Diabetes, Obesity & Metabolism最新文献

{"title":"The coordinated changes in insulin sensitivity and insulin secretion associated with the remission of type 2 diabetes following short-term insulin therapy.","authors":"Ravi Retnakaran, Jiajie Pu, Alexandra Emery, Caroline K Kramer, Bernard Zinman","doi":"10.1111/dom.16315","DOIUrl":"https://doi.org/10.1111/dom.16315","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565706","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":"An overview of insulin therapy for the non-specialist.","authors":"Philip D Home","doi":"10.1111/dom.16280","DOIUrl":"https://doi.org/10.1111/dom.16280","url":null,"abstract":"<p><p>Nearly all health professionals, whatever their practice or speciality, now have contact with a significant number of insulin-using people with diabetes. People with type 1 diabetes are nearly universally managed on more complex insulin regimens, increasingly with complex support technology, and with some understanding of the concepts underlying these needed by anyone with responsibility for other aspects of their health care. People with type 2 diabetes usually come to insulin therapy in time, now with a prevalence for insulin administration of ≈50%, thanks to improved management of associated health risks giving longer life expectancy. But while some understandings have simplified the usual approach (basal insulin, self-adjustment dose algorithms), the advent of other medical products offering cardio-renal protection, the use of insulin in combination with these, and the marketing of novel insulin analogues and biosimilars, have all added complexity to clinical decision making. However for the insulin user in the mainstream of care (ambulatory diabetes services in primary and secondary care) the broad principles of choice and management of insulin therapy are fairly easily applied. In the current article, the complexity is dissected and addressed, some of the stigma around insulin therapy is neutralised, and the fundamental approach in regular care drawn into focus. PLAIN LANGUAGE SUMMARY: Insulin therapy is used in their diabetes lifetime by nearly all people with type 2 diabetes (T2DM), as well as in all people with type 1 diabetes (T1DM). In T2DM this is in the context of the usual progression of islet B-cell secretory failure, but also very often in the context of other conditions, from cancer or steroid therapy to acute arterial events or major surgery. Its prescription in these circumstances means that, in pharmaco-epidemiological studies, insulin use is invariably associated with poor health outcomes, but in a series of major RCTs of 5-15 years duration no excess of vascular or oncological adverse health outcomes was found. Physiologically insulin secretion occurs in two scenarios, namely basal insulin at night and between meals (≈50%), and in short (≈4 h) bursts with meals (≈50%). The former suppresses liver glucose production, which in its absence causes plasma glucose to rise threefold to around 12 mmol/l (but much higher if metabolic stress or with sugar-containing drinks). Meal-time insulin secretion in addition promotes glucose storage in skeletal muscle. People with T1DM, having no endogenous insulin secretion, thus require a multiple injection regimen (basal + meal-time), or pumped insulin, often now moderated by continuous glucose monitoring (CGM). Basal and meal-time preparations of pharmaceutical insulin analogues are also used for T2DM, with GLP-1RA and metformin usually continued. The starting regimen is normally basal only, usually with insulin glargine (100 U/ml), originator or biosimilar, while insulin degludec or g","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539606","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":"Regional trends and disparities in newer GLP1 receptor agonist initiation among real-world adult patients eligible for obesity treatment.","authors":"Rotana M Radwan, Yao An Lee, Pareeta Kotecha, Davene R Wright, Inmaculada Hernandez, Ronald Ramon, William T Donahoo, Yong Chen, John M Allen, Jiang Bian, Jingchuan Guo","doi":"10.1111/dom.16318","DOIUrl":"10.1111/dom.16318","url":null,"abstract":"<p><strong>Aims: </strong>To characterize trends in the initiation of newer anti-obesity medications (AOMs) and determine factors associated with their use among obese/overweight populations.</p><p><strong>Materials and methods: </strong>This study utilized electronic health record data from OneFlorida+ (2015-2024). Adults eligible for AOMs were included, defined as having a body mass index (BMI) ≥30 kg/m² or a BMI of 27-29.9 kg/m² with at least one obesity-related comorbidity. The primary outcome was the initiation of newer AOMs, specifically glucagon-like peptide-1 receptor agonists (GLP-1 RAs) including liraglutide, semaglutide and tirzepatide. Trends across years were examined, and a multivariable logistic regression identified sociodemographic, clinical and healthcare utilization factors associated with AOM initiation.</p><p><strong>Results: </strong>Of 319,949 adults, 1.8% initiated newer AOMs. Semaglutide accounted for 77.9% of initiations, tirzepatide 19.7% and liraglutide 17.8%. Initiation trends showed liraglutide uptake peaked at 5% in 2018 but declined afterward, while semaglutide and tirzepatide uptake increased exponentially since 2022. Odds of initiation were lower for Black (aOR [95% CI]: 0.87 [0.80-0.94]) and Hispanic (0.84 [0.78-0.91]) groups versus Whites, and for Medicaid (0.69 [0.63-0.76]) and uninsured (0.81 [0.74-0.87]) patients versus privately insured. Higher odds were associated with being female, middle-aged, having more outpatient visits and visiting endocrinologists.</p><p><strong>Conclusions: </strong>The initiation of newer AOMs among overweight and obese populations remains low, but uptake has increased exponentially since 2022. Our findings reveal significant disparities in obesity care, highlighting the importance of addressing inequities in AOM access to improve obesity outcomes.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539714","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":"Genetic evidence for the effects of glucokinase activation on frailty-related outcomes: A Mendelian randomisation study.","authors":"Rong Hua, Mai Shi, Elaine Chow, Aimin Yang, Yin Ting Cheung","doi":"10.1111/dom.16312","DOIUrl":"https://doi.org/10.1111/dom.16312","url":null,"abstract":"<p><strong>Aims: </strong>We aimed to use the Mendelian randomisation (MR) design to investigate the potential causal effects of glucokinase (GK) activation on frailty-related outcomes and to explore the potential mediating effects of metabolic and inflammatory biomarkers.</p><p><strong>Materials and methods: </strong>Seventeen independent single-nucleotide polymorphisms (SNPs) located within the GCK gene and significantly correlated with the glycated haemoglobin (HbA_1c) level were used as genetic proxies for the effect of GK activation. We employed two-sample MR analysis to assess the relationship between genetically proxied GK activation and multifactorial frailty-related outcomes (frailty index, grip strength, walking pace, appendicular lean mass [ALM] and telomere length) We also explored the potential mediating effects using two-step MR.</p><p><strong>Results: </strong>Genetically proxied GK activation was significantly associated with a lower frailty index (beta: -0.161 per 1% decrease in HbA_1c level due to GK activation, 95% confidence interval: -0.282 to -0.040, false discovery rate-adjusted p = 0.011). Additionally, GK activation showed significant associations with increased grip strength, higher ALM, faster walking pace and longer telomere length. GK activation also demonstrated a significant indirect effect on total grip strength and telomere length by reducing C-reactive protein levels (proportion of mediation: 6.79% to 8.21%).</p><p><strong>Conclusion: </strong>Our study provides genetic evidence supporting the causal effects of GK activation on lowering the risk of frailty. These findings suggest that GK activators (GKAs) may aid in the management of frailty and sarcopaenia in people with diabetes; however, future randomized controlled trials are necessary to validate these results and establish their clinical applicability.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539712","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":"Joint association of remnant cholesterol and lipoprotein-associated phospholipase A2 with composite adverse events: A 12-year follow-up study from Asymptomatic Polyvascular Abnormalities Community study","authors":"Yuhe Liu MSc,&nbsp;Liang Zhang MM,&nbsp;Yuehao Xu PhD,&nbsp;Tianyun Zhou MSc,&nbsp;Wenqian Wu BSc,&nbsp;Kangnan Zhang MSc,&nbsp;Rongdi Xu BSc,&nbsp;Wangyang Chen PhD,&nbsp;Weifang Xu MSc,&nbsp;Yong Zhou PhD,&nbsp;Xingdong Zheng PhD,&nbsp;Baofu Chen MD","doi":"10.1111/dom.16286","DOIUrl":"10.1111/dom.16286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the association of remnant cholesterol (RC) and lipoprotein-associated phospholipase A2 (Lp-PLA2) with composite adverse events in a large-scale prospective study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All data were collected from the Asymptomatic Polyvascular Abnormalities Community study between 2010 and 2022. Serum cholesterol levels and Lp-PLA2 were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their RC and Lp-PLA2 levels: low-RC/Lp-PLA2−, high-RC/Lp-PLA2−, low-RC/Lp-PLA2+ and high-RC/Lp-PLA2+. The composite endpoint was a combination of first-ever stroke, myocardial infarction or all-cause mortality. Cox regression analyses were performed to evaluate associations of RC and Lp-PLA2 with composite adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 1864 eligible participants, the average age was 60.6 years, and 74.3% were male. Over a follow-up of 12 years, we identified 500 composite adverse events, including 210 major adverse cardiovascular events and 342 all-cause deaths. When compared with the group of low-RC/Lp-PLA2−, the hazard ratios with 95% confidence intervals in the group of high-RC/Lp-PLA2+ for stroke, myocardial infarction, major adverse cardiovascular event, all-cause death and composite endpoints were 1.37 (0.87–2.16), 0.72 (0.28–1.82), 1.29 (0.85–1.95), 1.61 (1.10–2.38) and 1.43 (1.07–1.91), respectively. A significant interaction between RC and Lp-PLA2 status has been found for all-cause death and composite endpoint (<i>p</i> for interaction &lt;0.05). In addition, joint association of RC and Lp-PLA2 with all-cause death was modified by sex and age of &lt;60 versus ≥60 years (<i>p</i> for interaction: 0.035 and 0.01, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated RC and Lp-PLA2 levels were associated with an increased risk of composite adverse events, with these associations significantly influenced by sex and age. Our study highlights the synergistic effect of RC and Lp-PLA2 on the composite adverse events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 5","pages":"2790-2799"},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dom.16286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539713","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":"A systematic literature review on the burden of diabetic ketoacidosis in type 2 diabetes mellitus","authors":"Carol Wysham MD,&nbsp;Anila Bindal MD,&nbsp;Fleur Levrat-Guillen PharmD,&nbsp;Desislava Kostadinova MBiol,&nbsp;Yeesha Poon PhD","doi":"10.1111/dom.16282","DOIUrl":"10.1111/dom.16282","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To understand the existing literature on the epidemiology and clinical, humanistic, and economic burden of diabetic ketoacidosis (DKA) in people living with type 2 diabetes mellitus (T2DM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>MEDLINE, Embase and the Cochrane library were systematically searched for studies published between 1 January 2014 and 14 December 2023. Clinical trials and observational studies, conducted in people living with T2DM, were included if they provided data on DKA epidemiology, morbidity, mortality, hospitalizations or patient-reported outcomes. Studies of DKA-associated costs in T2DM were also included. Data were summarized descriptively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 197 publications were included. We found wide variations in DKA prevalence (0.0%–50.0%; 5th–95th percentile: 0.02%–26%; 126 publications) and incidence (0.0–24.5 events per 1000 patient years; 5th–95th percentile: 0.004–7.6 events per 1000 patient years; 37 publications). Populations at increased risk of DKA included patients using sodium–glucose cotransporter-2 inhibitors, those using insulin and those with poor glycaemic control. The most common precipitating factors were infection and non-adherence to treatment. There was limited evidence on the humanistic burden of DKA, but the results highlighted a high burden of complications including acute kidney injury or failure. The length of hospital stay ranged from days to several weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DKA is associated with a high clinical burden in people living with T2DM. Resources to screen for and potentially prevent DKA may reduce the burden of DKA for patients with T2DM and the healthcare system.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 5","pages":"2750-2767"},"PeriodicalIF":5.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dom.16282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539605","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":"Effect of tirzepatide on weight and metabolism in a multiethnic cohort with and without diabetes","authors":"Sara El Ghandour MD,&nbsp;Fatemeh Akbarpoor,&nbsp;Momina Malik,&nbsp;Madeeha Kalsekar,&nbsp;Sara Vidha,&nbsp;Prisha Bhatia,&nbsp;Nisrine Al Ghazal MD,&nbsp;Jeyaseelan Lakshmanan PhD,&nbsp;Rabia Cherquaoui MD,&nbsp;Farah Al Abed MD,&nbsp;Mona Jomaa BS,&nbsp;Georges Hajje MD,&nbsp;Samuel B. Ho MD,&nbsp;Maryam Alsaeed MD","doi":"10.1111/dom.16287","DOIUrl":"10.1111/dom.16287","url":null,"abstract":"&lt;p&gt;Obesity is defined as excessive fat accumulation that adversely affects health. Body mass index (BMI) is commonly used to classify overweight (BMI ≥25) and obesity (BMI ≥30). Over one billion people worldwide are affected by obesity.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; In the United Arab Emirates (UAE), 40.1% of adults are overweight and 27.8% are obese.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Among children, overweight and obesity prevalence is 22.3% and 18.9%, respectively. Excess weight is associated with cardiometabolic diseases, mechanical stress and psychosocial challenges. In the UAE, type 2 diabetes affects 19.3% of Emirati nationals and 12.4% of expatriates.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Weight loss through lifestyle changes, medication or surgery improves metabolic markers, with reductions &gt;15% potentially leading to diabetes remission and lower mortality.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Recent advances in pharmacotherapy, particularly GLP-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP receptor agonists have led to significant weight loss.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Tirzepatide, a dual GLP-1/GIP agonist, has demonstrated glycaemic efficacy and substantial weight loss in clinical trials. This study aims to assess weight changes, glycaemic effectiveness and cardiometabolic improvements in a multiethnic cohort using tirzepatide with and without type 2 diabetes in Dubai, UAE.&lt;/p&gt;&lt;p&gt;Our study provides real-world data on tirzepatide's effectiveness in a diverse multiethnic UAE cohort, including people with and without type 2 diabetes (T2DM). At 6 months, the average HbA1c reduction was 1.02%, with most participants on 5 or 7.5 mg doses (mean dose: 7.3 mg in people with type 2 diabetes, 6.8 mg in those without). This reduction is lower than the 1.9%–2.58% reported in the SURPASS trials,&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; which used higher doses and longer follow-up periods. However, our findings align with other real-world studies&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; and reinforce tirzepatide's effectiveness in glycaemic control. Weight loss in our cohort was substantial, with an overall average reduction of 10.7% at 6 months (7.9% in people with type 2 diabetes and 13.8% in those without), closely resembling results from the SURPASS trials. This suggests that tirzepatide remains effective in promoting weight loss, even at lower doses and over a shorter duration. The findings also support prior observational studies showing reductions of 10.1%–14.5% in 6 months, with some variations due to dosing differences.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Furthermore, meta-analyses confirm tirzepatide's efficacy in diverse populations. Improvements in cardiometabolic parameters, including LDL, AST and ALT, were observed—findings that are consistent with results from recent clinical trials.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; However, the reduction in systolic blood pressure was not statistically significant. These changes reflect broader findings from real-world data and meta-analyses. A subgroup analysis showed promising r","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 5","pages":"2891-2895"},"PeriodicalIF":5.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dom.16287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539710","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":"Five-year trajectories of HbA1c by age, sex, ethnicity and deprivation in adults with newly diagnosed type 2 diabetes: Observational study in England","authors":"Atanu Bhattacharjee PhD,&nbsp;Mohammad R. Ali PhD,&nbsp;David Kloecker MPhil,&nbsp;Suping Ling PhD,&nbsp;Gayathri Victoria Balasubramanian PhD,&nbsp;Clare Gillies PhD,&nbsp;Melanie Davies MD,&nbsp;Kamlesh Khunti PhD,&nbsp;Francesco Zaccardi PhD","doi":"10.1111/dom.16288","DOIUrl":"10.1111/dom.16288","url":null,"abstract":"&lt;p&gt;The burden of diabetes mellitus (DM) is increasing worldwide, putting significant pressure on healthcare systems. Diabetes is often managed in primary care and includes a significant proportion of adults needing treatment. HbA1c is considered the gold standard for monitoring overall glycaemic level control: while guidelines generally recommend maintaining HbA1c levels below 52 mmol/mol (7%) for most individuals with diabetes, personalized management strategies are advocated.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, the regular monitoring of HbA1c in real-world settings differs from that in controlled clinical trials.&lt;/p&gt;&lt;p&gt;This study investigates five-year HbA1c trajectories in newly diagnosed individuals with type 2 diabetes (T2DM) in routine primary care clinical practice in relation to age, sex, ethnicity and socioeconomic deprivation. We aim to identify disparities in HbA1c trajectories arising from these demographic factors, and to inform the development of more personalized and equitable approaches to diabetes care by identifying subgroups that may require targeted interventions or additional strategies for better diabetes glycaemic management.&lt;/p&gt;&lt;p&gt;We conducted this retrospective observational study, with approval from the Independent Scientific Advisory Committee (ISAC protocol No. 20_122), following the RECORD guidelines (checklist in the Supplementary material).&lt;/p&gt;&lt;p&gt;From an initial sample of 788 069 individuals, we excluded 237 421 without linkage to hospital records and 9944 with missing data on ethnicity and deprivation, leaving 540 704 individuals for the analyses reporting 3 886 451 measurements of HbA1c (1 396 464 in GOLD and 2 489 987 in Aurum database) during the 5 years of follow-up. The mean and median HbA1c were 51.0 (SD 36.4) mmol/mol and 48 (IQR: 41.0–58.5) mmol/mol, respectively. The median age at diagnosis was 62 (IQR: 52–71) (Table 1). There were fewer females (244 760 [45.3%]) than males. The largest proportion of participants (64 732; 12.0%) fell into the second most deprived group (ninth decile), while the smallest proportion (42 611, 7.9%) into the first decile. The majority of the cohort was of White ethnicity (49.9%), followed by Others/Unknown (37.4%), South Asian (8.2%) and Black (4.6%) ethnicity.&lt;/p&gt;&lt;p&gt;Across all groups, HbA1c levels showed an initial decrease until the first year from the diagnosis and an increase thereafter (Figure 1). The largest differences were observed for age and ethnicity: in terms of age, those between 18 and 30 years had an average HbA1c of 62 (95% CI: 61, 63) mmol/mol (results reported in % in Supplementary text) at diagnosis, 56 (55, 58) at 1 year and 64 (60, 67) at 5 years; corresponding estimates in the oldest group (≥80 years) were 52 (51, 52), 46 (45, 46) and 47 (47, 48). In White and Others/Unknown ethnicities, the trajectories of HbA1c were similar: at diagnosis, 1- and 5-year values were 55 (55, 55), 48 (48, 48) and 52 (52, 52) mmol/mol, respectively, in White; and 54 (54, 54), ","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 5","pages":"2896-2900"},"PeriodicalIF":5.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dom.16288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539711","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":"The safety, tolerability, pharmacokinetics and pharmacodynamics of GZR18 in healthy American and Chinese adult subjects","authors":"Yue Liu MD,&nbsp;Wei Chen PhD,&nbsp;Xuemei He MD,&nbsp;Anshun He PhD,&nbsp;Liyuan Zhao PhD,&nbsp;Tian Xie MS,&nbsp;Yue Li MS,&nbsp;Jing Zhao MM,&nbsp;Allen Hunt MD,&nbsp;Aixin Shi MD,&nbsp;Zhong-Ru Gan PhD","doi":"10.1111/dom.16285","DOIUrl":"10.1111/dom.16285","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aims&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;GZR18, a novel long-acting GLP-1 receptor agonist, has demonstrated substantial metabolic improvements in diabetic and obese animal models. The present studies aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the ascending dose of GZR18 in healthy American and Chinese subjects.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In these phases 1, randomized, double-blind, placebo-controlled, sequential, dose-escalation US and Chinese studies, healthy American and Chinese adults with similar age were enrolled to once-weekly subcutaneous injection of GZR18 or placebo. The studies included three cohorts of male American subjects (cohorts US-1–3) and six cohorts of Chinese subjects (cohorts CN-1–6, male and female), each with a specified target dose of GZR18 ranging from 1 to 50 μg/kg (1–10 μg/kg for US study and 5–50 μg/kg for Chinese study). The primary endpoints were the safety and tolerability of GZR18. Blood samples were collected for PK and PD analysis of GZR18 before and after dosing. A population PK analysis of GZR18 was conducted to ascertain whether there are ethnic PK differences between American and Chinese adults.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The exposure of GZR18 was comparable between healthy American and Chinese subjects, with the geometric mean ratio between the two populations for AUC&lt;sub&gt;0-t&lt;/sub&gt; and &lt;i&gt;C&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt; close to 1. A dose-dependent increase in AUC&lt;sub&gt;0–t&lt;/sub&gt; and &lt;i&gt;C&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt; occurred in both populations. The median time to maximum plasma concentrations (&lt;i&gt;T&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt;) in American subjects ranged from 72 to 96 h, and the mean &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt; ranged from 60 to 72 h in Chinese subjects. The half-life of GZR18 was approximately 7 days in both American and Chinese subjects. Evident body weight reduction was observed in GZR18 treatment groups in Chinese subjects (cohorts CN-3–6 on Day 15, −1.25 to −1.86 kg; −1.88% to −3.11%). No deaths, serious adverse events or hypoglycaemia were reported. Decreased appetite and nausea were the most frequently reported treatment-emergent adverse events, observed in Chinese study and mild in severity. The safety profile of GZR18 was generally consistent with the same class of drugs.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;GZR18 demonstrates good tolerability in healthy American and Chinese subjects. No ethnic differences were observed between healthy American and Chinese subjects. The safety, PK and PD profiles of GZR18 support its further clinical evaluation for glycaemic and body weight control.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 5","pages":"2777-2789"},"PeriodicalIF":5.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539716","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":"The extent and predictors of off-label use of GLP-1 receptor agonists for weight loss management.","authors":"Zbigniew Siudak, Filip Tkaczyk, Monika Tomaszewska, Krzysztof P Malinowski, Lukasz Szarpak, Iwona Kowalska-Bobko","doi":"10.1111/dom.16313","DOIUrl":"https://doi.org/10.1111/dom.16313","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539715","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}