Soft tissue tumors in the hand have a broad differential diagnosis. Included in the list of differential diagnoses for these tumors are Schwannomas, which are benign tumors within the peripheral nervous system [1]. Sc...Soft tissue tumors in the hand have a broad differential diagnosis. Included in the list of differential diagnoses for these tumors are Schwannomas, which are benign tumors within the peripheral nervous system [1]. Schwannomas are uncommon within the upper extremity, and they are exceedingly rare within the hand and wrist [1]. We describe a case of an 80-year-old female presented with a soft tissue mass within her right thumb. She underwent excisional biopsy of the mass, and pathology showed features consistent with schwannoma. She had resolution of her symptoms thereafter. We discuss the differential diagnosis for soft-tissue tumors in this location. When assessing patients with soft tissue tumors of the hand and wrist, it is important for the treating provider to maintain a broad differential diagnosis in order to facilitate appropriate management of these lesions.展开更多
High-resolution photoelectron spectra of cryogenically cooled TiO_(2)CH_(3)OH^(−)anions obtained with slow electron velocity-map imaging are reported and used to explore the reactions of TiO_(2)^(−/0)with methanol.The...High-resolution photoelectron spectra of cryogenically cooled TiO_(2)CH_(3)OH^(−)anions obtained with slow electron velocity-map imaging are reported and used to explore the reactions of TiO_(2)^(−/0)with methanol.The highly structured spectra were compared with results from DFT calculations to determine the dominant structure to be cis-CH_(3)OTi(O)OH^(−),a dissociative adduct in which CH3OH is split by TiO_(2)^(−).The experiment yields an electron affinity of 1.2152(7)eV for TiO_(2)CH^(3)OH as well as several vibrational frequencies for the neutral species.Comparison to Franck−Condon(FC)simulations shows that while most experimental features appear in the simulations,several are not and are assigned to FC-forbidden transitions involving non-totally symmetric vibrational modes.The FC-allowed and forbidden transi-tions also exhibit different photoelectron angular distributions.The FC-forbidden transitions are attributed to Herzberg−Teller(HT)coupling with the A^(2)A″excited state of the anion.The results are compared to previous cryogenic slow electron velocity-map imaging(cryo-SE-Ⅵ)studies of bare TiO_(2)^(−)and the water-split adduct TiO_(3)H_(2)^(−).展开更多
BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the ther...BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The change from baseline in body weight was the primary outcome;secondary outcomes included changes in body mass index(BMI),waist circumference(WC),blood pressure,glycemic parameters,lipids,and adverse events(AEs).RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MDs),odds ratios(ORs),or risk ratios(RRs)with 95%confidence intervals(95%CIs).RESULTS Six RCTs(n=800)with mostly some concerns about the risk of bias were included.Over 12-24 weeks,beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total(MD=-3.25 kg,95%CI:-4.52 to-1.98,I^(2)=84%,P<0.00001)and percent(MD=-4.13%,95%CI:-4.87 to-3.39,I^(2)=54%,P<0.00001)body weight reduction.Beinaglutide also outperformed the control group in achieving weight loss by 5%(OR 4.61)and 10%(OR=5.34).The superiority of beinaglutide vs the control group was also found in reducing BMI(MD=-1.22 kg/m^(2),95%CI:-1.67 to-0.77)and WC(MD=-2.47 cm,95%CI:-3.74 to-1.19]).Beinaglutide and the control group had comparable impacts on blood pressure,glycemic parameters,insulin resistance,hepatic transaminases,and lipid profile.Beinaglutide posed higher risks of treatment discontinuation due to AEs(RR=3.15),nausea(RR=4.51),vomiting(RR=8.19),palpitation(RR=3.95),headache(RR=2.87),and dizziness(RR=6.07)than the control.However,the two groups had identical risks of total and serious AEs,diarrhea,fatigue,and hypoglycemia.CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight,BMI,and WC,with no significant difference in glycemic and other metabolic endpoints compared to the control arm.Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class.Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide.展开更多
BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effec...BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations.AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan.METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm.The primary outcome was adverse events(AEs)during Ramadan for both groups;other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period.RESULTS Four studies[three randomized-controlled trials with low risk of bias(RoB)and one prospective observational study with serious RoB]involving 754 subjects were analyzed.GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group[mean difference(MD):-0.31%,95%CI:-0.61 to-0.01,P=0.04,I2=77%]with a lower risk of documented symptomatic hypoglycemia(risk ratio=0.38,95%CI:0.16 to 0.88,P=0.02).Any AEs,serious AEs,or AEs that led to treatment discontinuation were comparable between the two groups.The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group(MD:-2.0 kg,95%CI:-3.37 to-0.63,P=0.004,I2=95%).There were comparable changes in blood pressure and lipid profile between the two groups.GLP-1RA users experienced higher risks of gastrointestinal AEs,nausea,and vomiting;however,the risks of heartburn,abdominal pain,and diarrhea were similar in both groups.CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan,offering modest benefits in blood sugar control and weight loss.Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations,improving clinical practice decision-making.展开更多
BACKGROUND Despite therapeutic benefits,discontinuation of tirzepatide is common in randomized controlled trials(RCTs)due to adverse events(AEs)and other causes.No previous systematic reviews have explored the reasons...BACKGROUND Despite therapeutic benefits,discontinuation of tirzepatide is common in randomized controlled trials(RCTs)due to adverse events(AEs)and other causes.No previous systematic reviews have explored the reasons for discontinuing tirzepatide in the RCTs.AIM To explore the reasons for permanent discontinuation of tirzepatide vs controls[placebo,insulin,and glucagon-like peptide-1 receptor agonists(GLP-1Ras)]in RCTs.METHODS Relevant RCTs were systematically searched using related terms through multiple databases such as MEDLINE(via PubMed),Scopus,Cochrane Central Register,and ClinicalTrials.gov from their inception until June 20,2024.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as risk ratios(RR)with 95%confidence intervals(CI).RESULTS Seventeen RCTs(n=14645),mostly having low risks of bias,were analyzed.Compared to placebo,the risk of permanent discontinuation of the study drug was substantially lower with tirzepatide 10 mg(RR:0.69,95%CI:0.51-0.93,P=0.02)and similar with tirzepatide 5 mg(RR:0.74,95%CI:0.47-1.17,P=0.20)and 15 mg(RR:0.94,95%CI:0.68-1.31,P=0.71).Tirzepatide had identical discontinuation risks when compared to insulin at 5 mg(RR:0.96,95%CI:0.75-1.24,P=0.77)and 10 mg(RR:1.19,95%CI:0.77-1.82,P=0.44)doses,whereas such risk was higher with tirzepatide 15 mg than insulin(RR:1.31,95%CI:1.03-1.67,P=0.03).Compared to GLP-1RA,the permanent discontinuation risk was similar with tirzepatide 5 mg(RR:0.98,95%CI:0.70-1.37,P=0.90)but was higher with tirzepatide 10 mg(RR:1.40,95%CI:1.03-1.90,P=0.03)and 15 mg(RR:1.70,95%CI:1.27-2.27,P=0.0004).Tirzepatide,at all doses,had higher risks of AE-related discontinuation than insulin;such risks were only greater with higher doses of tirzepatide than with placebo or GLP-1RA.Discontinuation risk due to withdrawal by the study subjects was lower with tirzepatide than with placebo or insulin.Compared to the placebo,tirzepatide(all doses)conferred a lower risk of study drug discontinuation due to other causes not specifically mentioned.CONCLUSION The discontinuation risk is not higher in tirzepatide group than in the placebo arm.Many factors other than AEs led to drug discontinuation in the included RCTs.展开更多
BACKGROUND Efruxifermin(EFX),a fibroblast growth factor 21 analogue,has demonstrated the potential to improve liver fat and markers of liver injury,fibrosis,and key metabolic biomarkers in individuals with metabolic d...BACKGROUND Efruxifermin(EFX),a fibroblast growth factor 21 analogue,has demonstrated the potential to improve liver fat and markers of liver injury,fibrosis,and key metabolic biomarkers in individuals with metabolic dysfunction-associated steatohepatitis(MASH)in phase 2 clinical trials.AIM To summarize the safety and effectiveness of EFX in managing MASH.METHODS Electronic databases and registries were systematically searched from their inception to May 15,2025,for randomized-controlled trials(RCTs)that included EFX in the intervention arm and placebo in the control arm in individuals with MASH.The primary outcome was the safety of EFX,while additional outcomes included its efficacy in altering hepatic and metabolic parameters.Meta-analyses were conducted using the RevMan web computer program with the random-effects model.RESULTS Four phase 2 RCTs(five reports),mostly with low risk of bias,involving 450 subjects,were analyzed.Compared to the placebo,EFX 50 mg was associated with higher risks of treatment-emergent adverse events(TEAEs)[risk ratio(RR)=1.05],TEAEs leading to discontinuation(RR=3.05),nausea(RR=1.78),and diarrhea(RR=1.9).EFX 28 mg increased risks of vomiting(RR=2.17)and frequent bowel movements(RR=8.98).Both doses of EFX were associated with higher risks of drug-related TEAEs(28 mg:RR=1.45;50 mg:RR=1.67)and increased appetite(28 mg:RR=3.16;50 mg:RR=5.66).EFX(28 and 50 mg)and placebo exhibited identical risks for severe TEAEs,serious AEs,abdominal pain,fatigue,headache,injection site erythema,and injection site reactions.EFX(28 and 50 mg)was associated with improvements in hepatic safety outcomes,including liver enzymes and urate levels.EFX outperformed the placebo in both relative and absolute reductions in hepatic fat fraction.Reductions in enhanced liver fibrosis score,Pro-C3,and liver stiffness were also more robust with EFX.EFX was superior in terms of MASH resolution and improvement in fibrosis stage,MASH resolution and no worsening of the fibrosis stage,and fibrosis regression by≥1 stage and no worsening in steatohepatitis.Furthermore,EFX also improved metabolic parameters,including reductions in HbA1c and insulin resistance,as well as improvements in adiponectin and lipid parameters.CONCLUSION EFX demonstrates promising dual efficacy on liver histology and metabolic markers in MASH.However,gastrointestinal side effects and the need for parenteral administration require caution.Long-term data are still necessary to fully evaluate safety and long-term effectiveness.展开更多
BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefi...BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m^(2));the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P<0.0001]and 15 mg[MD-18.03%(-28.58,-7.47),P=0.0008]were superior to placebo in percent reductions of UACR.Tirzepatide,at all doses,outperformed insulin in percent reductions of UACR.Compared to the placebo,the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D(MD-33.25%vs-7.93%;P=0.001).The CFB in eGFR with all doses of tirzepatide was comparable[5 mg:MD 0.36(-1.41,2.14);10 mg:MD 1.17(-0.22,2.56);15 mg:MD 1.42(-0.04,2.88)];P>0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD.展开更多
BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patie...BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patients have been inadequately explored by systematic reviews and meta-analyses.AIM To provide a comprehensive understanding of the optimal use of AID in managing insulin-treated outpatients with T2D.METHODS A systematic search of multiple databases and registries,including MEDLINE,Scopus,Web of Science,Cochrane Library,and ClinicalTrials.gov,was conducted from inception to May 15,2025,to identify studies on AID use for outpatients with T2D.The co-primary outcomes were the change in glycated hemoglobin(HbA1c)and continuous glucose monitoring(CGM)metrics.Statistical analyses were conducted using Review Manager Web software with random-effects models and the inverse variance statistical method.The results were presented as mean differences(MDs)or risk ratios(RRs)with 95%CI.RESULTS A total of 15 studies with 28985 participants were identified,including 6 randomized trials(n=748;3 crossover and 3 parallel-group trials)and 9 single-arm studies.All included randomized trials raised some concerns,and the single-arm studies had serious risks of overall bias.Meta-analysis of randomized trials showed that AID is more effective than the control group in lowering HbA1c(MD:-0.89%,95%CI:-1.32 to-0.46,P<0.0001,I2=82%).Compared to control interventions,AID use was linked to a higher percentage of time in range(MD:19.25%,95%CI:11.43-27.06,P<0.00001,I2=74%)and a lower percentage of time above range>10 mmol/L(MD:-19.48%,95%CI:-27.14 to-11.82,P<0.00001,I2=73%);however,time below range remained similar between the two groups.The mean sensor glucose level was lower in the AID group;however,the coefficient of variation of glucose was the same in both groups.AID use also led to a reduction in insulin dose,but this is not a consistent finding across all study designs.The risks of serious adverse events(AEs)and severe hypoglycemia were similar in both groups;however,AID use raised the risk of device deficiency.Single-arm studies with participants using AID systems also demonstrated reductions in HbA1c(ranging from 0.7%to 2.07%)and improvements in CGM metrics,along with acceptable safety data.CONCLUSION Based on short-term study data,the use of AID systems in outpatients with T2D appears to improve glycemic outcomes and CGM metrics,with no significant AEs.Larger and longer-term randomized controlled trials involving diverse populations,along with a cost-benefit analysis,are needed to guide more informed clinical practice decisions.展开更多
BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of co...BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.展开更多
BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asi...BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asia has a high T2D burden,and many studies have reported varying prevalence rates of DD in this area.AIM To estimate the pooled prevalence of DD among patients with T2D in South Asia,as it is crucial for developing effective therapeutic strategies.METHODS This systematic review and meta-analysis included cross-sectional studies conducted in South Asian countries involving adults with T2D and reported the prevalence of DD.The studies were identified by searching multiple electronic databases and registries from the inception of each database to January 30,2025,using prespecified search terms.Four authors screened and extracted data independently.Meta-analyses were conducted using RStudio software with a random-effects model.The primary outcome was the pooled prevalence of DD.RESULTS Thirty-seven cross-sectional studies(28 from India,five from Bangladesh,and two each from Pakistan and Sri Lanka)with mostly high methodological quality involving 11500 subjects were included.The pooled prevalence of DD was 44%(95%confidence interval:35-53,I2=97.4%).The prevalence of DD was highest in Pakistan(85%),followed by India and Bangladesh(42%each),and Sri Lanka(25%).Emotional burden was the most prevalent form of DD(60%),followed by treatment regimen-related distress(51%),interpersonal distress(31%),and physician-related distress(17%).Meta-regression analysis revealed no significant associations between the prevalence of DD and publication year,sample size,proportion of females,age,duration of diabetes,insulin usage,glycated hemoglobin levels,or diabetic complications.CONCLUSION South Asians with T2D seem to experience a relatively high burden of DD,and the emotional burden is the most common form of DD in this area.Larger studies utilizing unique tools and involving a broader participant base from the region would provide better epidemiological data for effectively planning high-quality diabetes care in South Asian countries.展开更多
文摘Soft tissue tumors in the hand have a broad differential diagnosis. Included in the list of differential diagnoses for these tumors are Schwannomas, which are benign tumors within the peripheral nervous system [1]. Schwannomas are uncommon within the upper extremity, and they are exceedingly rare within the hand and wrist [1]. We describe a case of an 80-year-old female presented with a soft tissue mass within her right thumb. She underwent excisional biopsy of the mass, and pathology showed features consistent with schwannoma. She had resolution of her symptoms thereafter. We discuss the differential diagnosis for soft-tissue tumors in this location. When assessing patients with soft tissue tumors of the hand and wrist, it is important for the treating provider to maintain a broad differential diagnosis in order to facilitate appropriate management of these lesions.
基金funded by the Air Force Office of Scientific Research (AFOSR) under Grant (No.FA955023-1-0545)。
文摘High-resolution photoelectron spectra of cryogenically cooled TiO_(2)CH_(3)OH^(−)anions obtained with slow electron velocity-map imaging are reported and used to explore the reactions of TiO_(2)^(−/0)with methanol.The highly structured spectra were compared with results from DFT calculations to determine the dominant structure to be cis-CH_(3)OTi(O)OH^(−),a dissociative adduct in which CH3OH is split by TiO_(2)^(−).The experiment yields an electron affinity of 1.2152(7)eV for TiO_(2)CH^(3)OH as well as several vibrational frequencies for the neutral species.Comparison to Franck−Condon(FC)simulations shows that while most experimental features appear in the simulations,several are not and are assigned to FC-forbidden transitions involving non-totally symmetric vibrational modes.The FC-allowed and forbidden transi-tions also exhibit different photoelectron angular distributions.The FC-forbidden transitions are attributed to Herzberg−Teller(HT)coupling with the A^(2)A″excited state of the anion.The results are compared to previous cryogenic slow electron velocity-map imaging(cryo-SE-Ⅵ)studies of bare TiO_(2)^(−)and the water-split adduct TiO_(3)H_(2)^(−).
文摘BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The change from baseline in body weight was the primary outcome;secondary outcomes included changes in body mass index(BMI),waist circumference(WC),blood pressure,glycemic parameters,lipids,and adverse events(AEs).RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MDs),odds ratios(ORs),or risk ratios(RRs)with 95%confidence intervals(95%CIs).RESULTS Six RCTs(n=800)with mostly some concerns about the risk of bias were included.Over 12-24 weeks,beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total(MD=-3.25 kg,95%CI:-4.52 to-1.98,I^(2)=84%,P<0.00001)and percent(MD=-4.13%,95%CI:-4.87 to-3.39,I^(2)=54%,P<0.00001)body weight reduction.Beinaglutide also outperformed the control group in achieving weight loss by 5%(OR 4.61)and 10%(OR=5.34).The superiority of beinaglutide vs the control group was also found in reducing BMI(MD=-1.22 kg/m^(2),95%CI:-1.67 to-0.77)and WC(MD=-2.47 cm,95%CI:-3.74 to-1.19]).Beinaglutide and the control group had comparable impacts on blood pressure,glycemic parameters,insulin resistance,hepatic transaminases,and lipid profile.Beinaglutide posed higher risks of treatment discontinuation due to AEs(RR=3.15),nausea(RR=4.51),vomiting(RR=8.19),palpitation(RR=3.95),headache(RR=2.87),and dizziness(RR=6.07)than the control.However,the two groups had identical risks of total and serious AEs,diarrhea,fatigue,and hypoglycemia.CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight,BMI,and WC,with no significant difference in glycemic and other metabolic endpoints compared to the control arm.Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class.Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide.
基金thankful to Dr.Marina George Kudiyirickal MSc,MJDF-RCS,PhD for providing us the audio core tip of this article.
文摘BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations.AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan.METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm.The primary outcome was adverse events(AEs)during Ramadan for both groups;other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period.RESULTS Four studies[three randomized-controlled trials with low risk of bias(RoB)and one prospective observational study with serious RoB]involving 754 subjects were analyzed.GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group[mean difference(MD):-0.31%,95%CI:-0.61 to-0.01,P=0.04,I2=77%]with a lower risk of documented symptomatic hypoglycemia(risk ratio=0.38,95%CI:0.16 to 0.88,P=0.02).Any AEs,serious AEs,or AEs that led to treatment discontinuation were comparable between the two groups.The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group(MD:-2.0 kg,95%CI:-3.37 to-0.63,P=0.004,I2=95%).There were comparable changes in blood pressure and lipid profile between the two groups.GLP-1RA users experienced higher risks of gastrointestinal AEs,nausea,and vomiting;however,the risks of heartburn,abdominal pain,and diarrhea were similar in both groups.CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan,offering modest benefits in blood sugar control and weight loss.Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations,improving clinical practice decision-making.
文摘BACKGROUND Despite therapeutic benefits,discontinuation of tirzepatide is common in randomized controlled trials(RCTs)due to adverse events(AEs)and other causes.No previous systematic reviews have explored the reasons for discontinuing tirzepatide in the RCTs.AIM To explore the reasons for permanent discontinuation of tirzepatide vs controls[placebo,insulin,and glucagon-like peptide-1 receptor agonists(GLP-1Ras)]in RCTs.METHODS Relevant RCTs were systematically searched using related terms through multiple databases such as MEDLINE(via PubMed),Scopus,Cochrane Central Register,and ClinicalTrials.gov from their inception until June 20,2024.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as risk ratios(RR)with 95%confidence intervals(CI).RESULTS Seventeen RCTs(n=14645),mostly having low risks of bias,were analyzed.Compared to placebo,the risk of permanent discontinuation of the study drug was substantially lower with tirzepatide 10 mg(RR:0.69,95%CI:0.51-0.93,P=0.02)and similar with tirzepatide 5 mg(RR:0.74,95%CI:0.47-1.17,P=0.20)and 15 mg(RR:0.94,95%CI:0.68-1.31,P=0.71).Tirzepatide had identical discontinuation risks when compared to insulin at 5 mg(RR:0.96,95%CI:0.75-1.24,P=0.77)and 10 mg(RR:1.19,95%CI:0.77-1.82,P=0.44)doses,whereas such risk was higher with tirzepatide 15 mg than insulin(RR:1.31,95%CI:1.03-1.67,P=0.03).Compared to GLP-1RA,the permanent discontinuation risk was similar with tirzepatide 5 mg(RR:0.98,95%CI:0.70-1.37,P=0.90)but was higher with tirzepatide 10 mg(RR:1.40,95%CI:1.03-1.90,P=0.03)and 15 mg(RR:1.70,95%CI:1.27-2.27,P=0.0004).Tirzepatide,at all doses,had higher risks of AE-related discontinuation than insulin;such risks were only greater with higher doses of tirzepatide than with placebo or GLP-1RA.Discontinuation risk due to withdrawal by the study subjects was lower with tirzepatide than with placebo or insulin.Compared to the placebo,tirzepatide(all doses)conferred a lower risk of study drug discontinuation due to other causes not specifically mentioned.CONCLUSION The discontinuation risk is not higher in tirzepatide group than in the placebo arm.Many factors other than AEs led to drug discontinuation in the included RCTs.
文摘BACKGROUND Efruxifermin(EFX),a fibroblast growth factor 21 analogue,has demonstrated the potential to improve liver fat and markers of liver injury,fibrosis,and key metabolic biomarkers in individuals with metabolic dysfunction-associated steatohepatitis(MASH)in phase 2 clinical trials.AIM To summarize the safety and effectiveness of EFX in managing MASH.METHODS Electronic databases and registries were systematically searched from their inception to May 15,2025,for randomized-controlled trials(RCTs)that included EFX in the intervention arm and placebo in the control arm in individuals with MASH.The primary outcome was the safety of EFX,while additional outcomes included its efficacy in altering hepatic and metabolic parameters.Meta-analyses were conducted using the RevMan web computer program with the random-effects model.RESULTS Four phase 2 RCTs(five reports),mostly with low risk of bias,involving 450 subjects,were analyzed.Compared to the placebo,EFX 50 mg was associated with higher risks of treatment-emergent adverse events(TEAEs)[risk ratio(RR)=1.05],TEAEs leading to discontinuation(RR=3.05),nausea(RR=1.78),and diarrhea(RR=1.9).EFX 28 mg increased risks of vomiting(RR=2.17)and frequent bowel movements(RR=8.98).Both doses of EFX were associated with higher risks of drug-related TEAEs(28 mg:RR=1.45;50 mg:RR=1.67)and increased appetite(28 mg:RR=3.16;50 mg:RR=5.66).EFX(28 and 50 mg)and placebo exhibited identical risks for severe TEAEs,serious AEs,abdominal pain,fatigue,headache,injection site erythema,and injection site reactions.EFX(28 and 50 mg)was associated with improvements in hepatic safety outcomes,including liver enzymes and urate levels.EFX outperformed the placebo in both relative and absolute reductions in hepatic fat fraction.Reductions in enhanced liver fibrosis score,Pro-C3,and liver stiffness were also more robust with EFX.EFX was superior in terms of MASH resolution and improvement in fibrosis stage,MASH resolution and no worsening of the fibrosis stage,and fibrosis regression by≥1 stage and no worsening in steatohepatitis.Furthermore,EFX also improved metabolic parameters,including reductions in HbA1c and insulin resistance,as well as improvements in adiponectin and lipid parameters.CONCLUSION EFX demonstrates promising dual efficacy on liver histology and metabolic markers in MASH.However,gastrointestinal side effects and the need for parenteral administration require caution.Long-term data are still necessary to fully evaluate safety and long-term effectiveness.
文摘BACKGROUND Type 2 diabetes(T2D),as well as obesity,are risk factors for chronic kidney disease(CKD)and end-stage renal disease.The renal impacts of glucose-lowering and weight-lowering drugs and their potential benefits in preventing CKD often guide clinicians in choosing them appropriately.Only limited data based on randomized controlled trials(RCTs)is currently available on the renal effects and safety profile of tirzepatide.AIM To explore the renal benefits and safety of tirzepatide vs controls.METHODS RCTs involving patients receiving tirzepatide for any indication in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The co-primary outcomes were percent change from baseline(CFB)in urine albumin-to-creatinine ratio(UACR)and absolute CFB in estimated glomerular filtration rate(eGFR;in mL/min/1.73 m^(2));the secondary outcome was tirzepatide’s renal safety profile.RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MD)or risk ratios with 95%confidence intervals.RESULTS Fifteen RCTs(n=14471)with mostly low risk of bias(RoB)were included.Over 26-72 weeks,tirzepatide 10 mg[MD-26.95%(-40.13,-13.76),P<0.0001]and 15 mg[MD-18.03%(-28.58,-7.47),P=0.0008]were superior to placebo in percent reductions of UACR.Tirzepatide,at all doses,outperformed insulin in percent reductions of UACR.Compared to the placebo,the percent UACR reduction was greater in subjects with T2D than those with obesity but without T2D(MD-33.25%vs-7.93%;P=0.001).The CFB in eGFR with all doses of tirzepatide was comparable[5 mg:MD 0.36(-1.41,2.14);10 mg:MD 1.17(-0.22,2.56);15 mg:MD 1.42(-0.04,2.88)];P>0.05 for all vs insulin.Tirzepatide(pooled and separate doses)did not increase the risks of adverse renal events,urinary tract infection,nephrolithiasis,acute kidney injury,and renal cancer compared to the placebo,insulin,and glucagon-like peptide-1 receptor agonists.CONCLUSION Short-term data from RCTs with low RoB suggests that tirzepatide positively impacts UACR without detrimental effects on eGFR in subjects with T2D and obesity without T2D,with a reassuring renal safety profile.Larger RCTs are warranted to prove the longer-term renal benefits of tirzepatide,which might also prevent eGFR decline and worsening of CKD.
文摘BACKGROUND Automated insulin delivery(AID)systems have demonstrated benefits in managing patients with type 2 diabetes(T2D),but data are still limited.Moreover,the efficacy and safety of the AID systems in these patients have been inadequately explored by systematic reviews and meta-analyses.AIM To provide a comprehensive understanding of the optimal use of AID in managing insulin-treated outpatients with T2D.METHODS A systematic search of multiple databases and registries,including MEDLINE,Scopus,Web of Science,Cochrane Library,and ClinicalTrials.gov,was conducted from inception to May 15,2025,to identify studies on AID use for outpatients with T2D.The co-primary outcomes were the change in glycated hemoglobin(HbA1c)and continuous glucose monitoring(CGM)metrics.Statistical analyses were conducted using Review Manager Web software with random-effects models and the inverse variance statistical method.The results were presented as mean differences(MDs)or risk ratios(RRs)with 95%CI.RESULTS A total of 15 studies with 28985 participants were identified,including 6 randomized trials(n=748;3 crossover and 3 parallel-group trials)and 9 single-arm studies.All included randomized trials raised some concerns,and the single-arm studies had serious risks of overall bias.Meta-analysis of randomized trials showed that AID is more effective than the control group in lowering HbA1c(MD:-0.89%,95%CI:-1.32 to-0.46,P<0.0001,I2=82%).Compared to control interventions,AID use was linked to a higher percentage of time in range(MD:19.25%,95%CI:11.43-27.06,P<0.00001,I2=74%)and a lower percentage of time above range>10 mmol/L(MD:-19.48%,95%CI:-27.14 to-11.82,P<0.00001,I2=73%);however,time below range remained similar between the two groups.The mean sensor glucose level was lower in the AID group;however,the coefficient of variation of glucose was the same in both groups.AID use also led to a reduction in insulin dose,but this is not a consistent finding across all study designs.The risks of serious adverse events(AEs)and severe hypoglycemia were similar in both groups;however,AID use raised the risk of device deficiency.Single-arm studies with participants using AID systems also demonstrated reductions in HbA1c(ranging from 0.7%to 2.07%)and improvements in CGM metrics,along with acceptable safety data.CONCLUSION Based on short-term study data,the use of AID systems in outpatients with T2D appears to improve glycemic outcomes and CGM metrics,with no significant AEs.Larger and longer-term randomized controlled trials involving diverse populations,along with a cost-benefit analysis,are needed to guide more informed clinical practice decisions.
文摘BACKGROUND Cotadutide(MEDI0382)is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors.Several randomized controlled trials(RCTs)have been published evaluating the use of cotadutide in individuals with type 2 diabetes(T2D),showing promising results.However,the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.AIM To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.METHODS The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews(CRD42024511703),and the protocol summary can be accessed online.Several databases and registries,including MEDLINE(via PubMed),Scopus,Web of Science,the Cochrane Central Register of Controlled Trials,and ClinicalTrials.gov,were systematically searched using related terms from their inception to May 15,2025,for RCTs involving individuals with T2D receiving cotadutide in the intervention group.Review Manager web was used to conduct meta-analysis using random-effects models.The co-primary outcomes of interest were the changes in glycated hemoglobin(HbA1c)and the percent changes in body weight from baseline.The results of the outcomes were expressed as mean differences(MDs)or risk ratios(RRs)with 95%confidence intervals(CIs).The analysis of outcomes was stratified according to whether the control group received a placebo,denoted as the placebo control group(PCG),or an active comparator,referred to as the active control group(ACG).RESULTS Nine RCTs(mostly phase 2 RCTs,n=1525)with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed;five studies had a low overall risk of bias,while the other four had some concerns.Compared to the PCG,greater reductions in HbA1c were achieved with cotadutide 100μg(MD-0.77%,95%CI:-1.06 to-0.47),200μg(MD-0.68%,95%CI:-1.12 to-0.23),300μg(MD-0.67%,95%CI:-0.79 to-0.56),and 600μg(MD-0.69%,95%CI:-0.97 to-0.41).Cotadutide 100μg(MD-1.74%,95%CI:-3.23 to-0.25),200μg(MD-2.56%,95%CI:-3.37 to-1.75),300μg(MD-3.49%,95%CI:-4.14 to-2.84),and 600μg(MD-5.45%,95%CI:-7.17 to-3.73)achieved greater percent reductions in body weight from baseline.However,the certainty of evidence for HbA1c and percent body weight reductions was very low to low.Cotadutide,at all doses,also outperformed PCG in reducing fasting plasma glucose and absolute body weight.The changes in HbA1c,percent body weight,fasting plasma glucose,and absolute body weight were similar between the cotadutide group and the ACG.Compared to PCG,pooled doses of cotadutide increased the risks of treatment-emergent adverse events(AEs),treatment-related AEs,and discontinuation of the study drug due to AEs,but not for serious AEs.More subjects experienced overall gastrointestinal AEs,dyspepsia,nausea,vomiting,constipation,and decreased appetite with cotadutide than with PCG.Compared to the ACG,none of the AEs showed increased risk in the cotadutide group.CONCLUSION Cotadutide demonstrated glycemic control and weight-loss benefits in short-term,small RCTs(mostly phase 2).However,small sample sizes,very low to low certainty of evidence,and the absence of data on long-term cardiovascular and renal outcomes highlight substantial uncertainties,warranting cautious interpretation and further investigation in larger,longer-term trials to establish its safety and efficacy profile.
文摘BACKGROUND Diabetes distress(DD),an emotional problem arising from the challenges of living with diabetes and the relentless burden of daily self-management,is common among patients with type 2 diabetes(T2D).South Asia has a high T2D burden,and many studies have reported varying prevalence rates of DD in this area.AIM To estimate the pooled prevalence of DD among patients with T2D in South Asia,as it is crucial for developing effective therapeutic strategies.METHODS This systematic review and meta-analysis included cross-sectional studies conducted in South Asian countries involving adults with T2D and reported the prevalence of DD.The studies were identified by searching multiple electronic databases and registries from the inception of each database to January 30,2025,using prespecified search terms.Four authors screened and extracted data independently.Meta-analyses were conducted using RStudio software with a random-effects model.The primary outcome was the pooled prevalence of DD.RESULTS Thirty-seven cross-sectional studies(28 from India,five from Bangladesh,and two each from Pakistan and Sri Lanka)with mostly high methodological quality involving 11500 subjects were included.The pooled prevalence of DD was 44%(95%confidence interval:35-53,I2=97.4%).The prevalence of DD was highest in Pakistan(85%),followed by India and Bangladesh(42%each),and Sri Lanka(25%).Emotional burden was the most prevalent form of DD(60%),followed by treatment regimen-related distress(51%),interpersonal distress(31%),and physician-related distress(17%).Meta-regression analysis revealed no significant associations between the prevalence of DD and publication year,sample size,proportion of females,age,duration of diabetes,insulin usage,glycated hemoglobin levels,or diabetic complications.CONCLUSION South Asians with T2D seem to experience a relatively high burden of DD,and the emotional burden is the most common form of DD in this area.Larger studies utilizing unique tools and involving a broader participant base from the region would provide better epidemiological data for effectively planning high-quality diabetes care in South Asian countries.
