Diabetes, Obesity & Metabolism最新文献

{"title":"Risk of insulin initiation with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: A real-world claims database study in Japan.","authors":"Ryo Suzuki, Shingo Shoji, Yoko Yoshinaga, Yoshinori Kosakai, Mami Shintani-Tachi","doi":"10.1111/dom.16188","DOIUrl":"https://doi.org/10.1111/dom.16188","url":null,"abstract":"<p><strong>Aims: </strong>Insulin therapy is a cornerstone in type 2 diabetes mellitus (T2DM) management, but its use is associated with several barriers, including hypoglycaemia, fear of injections and high costs. We compared the risk of insulin initiation and other treatment intensification between patients with T2DM newly treated with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) versus those newly treated with a dipeptidyl peptidase-4 inhibitor (DPP4i).</p><p><strong>Materials and methods: </strong>This Japanese retrospective cohort study was conducted between 1 January 2015 and 31 March 2023 using the JMDC Claims Database. Patients with T2DM newly treated with an SGLT2i or a DPP4i were matched 1:1 using propensity score (n = 18 488 each). Incidence rates (IR) of insulin initiation, other antidiabetic drugs (OAD) and antihypertensive drugs added onto baseline treatment were calculated for each treatment group. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a Cox proportional hazards model.</p><p><strong>Results: </strong>The IR of insulin initiation was 0.95 and 2.12 per 1000 person-years in the SGLT2i and DPP4i groups, respectively, with significantly lower risk in the SGLT2i group than in the DPP4i group (HR 0.46, 95% CI: 0.28-0.74, p = 0.001). The risks of OAD (HR 0.66, 95% CI: 0.64-0.69, p < 0.001) and antihypertensive drugs (HR 0.90, 95% CI: 0.85-0.95, p < 0.001) added onto baseline treatment were lower in the SGLT2i group than in the DPP4i group.</p><p><strong>Conclusions: </strong>The risk of insulin initiation was lower in patients with T2DM newly treated with an SGLT2i than in those newly treated with a DPP4i. SGLT2i may reduce or delay the need for insulin therapy.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub-analysis of a randomized controlled study.","authors":"Kiichi Hirayama, Masaya Koshizaka, Ryoichi Ishibashi, Mayumi Shoji, Takuro Horikoshi, Kenichi Sakurai, Koutaro Yokote","doi":"10.1111/dom.16198","DOIUrl":"https://doi.org/10.1111/dom.16198","url":null,"abstract":"<p><strong>Aims: </strong>To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis.</p><p><strong>Materials and methods: </strong>In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m² and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, were compared in the sub-analyses. The correlations between changes in each index and VFA were evaluated.</p><p><strong>Results: </strong>At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (-9.24 ± 10.7 vs. -3.45 ± 11.8, p = 0.013), HSI (-1.45 ± 2.32 vs. -0.45 ± 1.87, p = 0.021), NAFLD-LFS (-0.70 ± 1.46 vs. -0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (-0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction (r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively).</p><p><strong>Conclusions: </strong>Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term blood glucose control via glucose-activated transcriptional regulation of insulin analogue in type 1 diabetes mice.","authors":"Wanling Lu, Lifang Xie, Yanhan Zhang, Hong Gao, David Geng, Chunguang Xie, Ming Liu, Gang Wang","doi":"10.1111/dom.16197","DOIUrl":"https://doi.org/10.1111/dom.16197","url":null,"abstract":"<p><strong>Aim: </strong>To achieve glucose-activated transcriptional regulation of insulin analogue in skeletal muscle of T1D mice, thereby controlling blood glucose levels and preventing or mitigating diabetes-related complications.</p><p><strong>Materials and methods: </strong>We developed the GANIT (Glucose-Activated NFAT-regulated INSA-F Transcription) system, an innovative platform building upon the previously established intramuscular plasmid DNA (pDNA) delivery and expression system. In the GANIT system, skeletal muscle cells are genetically engineered to endogenously produce the insulin analogue INSA-F (Insulin Aspart with Furin cleavage sites). The transcription of INSA-F is precisely controlled by a glucose-responsive promoter containing NFAT (Nuclear Factor of Activated T-cells) regulatory motifs, which can be activated in response to changes in extracellular glucose concentrations. This design enables glucose-dependent regulation of insulin analogue expression, mimicking physiological glucose-responsive insulin secretion.</p><p><strong>Results: </strong>T1D mice that received two GANIT treatments over a 2-month experimental period demonstrated significant improvements in glucose homeostasis, glucose tolerance and glycated haemoglobin (HbA1c) levels. Additionally, the treatment effectively reduced oxidative stress and alleviated cardiac and renal fibrosis, while maintaining a favourable biosafety profile.</p><p><strong>Conclusion: </strong>The GANIT system provides significant advantages in terms of efficiency, convenience and cost-effectiveness, making it a promising approach for regulating blood glucose levels and alleviating diabetes-related complications in insulin-deficient diabetes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unexpected cardiovascular risks of glucagon-like peptide-1 receptor agonist and aspirin co-administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study.","authors":"Chia-Ming Lin, Jo-Ching Chen, Gideon Meyerowitz-Katz, Yu-Nan Huang, Pen-Hua Su","doi":"10.1111/dom.16191","DOIUrl":"https://doi.org/10.1111/dom.16191","url":null,"abstract":"<p><strong>Aims: </strong>To examine the cardiovascular safety of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D).</p><p><strong>Materials and methods: </strong>This propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP-1 RA plus aspirin versus those receiving GLP-1 RA alone, for both diabetic and non-diabetic individuals. Cardiovascular outcomes and adverse events were evaluated over 5 years using Cox proportional hazards models.</p><p><strong>Results: </strong>Individuals with obesity treated with GLP-1 RAs plus aspirin showed significantly higher risks of various cardiovascular events compared to those on GLP-1 RAs alone. In non-diabetic obese individuals, the combination therapy increased risks of hypertensive heart diseases (HR 1.40, 95% CI 1.15-1.60), ischaemic heart disease (HR 2.39, 95% CI 1.92-2.97) and heart failure (HR 1.97, 95% CI 1.54-2.53). Similar patterns were observed in individuals with T2D. Atrial fibrillation and cardiac arrhythmias showed increasing hazard ratios over time. The combination therapy also led to more frequent adverse events, including gastrointestinal bleeding.</p><p><strong>Conclusions: </strong>The combination of GLP-1 RAs with aspirin in individuals with obesity, both with and without T2D, was associated with increased cardiovascular risks compared to GLP-1 RA monotherapy. These findings suggest that there may be risks associated with the combined use of these treatments and highlight the need for further research into this possible complication with regard to treatment.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study”","authors":"","doi":"10.1111/dom.16204","DOIUrl":"10.1111/dom.16204","url":null,"abstract":"<p>\u0000 <span>Huang, YN</span>, <span>Liao, WL</span>, <span>Huang, JY</span>, et al. <span>Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study</span>. <i>Diabetes Obes Metab.</i> <span>2024</span>; <span>26</span>(<span>11</span>): <span>5222</span>–<span>5232</span>. doi:10.1111/dom.15869\u0000 </p><p>In Table 1, under Laboratory baseline characteristics, the last cell incorrectly states “HbA1c &gt; 7%”, when it should be “HbA1c &lt; 7%”.</p><p>In Figure 4, under “No. at Risk”, the GLP-1 RA number at day 0 is incorrectly shown as “12 109”, when it should be “12 019”.</p><p>We apologize for this error.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 3","pages":"1630"},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dom.16204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends and analysis of risk factor differences in the global burden of chronic kidney disease due to type 2 diabetes from 1990 to 2021: A population-based study.","authors":"Yifei Wang, Ting Lin, Jiale Lu, Wenfang He, Hongbo Chen, Tiancai Wen, Juan Jin, Qiang He","doi":"10.1111/dom.16183","DOIUrl":"https://doi.org/10.1111/dom.16183","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chronic kidney disease (CKD) is a significant contributor to the global burden of disease. Among its causes, chronic kidney disease due to type 2 diabetes (CKD-T2D) is the primary subtype. This study aims to provide an updated assessment of the global disease burden of CKD-T2D from 1990 to 2021. It will analyse the trends in the global burden of CKD-T2D and the differences in risk factors, as well as project changes over the next 15 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The data for this study were derived from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021. Estimates of prevalence, incidence, deaths and disability-adjusted life years (DALYs) for CKD-T2D, along with their 95% uncertainty intervals (UIs), were extracted. The trends in CKD-T2D burden from 1990 to 2021 were analysed from overall and local perspectives. An age-period-cohort model was used to estimate the age, period and cohort effects on the prevalence and incidence of CKD-T2D between 1990 and 2021. A decomposition analysis was conducted to assess the contribution of population size, age structure and epidemiological changes to the burden of CKD-T2D. Population-attributable fractions were determined for each risk factor, and a difference analysis was conducted. Additionally, projections were made regarding changes in the burden of CKD-T2D over the next 15 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In 2021, the global burden of CKD-T2D remained significant, with a total of 107 559 955 cases. The age-standardized prevalence rate (ASPR) was 1259.63 per 100 000 people. The age-standardized incidence rate (ASIR) was 23.07 per 100 000 people, and the age-standardized death rate (ASDR) was 5.72 per 100 000 people. The age-standardized disability-adjusted life years (DALYs) was 131.08 per 100 000. The global burden of CKD-T2D showed variation across different socio-demographic index (SDI) regions. In 2021, the overall burden of CKD-T2D continued to rise, with the age effect increasing with age. Both prevalence and incidence risks showed an upward trend over time. Decomposition analysis indicated that population growth and ageing were the primary contributors to the global burden of DALYs related to CKD-T2D. Metabolic risk factors such as high fasting plasma glucose and high body mass index (BMI) are the most significant attributable risk factors. It is projected that by 2036, the trends in ASPR, ASIR, ASDR and age-standardized DALYs will stabilize. However, ASIR and age-standardized DALYs are expected to continue rising, and the number of cases of prevalence, incidence, mortality and DALYs will persist in their upward trend.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;CKD-T2D imposes a significant global disease burden, with health disparities and unequal disease outcomes continuing to worsen across countries and regions due to differences in socio-economic development levels. This burden is primarily driven by population growth, ageing and meta","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta cell function and global glucose metabolism are impaired in Dp(16)1Yey mouse model of Down syndrome","authors":"Stefania Tolu PhD,&nbsp;Rim Hamzé PhD,&nbsp;Manon Moreau PhD,&nbsp;Romane Bertrand MSc,&nbsp;Nathalie Janel PhD,&nbsp;Jamileh Movassat PhD","doi":"10.1111/dom.16155","DOIUrl":"10.1111/dom.16155","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Down syndrome (DS) or trisomy 21 is the most prevalent genetic disorder in the world. In addition to common symptoms such as intellectual disabilities and morphological abnormalities, several comorbidities are associated with DS, including metabolic dysfunction. Obesity and diabetes are more prevalent in people with DS compared with the general population. However, the mechanisms linking obesity/diabetes to DS remain poorly understood. Systematic investigation of metabolic disorders in animal models of DS is scarce.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We used the Dp(16)1Yey mouse model of DS to evaluate the energy and glucose metabolism in both male and female Dp(16)1Yey mice at 3 and 6 months of age. We assessed the whole-body glucose metabolism by glucose and insulin tolerance tests, and investigated the pancreatic functions in terms of insulin synthesis, ß cell mass and the glucose-induced insulin secretion in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We show that Dp(16)1Yey mice do not present signs of obesity when they are fed with chow diet. However, these mice are glucose intolerant and insulin resistant, and exhibit dysfunctions of their endocrine pancreas, reflected by decreased insulin content and defective glucose-induced insulin secretion (GIIS) in vivo. The impairment of metabolic parameters is similar between males and females trisomic mice, indicating the absence of metabolic sexual dimorphism in this model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study suggests that Dp(16)1Yey model is suitable for the assessment of metabolic disorders associated with DS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 3","pages":"1477-1487"},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world retrospective study in elderly patients aged 65 years and older with type 2 diabetes mellitus treated with daily oral semaglutide (SEMA-elderly).","authors":"Vincenzo Fiore, Giovanni Carbotta, Sonia Barraco, Paolo Falasca, Concetta Nadia Aricò, Alessandra Barucca","doi":"10.1111/dom.16174","DOIUrl":"https://doi.org/10.1111/dom.16174","url":null,"abstract":"<p><strong>Aim: </strong>This real-world, retrospective cohort study aimed to assess the efficacy, safety and tolerability of oral semaglutide-the first GLP-1 receptor agonist available in oral form-in patients aged 65 years and older with type 2 diabetes mellitus (T2DM).</p><p><strong>Materials and methods: </strong>The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline (V1) to six months (V3). Secondary endpoints included change in body weight, proportion of patients achieving HbA1c <7%, proportion of patients achieving both an HbA1c reduction of ≥1% and a body weight reduction of ≥5%. Exploratory endpoints were also assessed, including evaluations at three months (V2).</p><p><strong>Results: </strong>One hundred and one patients (mean age 74.7 ± 6.1 years) started oral semaglutide treatment. Mean HbA1c decreased significantly from V1 to V3 (change: -0.44%, p < 0.001), with reductions already evident at V2. The proportion of patients achieving an HbA1c ≤7% increased from 36.6% at V1 to 61.7% at V3. At V3, 9.6% of patients achieved an HbA1c reduction of ≥1% and a weight loss of ≥5%. Body weight decreased from a baseline mean of 76.8-73.7 kg at V3 (p < 0.001). Body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and systolic blood pressure decreased significantly from V1 to V3, with changes already evident at V2. Eleven patients (10.9%) reported adverse events. Seven patients (6.9%) discontinued treatment.</p><p><strong>Conclusion: </strong>Oral semaglutide effectively improves glycaemic control and weight management in elderly patients with T2DM while improving lipid and cardiovascular parameters and proving to be safe and well tolerated.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of a very low-calorie ketogenic diet on metabolic and microbiota outcomes in post-bariatric patients and bariatric-Naïve individuals: A comparative pilot study.","authors":"Ilaria Ernesti, Maria Chiara Massari, Fiammetta Cipriani, Davide Masi, Krzysztof Glaser, Martina Genco, Dario Tuccinardi, Carla Lubrano, Stefania Mariani, Antonio Angeloni, Lucio Gnessi, Sabrina Basciani, Mikiko Watanabe","doi":"10.1111/dom.16187","DOIUrl":"https://doi.org/10.1111/dom.16187","url":null,"abstract":"<p><strong>Aims: </strong>To date, bariatric surgery (BS) is the most effective long-term treatment for obesity, but weight regain (WR) is common. The very low-calorie ketogenic diet (VLCKD) is effective for weight loss and may influence gut microbiota (GM) composition, but it has been scarcely evaluated in post-bariatric patients. This study compared the efficacy and safety of a VLCKD in patients with WR post-bariatric surgery (BS+) and in bariatric surgery-naïve patients (BS-).</p><p><strong>Methods: </strong>In this prospective, case-control study, 33 patients (15 BS+, 18 BS-) underwent an 8-week-long VLCKD. Outcomes included weight loss, metabolic profile, safety and GM composition.</p><p><strong>Results: </strong>Both groups achieved significant weight loss (BS+: -6.9%, BS-: -8.3%), but the BS+ group showed slightly less metabolic improvement, particularly in insulin resistance and triglycerides. GM composition differed at baseline, reflecting the lasting effects of BS, and VLCKD led to significant changes in both groups. Microbial diversity and specific taxonomic shifts were more pronounced in BS- patients. Mild renal function changes were noted in BS+ patients, though these remained within clinically acceptable ranges.</p><p><strong>Conclusion: </strong>VLCKD is effective in both BS+ and BS- patients, though metabolic and microbial responses may be less robust post-surgery, possibly due to anatomical and physiological changes. Tailored approaches may be therefore needed to optimize outcomes in post-bariatric patients.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal tolerability and weight reduction associated with tirzepatide in adults with obesity or overweight with and without type 2 diabetes in the SURMOUNT-1 to -4 trials.","authors":"Domenica M Rubino, Sue D Pedersen, Lisa Connery, Dachuang Cao, Farai Chigutsa, Adam Stefanski, Julia Fraseur Brumm, Ryan Griffin, Claire Gerber","doi":"10.1111/dom.16176","DOIUrl":"https://doi.org/10.1111/dom.16176","url":null,"abstract":"<p><strong>Aims: </strong>This analysis evaluated whether gastrointestinal (GI) adverse events (AEs) including nausea, vomiting, diarrhoea (N/V/D) and dyspepsia were associated with weight reduction with tirzepatide across the SURMOUNT-1 to -4 trials.</p><p><strong>Materials and methods: </strong>SURMOUNT-1 to -4 were global Phase 3 clinical trials evaluating the safety and efficacy of tirzepatide among participants with obesity or overweight with or without type 2 diabetes (T2D). Participants were randomly assigned to receive once weekly subcutaneous tirzepatide or placebo. This post hoc analysis investigated weight change at the primary endpoint from baseline among participants who self-reported no N/V/D, any N/V/D or nausea alone. Mediation analyses evaluated the contribution of N/V/D and dyspepsia on weight reduction. Time to first use of antidiarrheal and antiemetic usage was reported by time intervals.</p><p><strong>Results: </strong>Baseline characteristics were similar between participants who reported N/V/D and those who did not. More participants reported GI AEs in the tirzepatide treatment arms (27.8%-72.8%) than with placebo (12.2%-32.5%). Most GI AEs were non-serious and occurred during dose escalation. Between 1.0% and 10.5% of tirzepatide-treated participants discontinued treatment due to GI AEs. Weight reduction with tirzepatide was similar among participants reporting no nausea, nausea alone, or any N/V/D. Mediation analyses suggested that N/V/D and dyspepsia were associated with up to 3.1% of total weight reduction. When required, first use of antidiarrheal and antiemetic medication was most commonly reported during dose escalation.</p><p><strong>Conclusions: </strong>In this post hoc analysis, GI AEs appeared to contribute slightly to the weight reduction seen with tirzepatide in participants with obesity or overweight with or without T2D.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}