We reported a case of an overweight 34-year-old woman who unexpectedly became pregnant while undergoing semaglutide in early pregnancy and delivered a healthy male infant by caesarean section at 37 weeks and 4 days of...We reported a case of an overweight 34-year-old woman who unexpectedly became pregnant while undergoing semaglutide in early pregnancy and delivered a healthy male infant by caesarean section at 37 weeks and 4 days of gestation.Until now,the safety of semaglutide for use during pregnancy was unknown.This report may contribute to the limited knowledge available on pregnant women exposure to semaglutide.展开更多
GLP-1 receptor agonists (GLP-1 RAs) are among the most successful medications for treating people with type 2 diabetes mellitus (T2DM), giving reasonable glycemic control with a low risk of hypoglycemia in those who h...GLP-1 receptor agonists (GLP-1 RAs) are among the most successful medications for treating people with type 2 diabetes mellitus (T2DM), giving reasonable glycemic control with a low risk of hypoglycemia in those who have failed to control their condition with other oral anti-diabetic drugs (OADs). However, GLP-1RAs are underutilized—as time patients remained on their last oral treatment regimen with inadequate glycemic control prior to GLP-1RA initiation is on average of 19 month—despite evidence supporting their effectiveness, safety, and possible CV outcome advantages. With the new advances in GLP-1 RAs, the first oral form for the semaglutide molecule was developed with proven efficacy, safety, and patient preferences that may help pave the road for more utilization of this class. Therefore, we, a Saudi task force, gathered to develop an explicit, evidence-based consensus on oral semaglutide use in Saudi patients with diabetes. The panel recommends a GLP-1RA in those T2DM patients with or without or at high risk for ASCVD, HF, and/or CKD when there is a need to minimize weight gain or promote weight loss, or when there is a need to minimize hypoglycemia. Ensure that people with T2DM and ASCVD, HF, or CKD are treated appropriately with an SGLT-2i or GLP-1 RA. This approach should be initiated independent of background therapy, glycaemic control, or individualized treatment goals. Healthcare professionals should do their best to prevent clinical inertia in T2DM to help people with T2DM achieve better glycemic control and prevent or delay diabetes-related complications. The availability of oral forms of GLP-1RA medications could help combat this problem of clinical inertia to start GLP-1RA at the right time, as patients prefer oral to injectable forms. The availability of oral GLP-1RA can help in starting this class early and encourage healthcare professionals in prescribing it at the right time. Moreover, it can help those patients who fear of the injections. The panel recommends the oral GLP-1RA semaglutide to be used early and encourage healthcare professionals in prescribing it at the right time. The injectable form can be preserved for further intensification of therapy whenever needed as add-on therapy particulary for poly-medicated patients for better compliance at this stage. .展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease.The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare e...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease.The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower healthrelated quality of life.To date,there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis(NASH).Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD.AIM To investigate the efficacy and safety of semaglutide in patients with NAFLD.METHODS MEDLINE,CENTRAL,and EMBASE were searched from inception to May 1,2023,to identify eligible randomized controlled trials(RCTs).Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences(MD)or standardized MDs(SMD),and dichotomous outcomes as odds ratios(OR)with 95%confidence intervals(CI).Statistical heterogeneity was assessed using the Cochran’s Q test and I2 statistic.RESULTS Three RCTs involving 458 patients were included.Semaglutide increased the likelihood of NASH resolution(OR:3.18,95%CI:1.70,5.95;P<0.001),improvement in steatosis(OR:2.83,95%CI:1.19,6.71;P=0.03),lobular inflammation(OR:1.81,95%CI:1.11,2.96;P=0.02),and hepatocellular ballooning(OR:2.92,95%CI:1.83,4.65;P<0.001),but not fibrosis stage(OR:0.71,95%CI:0.15,3.41;P=0.67).Radiologically,semaglutide reduced liver stiffness(SMD:-0.48,95%CI:-0.86,-0.11;P=0.01)and steatosis(MD:-4.96%,95%CI:-9.92,0.01;P=0.05).It also reduced alanine aminotransferase(MD:-14.06 U/L,95%CI:-22.06,-6.07;P<0.001)and aspartate aminotransferase(MD:-11.44 U/L,95%CI:-17.23,-5.65;P<0.001).Semaglutide led to improved cardiometabolic outcomes,including decreased HgA1c(MD:-0.77%,95%CI:-1.18,-0.37;P<0.001)and weight loss(MD:-6.53 kg,95%CI:-11.21,-1.85;P=0.006),but increased the occurrence of GIrelated side effects(OR:3.72,95%CI:1.68,8.23;P=0.001).Overall risk of serious adverse events was similar compared to placebo(OR:1.40,95%CI:0.75,2.62;P<0.29).CONCLUSION Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile.Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD.展开更多
There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in th...There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASHcirrhotic population. We report herein the first documented case of liver decompensationand need for liver transplant waitlisting in a patient with NASHcirrhosistreated with semaglutide. Rapid weight loss led to the development ofascites and hepatic encephalopathy and an increase in the patients Model forEndstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritionalsupplementation was commenced and the semaglutide was stopped. Overthe following months she regained her weight and her liver recompensated andher MELD-Na decreased to 13, allowing her to be delisted from the transplantwaitlist. This case serves as a cautionary tale to clinicians using semaglutide in thecirrhotic population and highlights the need for more safety data in this patientgroup.展开更多
Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and,more recently,at higher doses,for the treatment of...Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and,more recently,at higher doses,for the treatment of obesity.Both diseases are reaching epidemic proportions and often coexist,posing patients with a high risk for cardiovascular disease and death.Therefore,an agent such as semaglutide,which offers clinically significant weight loss and cardiovascular benefits,is essential and will be increasingly used in high-risk patients.However,during the SUSTAIN clinical trial program(Semaglutide Unabated Sustainability in treatment of type 2 diabetes),a safety issue concerning the progression and worsening of diabetic retinopathy emerged.The existing explanation so far mainly supports the role of the magnitude and speed of HbA1c reduction,a phenomenon also associated with insulin treatment and bariatric surgery.Whether and to which extent the effect is direct is still a matter of debate and an intriguing topic to investigate for suitable preventative and rehabilitative purposes.In this minireview,we will summarize the available data and suggest guidelines for a comprehensive semaglutide clinical utilization until new evidence becomes available.展开更多
Metabolically associated fatty liver disease(MAFLD)is a liver manifestation of metabolic syndrome potentially related to unfavorable hepatic and extrahepatic outcomes and progression to cirrhosis.Up to date,there are ...Metabolically associated fatty liver disease(MAFLD)is a liver manifestation of metabolic syndrome potentially related to unfavorable hepatic and extrahepatic outcomes and progression to cirrhosis.Up to date,there are no approved pharmacotherapies for the treatment of MAFLD,so management focused on lifestyle interventions to encourage weight loss,and treatment of coexisting conditions is the only available option.Unfortunately,the aforementioned is often not potent enough to offer reversal or slow down hepatic inflammation and fibrosis.Glucagon-like peptide-1 receptor agonists have a favorable effect on glycemic management and weight loss of patients with type 2 diabetes mellitus and recently published data suggest their potential in MAFLD treatment.In addition,some of the agents have proven cardiovascular and renal benefits in dedicated cardiovascular outcome trials,making them an interesting therapeutic option.In this opinion review,we discuss the role of semaglutide in MAFLD.展开更多
Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insu...Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.展开更多
Obesity is an important risk factor of type 2 diabetes(T2D),which has become an important factor threatening human health.However,no perfect drug choice for obesity exists.Semaglutide is a kind of human glucagon-like ...Obesity is an important risk factor of type 2 diabetes(T2D),which has become an important factor threatening human health.However,no perfect drug choice for obesity exists.Semaglutide is a kind of human glucagon-like peptide-1(GLP-1)analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism.GLP-1 can also delay stomach emptying and suppress appetite to help lose weight.This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the most rapidly growing contributor to liver mortality and morbidity.Hepatocellular injury in nonalcoholic steatohepatitis(NASH)is caused by an increase in metabolic substrat...Nonalcoholic fatty liver disease(NAFLD)is the most rapidly growing contributor to liver mortality and morbidity.Hepatocellular injury in nonalcoholic steatohepatitis(NASH)is caused by an increase in metabolic substrates(glucose,fructose,and fatty acids),leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury.The pathogenesis of this disease is largely associated with obesity,type 2 diabetes,and increasing age.To date,there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis.Since one of the pathogenic drivers of NASH is insulin resistance,therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH.Currently,the glucagon-like peptide-1 receptor agonist(GLP-1RA)semaglutide is a safe,well-studied therapeutic for NAFLD/NASH patients.Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis.However,improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD.Given the complex pathophysiology of NASH,combining therapies with complementary mechanisms may be beneficial.Researchers have conducted trials of semaglutide in combination with antifibrotic drugs.However,the results have not fully met expectations,and it cannot be ruled out that the reason is the short trial time.We should continue to pay increasing attention to GLP-1RAs.展开更多
Hyperglycaemia contributes to the onset and progression of diabetic kidney disease(DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Ti...Hyperglycaemia contributes to the onset and progression of diabetic kidney disease(DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro-or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient. Recently, empagliflozin which is an oral glucose lowering agent of the sodium glucose cotransporter-2 inhibitor class has been shown to have renal protective effects. However, the magnitude of empagliflozin's reno-protective properties are over and above that expected from its glucose lowering effects and most likely largely result from mechanisms involving alterations in intra-renal haemodynamics. Liraglutide and semaglutide, both injectable glucose lowering agents which are analogues of human glucagon like peptide-1 have also been shown to reduce progression to macroalbuminuria through mechanisms that remain to be fully elucidated. Here we review the evidence from observational and interventional studies that link good glucose control with improved renal outcomes. We also briefly review the potential reno-protective effects ofnewer glucose lowering agents.展开更多
Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diab...Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.展开更多
Glucagon-like peptide receptor agonists(GLP-1RA)are used to treat type 2 diabetes mellitus and,more recently,have garnered attention for their effect-iveness in promoting weight loss.They have been associated with sev...Glucagon-like peptide receptor agonists(GLP-1RA)are used to treat type 2 diabetes mellitus and,more recently,have garnered attention for their effect-iveness in promoting weight loss.They have been associated with several gastrointestinal adverse effects,including nausea and vomiting.These side effects are presumed to be due to increased residual gastric contents.Given the potential risk of aspiration and based on limited data,the American Society of Anesthesi-ologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023.They included the duration of mandated cessation of GLP-1RA before sedation and usage of“full stomach”precautions if these medications were not appropriately held before the procedure.This has led to additional challenges,such as extended waiting time,higher costs,and increased risk for patients.In this editorial,we review the current societal guidelines,clinical practice,and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.展开更多
基金The Undergraduate Research Project on Innovation and Entrepreneurship at Southern Medical University(No.2023YXYDC028).
文摘We reported a case of an overweight 34-year-old woman who unexpectedly became pregnant while undergoing semaglutide in early pregnancy and delivered a healthy male infant by caesarean section at 37 weeks and 4 days of gestation.Until now,the safety of semaglutide for use during pregnancy was unknown.This report may contribute to the limited knowledge available on pregnant women exposure to semaglutide.
文摘GLP-1 receptor agonists (GLP-1 RAs) are among the most successful medications for treating people with type 2 diabetes mellitus (T2DM), giving reasonable glycemic control with a low risk of hypoglycemia in those who have failed to control their condition with other oral anti-diabetic drugs (OADs). However, GLP-1RAs are underutilized—as time patients remained on their last oral treatment regimen with inadequate glycemic control prior to GLP-1RA initiation is on average of 19 month—despite evidence supporting their effectiveness, safety, and possible CV outcome advantages. With the new advances in GLP-1 RAs, the first oral form for the semaglutide molecule was developed with proven efficacy, safety, and patient preferences that may help pave the road for more utilization of this class. Therefore, we, a Saudi task force, gathered to develop an explicit, evidence-based consensus on oral semaglutide use in Saudi patients with diabetes. The panel recommends a GLP-1RA in those T2DM patients with or without or at high risk for ASCVD, HF, and/or CKD when there is a need to minimize weight gain or promote weight loss, or when there is a need to minimize hypoglycemia. Ensure that people with T2DM and ASCVD, HF, or CKD are treated appropriately with an SGLT-2i or GLP-1 RA. This approach should be initiated independent of background therapy, glycaemic control, or individualized treatment goals. Healthcare professionals should do their best to prevent clinical inertia in T2DM to help people with T2DM achieve better glycemic control and prevent or delay diabetes-related complications. The availability of oral forms of GLP-1RA medications could help combat this problem of clinical inertia to start GLP-1RA at the right time, as patients prefer oral to injectable forms. The availability of oral GLP-1RA can help in starting this class early and encourage healthcare professionals in prescribing it at the right time. Moreover, it can help those patients who fear of the injections. The panel recommends the oral GLP-1RA semaglutide to be used early and encourage healthcare professionals in prescribing it at the right time. The injectable form can be preserved for further intensification of therapy whenever needed as add-on therapy particulary for poly-medicated patients for better compliance at this stage. .
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease.The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower healthrelated quality of life.To date,there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis(NASH).Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD.AIM To investigate the efficacy and safety of semaglutide in patients with NAFLD.METHODS MEDLINE,CENTRAL,and EMBASE were searched from inception to May 1,2023,to identify eligible randomized controlled trials(RCTs).Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences(MD)or standardized MDs(SMD),and dichotomous outcomes as odds ratios(OR)with 95%confidence intervals(CI).Statistical heterogeneity was assessed using the Cochran’s Q test and I2 statistic.RESULTS Three RCTs involving 458 patients were included.Semaglutide increased the likelihood of NASH resolution(OR:3.18,95%CI:1.70,5.95;P<0.001),improvement in steatosis(OR:2.83,95%CI:1.19,6.71;P=0.03),lobular inflammation(OR:1.81,95%CI:1.11,2.96;P=0.02),and hepatocellular ballooning(OR:2.92,95%CI:1.83,4.65;P<0.001),but not fibrosis stage(OR:0.71,95%CI:0.15,3.41;P=0.67).Radiologically,semaglutide reduced liver stiffness(SMD:-0.48,95%CI:-0.86,-0.11;P=0.01)and steatosis(MD:-4.96%,95%CI:-9.92,0.01;P=0.05).It also reduced alanine aminotransferase(MD:-14.06 U/L,95%CI:-22.06,-6.07;P<0.001)and aspartate aminotransferase(MD:-11.44 U/L,95%CI:-17.23,-5.65;P<0.001).Semaglutide led to improved cardiometabolic outcomes,including decreased HgA1c(MD:-0.77%,95%CI:-1.18,-0.37;P<0.001)and weight loss(MD:-6.53 kg,95%CI:-11.21,-1.85;P=0.006),but increased the occurrence of GIrelated side effects(OR:3.72,95%CI:1.68,8.23;P=0.001).Overall risk of serious adverse events was similar compared to placebo(OR:1.40,95%CI:0.75,2.62;P<0.29).CONCLUSION Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile.Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD.
文摘There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASHcirrhotic population. We report herein the first documented case of liver decompensationand need for liver transplant waitlisting in a patient with NASHcirrhosistreated with semaglutide. Rapid weight loss led to the development ofascites and hepatic encephalopathy and an increase in the patients Model forEndstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritionalsupplementation was commenced and the semaglutide was stopped. Overthe following months she regained her weight and her liver recompensated andher MELD-Na decreased to 13, allowing her to be delisted from the transplantwaitlist. This case serves as a cautionary tale to clinicians using semaglutide in thecirrhotic population and highlights the need for more safety data in this patientgroup.
文摘Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and,more recently,at higher doses,for the treatment of obesity.Both diseases are reaching epidemic proportions and often coexist,posing patients with a high risk for cardiovascular disease and death.Therefore,an agent such as semaglutide,which offers clinically significant weight loss and cardiovascular benefits,is essential and will be increasingly used in high-risk patients.However,during the SUSTAIN clinical trial program(Semaglutide Unabated Sustainability in treatment of type 2 diabetes),a safety issue concerning the progression and worsening of diabetic retinopathy emerged.The existing explanation so far mainly supports the role of the magnitude and speed of HbA1c reduction,a phenomenon also associated with insulin treatment and bariatric surgery.Whether and to which extent the effect is direct is still a matter of debate and an intriguing topic to investigate for suitable preventative and rehabilitative purposes.In this minireview,we will summarize the available data and suggest guidelines for a comprehensive semaglutide clinical utilization until new evidence becomes available.
文摘Metabolically associated fatty liver disease(MAFLD)is a liver manifestation of metabolic syndrome potentially related to unfavorable hepatic and extrahepatic outcomes and progression to cirrhosis.Up to date,there are no approved pharmacotherapies for the treatment of MAFLD,so management focused on lifestyle interventions to encourage weight loss,and treatment of coexisting conditions is the only available option.Unfortunately,the aforementioned is often not potent enough to offer reversal or slow down hepatic inflammation and fibrosis.Glucagon-like peptide-1 receptor agonists have a favorable effect on glycemic management and weight loss of patients with type 2 diabetes mellitus and recently published data suggest their potential in MAFLD treatment.In addition,some of the agents have proven cardiovascular and renal benefits in dedicated cardiovascular outcome trials,making them an interesting therapeutic option.In this opinion review,we discuss the role of semaglutide in MAFLD.
文摘Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.
文摘Obesity is an important risk factor of type 2 diabetes(T2D),which has become an important factor threatening human health.However,no perfect drug choice for obesity exists.Semaglutide is a kind of human glucagon-like peptide-1(GLP-1)analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism.GLP-1 can also delay stomach emptying and suppress appetite to help lose weight.This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.
文摘Nonalcoholic fatty liver disease(NAFLD)is the most rapidly growing contributor to liver mortality and morbidity.Hepatocellular injury in nonalcoholic steatohepatitis(NASH)is caused by an increase in metabolic substrates(glucose,fructose,and fatty acids),leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury.The pathogenesis of this disease is largely associated with obesity,type 2 diabetes,and increasing age.To date,there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis.Since one of the pathogenic drivers of NASH is insulin resistance,therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH.Currently,the glucagon-like peptide-1 receptor agonist(GLP-1RA)semaglutide is a safe,well-studied therapeutic for NAFLD/NASH patients.Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis.However,improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD.Given the complex pathophysiology of NASH,combining therapies with complementary mechanisms may be beneficial.Researchers have conducted trials of semaglutide in combination with antifibrotic drugs.However,the results have not fully met expectations,and it cannot be ruled out that the reason is the short trial time.We should continue to pay increasing attention to GLP-1RAs.
文摘Hyperglycaemia contributes to the onset and progression of diabetic kidney disease(DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro-or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient. Recently, empagliflozin which is an oral glucose lowering agent of the sodium glucose cotransporter-2 inhibitor class has been shown to have renal protective effects. However, the magnitude of empagliflozin's reno-protective properties are over and above that expected from its glucose lowering effects and most likely largely result from mechanisms involving alterations in intra-renal haemodynamics. Liraglutide and semaglutide, both injectable glucose lowering agents which are analogues of human glucagon like peptide-1 have also been shown to reduce progression to macroalbuminuria through mechanisms that remain to be fully elucidated. Here we review the evidence from observational and interventional studies that link good glucose control with improved renal outcomes. We also briefly review the potential reno-protective effects ofnewer glucose lowering agents.
文摘Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.
文摘Glucagon-like peptide receptor agonists(GLP-1RA)are used to treat type 2 diabetes mellitus and,more recently,have garnered attention for their effect-iveness in promoting weight loss.They have been associated with several gastrointestinal adverse effects,including nausea and vomiting.These side effects are presumed to be due to increased residual gastric contents.Given the potential risk of aspiration and based on limited data,the American Society of Anesthesi-ologists updated the guidelines concerning the preoperative management of patients on GLP-1RA in 2023.They included the duration of mandated cessation of GLP-1RA before sedation and usage of“full stomach”precautions if these medications were not appropriately held before the procedure.This has led to additional challenges,such as extended waiting time,higher costs,and increased risk for patients.In this editorial,we review the current societal guidelines,clinical practice,and future directions regarding the usage of GLP-1RA in patients undergoing an endoscopic procedure.
