Diabetes, Obesity and Metabolism Now最新文献

{"title":"Tirzepatide shown to improve clinical outcomes for patients with heart failure with preserved ejection fraction (HFpEF) and obesity","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70008","DOIUrl":"https://doi.org/10.1002/doi2.70008","url":null,"abstract":"<p>The last decade has seen the emergence of novel and highly effective therapies to induce weight loss and subsequent improvement in obesity-related co-morbidities. Heart failure has also increasingly been recognized to be highly prevalent and an important adverse outcome in patients with cardio-metabolic diseases such as obesity. Although most patients with heart failure have preserved ejection fraction (HFpEF) rather than reduced ejection fraction (HFrEF), treatment options for HFpEF remain limited. For example, while previous trials using the glucagon-like peptide-1 (GLP-1) agonist, semaglutide—STEP HFpEF<span><sup>1</sup></span> and STEP HFpEF Diabetes<span><sup>2</sup></span> which enrolled patients with HFpEF and obesity showed improvements in quality of life, physical limitations, and weight loss, these studies were not powered for a reduction in major clinical outcomes.</p><p>The SUMMIT trial was therefore the first trial to investigate the efficacy of tirzepatide, a long-acting dual agonist of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors on a composite outcomes of death from cardiovascular causes or a worsening heart failure event. The study has shown for the first time that a drug therapy can reduce major heart failure clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. The study is published in the <i>New England Journal of Medicine</i>.<span><sup>3</sup></span></p><p>In this study, 731 patients with heart failure and an ejection fraction of more than 50%, who also had obesity defined as a body mass index of at least 30 kg/m<sup>2</sup> were randomized to receive tirzepatide up to 15 mg subcutaneously once per week or placebo for at least 52 weeks. The mean duration of follow-up was 104 weeks.</p><p>The two co-primary endpoints were a composite of adjudicated death from cardiovascular causes or a worsening heart failure event and change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better quality of life).</p><p>Results showed tirzepatide significantly reduce death from cardiovascular causes or a worsening heart failure event by 38% (hazard ratio [HR], 0.62; 95% CI, 0.41–0.95; <i>p</i> = .026). The significant results were largely driven by a reduction in worsening heart failure events defined as those requiring hospitalization or urgent intravenous drug therapy, which occurred in 8.0% and 14.2% of the tirzepatide and placebo groups, respectively (HR, 0.54; 95% CI, 0.34–0.85). Death rate from cardiovascular causes observed in the study was actually quite small and occurred only in eight patients (2.2%) and five patients (1.4%), for Tirzepatide versus placebo respectively (HR, 1.58; 95% CI, 0.52–4.83).</p><p>Tirzepatide also showed improvement in KCCQ-CSS score of 19.5 in the tirzepatide group versus 12.7 with placebo. Reported secondary endp","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-society consensus guidance on handling of GLP-1 therapy prior to general anaesthesia","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70009","DOIUrl":"https://doi.org/10.1002/doi2.70009","url":null,"abstract":"<p>GLP-1 receptor agonists and dual GLP-1 and GIP agonists are widely used in people with type 2 diabetes and increasingly in people living with excess weight and/or obesity. Recent concerns have emerged regarding their potential increased risks of regurgitation, aspiration and airway compromise during anaesthesia. These concerns have led the American Society of Anaesthesia (ASA) to recommend holding these agents for 1 week for the injectable form and 1 day for the oral form before all procedures requiring anaesthesia in their 2023 guideline.<span><sup>1</sup></span> The latest FDA label change warns about the risk for pulmonary aspiration but recognizes that there is currently no adequate data to inform evidence-based recommendations to reduce risk in at-risk patients. The ongoing concerns and uncertainties have resulted in inconsistencies in the recommendations on appropriate guidance for the use of these therapies prior to general anaesthesia. This has also led to unnecessary cancellations and postponements of important procedures.</p><p>In view of this, a new joint-society guidance was published to provide some guidance on this issue. The five endorsing organizations are the American Society for Metabolic and Bariatric Surgery, American Society of Anaesthesiologists (ASA), American Gastroenterological Association, International Society of Perioperative Care of Patients with Obesity, and Society of American Gastrointestinal and Endoscopic Surgeons and was led by the ASA.<span><sup>2</sup></span></p><p>The guideline highlights three main considerations. First is a need for preoperative assessment to identify individuals who are at an increased risk for delayed gastric emptying. These include patients who are undergoing the dose escalation phase rather than the maintenance phase and those on higher doses of treatment who are at a greater the risk for gastrointestinal (GI) side effects. In addition, GI side effects are more common with weekly versus daily formulations. Patients should be assessed for GI symptoms such as nausea, vomiting, abdominal pain, dyspepsia, and constipation all of which may suggest delayed gastric emptying. Finally, general assessment for risk of delayed gastric emptying beyond GLP-1 should include assessment for conditions associated with bowel dysmotility, gastroparesis and Parkinson's disease. These risk factors need to be assessed in advance to allow sufficient time to adjust preoperative care. Second, if there is concerns regarding the risk of delayed gastric emptying and therefore aspirations, a 24-h preoperative liquid diet, can be utilized to reduce risks. If retained gastric contents are a concern on the day of a procedure, point-of-care gastric ultrasound could be used to assess aspiration risk. Lastly, when concern about retained gastric contents exists on procedure day, providers should engage patients in a shared decision-making model and consider the benefits and risks of rapid-sequence induction of general a","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision medicine approach to detect obese people who are at high risk of developing diabetes","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70007","DOIUrl":"https://doi.org/10.1002/doi2.70007","url":null,"abstract":"<p>It is well-recognized that obesity predisposes an individual to an increased risk of developing type 2 diabetes. However, a variety of factors can play a role in the risk of developing type 32 diabetes. Various strategies have been utilized to help identify obese individuals who are at high risk of developing type 2 diabetes so as appropriate intervention can be prioritized to reduce the risks of developing obesity related complications. Precision medicine approach has attracted significant amount of clinical and research interests to help predict, prevent, diagnose and manage patients with a variety of conditions.</p><p>Stratification of Obesity Phenotypes to Optimise Future Obesity Therapy (SOPHIA) is a European Union-funded innovative medicine initiative (IMI) to help develop tests and therapies which may allow the prediction of risk of obesity related co-morbidities and the prediction of response to obesity treatments. A recent publication in the journal <i>Nature Medicine</i> from the IMI SOPHIA consortium have reported and described a new precision prediction algorithm that distinguish subpopulations where cardiometabolic risk differs from the risk expected for their given body mass index (BMI).<span><sup>1</sup></span> This is important because multiple factors are in play when determining an obese person's individual risk of developing type 2 diabetes and heart disease. For example, while BMI is the common metric used by epidemiologists, health professionals and others to characterize obesity, it is insufficient for accurate classification of the disease of obesity at an individual level because people with similar BMIs often exhibit different health risks. This is partially because BMI is an imperfect measure of excess adiposity as it does not distinguish the proportion or distribution of fat mass and fat-free mass in the body.</p><p>The research was led by scientists at Lund University Diabetes Centre in Sweden, and Maastricht Centre for Systems Biology and Erasmus MC University Medical Centre in The Netherlands, in collaboration with other researchers from the IMI SOPHIA consortium. The study focused on clinical data of 170 000 adults derived from the UK Biobank, The Rotterdam Study, the Maastricht study and the Gutenberg Health study. Machine learning was then utilized to develop algorithm that would split obesity into five subtypes based on different diagnostic profiles, each with different risks of developing obesity related complications. The five phenotypic profiles consists of individuals with cardiometabolic biomarkers higher or lower than expected based on their BMI, which generally increases disease risk, representing 20% of the total population. Conversely, the study showed that 80% of people had health markers that matched their cardiometabolic risk expected for their BMI. The discordant phenotype identified for example 8% of women with higher blood pressure than expected for their weight but associated with higher protec","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing excess to weight loss injection shown to save thousands of lives a year","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70006","DOIUrl":"https://doi.org/10.1002/doi2.70006","url":null,"abstract":"<p>The last 5 years have seen an explosion of research and development of novel and very effective anti-obesity therapy. These therapies have shown to produce up to 25% of weight loss as well as other health benefits among patients with cardio-metabolic diseases.</p><p>In a recently published study conducted by researchers at the Yale School of Public Health and the University of Florida, investigators have reported that expanding access to new, highly effective anti-obesity therapies could prevent more than 40 000 deaths a year in the United States.<span><sup>1</sup></span></p><p>To undertake the study, investigators utilized publicly available data to calculate mortality risk associated with different body mass index (BMI) categories and obesity prevalence. The annual mortality in the United States was recalculated by applying the BMI category-specific annual mortality rates to the new population distribution across various BMI categories resulting from the weight-loss associated with drug use. Using survey studies, prescription data, and cohort studies, current uptake rate of the drugs among eligible populations for obesity and for diabetes was calculated to be 10.8% and 10.7%–13.6%, respectively. The uptake rate was then recalculated based on the expanded assess scenario.</p><p>The study analysis showed that if access to these new medications were expanded to include all eligible individuals, 42 027 deaths could be avoided annually. This estimate includes approximately 11 769 deaths among individuals with type 2 diabetes. Even under current scenario of limited access due to costs and inadequate insurance coverage, the researchers project that around 8592 lives are saved each year, primarily among those with private insurance. Considering the geographic distribution of obesity and diabetes on a per capita basis, expanded access to weight-loss drugs among eligibles could lead to an annual mortality reduction of 9.6–15.7 deaths per 100 000 population. While all states could achieve a reduction of at least 9.6 deaths per 100 000 population, West Virginia, Mississippi, and Oklahoma are expected to experience the largest per capita reduction due to highest rates of obesity and type 2 diabetes in these states.</p><p>With the expanded access, 9977 deaths averted would be among Medicare beneficiaries and 2804 would be among uninsured. To account for the impact of socioeconomic factors on individuals' mortality risk beyond access to these drugs, investigators also adjust individuals' mortality reduction based on their income status. This leads to a conservative estimate of 32 906 fewer annual deaths. In contrast, as many as 165 574 annual deaths could be averted under the optimistic scenario of willingness and adherence. Increase access however needs to be balance with the caveat of stock supplies due to any limitations to the production of these therapies. Multifaceted public health approach will need to be implemented in order to successfully increas","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide shown to improve cardiovascular outcomes among patients with type 2 diabetes with any forms of heart failure","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70004","DOIUrl":"https://doi.org/10.1002/doi2.70004","url":null,"abstract":"<p>Previous studies have shown the efficacy and effectiveness of semaglutide to help to reduce major adverse cardiac events (MACE) such as heart attacks and strokes for people with obesity or who were overweight and had cardiovascular disease.<span><sup>1</sup></span> Whether the benefit persists specifically in patients with heart failure at baseline is unclear. This is important since a diagnosis of heart failure is associated with adverse cardiovascular outcomes.</p><p>A new study published in <i>The Lancet</i>, have now found similar cardiovascular benefits for a subgroup of study participants who were determined to have heart failure at the start of the trial.<span><sup>2</sup></span></p><p>The study investigated data from 4286 people—out of a total of 17 605 from the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial who were randomly assigned either semaglutide or a placebo. Patients were followed up over an average of more than 3 years.</p><p>Their analysis found that semaglutide was associated with a 28% reduction in major adverse cardiac events (12.3% in the placebo group compared to 9.1% in the semaglutide group). Among people with pre-existing heart failure, there was a 24% reduction in cardiovascular disease-related deaths and a 19% reduction in deaths of any cause. In addition, the study found the clinical benefit of semaglutide was observed irrespective of type of heart failure (i.e., heart failure with sreduced and preserved ejection fraction). It was also found to be independent of age, sex, baseline BMI, and clinical status. Serious adverse events were reported more frequently in the placebo group than in the semaglutide group. Treatment was discontinued more often in the semaglutide group, primarily driven by the well recognized gastrointestinal disorders (14.7% vs. 9.0% in the heart failure groups; and 17.2% vs. 7.9% in non-heart failure groups).</p><p>This study therefore extends the observation from the previously published SELECT which showed benefits of semaglutide for people with cardiovascular disease who had obesity or were overweight. This new study reports that among similar patient group with obesity or overweight, people with heart failure did as well as people without heart failure in reducing major adverse cardiovascular events, cardiovascular related death or any cause of mortality. This is important as there were some uncertainties regarding the safety of Liraglutide, another Glucagon like peptide-1 analogue in people with heart failure with reduced ejection fraction.<span><sup>3</sup></span></p><p>So where does evidence from this study sit in our current strategy to manage heart failure in people with type 2 diabetes? It is important to note that Semaglutide is not licenced for the management of heart failure. Conversely, evidence based from the sodium glucose co-transporter 2 inhibitor suggest clear benefit for patients with heart failure, irrespective of disease status or whether heart failure is","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real world study provided reassurance of the safety of GLP-1 therapy on mental health and suicide risk","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70005","DOIUrl":"https://doi.org/10.1002/doi2.70005","url":null,"abstract":"<p>In July of 2023, the European Medicines Agency announced that it was conducting a formal review into reports that the use of these drugs could increase the risk for suicide and suicidal thoughts. This was based on The Icelandic Medicines Agency receiving reports of up to 150 people who took the drugs and experienced suicidal thoughts or self-injury.</p><p>This was surprising since there was no signal of this potential adverse effect in the randomized trial data. However, since randomized trials have strict inclusion criteria to exclude people with psychological issues at baseline, trial safety data may not observe concerns about psychiatric safety risks.</p><p>As such, the other approach is to look at real world data. To this end, a study published in JAMA medicine have reported this.<span>¹</span></p><p>In the study, investigators identified everyone in Sweden and Denmark who started taking semaglutide or liraglutide (<i>N</i> = 124 517) for diabetes from 2013 to 2021. Use of SGLT2 inhibitor (<i>N</i> = 174 036) at the same time but not GLP-1 therapy was used as a control group.</p><p>In any case, 124 517 adults were prescribed Ozempic or an Ozempic-like drug, and 174 036 started taking an SGLT2 inhibitor. Interestingly, those who were prescribed Ozempic were more likely to be using or to have previously used antidepressants and to have had an outpatient visit for a psychiatric diagnosis. Analysis was undertaken via a propensity score analysis to adjust for confounders. The study showed that 77 new Ozempic users died from suicide (6 out of 10 000 people) as did 71 new SGLT2 inhibitor users (4 out of 10 000 people). While there was a slight increase risk with GLP-1, the margin of error is very large. Crucially, when death from suicide and nonfatal self-harm were combined, GLP-1 receptor agonists appear to be protective (HR, 0.83; 95% CI, 0.07–0.97), while no difference was noted between GLP-1 and SGLT2 inhibitor on new psychiatric disorder.</p><p>In my opinion therefore, the outcome is equivocal and that there is no significant association between Ozempic and suicide. These findings are reassuring but further monitoring and surveillance is needed to monitor its safety.</p>","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can diet and exercise intervention prevent type 2 diabetes in individuals with a high genetic risk?","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70002","DOIUrl":"https://doi.org/10.1002/doi2.70002","url":null,"abstract":"<p>Previous studies have shown clear benefits of lifestyle intervention for the prevention of type 2 diabetes. Since then advances in gene technology have allowed researchers to identify more than 500 genetic variants that predispose individuals to type 2 diabetes. However, lifestyle factors are also important determinants of increased risk of developing type 2 diabetes. Whether type 2 diabetes can be prevented by lifestyle changes among individuals carrying numerous genetic variants that predispose them to type 2 diabetes however is not known. To clarify this, a new study from the University of Eastern Finland is the first to show that a healthy diet and regular exercise reduce the risk of type 2 diabetes even in individuals with a high genetic risk.<span>¹</span></p><p>The T2D-GENE trial was a three-year lifestyle intervention that involved 973 men with the Metabolic Syndrome, aged 50–75 years, body mass index ≥25 kg/m², fasting plasma glucose 5.6–6.9 mmol/L and haemoglobin A1c &lt; 48 mmol/mol. Genetic risk was determined based on 76 gene variants known to predispose to type 2 diabetes. There were 2 intervention groups, a low (<i>n</i> = 315) and high genetic risk for Type 2 Diabetes (<i>n</i> = 313), and the remaining participants served as a control group. Men in the intervention group were provided with a 3-year group-based intervention with access to a web portal focused on healthy diet and physical activity. The corresponding population-based control groups have low (<i>n</i> = 196) and high (<i>n</i> = 149) genetic risk for Type 2 Diabetes and received general health advice similar to the intervention group.</p><p>Men participating in the lifestyle intervention increased their intake of dietary fibre, improved the quality of fats in their diet and increased their consumption of vegetables, fruits and berries.</p><p>The intervention significantly lowered the risk of Type 2 Diabetes among the participants with a high genetic risk for T2D by 70%, whereas in the low genetic risk group the effect was not significant. The intervention effect was not significantly different between the high and low genetic risk groups (<i>p</i> = .135). The intervention significantly prevent the worsening of glucose levels and decreased weight both in the low and high genetic risk groups.</p><p>The study therefore was the first to show that individuals with a high genetic risk for T2D benefitted from a simple group-based intervention programme focusing on healthy diet and physical activity.</p>","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real world data showed that the dual GLP gip agonist, Tirzepatide is associated with lower mortality, cardiovascular events and adverse kidney events compared with GLP-1 analogue","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70003","DOIUrl":"https://doi.org/10.1002/doi2.70003","url":null,"abstract":"<p>Tirzepatide is a novel, dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) analogue. Studies have shown superiority of Tirzepatide compared with Semaglutide, a once weekly GLP-1 agonist in reducing HbA1c and weight, but whether these metabolic improvements lead to improvements in cardiovascular and kidney outcomes remains unclear. Semaglutide meanwhile has been shown to reduce cardiovascular events and reduce risk of heart failure progression in patients with or without type 2 diabetes.<span>^{1, 2}</span> There is currently no studies which have directly compared tirzepatide with GLP-1 RAs.</p><p>In view of this, the publication in the journal <i>JAMA Network Open</i> comparing the cardio-renal benefits of Tirzepatide versus Semaglutide in people with type 2 diabetes is welcoming.<span>³</span></p><p>This was retrospective cohort study using US Collaborative Network of TriNetX data and collected clinical information of individuals with type 2 diabetes aged 18 years. Patients with stage 5 chronic kidney disease or kidney failure at baseline; myocardial infarction or ischemic or hemorrhagic stroke within 60 days of drug initiation were excluded. The primary outcome was all-cause mortality, and secondary outcomes included major adverse cardiovascular events (MACEs), the composite of MACEs and all-cause mortality, kidney events, acute kidney injury, and major adverse kidney events.</p><p>14 834 patients treated with tirzepatide and 125 474 treated with GLP-1 RA were analysed. Mean age was 58.1 years. After a median follow-up of 10.5 months, 95 patients (0.6%) in the tirzepatide group and 166 (1.1%) in the GLP-1 RA group died. Tirzepatide treatment was associated with a 42% lower risk of all-cause mortality, 20% lower risk of Major Adverse Cardiovascular events (MACE) and 24% reduced risk of combined all-cause mortality and MACE. Kidney events was also reduced by 48%, acute kidney injury by 22% and major adverse kidney events by 46% with Tirzepatide compared with Semaglutide. Perhaps unexpectedly, treatment with tirzepatide was also associated with greater decreases in glycated haemoglobin (treatment difference, −0.34 percentage points) and body weight (treatment difference, −2.9 kg compared with semaglutide. An interaction test for subgroup analysis revealed consistent results when stratified by estimated glomerular filtration rate, glycated haemoglobin level, body mass index, concurrent therapies and comorbidities.</p><p>While this is a retrospective study with its usual caveat and limitations – namely allocation bias and residual confounders, evidence from this study provide novel and preliminary evidence of the effectiveness of Tirzepatide when used in routine clinical practice compared with Semaglutide. I look forward to evidence of cardio-renal benefits of Tirzepatide in a randomized clinical trial setting, especially when compared with high dose Semaglutide at 2.4 mg once weekly.</p>","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142169989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide shown to be effective at reducing sleep disturbances in patients with obstructive sleep apnoea","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70000","DOIUrl":"https://doi.org/10.1002/doi2.70000","url":null,"abstract":"<p>Obstructive sleep apnoea (OSA) is highly prevalent in patients with obesity with or without type 2 diabetes. Data from the American diabetes Association reported that around 40% of patients with obesity have OSA. Continuous Positive Airway pressure (CPAP) is an effective and the most-used intervention for OSA, but many patients may not be able to tolerate the device or stop using it. Tirzepatide a dual GLP-1 GIP agonist has been shown to induce significant weight loss and improve glycaemic control in people with type 2 diabetes. Whether the weight loss induced by Tirzepatide could positively affect the severity and improve outcome in people with OSA however remains unclear.</p><p>To clarify this, SURMOUNT-OSA was undertaken. This was a combination of two phase 3, multi-center, randomized, double-blind, parallel, placebo-master protocol studies, comparing the efficacy and safety of tirzepatide to placebo in adults living with moderate-to-severe obstructive sleep apnea and obesity who were unable or unwilling to use CPAP (Study 1) and those who were and planned to stay on CPAP therapy during the duration of the trial (Study 2). The trials randomized 469 participants from 60 sites across 9 countries, in a 1:1 ratio to receive tirzepatide maximum tolerated dose 10 mg or 15 mg or placebo. The primary objective of both studies was to demonstrate that tirzepatide is superior in change in apnea-hypopnea index (AHI) from baseline at 52 weeks as compared to placebo. The study was published online in the New England J of Medicine.<span>¹</span></p><p>Patients were enrolled if they had moderate-to-severe OSA, defined as more than 15 events per hour (using the AHI and a body mass index of 30 kg/m² or greater. In study 1, 114 individuals received tirzepatide and 120 received placebo. For study 2, 119 patients received tirzepatide and 114 received placebo. All participants received regular lifestyle counselling sessions about nutrition and were instructed to reduce food intake by 500 kcal/day and to engage in at least 150 min/week of physical activity.</p><p>At baseline, 65%–70% of participants had severe OSA, with more than 30 events/hour on the AHI scale and a mean of 51.5 events/h in study 1 and 49.5 in study 2.</p><p>By 1 year, patients taking tirzepatide had 27–30 fewer events/hour compared with 4–6 fewer events/hour for those taking placebo. Up to half of those who received tirzepatide in both trials had less than 5 events/h or 5–14 AHI events/h and an Epworth Sleepiness Scale score of 10 or less. This translate to around 40%–50% of patient who were no longer required to use CPAP therapy for the management of their OSA. Patients who received tirzepatide also reported fewer daytime and night-time disturbances, as measured using the Patient-Reported Outcomes Measurement Information System Short Form scale for Sleep-Related Impairment and Sleep Disturbance. Patients in the tirzepatide group also had a decrease in systolic blood press","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The glucagon like peptide-1 linked to nonarteritic anterior ischemic optic neuropathy","authors":"Iskandar Idris DM","doi":"10.1002/doi2.70001","DOIUrl":"https://doi.org/10.1002/doi2.70001","url":null,"abstract":"<p>Previous evidence have reported an risk of retinopathy progression following rapid reduction of Hba1c level (~2.5%) with Semaglutide.<span>¹</span> At risk patients were those who had high baseline HbA1c, long diabetes duration or had evidence of significant diabetic retinopathy prior to treatment initiation. A recent study have raised new evidence linking Semaglutide with an increased risk of developing, nonarteritic anterior ischemic optic neuropathy, an uncommon condition that can cause vision loss.<span>²</span></p><p>This was a retrospective data base analysis involving 16 827 patients at Massachusetts Eye and Ear in Boston. Despite the large number, their analysis only focuses on 710 patients with type 2 diabetes (194 of whom had been prescribed semaglutide) and 979 patients with overweight or obesity (361 prescribed semaglutide). The researchers compared patients prescribed semaglutide with those prescribed a medication other than a GLP-1 agent. They matched patients by factors such as age and sex and whether they had hypertension, obstructive sleep apnea, or coronary artery disease. Cumulative incidence of nonarteritic anterior ischemic optic neuropathy (NAION) were assessed during 36 months of follow-up.</p><p>The study showed that Semaglutide use was associated with a 4.3 fold increased risk for NAION in patients with type 2 diabetes and 7.6 fold increased risk in patients with overweight or obesity. Among patients with type 2 diabetes, the cumulative incidence of NAION over 36 months was 8.9% for those prescribed semaglutide versus 1.8% among those taking non-GLP-1 medications. For patients with overweight or obesity, the cumulative incidence of NAION over 36 months was 6.7% for the semaglutide cohort versus 0.8% for those in the other group.</p><p>The study has significant limitations. First it is a retrospective study. As such evidence derived from this may not be fully adjusted for residual confounders. Specifically, the study did not adjust for baseline or cumulative HbA1c or diabetes duration—two important factors which determine risk of retinopathy progression. The results were driven by a relatively small number of NAION cases in the patients exposed to semaglutide. The study does not establish that semaglutide directly causes NAION, but rather provide an association which needs to be tested in larger clinical trials or a post-market analysis of all GLP-1 RA drugs. The generalizability of the study is also unclear since the study was undertaken from patients which attend a specialist eye hospital. Interestingly, since risk of NAION was also seen in people without Type 2 diabetes, the potential mechanism for increased risk of NAION is unlikely to be driven by rapid lowering of HbA1c levels as reported in SUSTAIN-6.<span>¹</span></p><p>In clinical practise, the evidence form this study, in my opinion should not detract the continued use of semaglutide—given its well-recognized benefits in improv","PeriodicalId":100370,"journal":{"name":"Diabetes, Obesity and Metabolism Now","volume":"2 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/doi2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}