Diabetes Obesity Research Articles

Kidney transplant outcomes of Māori and Pasifika people receiving transplantation in Australia: an Australia and New Zealand Dialysis and Transplant Registry study.

The numbers of Māori and Pasifika peoples with kidney failure living in Australia are rising. However, data describing outcomes of those proceeding to transplantation are limited. This study describes clinical outcomes of Māori and Pasifika peoples who received a kidney transplant in Australia. This study describes clinical outcomes of Maori and Pasifika peoples who received a kidney transplant in Australia. A retrospective review was conducted of kidney transplant recipients aged ≥18 years receiving their first graft between 1 January 2002 and 31 December 2021, as recorded in the Australia and New Zealand Dialysis and Transplant Registry. The primary outcome was death-censored graft survival. Secondary outcomes included delayed graft function (DGF), rejection and patient survival. Of 12 543 transplant recipients, mean age was 50 years and the majority identified as male sex. A total of 89 patients identified as Māori and 313 as Pasifika. Māori and Pasifika patients were more likely to have diabetic kidney disease or obesity at time of transplantation (body mass index > 30 kg/m2) and be current or former smokers compared to other ethnicities. Times to graft loss were shorter for Māori (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.36-3.11) and Pasifika (adjusted HR 1.78, 95% CI 1.39-2.029, P < 0.001) people compared to other ethnicities. The incidences of DGF were significantly higher in the Māori (30%) and Pasifika groups (28%) compared with 22% for other ethnicities (P < 0.005). Overall patient survival was comparable (Māori HR 0.93, 95% CI 0.57-1.49, P = 0.75; Pasifika HR 1.18, Cl 0.88-1.60, P = 0.26). Times to graft loss for Māori and Pasifika kidney transplant patients were shorter than for other ethnicities.

Addressing the essentials of the recent guidelines for managing patients with metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of end-stage liver disease and liver transplantation in the Western world, with an approximate prevalence of 30% worldwide which is continuously rising. It is characterized by intrahepatic fat deposition along with at least one cardiometabolic risk factor, such as diabetes mellitus, obesity, hypertriglyceridemia, and hypertension. MASLD consists of a spectrum of liver diseases ranging from simple liver steatosis to steatohepatitis, liver fibrosis, and cirrhosis. Recently, the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD), and the European Association for the Study of Obesity (EASO) released the latest guidelines regarding the management of patients with MASLD. This article highlights the critical points of these guidelines and emphasizes problematic issues that need further evaluation.

MetAP2 as a Therapeutic Target for Obesity and Type 2 Diabetes: Structural Insights, Mechanistic Roles, and Inhibitor Development

Type 2 Diabetes Mellitus (T2DM) and obesity are globally prevalent metabolic disorders characterized by insulin resistance, impaired glucose metabolism, and excessive adiposity. Methionine aminopeptidase 2 (MetAP2), an intracellular metalloprotease, has emerged as a promising therapeutic target due to its critical role in regulating lipid metabolism, energy balance, and protein synthesis. This review provides a comprehensive analysis of MetAP2, including its structural characteristics, catalytic mechanism, and functional roles in the pathophysiology of T2DM and obesity. The unique architecture of MetAP2’s active site and its interactions with substrates are examined to elucidate its enzymatic function. The review also explores the development of MetAP2 inhibitors, focusing on their mechanisms of action, preclinical and clinical findings, and therapeutic potential. Special emphasis is placed on docking studies to analyze the binding interactions of six key inhibitors (fumagillin, TNP-470, beloranib, ZGN-1061, indazole, and pyrazolo[4,3-b]indole) with MetAP2, revealing their structural determinants for efficacy and specificity. These findings underscore the potential of MetAP2 as a therapeutic target and provide valuable insights for the rational design of next-generation inhibitors to address obesity and T2DM.

An exploratory analysis of glucagon-like peptide-1 (GLP-1) agonists and biosimilars: A literature review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are at the forefront of treating the global health crisis of diabetes mellitus (DM) and obesity. However, the demand for GLP-1 RAs has far outstripped its supply and comes with a high monthly cost. Thus, the development of GLP-1 RA biosimilars can potentially address these barriers by providing greater access to medications that provide clinical outcomes similar to those of the reference products. A narrative review was conducted to examine the current and future developments for GLP-1 RA biosimilars. Liraglutide and semaglutide are the predominant GLP-1 RAs being investigated for the development of biosimilars. Preliminary liraglutide biosimilar comparisons to reference liraglutide have demonstrated similar clinical efficacy and safety profiles. Semaglutide and beinaglutide biosimilars are currently under investigation as well. With the growing popularity of GLP-1 RAs, accessibility and affordability remain a challenge as monthly costs without insurance for liraglutide, semaglutide and tirzepatide are $1418, $892, and $974 respectively. This trend negatively impacts patients with obesity and DM as well as patients who can utilize it for off-label indications for conditions that benefit from weight loss such as obstructive sleep apnoea and non-alcoholic fatty liver disease. A substantial number of pharmaceutical and healthcare companies worldwide are conducting clinical trials on their GLP-1 RA biosimilars. Preliminary results from liraglutide biosimilars are promising, and several semaglutide biosimilars are currently being investigated. Future research should focus on conducting comparative head-to-head trials to determine the clinical outcomes between biosimilars and reference products.

Efficacy of red algae and artichoke extracts in disrupting antioxidant/PI3K/RBP-4 pathway in high-fat diet-induced metabolic disorders in rats

BackgroundInsulin resistance (IR) leads to various metabolic abnormalities, including diabetes mellitus, obesity, nonalcoholic steatohepatitis, and neurodegenerative disorders. Natural products rich in nontoxic phytochemicals are cost-effective and widely used to manage insulin resistance, reducing drug interactions. Artichoke stems and red algae contain several phytochemical compounds that exert antioxidant and anti-inflammatory effects.AimThis study aims to explore and compare the preventive and therapeutic effects of red algae and artichoke stem extracts against high-fat diet-induced insulin resistance and then compare their impacts with those of the reference drug metformin, which is commonly used for treating type 2 diabetes.MethodsThe animals were fed a high-fat diet for eight weeks to induce insulin resistance. The plants were then treated orally with 100 mg/kg body weight red algae, artichoke extracts, or metformin per day for 14 days. The protective rat groups received the extracts at the same dose for 14 days before being fed the high-fat diet for eight weeks. Commercial kits and standardized methods were used to measure blood diabetic profiles (glucose, insulin, lipid profile, fructosamine, and retinol-binding protein-4 (RBP-4)) and liver oxidative stress parameters, nuclear factor-κβ (NF-κβ), peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), retinol-binding protein-4 (RBP-4), and phosphatase and tensin homolog (PTEN).ResultsOur results showed that both extracts inhibited NF-κB and PTEN while enhancing PI3K, RPB-4, and PPAR-γ due to their potent antioxidant properties. They also increased insulin sensitivity, as reflected by reduced blood glucose and lipid profile levels and normalized fructosamine and RBP-4. Additionally, these extracts prevent oxidative stress-induced hepatic and nephric cell dysfunction, as confirmed by improved blood, liver, and kidney parameters.ConclusionTherefore, both extracts could be good antioxidant treatments for oxidative stress-related insulin resistance because they restore the balance of the PI3K/PPAR-γ/RBP-4 pathway. This pathway increases glucose uptake, stops gluconeogenesis, speeds up lipid metabolism, and stops the inflammation pathway.

SGLT2 inhibitors reduce epicardial adipose tissue more than GLP-1 agonists or exercise interventions in patients with type 2 diabetes mellitus and/or obesity: A systematic review and network meta-analysis.

Epicardial adipose tissue (EAT) plays a significant role in several cardiovascular diseases. As a correctable risk factor and potential therapeutic target, reducing EAT has multiple cardiovascular benefits, especially in those with abnormal glucolipid metabolism. The objective of this research was to compare the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, and exercise on the thickness of EAT and indicators of glucolipid metabolism in people with type 2 diabetes mellitus (T2DM), obesity, and T2DM with obesity. We searched four electronic databases: PubMed, EMBASE, the Cochrane Library, and Web of Science for articles before 31 January 2024, regardless of language. We included randomized controlled trials and a small number of case-control studies in this network meta-analysis. Differences in mean changes in EAT, body mass index, and glucolipid metabolism-related metrics were assessed. A comprehensive analysis was conducted on 16 trials (15 randomized controlled trials and one case-control study), comprising a total of 867 people. SGLT2 inhibitors were significantly better at reducing EAT than placebo (standard mean different [SMD] = -0.85 cm [95% confidence interval (CI) -1.39, -0.31]); a similar result was observed for exercise compared with placebo (SMD = -0.78 cm [95% CI -1.37, -0.18]). SGLT2 inhibitors were also significantly better at reducing EAT than GLP-1 agonists and conventional hypoglycaemic therapy (e.g., metformin or insulin; SMD = -0.74 cm [95% CI -1.45, -0.02] and SMD = -1.69 cm [95% CI -2.38, -0.99], respectively). SGLT2 inhibitors were significantly better than placebo at reducing body mass index (MD = -0.90 kg/m2 [95% CI -1.14, -0.66]) and glycosylated haemoglobin (MD = -0.52% [95%CI -0.86, -0.18]). A similar result was observed when comparing GLP-1 agonists and placebo (MD = -0.48% [95% CI -0.93, -0.03]). Changes in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were not statistically significant between interventions. SGLT2 inhibitors have a distinct advantage over both placebo and other therapies at lowering EAT thickness, a result supported by direct comparisons and surface under the cumulative ranking curve analysis. Therefore, SGLT2 inhibitors should be prioritized as a treatment to reduce EAT in individuals with aberrant glucolipid levels, such as patients with T2DM and/or obesity.

Role of Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors in Weight Loss: Understanding the Clinical Evidence

Obesity is ubiquitous, affecting millions of people all over the world. Its prevalence is increasing day by day in all age groups, ranging from children to adolescents to adults. It has a significant impact on the overall quality of life. Obesity has a strong relationship with various chronic conditions, including type 2 diabetes mellitus. The risk of developing diabetic mellitus considerably increases in obese individuals. Similarly, obesity in diabetic patients increases their probability of developing serious complications. Moreover, the optimal approach to managing diabetes mellitus (type 2) and obesity should be carried out by means of sustained weight loss and glycemic control. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to be a revolutionary class of medications with noteworthy weight-loss benefits in addition to their ability to lower blood sugar levels. These remarkable benefits are mentioned in detail in several different clinical trials. Additionally, diverse mechanisms have also been demonstrated comprehensively via which SGLT-2 inhibitors put forth their function of weight loss. FDA-approved SGLT2 inhibitors show a unique mechanism of action by inhibiting the reabsorption of glucose in the renal proximal tubule. By excreting glucose in the urine and by visceral fat lipolysis, these drugs provide a new avenue for weight reduction. SGLT2 inhibitors are now fundamental parts of weight-loss regimens in patients with type 2 diabetes, going beyond their original role as anti-diabetic medications. This article attempts to review the up-to-date literature on the effectiveness of this particular contemporary function of SGLT2 inhibitors.

Glucagon-like peptide-1 receptor agonist use and the risk of residual gastric content and aspiration in patients undergoing gastrointestinal endoscopy: a systematic review and a meta-analysis.

GLP-1 receptor agonists are used for type 2 diabetes mellitus and obesity, but safety concerns have been raised for users undergoing gastrointestinal endoscopy, regarding retained food and aspiration events. We aim to compare the risk of complications for GLP-1 users and non-users undergoing endoscopy. We conducted a systematic review and meta-analysis (PROSPERO Registration: CRD42024556732). A systematic search in PubMed, Scopus, Web of Science, and Cochrane Central was performed from their inception until 1st July, 2024 (Embase from 1974 to 28th June, 2024). Double-arm human adult original studies (observational, RCT) with a sample size of 20 or more undergoing EGD or endoscopy with no GLP-1 RA use in the control arm were searched. Studies were excluded if they were single-arm and had any use of GLP-1 before the procedure in the control arm. Residual gastric contents (RGC), aspiration pneumonia, and premature endoscopy termination were the main outcomes. The random-effects model was used to pool and get final effect estimates. 23 observational studies were selected consisting of 262,018 patients. GLP1 RA users had a statistically significant increase in the risk of RGC (OR 4.54, 95% CI 3.30-6.24, p<0.00001, I2= 68%) and premature endoscopy termination (OR 4.54, 95% CI 3.05-6.75, p<0.00001, I2= 0%). There was no significant difference in the risk of aspiration pneumonia (OR 0.96, 95% CI 0.53-1.75, p=0.90, I2= 70%). A significant reduction was seen in RGC when EGD & colonoscopy (OR= 0.28 [0.22, 0.36], p<0.00001; I2= 0%) were done the same day vs EGD alone (Figure 1 Graphical abstract). GLP-1 RA use was associated with an increased risk of RGC and premature endoscopy termination, but no significant difference was found in the risk of aspiration pneumonia patients undergoing endoscopy.

“Prevalence And Risk Factors Of Cardiovascular Diseases Among Adults Of Selected Rural Community At Siliguri, West Bengal.”

Background: Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels and include coronary heart disease, cerebrovascular disease, rheumatic heart disease, and other conditions. More than four out of five CVD deaths are due to heart attacks and strokes, and one-third of these deaths occur prematurely. Since there are not many studies on these rural communities to identify the prevalence rate and associated risk factors, so the investigators have selected this study for proper risk identification, assessing the prevalence rate and educating and motivating adults on appropriate screening, prevention, and treatment. Materials and Methods: A descriptive cross sectional study was conducted in a rural community in West Bengal, India. Total 100 numbers of adults were selected for the study. The prevalence rate and risk factors of cardiovascular diseases were assessed using the structured interview schedule and physical measurements. Results: The result reveals that regarding behavioural risk factors of Cardiovascular diseases, among the 100 participants, 60(60%) consume Tobacco products and 81 (81%) consume Alcohol, Adequate consumption of Fruits and vegetables is only 10(10%) i.e. more than 5 times in a week, 19(19%) perform sufficient physical activity/exercise i.e more than 150 minutes/week. Regarding physical assessments, the overweight was 19(19%) and obesity was 9(9%), the abdominal obesity in males was 31(31%), and in females was 35 (35%). The prevalence rate of Hypertension was 23(23%), Stroke was 2(2%), Coronary Heart Disease was 7(7%), High blood cholesterol was 2(2%), and Diabetes Mellitus was 11(11%). Conclusion: The study demonstrated the high burden of fatal CVDs and identified the impact of CVDs risk factors such as hypertension, self-reported diabetes, high cholesterol, smoking, alcohol, and abdominal obesity. The significant incidence of CVDs risk factors in the rural communities, particularly among those who are overweight or obese, necessitates early clinical identification, referral and appropriate management of clients in primary health care settings

Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity

It is well recognized that type II Diabetes (T2D) and overweight/obesity are established risk factors for stroke, worsening also their consequences. However, the underlying mechanisms by which these disorders aggravate outcomes are not yet clear limiting the therapeutic opportunities. To fill this gap, we characterized, for the first time, the effects of T2D and obesity on the brain repair mechanisms occurring 7 days after stroke, notably glial scarring. In the present study, by performing a 30-minute middle cerebral artery occlusion (MCAO) on db/db (obese diabetics mice) and db/+ (controls) mice, we demonstrated that obese and diabetic mice displayed larger lesions (i.e. increased infarct volume, ischemic core, apoptotic cell number) and worsened neurological outcomes compared to their control littermates. We then investigated the formation of the glial scar in control and db/db mice 7 days post-stroke. Our observations argue in favor of a stronger and more persistent activation of astrocytes and microglia in db/db mice. Furthermore, an increased deposition of extracellular matrix (ECM) was observed in db/db vs control mice (i.e. chondroitin sulfate proteoglycan and collagen type IV). Consequently, we demonstrated for the first time that the db/db status is associated with increased astrocytic and microglial activation 7 days after stroke and resulted in higher deposition of ECM within the damaged area. Interestingly, the injury-induced neurogenesis appeared stronger in db/db as shown by the labeling of migrating neuroblast. This increase appeared correlated to the larger size of lesion. It nevertheless raises the question of the functional integration of the new neurons in db/db mice given the observed dense ECM, known to be repulsive for neuronal migration. Carefully limiting glial scar formation after stroke represents a promising area of research for reducing neuronal loss and limiting disability in diabetic/obese patients.

Association of overweight and obesity with gestational diabetes mellitus among pregnant women attending antenatal care clinics in Addis Ababa, Ethiopia: a case-control study

ObjectiveMaternal obesity and gestational diabetes mellitus (GDM) are becoming major public health concerns in developing countries. Understanding their relationship can help in developing contextually appropriate and targeted prevention strategies and...

Effectiveness of glucagon-like peptide-1 receptor agonists for reduction of body mass index and blood glucose control in patients with type 2 diabetes mellitus and obesity: A retrospective cohort study and difference-in-difference analysis

ObjectiveThis study aimed to evaluate the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RA) in reducing body mass index (BMI) and blood glucose levels in individuals with type 2 diabetes mellitus...

A biological rhythm in the hypothalamic system links sleep-wake cycles with feeding-fasting cycles

The hypothalamus senses the appetite-regulating hormones and also coordinates the metabolic function in alignment with the circadian rhythm. This alignment is essential to maintain the physiological conditions that prevent clinically important comorbidities, such as obesity or type-2 diabetes. However, a complete model of the hypothalamus that relates food intake with circadian rhythms and appetite hormones has not yet been developed. In this work, we present a computational model that accurately allows interpreting neural activity in terms of hormone regulation and sleep-wake cycles. We used a conductance-based model, which consists of a system of four differential equations that considers the ionotropic and metabotropic receptors, and the input currents from homeostatic hormones. We proposed a logistic function that fits available experimental data of insulin hormone concentration and added it into a short-term ghrelin model that served as an input to our dynamical system. Our results show a double oscillatory system, one synchronized by light-regulated sleep-wake cycles and the other by food-regulated feeding-fasting cycles. We have also found that meal timing frequency is highly relevant for the regulation of the hypothalamus neurons. We therefore present a mathematical model to explore the plausible link between the circadian rhythm and the endogenous food clock.

Risk of biliary diseases in patients with type 2 diabetes or obesity treated with tirzepatide: A meta-analysis.

To investigate the risk of biliary diseases in patients with type 2 diabetes mellitus (T2DM) or obesity treated with tirzepatide. Literature searches were performed using the PubMed, Web of Science, Cochrane Library, and CNKI databases until 20 May 2024. Randomized controlled studies (RCTs) investigating the safety of tirzepatide vs placebo/other hypoglycemic drugs in patients with T2DM or obesity were included. The safety outcomes mainly included the incidence of cholelithiasis, pancreatitis, cholecystitis, and gallbladder/biliary diseases. Cochrane Collaboration's tool for assessing the risk of bias was used to assess the quality of literature. Heterogeneity was evaluated using I2 statistics. A total of 12 high-quality RCTs (involving 12,351 patients) were included. The results of meta-analysis showed that tirzepatide was associated with gallbladder/biliary diseases (RR = 1.52; 95%CI: 1.17-1.98; I2 = 0%, P = 0.76) and cholelithiasis (RR = 1.67; 95%CI: 1.14-2.44; I2 = 0%, P = 0.95). Subgroup analysis based on the dose of tirzepatide found no dose-response relationship between different doses of tirzepatide and the risk of gallbladder/biliary diseases and cholelithiasis. Based on the data currently available, tirzepatide is associated with the development of cholelithiasis in patients. However, the findings from RCTs still need to be further investigated in many post-marketing safety surveillance programs.

The potential role of targeting the leptin receptor as a treatment for breast cancer in the context of hyperleptinemia: a literature review.

Since cancer is becoming a leading cause of death worldwide, efforts should be concentrated on understanding its underlying biological alterations that would be utilized in disease management, especially prevention strategies. Within this context, multiple bodies of evidence have highlighted leptin's practical and promising role, a peptide hormone extracted from adipose and fatty tissues with other adipokines, in promoting the proliferation, migration, and metastatic invasion of breast carcinoma cells. Excessive blood leptin levels and hyperleptinemia increase body fat content and stimulate appetite. Also, high leptin level is believed to be associated with several conditions, including overeating, emotional stress, inflammation, obesity, and gestational diabetes. It has been noted that when leptin has impaired signaling in CNS, causing the lack of its normal function in energy balance, it results in leptin resistance, leading to a rise in its concentration in peripheral tissues. Our research paper will shed highlighting on potentially targeting the leptin receptor and its cellular signaling in suppressing breast cancer progression.

Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis.

The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome. This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits. In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.

Tirzepatide for Obesity Treatment and Diabetes Prevention.

Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified. Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

Abstract 4134308: Re-evaluating the safety profile of Semaglutide: An updated meta-analysis

Background: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. Methods: Randomized controlled trials assessing the safety of semaglutide versus placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia and new-onset neoplasm. Results: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. (See Figure 1) Conclusion: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice.

Abstract 4138482: The burden of ischemic heart disease, hypertension, diabetes mellitus, and obesity among older Latino and Chinese adults with and without limited English proficiency

Background: An estimated 15% of Latinos and 34% of Chinese in the US have limited English proficiency (LEP). However, there is limited information on whether ischemic heart disease (IHD) and its risk factors (hypertension, HTN; diabetes mellitus, DM; and obesity) vary by LEP vs. non-LEP status in these ethnic groups. This information may be valuable for targeting healthcare interventions. METHODS: This cross-sectional study used data for Latino (79,588 men, 85,560 women), and Chinese (25,944 men, 32,586 women) adults aged 50-79 years who were members of a northern California health plan in 2018-2019. Age, sex, language preference, obesity (BMI ≥30 for Latino and ≥27.5 kg/m2 for Chinese), and IHD, HTN, and DM diagnoses were abstracted from electronic health records. LEP was defined as Spanish/Chinese vs. English (non-LEP) language preference. Prevalence was compared by LEP status within age-sex groups. Modified Poisson regression was used to estimate age-adjusted prevalence ratios. RESULTS: Among Latino men aged 50-64 (57,835, 39% LEP) and 65-79 (21,753, 30% LEP) and Chinese men aged 50-64 (14,751, 42% LEP) and 65-79 (11,193, 40.3% LEP) years, IHD prevalence was lower in LEP vs. non-LEP (Latino: 3.5% vs. 6.0% and 13.8% vs. 19.0%; Chinese: 3.6% vs. 5.8% and 11.9% vs. 14.5%). Similar trends were observed in women, but IHD prevalence was much lower. Among Latino and Chinese men, HTN and obesity prevalence was lower, but DM was similar. For women, HTN was similar, but DM was higher in LEP Latina (age 50-79) and Chinese adults (age 65-79), while obesity was lower in LEP Chinese but not Latina adults. Differences remained after adjusting for age (aPR). CONCLUSION: The burden of IHD, HTN, and obesity is similar or lower among LEP vs. non-LEP Latino and Chinese adults, while the burden of DM is higher for LEP vs. non-LEP Latina and Chinese women. These findings suggest that while DM prevalence is already high, acculturation is associated with higher risk of developing some chronic CVD conditions, underscoring the need for targeted healthcare interventions. Further research is needed to explore mechanisms driving these disparities and to develop culturally appropriate strategies to improve health outcomes.

Dual Benefits of Tirzepatide: Anti-Obesity and Antidiabetic Efficacy: A Mini review

Background: Diabetes mellitus and obesity are two linked conditions that have reached epidemic proportions globally. According to a study published in 2023 by the Indian Council of Medical Research (ICMR) , India has 10.1 crore people with diabetes. The prevalence of obesity, especially abdominal obesity is increasing continuously due to the intake of foods that are high in carbohydrates and processed foods. Obesity can cause inflammation, insulin resistance, and pancreas overload which lead to diabetes mellitus. Main Body: The present - review focuses on the medicinal chemistry, organic chemistry and pharmacological aspects of trizepatide. Trizepatide is a new chemical moiety that shows dual agonist activity of glucagon-like peptide-1(GLP-1) receptors and glucose-dependent insulinotropic polypeptide(GIP).Trizepatide is a synthetic peptide that constitutes 39 amino acids. Trizepatide has a potent hypoglycemic effect , and it has antiobesity effects because of its adverse effect. Conclusion : Trizepatide's capacity to lower blood sugar and promote weight loss makes it an effective treatment for these conditions. Further research will confirm its safety and long-term advantages. Keywords : Trizepatide , Diabetes mellitus , Obesity, Hypoglycaemia