysis using a random-effects model to calculate risk ratios (RRs) and 95% confidence intervals (CIs). A total of 45 trials were included in the meta-analysis. Compared with placebo or other interventions, GLP-1 receptor agonists' use showed an association with an increased risk of overall thyroid disorders (RR 1.28, 95% CI 1.03-1.60). However, GLP-1 receptor agonists had no significant effects on the occurrence of thyroid cancer (RR 1.30, 95% CI 0.86-1.97), hyperthyroidism (RR 1.19, 95% CI 0.61-2.35), hypothyroidism (RR 1.22, 95% CI 0.80-1.87), thyroiditis (RR 1.83, 95% CI 0.51-6.57), thyroid mass (RR 1.17, 95% CI 0.43-3.20), and goiter (RR 1.17, 95% CI 0.74-1.86). Subgroup analyses and meta-regression analyses showed that underlying diseases, type of control, and trial durations were not related to the effect of GLP-1 receptor agonists on overall thyroid disorders (all P > 0.05). In conclusion, GLP-1 receptor agonists did not increase or decrease the risk of thyroid cancer, hyperthyroidism, hypothyroidism, thyroiditis, thyroid mass and goiter. However, due to the low incidence of these diseases, these findings need to be examined further.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/prospero/, identifier: CRD42021289121.
Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Goiter; Humans; Hyperthyroidism; Hypoglycemic Agents; Hypothyroidism; Randomized Controlled Trials as Topic; Thyroid Neoplasms
PubMed: 35898463
DOI: 10.3389/fendo.2022.927859 -
Diabetes Research and Clinical Practice Apr 2021To assess the cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT2) inhibitors in older people with... (Meta-Analysis)
Meta-Analysis
AIMS
To assess the cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT2) inhibitors in older people with type 2 diabetes.
METHODS
PubMed, Embase, and Cochrane library were searched up to November 2020 for cardiovascular outcomes trials with GLP-1 RAs or SGLT2 inhibitors that reported results for older patients with type 2 diabetes. Random-effects meta-analyses were conducted for different age subgroup categories.
RESULTS
A total of 11 studies (93,502 patients) were included. Consistent with their effect in the overall population, in patients ≥65 years, GLP-1 RAs reduced major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.80-0.92), cardiovascular death, stroke, and myocardial infarction. In the same age subgroup, SGLT2 inhibitors reduced MACE (HR, 0.90; 95% CI, 0.83-0.98) but had a neutral effect on its components. They also reduced heart failure hospitalization (HR, 0.62; 95% CI, 0.51-0.76), an effect that was not evident in patients <65 years, and the composite renal endpoint (HR, 0.57; 95% CI, 0.43-0.77). Meta-analyses for patients ≥75 years yielded similar results.
CONCLUSIONS
In older adults with diabetes, GLP-1 RAs reduced MACE and its components. SGLT2 inhibitors reduced MACE, and heart failure and renal outcomes.
Topics: Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide-1 Receptor; Humans; Male; Risk Factors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33705820
DOI: 10.1016/j.diabres.2021.108737 -
Diabetes, Obesity & Metabolism Mar 2024To conduct a meta-analysis of randomized clinical trials (RCTs) to investigate whether there is an association between glucagon-like peptide-1 receptor agonist (GLP-1RA)... (Meta-Analysis)
Meta-Analysis
AIM
To conduct a meta-analysis of randomized clinical trials (RCTs) to investigate whether there is an association between glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment and thyroid cancer.
MATERIALS AND METHODS
In this meta-analysis of RCTs, we included studies comparing a GLP-1RA with any comparator, lasting at least 52 weeks, and reporting the incidence of adverse events independently of the principal endpoint and population. All cases of thyroid cancer were collected.
RESULTS
We retrieved 64 trials, 26 of which reported at least one incident case of thyroid cancer. GLP-1RA treatment was associated with a significant increase in the risk of overall thyroid cancer (Mantel-Haenzel odds ratio [MH-OR] 1.52 [95% confidence interval {CI} 1.01, 2.29]; P = 0.04, I = 0%), with a fragility index of 1, and a 5-year number needed to harm of 1349. The association remained significant when including only trials lasting at least 104 weeks (MH-OR 1.76 [95% CI 1.00, 3.12]; P = 0.05). No significant association was found for papillary thyroid cancer (MH-OR 1.54 [95% CI 0.77, 3.06]; P = 0.22) or medullary thyroid cancer (MH-OR 1.44 [95% CI 0.23, 9.16]; P = 0.55).
CONCLUSIONS
Our meta-analysis showed that GLP-1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor Agonists; Randomized Controlled Trials as Topic; Thyroid Neoplasms; Glucagon-Like Peptide-1 Receptor
PubMed: 38018310
DOI: 10.1111/dom.15382