Comparative Efficacy of Glucagon-like Peptide 1 Receptor Agonists and Sodium Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular Events in Type 2 Diabetes: A Network Meta-analysis.

ABSTRACT: The comparative efficacy of different glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular events (MACE) in type 2 diabetes with or without cardiorenal disease is undefined. PubMed and Embase were searched for relevant randomized trials. We conducted network meta-analysis within the Bayesian framework. Effect sizes were measured using hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) values to rank drug interventions for different type 2 diabetic subgroups. Albiglutide (HR 0.76, 95% CI 0.63-0.93) and subcutaneous semaglutide (HR 0.71, 95% CI 0.52-0.95), with the maximum SUCRA values, significantly reduced MACE versus lixisenatide in people with diabetes with cardiovascular disease; albiglutide (HRs: 0.69 and 0.72), with the maximum SUCRA value, significantly reduced MACE versus dapagliflozin and exenatide in people with diabetes with heart failure; and canagliflozin (HRs: 0.72 and 0.72) and liraglutide (HRs: 0.68 and 0.68), with the maximum SUCRA values, significantly reduced MACE versus exenatide and lixisenatide in people with diabetes with chronic kidney disease. In preventing MACE in type 2 diabetes, subcutaneous semaglutide and albiglutide are most effective for diabetes with cardiovascular disease, albiglutide is most effective for diabetes with heart failure, and canagliflozin and liraglutide are most effective for diabetes with chronic kidney disease.

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials.

The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

SGLT2 inhibitors for prevention of cardiorenal events in people with type 2 diabetes without cardiorenal disease: A meta-analysis of large randomized trials and cohort studies.

To investigate whether sodium glucose cotransporter 2 inhibitors (SGLT2is) can reduce important cardiorenal endpoints in type 2 diabetic adults without established cardiovascular disease (ECD), in those without heart failure (HF), and in those without chronic kidney disease (CKD). We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov. Event-driven randomized controlled trials (RCTs) and cohort studies were included. We conducted random-effects meta-analysis, respectively based on RCTs and cohort studies, on eight cardiorenal endpoints in three type 2 diabetic subgroups. Thirteen large studies were included. Meta-analysis of RCTs showed the high quality evidences: compared with placebo, SGLT2is significantly reduced the risk of major adverse cardiovascular events, cardiovascular death or hospitalization for HF, and progression of CKD in type 2 diabetic adults without ECD [HRs (95 % CIs): 0.88 (0.82, 0.94), 0.76 (0.70, 0.82), and 0.59 (0.52, 0.66), respectively; risk differences (95 % CIs): -1.6 (-2.4, -0.8), -2.6 (-3.3, -2.0), and -2.4 (-2.8, -2.0) per 1000 patient-years, respectively], in those without HF [HRs (95 % CIs): 0.89 (0.82, 0.95), 0.74 (0.67, 0.81), and 0.61 (0.55, 0.67), respectively; risk differences (95 % CIs): -1.7 (-2.9, -0.8), -5.8 (-7.3, -4.2), and -2.3 (-2.6, -1.9) per 1000 patient-years, respectively], and in those without CKD [HRs (95 % CIs): 0.88 (0.82, 0.94), 0.77 (0.71, 0.83), and 0.63 (0.57, 0.70), respectively; risk differences (95 % CIs): -2.4 (-3.6, -1.2), -6.1 (-7.6, -4.5), and -2.2 (-2.6, -1.8) per 1000 patient-years, respectively]. Meta-analysis of cohort studies also showed the benefits of SGLT2is on the three composite outcomes in the three diabetic subgroups. SGLT2is also significantly reduced some other cardiorenal endpoints in these diabetic subgroups. SGLT2is can significantly reduce important cardiorenal events in type 2 diabetic adults without ECD, in those without HF, and in those without CKD; which supports SGLT2is used in these diabetic subpopulations to prevent cardiorenal events.

[Study of Surface Enhanced Raman Spectroscopy on Copper Films Modified by Ion Beam].

Surface-enhanced Raman Spectroscopy (SERS) was a rapid non-destructive testing. It was based on detecting molecule vibrational spectrum which was adsorbed on the metallic surface. Now it was widely used in surface adsorption, electrochemical catalysis, sensors, bio-medical testing, trace amount analysis and other fields. In our experiment, copper metallic films were deposited 50 nm on BK7 glass substrates by direct current magnetron sputtering. And then the films were employed for the Ar ion beam etching modification. The structure, morphology and optical properties was characterized by X-ray diffraction (XRD), Atomic Force Microscope (AFM), spectrophotometer and Raman spectroscopy. In the XRD graph, the peak value of modify copper film were the same with the untreated film. So the structure of copper film was not change. With increasing the power of Ar ion, the surface roughness was changed, and scattered spectrum intensity was increased by surface roughness added. With Rhodamine B (Rh B) as a probe molecule, Raman scattered spectrum was detected on modify copper film. Compared with the different samples, we can find the Raman signal was enhanced by surface roughness added. It will have some value on study the principles of SERS.

Research on the Penetration Characteristics of PELE Projectile with Reactive Inner Core.

With the improvement of protection technology, the damage power of conventional penetrators has become increasingly inferior. Reactive material is a new type of energetic material, which has strong energy release capabilities under high-velocity-impact conditions. In this paper, the reactive materials were put into the penetrator, and its penetration characteristics were studied. First, the penetrator with enhanced lateral effect (PELE) projectile structure with better penetration capability was obtained by numerical simulation. Then, based on the established polytetrafluoroethylene (PTFE)/Al reactive material reaction model, the numerical simulation and experimental research of the PELE projectile with a reactive inner core penetrating the target were carried out. The results show that the simulation results are in good agreement with the experimental results, which verifies the confidence of the numerical simulation. The PELE projectile had a significant increase in power with the use of a truncated conical head and reactive materials. The residual velocity of the truncated cone PELE projectile increases by 8.41-21% over conventional PELE projectiles. Its damage range is 43% higher than that of conventional penetrators. The simulation method and the conclusions obtained in this paper can provide support and reference for further research on reactive materials and on effectively improving the damage power of the penetrator.

3,3'-(Piperazine-1,4-diium-1,4-di-yl)di-propionate dihydrate.

During the recrystallization of 3-[4-(2-carb-oxy-eth-yl)piperazin-1-yl]propionic acid, the carb-oxy-lic acid H atoms were transferred to the piperazine N atoms, forming the title compound, C(10)H(18)N(2)O(4)·2H(2)O, in which the zwitterion lies about an inversion center. In the crystal, bifurcated N-H⋯(O,O) hydrogen bonds connect the zwitterions into a two-dimensional framework parallel to (-102) forming R(4) (4)(30) rings. O-H⋯O hydrogen bonds involving the solvent water mol-ecules connect the two-dimensional framework into a three-dimensional network. In addition, weak C-H⋯O hydrogen bonds are observed.

3,5,3',5'-Tetra-methyl-4,4'-bi(1H-pyrazol-yl) hemihydrate.

In the title compound, C(10)H(14)N(4)·0.5H(2)O, the amino H atom of one of the two pyrazole rings is disordered over its two N atoms in a 1:1 ratio. The pyrazole rings are aligned at 60.1 (1)°. In the crystal, two bipyrazolyl mol-ecules are linked by an N-H⋯N hydrogen bond, generating a dimer; the dimer is connected to the water mol-ecule, which lies on a twofold rotation axis, resulting in the formation of a chain that makes an angle of ca 45.3 (1)° with the ab plane. The chains are cross-linked by N-H⋯O and O-H⋯N inter-actions, forming a three-dimensional network.

Comparative Efficacy of Five SGLT2i on Cardiorenal Events: A Network Meta-analysis Based on Ten CVOTs.

BACKGROUND: The relative efficacy of different sodium-glucose transporter 2 inhibitors (SGLT2i) on cardiorenal outcomes is unclear. METHODS: We included cardiovascular outcome trials (CVOTs) of SGLT2i. The eight endpoints of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular death (CVD), CVD or hospitalization for heart failure (HHF), HHF, kidney function progression (KFP), and all-cause death (ACD). We conducted a Bayesian network meta-analysis and calculated the surface under the cumulative ranking curve (SUCRA) probability to rank treatments. RESULTS: We included ten CVOTs involving five SGLT2i. Canagliflozin (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.53-0.77), dapagliflozin (HR 0.70; 95% CI 0.62-0.79), empagliflozin (HR 0.68; 95% CI 0.59-0.78), ertugliflozin (HR 0.70; 95% CI 0.54-0.90), and sotagliflozin (HR 0.66; 95% CI 0.56-0.77) versus placebo reduced HHF, whereas none reduced MI and stroke. Empagliflozin reduced CVD or HHF (HR 0.81; 95% CI 0.67-0.99) and KFP (HR 0.65; 95% CI 0.45-0.93), and dapagliflozin reduced KFP (HR 0.69; 95% CI 0.52-0.92), versus ertugliflozin. Canagliflozin had the greatest SUCRA values for the reduction of MACE, stroke, and HHF, whereas empagliflozin had the greatest SUCRA values for the reduction of MI, CVD, CVD or HHF, KFP, and ACD. CONCLUSIONS: Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin versus placebo reduce HHF but none reduces MI and stroke. Canagliflozin is most effective in reducing MACE and HHF, and empagliflozin is most effective in reducing CVD, CVD or HHF, KFP, and ACD. These findings will guide the use of specific SGLT2i in the prevention of different cardiorenal events.

Research on the Constitutive Model of PTFE/Al/Si Reactive Material.

As a new type of energetic material, reactive materials are widely used at present; in particular, the metal/polymer mixtures type reactive materials show great advantages in engineering applications. This type of reactive material has good mechanical properties, and its overall performance is insensitive and high-energy under external impact loading. After a large number of previous studies, our team found that the energy release characteristics of PTFE/Al/Si reactive material are prominent. In order to master the mechanical properties of PTFE/Al/Si reactive materials, the quasi-static mechanical properties and dynamic mechanical properties were obtained by carrying out a quasi-static compression test and a dynamic SHPB test in this paper. Based on the experimental data, a Johnson-Cook constitutive model of PTFE/Al/Si reactive material considering strain hardening effect, strain rate hardening effect and thermal softening effect was constructed. The relevant research results will be used to guide future research on the reaction mechanism of PTFE/Al/Si reactive materials, in order to promote the engineering application of PTFE/Al/Si reactive materials.

Impact of time factor and patient characteristics on the efficacy of PCI vs CABG for left main coronary disease: A meta-analysis.

BACKGROUND: The impact of time factor and patient characteristics on the efficacy of percutaneous coronary intervention (PCI) with drug-eluting stents vs. coronary-artery bypass grafting (CABG) for left main coronary disease is unclear. METHODS: We searched PubMed and Embase for related trials. Two outcomes of interest were major adverse cardiac or cerebrovascular events (MACCE, defined as a composite of all-cause mortality, myocardial infarction, stroke, or unplanned revascularization) and a composite of all-cause mortality, myocardial infarction, or stroke. We conducted random-effects meta-analysis stratified by follow-up duration and 7 factors of interest related to patient characteristics. Random-effects meta-regression was performed to calculate P values for trend and those for subgroup differences. RESULTS: We included 11 articles from 5 trials. Compared with CABG, PCI increased MACCE at the end of 3-year (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.40, I2 = 0) and 5-year (HR 1.33, 95% CI 1.20-1.48, I2 = 0) follow-up, but did not increase all-cause mortality, myocardial infarction, or stroke. The logarithm of HR of PCI vs CABG for MACCE increased as follow-up duration increased (ß = 0.057, P = .025). PCI vs CABG consistently increased 5-year MACCE across various subgroups defined by 7 factors of interest (Psubgroup ranged from .156 to .830). CONCLUSIONS: The long-term benefit of CABG vs PCI on MACCE in patients with left main coronary disease is consistent across patients with different clinical characteristics. The relative benefit of CABG on MACCE is driven by that of CABG on unplanned revascularization, and becomes greater as time goes on.

Factors affecting the efficacy of SGLT2is on heart failure events: a meta-analysis based on cardiovascular outcome trials.

BACKGROUND: The efficacy of sodium-glucose transporter 2 inhibitors (SGLT2is) on heart failure outcomes is unestablished in various subgroups defined by clinically important factors. We intended to evaluate the effects of six important factors on the efficacy of SGLT2is on heart failure outcomes. METHODS: We included cardiovascular outcome trials (CVOTs) concerning SGLT2is. We assessed the heart failure composite outcome of cardiovascular death (CVD) or hospitalization for heart failure (HHF). Meta-analysis was conducted stratified by the following 6 factors: type of underlying diseases, type of SGLT2is, left ventricular ejection fraction (LVEF) level, New York Heart Association (NYHA) class, region, and race. RESULTS: Ten CVOTs were included. Compared with placebo, SGLT2is reduced heart failure composite outcome by 25% [hazard ratio (HR) 0.75, 95% confidence interval (CI), 0.72-0.78] independent of type of underlying diseases, type of SGLT2is, LVEF level, and region (Psubgroup: 0.673, 0.244, 0.429, and 0.127, respectively). SGLT2is led to greater reduction in the composite outcome in patients with NYHA class II (HR 0.66, 95% CI, 0.59-0.74) than in patients with NYHA class III or IV (HR 0.86, 95% CI, 0.75-0.99; Psubgroup=0.004), and in Black (HR 0.63, 95% CI, 0.49-0.82) and Asian (HR 0.64, 95% CI, 0.53-0.77) patients than in White patients (HR 0.81, 95% CI, 0.76-0.86; Psubgroup=0.016). CONCLUSIONS: SGLT2is reduce heart failure composite outcome by 25% independent of type of underlying diseases, type of SGLT2is, LVEF level, and region. SGLT2is lead to greater reduction in the composite outcome in patients with NYHA class II than in patients with NYHA class III or IV, and in Black and Asian patients than in White patients. KEYWORDS: Sodium-glucose transporter 2 inhibitors (SGLT2is); heart failure; chronic kidney disease (CKD); type 2 diabetes.

Effects of SGLT2 inhibitors on cardiovascular and renal outcomes in type 2 diabetes: A meta-analysis with trial sequential analysis.

BACKGROUND: It is unclear whether there are false positive or negative results in the effects of sodium-glucose transporter 2 (SGLT2) inhibitors on various cardiovascular and renal outcomes in patients with type 2 diabetes. We aimed to explore this issue by a meta-analysis with trial sequential analysis. METHODS: We included randomized trials evaluating the effects of SGLT2 inhibitors on cardiorenal endpoints in type 2 diabetic patients. Eight endpoints evaluated in the study were fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure (CVD or HHF), all-cause death (ACD), cardiovascular death (CVD), hospitalization for heart failure (HHF), and kidney function progression (KFP). Meta-analysis and trial sequential analysis was conducted for each endpoint. RESULTS: Seven randomized trials of SGLT2 inhibitors were included for pooled analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the risk of MACE (HR 0.89, 95% confidence interval [CI] 0.84-0.94), MI (HR 0.91, 95% CI 0.84-0.99), CVD (HR 0.86, 95% CI 0.79-0.93), CVD or HHF (HR 0.77, 95% CI 0.73-0.82), HHF (HR 0.67, 95% CI 0.62-0.74), KFP (HR 0.63, 95% CI 0.56-0.70), and ACD (HR 0.88, 95% CI 0.83-0.94), whereas SGLT2 inhibitors did not have significant effects on stroke (HR 0.98, 95% CI 0.88-1.09). Trial sequential analyses for MI and stroke showed that cumulative Z curve did not cross trial sequential monitoring boundary and required information size, whereas those for the other 6 endpoints showed that cumulative Z curve crossed trial sequential monitoring boundary and/or required information size. CONCLUSIONS: Compared with placebo, SGLT2 inhibitors conclusively reduce the risk of MACE, CVD or HHF, ACD, CVD, HHF, and KFP in patients with type 2 diabetes, whereas the effects of SGLT2 inhibitors on MI and stroke are not conclusive and need to be further assessed in future studies with the adequate sample size to reject or accept the effect size.

Comparison of the effects of 10 GLP-1 RA and SGLT2 inhibitor interventions on cardiovascular, mortality, and kidney outcomes in type 2 diabetes: A network meta-analysis of large randomized trials.

The relative efficacy of different sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in reducing cardiorenal events in type 2 diabetic adults is unclear. We searched PubMed and Embase. Three primary endpoints were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), and kidney function progression (KFP). Bayesian network meta-analysis was conducted to synthesize hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) to rank drug treatments. Subcutaneous semaglutide (HR 0.73, 95% CI 0.55-0.96) and albiglutide (HR 0.76, 95% CI 0.63-0.93) significantly reduced MACE versus lixisenatide. Canagliflozin (HRs: 0.69, 0.68, 0.67 and 0.58) and empagliflozin (HRs: 0.70, 0.69, 0.68 and 0.59) significantly reduced HHF versus dulaglutide, exenatide, lixisenatide and subcutaneous semaglutide. Dapagliflozin (HRs: 0.62, 0.60, 0.68 and 0.63) and empagliflozin (HRs: 0.64, 0.61, 0.69 and 0.64) significantly reduced KFP versus dulaglutide, exenatide, liraglutide and lixisenatide. Different drug treatments had the maximum SUCRA values as for preventing different cardiorenal endpoints. Different GLP-1 RAs and SGLT2 inhibitors have different efficacy in preventing cardiorenal endpoints in type 2 diabetes, and the most efficacious drugs are different as for preventing different cardiorenal endpoints.

Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors.

There are no relevant meta-analyses that have assessed the safety of the sodium-glucose transporter 2 (SGLT2) inhibitors in different chronic diseases. We aimed at evaluating the safety of four SGLT2 inhibitors in three chronic diseases by meta-analysis of the large randomized trials of SGLT2 inhibitors. We performed random-effects meta-analysis and carried out subgroup analysis according to type of underlying diseases and type of SGLT2 inhibitors. SGLT2 inhibitors versus placebo significantly reduced the risk of acute kidney injury (RR 0.75, 95% CI 0.66-0.85), and showed the reduced trend in the risk of severe hypoglycemia (RR 0.86, 95% CI 0.71-1.03). SGLT2 inhibitors significantly increased the risks of diabetic ketoacidosis (RR 2.57), genital infection (RR 3.75), and volume depletion (RR 1.14); and showed the increased trends in the risks of fracture (RR 1.07), amputation (RR 1.21), and urinary tract infection (RR 1.07). These effects exhibited by SGLT2 inhibitors were consistent across three chronic diseases (i.e. type 2 diabetes, chronic heart failure, and chronic kidney disease) and four SGLT2 inhibitors (i.e. dapagliflozin, empagliflozin, ertugliflozin, and canagliflozin) (all Psubgroup > 0.05). These findings will guide that specific adverse events are monitored when SGLT2 inhibitors are used in clinical practice.

Meta-Analysis on the Safety and Cardiorenal Efficacy of SGLT2 Inhibitors in Patients Without T2DM.

The cardiorenal benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) are established, whereas those in patients without T2DM are not established. We sought to assess the cardiorenal efficacy and safety of SGLT2 inhibitors in non-T2DM patients by performing a meta-analysis based on the subgroup data of non-T2DM patients from relevant secondary analysis articles in which subgroup analyses were done according to the status of diabetes. Compared to placebo, SGLT2 inhibitors significantly reduced heart failure hospitalization [risk ratio (RR) 0.70, 95% confidence interval (CI) 0.59-0.83] and kidney-specific composite outcome (RR 0.55, 95% CI 0.40-0.75) and increased Kansas City Cardiomyopathy Questionnaire total score by 1.15 (95% CI 1.05-1.25) in patients without T2DM with heart failure (HF) or chronic kidney disease (CKD), whereas gliflozins did not significantly affect cardiovascular death, all-cause mortality, volume depletion, fracture, and amputation in this vulnerable population. There was no event of major hypoglycemia or diabetic ketoacidosis observed in the non-T2DM subgroup in included trials. These findings will further prompt gliflozins to be used for the prevention of HF and renal failure events and for the improvement of life quality in patients without T2DM with HF or CKD.

Use of SGLT2 inhibitors and occurrence of noninfectious respiratory disorders: a meta-analysis of large randomized trials of SGLT2 inhibitors.

PURPOSE: The impact of use of sodium-glucose transporter 2 (SGLT2) inhibitors on occurrence of various kinds of respiratory disorders has not been established. We aimed at evaluating the relationship between use of SGLT2 inhibitors and occurrence of 9 kinds of noninfectious respiratory disorders. METHODS: Large randomized controlled trials (RCTs) of SGLT2 inhibitors were included in this study. We conducted fixed-effects meta-analysis to synthesize risk ratios (RRs) and 95% confidence intervals (CIs). We did subgroup analysis respectively stratified by type of underlying diseases and type of SGLT2 inhibitors. RESULTS: Nine Large RCTs were included for analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the occurrence of overall respiratory disorders (RR 0.75, 95% CI 0.62-0.91), acute pulmonary oedema (RR 0.51, 95% CI 0.29-0.88), asthma (RR 0.57, 95% CI 0.33-0.995), and sleep apnoea syndrome (RR 0.35, 95% CI 0.12-0.99). SGLT2 inhibitors showed the reduced trends in the risks of chronic obstructive pulmonary disease (COPD) (RR 0.79, 95% CI 0.61-1.02; P = 0.073) and pulmonary hypertension (RR 0.43, 95% CI 0.16-1.17; P = 0.098). SGLT2 inhibitors had no significant effects on three other respiratory disorders. These effects exhibited by SGLT2 inhibitors were consistent across different underlying diseases (Psubgroup ≥0.209) and different SGLT2 inhibitors (Psubgroup ≥0.192). CONCLUSIONS: SGLT2 inhibitors can significantly reduce the occurrence of acute pulmonary oedema, asthma, and sleep apnoea syndrome; and produce the reduced trends in the risks of COPD and pulmonary hypertension. These findings will prompt further investigation on SGLT2 inhibitors for primary and secondary prevention of various respiratory disorders.

Comparison of the risk of SGLT2is and NonSGLT2is in leading to amputation: A network meta-analysis.

OBJECTIVE: Whether sodium-glucose cotransporter 2 inhibitors (SGLT2is) increase the risk of amputation or not remains controversial. We aimed to evaluate the relative risk of different SGLT2is and Non-SGLT2i antihyperglycemic drugs (NonSGLT2is) in leading to amputation by network meta-analysis of large sample studies. METHODS: We searched Embase and PubMed for relevant large sample studies. We conducted Bayesian network meta-analysis using random-effects model. Effect size was presented as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Seventeen large studies involving 1 million SGLT2i users and 3 million NonSGLT2i users were included in network meta-analysis. SGLT2is [HR (95% CI): 1.38 (1.02, 1.91)] versus NonSGLT2is significantly increased the amputation risk, whereas SGLT2is [HR (95% CI): 1.45 (0.94, 2.17)] versus placebo did not. Compared with glucagon-like peptide 1 receptor agonists (GLP1RAs), canagliflozin [HR (95% CI): 1.5 (1.01, 2.33)] along with incorporative SGLT2is [HR (95% CI): 1.64 (1.07, 2.53)] significantly increased the amputation risk, whereas empagliflozin [HR (95% CI): 1.46 (0.83, 2.67)] and dapagliflozin [HR (95% CI): 1.22 (0.7, 2.23)] did not due to the wide 95% CIs of HRs. CONCLUSION: Although SGLT2is versus placebo do not significantly increase the amputation risk, SGLT2is (especially, canagliflozin) versus NonSGLT2is (especially, GLP1RAs) significantly increase that risk.