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Frontiers in Endocrinology 2021Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of... (Meta-Analysis)
Meta-Analysis
PURPOSE
Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients.
METHODS
Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas.
RESULTS
One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and sex distribution (0.63; 0.15-1.56).
CONCLUSIONS
We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients.
SYSTEMATIC REVIEW REGISTRATION
This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
Topics: Diabetes Mellitus, Type 2; Fractures, Bone; Humans; Hypoglycemic Agents; Network Meta-Analysis; Risk Factors
PubMed: 34721294
DOI: 10.3389/fendo.2021.735824 -
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 -
Annals of Internal Medicine May 2024Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes.
PURPOSE
To evaluate the effectiveness, comparative effectiveness, and harms of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, and long-acting insulins as monotherapy or combination therapy in adults with type 2 diabetes mellitus (T2DM).
DATA SOURCES
MEDLINE and EMBASE for randomized controlled trials (RCTs) published from 2010 through January 2023.
STUDY SELECTION
RCTs lasting at least 52 weeks that included at least 500 adults with T2DM receiving eligible medications and reported any outcomes of interest.
DATA EXTRACTION
Data were abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE) were done.
DATA SYNTHESIS
A total of 130 publications from 84 RCTs were identified. CoE was appraised using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria for direct, indirect, and network meta-analysis (NMA); the highest CoE was reported. Compared with usual care, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (high CoE) and major adverse cardiovascular events (MACE) (moderate to high CoE), SGLT2 inhibitors reduce progression of chronic kidney disease (CKD) and heart failure hospitalizations and GLP1 agonists reduce stroke (high CoE), and SGLT2 inhibitors reduce serious adverse events and severe hypoglycemia (high CoE). The threshold for minimally important differences, which was predefined with the American College of Physicians Clinical Guidelines Committee, was not met for these outcomes. Compared with usual care, insulin, tirzepatide, and DPP4 inhibitors do not reduce all-cause mortality (low to high CoE). Compared with insulin, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (low to moderate CoE). Compared with DPP4 inhibitors, GLP1 agonists reduce all-cause mortality (moderate CoE). Compared with DPP4 inhibitors and sulfonylurea (SU), SGLT2 inhibitors reduce MACE (moderate to high CoE). Compared with SU and insulin, SGLT2 inhibitors and GLP1 agonists reduce severe hypoglycemia (low to high CoE).
LIMITATIONS
Infrequent direct comparisons between drugs of interest; sparse data for NMA on most outcomes; possible incoherence due to differences in baseline patient characteristics and usual care; insufficient data on predefined subgroups, including demographic subgroups, patients with prior cardiovascular disease, and treatment-naive persons.
CONCLUSION
In adults with T2DM, SGLT2 inhibitors and GLP1 agonists (but not DPP4 inhibitors, insulin, or tirzepatide) reduce all-cause mortality and MACE compared with usual care. SGLT2 inhibitors reduce CKD progression and heart failure hospitalization and GLP1 agonists reduce stroke compared with usual care. Serious adverse events and severe hypoglycemia are less frequent with SGLT2 inhibitors and GLP1 agonists than with insulin or SU.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42022322129).
Topics: Humans; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Network Meta-Analysis; Insulin; Adult; Cardiovascular Diseases; Glucagon-Like Peptide 1; Hypoglycemia; Drug Therapy, Combination
PubMed: 38639549
DOI: 10.7326/M23-1490 -
Nutrients Oct 2020The prevalence of type 2 diabetes is on the increase worldwide, and it represents about 90% of adults who are diagnosed with diabetes. Overweight and obesity, lifestyle,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of type 2 diabetes is on the increase worldwide, and it represents about 90% of adults who are diagnosed with diabetes. Overweight and obesity, lifestyle, genetic predisposition and gut microbiota dysbiosis have been implicated as possible risk factors in the development of type 2 diabetes. In particular, low intake of dietary fibre and consumption of foods high in fat and sugar, which are common in western lifestyle, have been reported to contribute to the depletion of specific bacterial taxa. Therefore, it is possible that intake of high dietary fibre may alter the environment in the gut and provide the needed substrate for microbial bloom.
AIM
The current review is a systematic review and meta-analysis which evaluated the role of dietary fibre in modulating gut microbiota dysbiosis in patients with type 2 diabetes.
METHODS
This is a systematic review and meta-analysis of randomised controlled trials which relied on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Electronic searches were conducted using EBSCOHost with links to Health Sciences Research Databases, EMBASE and Google Scholar. The reference lists of articles were also searched for relevant studies. Searches were conducted from date of commencement of the database to 5 August 2020. The search strategy was based on the Population, Intervention, Comparator, Outcomes, Studies (PICOS) framework and involved the use of synonyms and medical subject headings (MesH). Search terms were combined with Boolean operators (OR/AND).
RESULTS
Nine studies which met the inclusion criteria were selected for the systematic review and meta-analysis, and four distinct areas were identified: the effect of dietary fibre on gut microbiota; the role of dietary fibre on short-chain fatty acids (SCFAs); glycaemic control; and adverse events. There was significant difference ( < 0.01) in the relative abundance of Bifidobacterium with a mean difference of 0.72 (95% CI, 0.56, 0.89) between the dietary fibre group compared with placebo. In relation to the meta-analysis for SCFAs, while there was significant difference ( = 0.02) between the dietary fibre group and placebo with a standardised mean difference of 0.5 (95% CI, 0.08, 0.91) regarding total SCFAs, the differences were not significant ( > 0.05) in relation to acetic acid, propionic acid and butyric acid. There was only significant improvement ( = 0.002) with respect to glycated haemoglobin with a mean difference of -0.18 (95% CI, -0.29, -0.06) between the dietary fibre group and placebo group. Differences between the two groups were not significant ( > 0.05) in relation to fasting blood glucose and homeostatic model assessment of insulin resistance (HOMA-IR). Furthermore, there were no significant differences between the two groups in subjects who reported adverse events. It is possible that the promotion of SCFA producers in greater diversity and abundance by dietary fibre in this review led to improvement in glycated haemoglobin, partly due to increased glucagon-like peptide-1 (GLP-1) production. In addition, Bifidobacterium lactis has been reported to increase glycogen synthesis, decrease expression of hepatic gluconeogenesis genes, improve translocation of glucose transport-4 and promote glucose uptake. It is also possible that the reduction in body weight of participants in the intervention group compared with control may have contributed to the observed improvement in glycated haemoglobin.
CONCLUSION
This systematic review and meta-analysis have demonstrated that dietary fibre can significantly improve ( < 0.05) the relative abundance of Bifidobacterium, total SCFAs and glycated haemoglobin. However, dietary fibre did not appear to have significant effect ( > 0.05) on fasting blood glucose, HOMA-IR, acetic acid, propionic acid, butyric acid and adverse events.
Topics: Adult; Diabetes Mellitus, Type 2; Dietary Fiber; Dysbiosis; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Glucagon-Like Peptide 1; Glycated Hemoglobin; Glycemic Control; Humans; Male; Randomized Controlled Trials as Topic
PubMed: 33113929
DOI: 10.3390/nu12113239 -
Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2 -
PloS One 2023Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.
METHODS
We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.
CONCLUSIONS
As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.
Topics: Adult; Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Angiotensin Receptor Antagonists; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Kidney Failure, Chronic; Angiotensins; Diabetes Mellitus
PubMed: 37917640
DOI: 10.1371/journal.pone.0293183 -
The Cochrane Database of Systematic... Oct 2021Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists... (Meta-Analysis)
Meta-Analysis
Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.
BACKGROUND
Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) were approved for treating people with type 2 diabetes mellitus. Although metformin remains the first-line pharmacotherapy for people with type 2 diabetes mellitus, a body of evidence has recently emerged indicating that DPP4i, GLP-1RA and SGLT2i may exert positive effects on patients with known CVD.
OBJECTIVES
To systematically review the available evidence on the benefits and harms of DPP4i, GLP-1RA, and SGLT2i in people with established CVD, using network meta-analysis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and the Conference Proceedings Citation Index on 16 July 2020. We also searched clinical trials registers on 22 August 2020. We did not restrict by language or publication status.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) investigating DPP4i, GLP-1RA, or SGLT2i that included participants with established CVD. Outcome measures of interest were CVD mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, all-cause mortality, hospitalisation for heart failure (HF), and safety outcomes.
DATA COLLECTION AND ANALYSIS
Three review authors independently screened the results of searches to identify eligible studies and extracted study data. We used the GRADE approach to assess the certainty of the evidence. We conducted standard pairwise meta-analyses and network meta-analyses by pooling studies that we assessed to be of substantial homogeneity; subgroup and sensitivity analyses were also pursued to explore how study characteristics and potential effect modifiers could affect the robustness of our review findings. We analysed study data using the odds ratios (ORs) and log odds ratios (LORs) with their respective 95% confidence intervals (CIs) and credible intervals (Crls), where appropriate. We also performed narrative synthesis for included studies that were of substantial heterogeneity and that did not report quantitative data in a usable format, in order to discuss their individual findings and relevance to our review scope.
MAIN RESULTS
We included 31 studies (287 records), of which we pooled data from 20 studies (129,465 participants) for our meta-analysis. The majority of the included studies were at low risk of bias, using Cochrane's tool for assessing risk of bias. Among the 20 pooled studies, six investigated DPP4i, seven studied GLP-1RA, and the remaining seven trials evaluated SGLT2i. All outcome data described below were reported at the longest follow-up duration. 1. DPP4i versus placebo Our review suggests that DPP4i do not reduce any risk of efficacy outcomes: CVD mortality (OR 1.00, 95% CI 0.91 to 1.09; high-certainty evidence), myocardial infarction (OR 0.97, 95% CI 0.88 to 1.08; high-certainty evidence), stroke (OR 1.00, 95% CI 0.87 to 1.14; high-certainty evidence), and all-cause mortality (OR 1.03, 95% CI 0.96 to 1.11; high-certainty evidence). DPP4i probably do not reduce hospitalisation for HF (OR 0.99, 95% CI 0.80 to 1.23; moderate-certainty evidence). DPP4i may not increase the likelihood of worsening renal function (OR 1.08, 95% CI 0.88 to 1.33; low-certainty evidence) and probably do not increase the risk of bone fracture (OR 1.00, 95% CI 0.83 to 1.19; moderate-certainty evidence) or hypoglycaemia (OR 1.11, 95% CI 0.95 to 1.29; moderate-certainty evidence). They are likely to increase the risk of pancreatitis (OR 1.63, 95% CI 1.12 to 2.37; moderate-certainty evidence). 2. GLP-1RA versus placebo Our findings indicate that GLP-1RA reduce the risk of CV mortality (OR 0.87, 95% CI 0.79 to 0.95; high-certainty evidence), all-cause mortality (OR 0.88, 95% CI 0.82 to 0.95; high-certainty evidence), and stroke (OR 0.87, 95% CI 0.77 to 0.98; high-certainty evidence). GLP-1RA probably do not reduce the risk of myocardial infarction (OR 0.89, 95% CI 0.78 to 1.01; moderate-certainty evidence), and hospitalisation for HF (OR 0.95, 95% CI 0.85 to 1.06; high-certainty evidence). GLP-1RA may reduce the risk of worsening renal function (OR 0.61, 95% CI 0.44 to 0.84; low-certainty evidence), but may have no impact on pancreatitis (OR 0.96, 95% CI 0.68 to 1.35; low-certainty evidence). We are uncertain about the effect of GLP-1RA on hypoglycaemia and bone fractures. 3. SGLT2i versus placebo This review shows that SGLT2i probably reduce the risk of CV mortality (OR 0.82, 95% CI 0.70 to 0.95; moderate-certainty evidence), all-cause mortality (OR 0.84, 95% CI 0.74 to 0.96; moderate-certainty evidence), and reduce the risk of HF hospitalisation (OR 0.65, 95% CI 0.59 to 0.71; high-certainty evidence); they do not reduce the risk of myocardial infarction (OR 0.97, 95% CI 0.84 to 1.12; high-certainty evidence) and probably do not reduce the risk of stroke (OR 1.12, 95% CI 0.92 to 1.36; moderate-certainty evidence). In terms of treatment safety, SGLT2i probably reduce the incidence of worsening renal function (OR 0.59, 95% CI 0.43 to 0.82; moderate-certainty evidence), and probably have no effect on hypoglycaemia (OR 0.90, 95% CI 0.75 to 1.07; moderate-certainty evidence) or bone fracture (OR 1.02, 95% CI 0.88 to 1.18; high-certainty evidence), and may have no impact on pancreatitis (OR 0.85, 95% CI 0.39 to 1.86; low-certainty evidence). 4. Network meta-analysis Because we failed to identify direct comparisons between each class of the agents, findings from our network meta-analysis provided limited novel insights. Almost all findings from our network meta-analysis agree with those from the standard meta-analysis. GLP-1RA may not reduce the risk of stroke compared with placebo (OR 0.87, 95% CrI 0.75 to 1.0; moderate-certainty evidence), which showed similar odds estimates and wider 95% Crl compared with standard pairwise meta-analysis. Indirect estimates also supported comparison across all three classes. SGLT2i was ranked the best for CVD and all-cause mortality.
AUTHORS' CONCLUSIONS
Findings from both standard and network meta-analyses of moderate- to high-certainty evidence suggest that GLP-1RA and SGLT2i are likely to reduce the risk of CVD mortality and all-cause mortality in people with established CVD; high-certainty evidence demonstrates that treatment with SGLT2i reduce the risk of hospitalisation for HF, while moderate-certainty evidence likely supports the use of GLP-1RA to reduce fatal and non-fatal stroke. Future studies conducted in the non-diabetic CVD population will reveal the mechanisms behind how these agents improve clinical outcomes irrespective of their glucose-lowering effects.
Topics: Cardiovascular Diseases; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Glucagon-Like Peptide 1; Glucose; Humans; Network Meta-Analysis; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 34693515
DOI: 10.1002/14651858.CD013650.pub2 -
Frontiers in Endocrinology 2023To assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM).
METHODS
A systemic review and meta-analysis were designed by reviewing articles published between 2000 January 1 and 2022 December 31 using PubMed system and Web of Science system based on the PRISMA 2020 guidelines. The end point of interest was gout (including gout flares, gout events, starting uric-acid lowering therapy and starting anti-gout drugs use) among patients with T2DM using SGLT2i versus not using SGLT2i. A random-effects model was utilized to measure the pooled hazard ratio (HR) with 95% confidence interval (CI) for the risk of gout associated with SGLT2i use.
RESULTS
Two prospective post-hoc analyses of randomized controlled trials and 5 retrospective electronic medical record-linkage cohort studies met the inclusion criteria. The meta-analysis demonstrated that there was a decreased risk of developing gout for SGLT2i use as comparing with non-use of SGLT2i among patients with T2DM (pooled HR=0.66 and 95%CI=0.57-0.76).
CONCLUSIONS
This meta-analysis demonstrates that SGLT2i use is associated with a 34% decreased risk of developing gout among patients with T2DM. SGLT2i may be the treatment options for patients with T2DM who are at high risk of gout. More randomized controlled trials and real-world data are needed to confirm whether there is a class effect of SGLT2i for the risk reduction of gout among patients with T2DM.
Topics: Sodium-Glucose Transporter 2 Inhibitors; Gout; Diabetes Mellitus, Type 2; Humans; Male; Female; Middle Aged; Placebos; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor
PubMed: 37288295
DOI: 10.3389/fendo.2023.1158153 -
Journal of the Royal Society of Medicine Sep 2023The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and...
Racial, ethnic and regional differences in the effect of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes: a systematic review and meta-analysis of cardiovascular outcome trials.
OBJECTIVES
The cardiorenal protective effects of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) across racial and ethnic groups are not well defined. By conducting a systematic review and meta-analysis of all randomised, placebo-controlled, cardiovascular disease (CVD) outcomes trials (CVOTs), we aimed to compare racial/ethnic as well as regional patterns in the effects of SGLT2-Is and GLP1-RAs on cardiovascular and renal outcomes in patients with type 2 diabetes (T2D).
DESIGN
Trials were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to 7 July 2023. Setting North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa.
SETTING
North America, South/Central America, Europe (Eastern and Western), Asia, Australia-New Zealand (Pacific), Asia/Pacific, and Africa.
PARTICIPANTS
people with type 2 diabetes enrolled in cardiovascular outcome trials of SGLT2-Is and GLP1-RAs.
MAIN OUTCOME MEASURES
Outcomes were (i) major adverse cardiovascular events (MACE), (ii) composite CVD death/heart failure (HF) hospitalization; (iii) composite renal outcome; and (iv) their components. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled.
RESULTS
In total, 14 unique CVOTs (7 comparing SGLT2-Is vs placebo and 7 comparing GLP1-RAs vs placebo) were eligible. The proportion of participants enrolled in the trials ranged from 66.6-93.2% for White populations, 1.2-21.6% for Asian populations, 2.4-8.3% for Black populations and 0.9-23.1% for Other populations. The HR (95% CI) for MACE comparing SGLT2-Is vs placebo was 0.92 (0.86-0.98), 0.69 (0.53-0.92) and 0.70 (0.54-0.91) for White, Asian and Hispanic/Latino populations, respectively. Comparing GLP1-RAs vs placebo, the corresponding HR (95% CI) was 0.88 (0.80-0.97), 0.76 (0.63-0.93) and 0.82 (0.70-0.95), respectively. SGLT2-Is reduced the risk of all other cardiorenal outcomes in White and Asian populations, except for HF hospitalizations in Asians. No effects were observed in Black populations except for a reduced risk of HF hospitalizations by SGLT2-I. SGLT1-Is reduced the risk of composite CVD death/HF hospitalization in North America and Europe, whereas GLP1-RAs reduced the risk of MACE in Europe. GRADE certainty of evidence ranged from moderate to high.
CONCLUSIONS
There appears to be substantial racial/ethnic differences in the cardiorenal effects of SGLT2-Is and GLP1-RAs in patients with T2D, with consistent benefits observed among White and Asian populations and consistent lack of benefits in Black populations. Whether the differences are due to issues with under-representation of Black populations and low statistical power or racial/ethnic variations in the pharmacokinetics, pharmacodynamics and safety of SGLT2-Is and GLP1-RAs need further investigation.PROSPERO Registration: CRD42023401734.
PubMed: 37734450
DOI: 10.1177/01410768231198442 -
BMC Endocrine Disorders Oct 2022Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes.
METHODS
Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES
MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs.
STUDY SELECTION
Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.
OUTCOMES
The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia.
SYNTHESIS OF RESULTS
Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780).
RESULTS
Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules.
CONCLUSION
Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.
Topics: Adult; Humans; Adolescent; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glipizide; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemia; Glucagon-Like Peptide 1; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Symporters; Glucose; Sodium
PubMed: 36261824
DOI: 10.1186/s12902-022-01158-5