Diabetes, Obesity & Metabolism最新文献

{"title":"Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis","authors":"Nikolaos Perakakis MD,&nbsp;Stefan R. Bornstein MD,&nbsp;Andreas L. Birkenfeld MD,&nbsp;Andreas Linkermann MD,&nbsp;Münevver Demir MD,&nbsp;Stefan D. Anker MD,&nbsp;Gerasimos Filippatos MD,&nbsp;Bertram Pitt MD,&nbsp;Peter Rossing MD,&nbsp;Luis M. Ruilope MD,&nbsp;Peter Kolkhof PhD,&nbsp;Robert Lawatscheck MD,&nbsp;Charlie Scott MSc,&nbsp;George L. Bakris MD,&nbsp;FIDELIO-DKD and FIGARO-DKD investigators","doi":"10.1111/dom.15305","DOIUrl":"10.1111/dom.15305","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index &gt;36); elevated transaminases [alanine transaminase (ALT) &gt;33 (males) and &gt;25 IU/L (females)]; and fibrosis-4 (FIB-4) index scores &gt;3.25, &gt;2.67 and &gt;1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma-glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ALT, aspartate aminotransferase and gamma-glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB-4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB-4 subgroups by 52% (&gt;3.25), 39% (&gt;2.67) and 24% (&gt;1.30) (<i>p</i> values for interaction = .01, .13 and .03, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB-4 scores who were at high risk of developing cardiovascular complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"191-200"},"PeriodicalIF":5.8,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.15305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41181541","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":"Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus","authors":"Kaisheng Yuan MD,&nbsp;Bing Wu MD,&nbsp;Ruiqi Zeng MM,&nbsp;Fuqing Zhou MM,&nbsp;Ruixiang Hu MD,&nbsp;Cunchuan Wang MD","doi":"10.1111/dom.15303","DOIUrl":"10.1111/dom.15303","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short-term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk-predicting model using a nomogram.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The prediction model developed in this study holds predictive value for short-term DR following BMS in patients with obesity and T2DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"169-179"},"PeriodicalIF":5.8,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41090424","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":"Ultra rapid lispro (Lyumjev®) shortens time to recovery from hyperglycaemia compared to Humalog® in individuals with type 1 diabetes on continuous subcutaneous insulin infusion","authors":"Jennifer Leohr PhD,&nbsp;Mary Anne Dellva MS,&nbsp;Elizabeth LaBell BS,&nbsp;David E. Coutant PhD,&nbsp;Jorge Arrubla MD,&nbsp;Leona Plum-Mörschel MD,&nbsp;Eric Zijlstra PhD,&nbsp;Tsuyoshi Fukuda PhD,&nbsp;Thomas Hardy MD","doi":"10.1111/dom.15307","DOIUrl":"10.1111/dom.15307","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To compare the time to hyperglycaemia recovery after ultra rapid lispro (URLi; Lyumjev®) versus Humalog in a randomized, double-blind crossover study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Thirty-two adults with type 1 diabetes on continuous subcutaneous insulin infusion participated in two periods: each period included hyperglycaemia induced by a missed mealtime bolus (day 1) and by suspension of basal insulin delivery (day 2). When hyperglycaemia [plasma glucose (PG) &gt;240 mg/dl] occurred, a correction bolus of URLi or Humalog was given and time to hyperglycaemia recovery (PG = 140 mg/dl), pharmacokinetics and glucodynamics were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following a missed mealtime bolus, URLi significantly reduced maximum PG (−13 mg/dl; <i>p</i> = .02), and produced numerically more rapid decline in PG (23 mg/dl/h; <i>p</i> = .07), and faster recovery from hyperglycaemia (−23 min; <i>p</i> = .1) versus Humalog, although differences were not significant. Following basal suspension, URLi significantly reduced maximum PG (−6 mg/dl; <i>p</i> = .02), and produced faster PG decline (24 mg/dl/h; <i>p</i> &lt; .001) and faster recovery from hyperglycaemia (−16 min; <i>p</i> &lt; .01) vs. Humalog. Following a correction bolus of URLi, accelerated insulin lispro absorption was observed versus Humalog: early 50% t_max was reduced by 6 or 12 min, and AUC0-15min was increased 2.5- or 4.3-fold after correction boluses by subcutaneous infusion (day 1) or injection (day 2), respectively (all <i>p</i> &lt; .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>During episodes of hyperglycaemia commonly experienced in people with type 1 diabetes, URLi provided a faster recovery versus Humalog from a missed mealtime bolus or during basal insulin suspension. URLi shows significant acceleration of insulin absorption versus Humalog when boluses are administered by subcutaneous infusion or injection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"215-223"},"PeriodicalIF":5.8,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.15307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41181542","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 effect of metformin on urate metabolism: Findings from observational and Mendelian randomization analyses","authors":"Huajie Dai MD,&nbsp;Tianzhichao Hou MD,&nbsp;Qi Wang MD,&nbsp;Zheng Zhu MD,&nbsp;Yijie Zhu MD,&nbsp;Zhiyun Zhao PhD,&nbsp;Mian Li PhD,&nbsp;Yu Xu PhD,&nbsp;Jieli Lu PhD,&nbsp;Tiange Wang PhD,&nbsp;Guang Ning PhD,&nbsp;Weiqing Wang PhD,&nbsp;Yufang Bi PhD,&nbsp;Jie Zheng PhD,&nbsp;Min Xu PhD","doi":"10.1111/dom.15310","DOIUrl":"10.1111/dom.15310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the effect of metformin on urate metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Using the UK Biobank, we first performed association analyses of metformin use with urate levels, risk of hyperuricaemia and incident gout in patients with diabetes. To explore the causal effect of metformin on urate and gout, we identified genetic variants proxying the glycated haemoglobin (HbA1c)-lowering effect of metformin targets and conducted a two-sample Mendelian randomization (MR) utilizing the urate and gout genetic summary-level data from the CKDGen (n = 288 649) and the FinnGen cohort. We conducted two-step MR to explore the mediation effect of body mass index and systolic blood pressure. We also performed non-linear MR in the UK Biobank (n = 414 055) to show the results across HbA1c levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 18 776 patients with type 2 diabetes in UK Biobank, metformin use was associated with decreased urate [β = −4.3 μmol/L, 95% confidence interval (CI) −7.0, −1.7, <i>p</i> = .001] and reduced hyperuricaemia risk (odds ratio = 0.87, 95% CI 0.79, 0.96, <i>p</i> = .004), but not gout. Genetically proxied averaged HbA1c-lowering effects of metformin targets, equivalent to a 0.62% reduction in HbA1c, was associated with reduced urate (β = −12.5 μmol/L, 95% CI −21.4, −4.2, <i>p</i> = .004). Body mass index significantly mediated this association (proportion mediated = 33.0%, <i>p</i> = .002). Non-linear MR results suggest a linear trend of the effect of metformin on urate reduction across various HbA1c levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The effect of metformin may reduce urate levels but not incident gout in the general population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"242-250"},"PeriodicalIF":5.8,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41100436","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 relationship between glycated haemoglobin and blood glucose-lowering treatment trajectories in type 2 diabetes: The Fremantle Diabetes Study Phase II","authors":"Timothy M. E. Davis FRACP,&nbsp;Wendy Davis PhD","doi":"10.1111/dom.15314","DOIUrl":"10.1111/dom.15314","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To examine the relationships between glycaemia and treatment complexity over 6 years in well-characterized community-based people with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Fremantle Diabetes Study Phase II participants who had type 2 diabetes with glycated haemoglobin (HbA1c) and blood glucose-lowering therapy (BGLT) data over 6 years were included. Group-based multi-trajectory modelling identified combined HbA1c/BGLT trajectory subgroups for diabetes durations of ≤1.0 year (Group 1; n = 160), &gt;1.0 to 10.0 years (Group 2; n = 382;) and &gt;10.0 years (Group 3; n = 357). Multinomial regression was used to identify baseline associates of subgroup membership.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The optimum numbers of trajectory subgroups were three in Group 1 (low, medium, high) and four in Groups 2 and 3 (low, low/high medium, high). Each low trajectory subgroup maintained a mean HbA1c concentration of &lt;53 mmol/mol (&lt;7.0%) on lifestyle measures, or monotherapy (Group 3). All five medium subgroups had stable HbA1c trajectories at &lt;58 mmol/mol (&lt;7.5%) but required increasing oral BGLT, or insulin (Group 3, high medium). The Group 1 high subgroup showed a falling then increasing HbA1c with steady progression to insulin. The high subgroups in Groups 2 and 3 showed stable HbA1c profiles at means of approximately 64 mmol/mol (8.0%) and 86 mmol/L (10.0%), respectively, on insulin. Non-Anglo Celt ethnicity, central obesity and hypertriglyceridaemia were strongly associated with Group 1 high subgroup membership. Younger age at diagnosis and central obesity were independent associates of the most adverse HbA1c trajectories in Groups 2 and 3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data demonstrate diabetes duration-dependent heterogeneity in glycaemic and treatment profiles and related clinical and laboratory variables, which have implications for management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"283-292"},"PeriodicalIF":5.8,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.15314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099223","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 impact of type 2 diabetes and glycaemic control on mortality and clinical outcomes in hospitalized patients with COVID-19 in the capital region of Denmark","authors":"Vivian Kliim-Hansen MD,&nbsp;Karl S. Johansson MD,&nbsp;Lærke S. Gasbjerg PhD,&nbsp;Espen Jimenez-Solem PhD,&nbsp;Tonny S. Petersen MD,&nbsp;Martin E. Nyeland PhD,&nbsp;Matilde Winther-Jensen PhD,&nbsp;Mikkel Zöllner Ankarfeldt PhD,&nbsp;Miriam G. Pedersen PhD,&nbsp;Anne-Marie Ellegaard PhD,&nbsp;Filip K. Knop MD,&nbsp;Mikkel B. Christensen MD","doi":"10.1111/dom.15302","DOIUrl":"10.1111/dom.15302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To explore the impact of type 2 diabetes (T2D), glycaemic control and use of glucose-lowering medication on clinical outcomes in hospitalized patients with COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>For all patients admitted to a hospital in the Capital Region of Denmark (1 March 2020 to 1 December 2021) with confirmed COVID-19, we extracted data on mortality, admission to intensive care unit (ICU), demographics, comorbidities, medication use and laboratory tests from the electronic health record system. We compared patients with T2D to patients without diabetes using Cox proportional hazards models adjusted for available confounding variables. Outcomes were 30-day mortality and admission to an ICU. For patients with T2D, we also analysed the association of baseline haemoglobin A1c (HbA1c) levels and use of specific glucose-lowering medications with the outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 4430 patients were analysed, 1236 with T2D and 2194 without diabetes. The overall 30-day mortality was 19% (n = 850) and 10% (n = 421) were admitted to an ICU. Crude analyses showed that patients with T2D both had increased mortality [hazard ratio (HR) 1.37; 95% CI 1.19-1.58] and increased risk of ICU admission (HR 1.28; 95% CI 1.04-1.57). When adjusted for available confounders, this discrepancy was attenuated for both mortality (adjusted HR 1.13; 95% CI 0.95-1.33) and risk of ICU admission (adjusted HR 1.01; 95% CI 0.79-1.29). Neither baseline haemoglobin A1c nor specific glucose-lowering medication use were significantly associated with the outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Among those hospitalized for COVID-19, patients with T2D did not have a higher risk of death and ICU admission, when adjusting for confounders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"160-168"},"PeriodicalIF":5.8,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.15302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093641","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":"Breaking a feedback loop: A reassessment of an investigator initiated OS-AID study","authors":"Katarina Braune MD,&nbsp;Sufyan Hussain MD,&nbsp;Rayhan Lal MD,&nbsp;Scott Leibrand BS,&nbsp;Dana M. Lewis BA,&nbsp;Shane O'Donnell PhD","doi":"10.1111/dom.15301","DOIUrl":"10.1111/dom.15301","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"400-402"},"PeriodicalIF":5.8,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41097533","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":"Abolishing β-arrestin recruitment is necessary for the full metabolic benefits of G protein-biased glucagon-like peptide-1 receptor agonists","authors":"Charlotte E. Hinds PhD,&nbsp;Ellie Peace BSc,&nbsp;Shiqian Chen MRes,&nbsp;Iona Davies MRes,&nbsp;Liliane El Eid MRes,&nbsp;Alejandra Tomas PhD,&nbsp;Tricia Tan MD,&nbsp;James Minnion PhD,&nbsp;Ben Jones MD,&nbsp;Stephen R. Bloom MD","doi":"10.1111/dom.15288","DOIUrl":"10.1111/dom.15288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Earlier studies have shown that peptide glucagon-like peptide-1 receptor (GLP-1R) agonists with reduced β-arrestin recruitment show enhanced anti-hyperglycaemic efficacy through avoidance of GLP-1R desensitization. However, the ligand modifications needed to decrease β-arrestin recruitment usually also reduces GLP-1R affinity, therefore higher doses are needed. Here we aimed to develop new, long-acting, G protein-biased GLP-1R agonists with acute signalling potency comparable with semaglutide, to provide insights into specific experimental and therapeutic scenarios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>New GLP-1R agonist peptides were assessed using a variety of in vitro and in vivo assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>First, we show that very substantial reductions in β-arrestin recruitment efficacy are required to realize fully the benefits of GLP-1R agonism on blood glucose lowering in mice, with more moderate reductions being less effective. Secondly, our lead compound (SRB107) performs substantially better than semaglutide for effects on blood glucose and weight loss, which may be jointly attributable to its biased agonist action and protracted pharmacokinetics. Thirdly, we show that biased agonist-specific GLP-1R internalization profiles occur at clinically relevant pharmacological concentrations. Finally, we show that SRB107 cAMP signalling is differentially modulated by single and double <i>GLP1R</i> coding variants seen in human populations, with implications for GLP-1R agonist pharmacogenomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Completely abolishing β-arrestin recruitment improves the anti-hyperglycaemic effects of GLP-1R agonists in mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"65-77"},"PeriodicalIF":5.8,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.15288","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101292","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":"Glycaemic control, body weight, and safety of tirzepatide versus dulaglutide by baseline glycated haemoglobin level in Japanese patients with type 2 diabetes: A subgroup analysis of the SURPASS J-mono study","authors":"Takeshi Osonoi MD,&nbsp;Tomonori Oura MSc,&nbsp;Tetsuaki Hirase MD","doi":"10.1111/dom.15296","DOIUrl":"10.1111/dom.15296","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate glycaemic control, body weight, and safety outcomes following treatment with tirzepatide or dulaglutide in patients with type 2 diabetes (T2D) with a baseline haemoglobin (HbA1c) level of ≤8.5% (≤69 mmol/mol) versus &gt;8.5% (&gt;69 mmol/mol).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>SURPASS J-mono was a 52-week, multicentre, randomized, double-blind, parallel, active-controlled, phase 3 study conducted in Japan. In this exploratory subgroup analysis of SURPASS J-mono, we examined mean change in HbA1c and body weight and the incidence of adverse events (AEs) in patients with a baseline HbA1c of ≤8.5% versus &gt;8.5% after treatment with tirzepatide (5, 10 or 15 mg) or dulaglutide 0.75 mg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 636 randomized participants, 203 had a baseline HbA1c of &gt;8.5% and 433 had a baseline HbA1c of ≤8.5% (range ≥7.0% to ≤10.0%). Both subgroups showed significantly greater reductions in HbA1c and body weight with any-dose tirzepatide versus dulaglutide 0.75 mg, with greater HbA1c reductions observed in patients with a baseline HbA1c of &gt;8.5% treated with tirzepatide (least squares mean [LSM] differences of −3.13% to −3.86%) or dulaglutide (LSM −1.81%) compared with patients with a baseline HbA1c of ≤8.5% (LSM −2.00% to −2.32%) or dulaglutide (LSM −1.05%; treatment-by-baseline HbA1c subgroup interaction <i>P</i> ≤ 0.001). For the tirzepatide treatment arms, LSM change from baseline in body weight ranged from −6.7 to −10.7 kg for the baseline HbA1c ≤8.5% subgroup and from −4.0 to −10.6 kg for the baseline HbA1c &gt;8.5% subgroup, compared with −0.6 kg and −0.4 kg, respectively, for the dulaglutide arm. The incidence of hypoglycaemia was low, with no substantial difference in hypoglycaemia or treatment-emergent AEs between subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Regardless of baseline HbA1c (≤8.5% or &gt;8.5%), tirzepatide at doses of 5, 10 and 15 mg is effective in Japanese patients with T2D compared with dulaglutide 0.75 mg in terms of glycaemic control and body weight reduction, with an adequate safety profile consistent with previous reports.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"126-134"},"PeriodicalIF":5.8,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.15296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41090613","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":"Incremental burden on health-related quality of life, health service utilization and direct medical expenditures associated with cognitive impairment among non-institutionalized people with diabetes aged 65 years and older","authors":"Dawei Guan MD,&nbsp;Motomori O. Lewis BS,&nbsp;Piaopiao Li MS,&nbsp;Yichen Zhang PhD,&nbsp;Ping Zhang PhD,&nbsp;Shichao Tang PhD,&nbsp;Joshua Brown PharmD,&nbsp;Jingchuan Guo MD,&nbsp;Yongkang Zhang PhD,&nbsp;Hui Shao MD","doi":"10.1111/dom.15313","DOIUrl":"10.1111/dom.15313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To quantify the incremental health and economic burden associated with cognitive impairment (CI) among non-institutionalized people with diabetes ≥65 years in the United States.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Using 2016-2019 Medical Expenditure Panel Surveys data, we identified participants ≥65 years with diabetes. We used propensity score weighting to quantify the CI-associated incremental burden on health-related quality of life measured by the 12-item Short Form Survey (SF-12), including the mental component summary score, physical component summary score and health utility. We also compared the annual health service utilization and expenditures on ambulatory visits, prescriptions, home care, emergency room (ER), hospitalizations and total annual direct medical expenditures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 5094 adults aged ≥65 with diabetes, of whom 804 had CI. After propensity score weighting, CI was associated with a lower mental component summary score (−8.4, <i>p</i> &lt; .001), physical component summary score (−5.2, <i>p</i> &lt; .001) and health utility (–0.12, <i>p</i> &lt; .001). The CI group had more ambulatory visits (+4.4, <i>p</i> = .004) and prescriptions (+9.9, <i>p</i> &lt; .001), with higher probabilities of having home care (+11.3%, <i>p</i> &lt; .001) and ER visits (+8.2%, <i>p</i> = .001). People with CI spent $5441 (<i>p</i> &lt; .001) more annually, $2039 (<i>p</i> = .002) more on prescriptions, $2695 (<i>p</i> &lt; .001) more on home care and $118 (<i>p</i> &lt; .001) more on ER visits. There is no statistically significant difference in the utilization and expenditure of hospitalizations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CI was associated with worse health-related quality of life, higher health service utilization and expenditures. Our findings can be used to monitor the health and economic burden of CI in non-institutionalized older persons with diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"26 1","pages":"275-282"},"PeriodicalIF":5.8,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41091745","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}