Use of Tirzepatide in Adults with Type 2 Diabetes Mellitus: Scientific Evidence and Practical Aspects.

Tirzepatide is a novel antidiabetic medication a single-molecule, agonist to the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. It is approved in the USA and EU for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Due to the potential novelty represented by incorporating tirzepatide to clinical practice, we aim to review practical aspects of tirzepatide use in T2DM and the supporting scientific evidence. A group of ten endocrinologists involved as investigators in the phase 3 SURPASS clinical trial program followed a nominal group technique, a qualitative research methodology designed as a semi-structured group discussion to reach a consensus on the selection of a set of practical aspects. The scientific evidence for tirzepatide has been reviewed with respect to a number of patients' clinical profiles and care goals. Information of interest related to adverse events, special warnings and precautions, and other considerations for tirzepatide use has been included. Finally, information provided to the patients has been summarized. The practical aspects reported herein may be helpful in guiding physicians in the use of tirzepatide and contribute to optimizing the management of T2DM.

A Retrospective Comparison of Phaco-Tube vs. Phaco-Trabeculectomy in Glaucoma Patients.

PURPOSE: To compare surgical outcomes of phacoemulsification combined with Baerveldt implantation (phaco-tube) or trabeculectomy with mitomycin-C (MMC) (phaco-trab) in patients without prior incisional ocular surgery. DESIGN: Single-center, retrospective, comparative case series. PARTICIPANTS: A total of 90 patients underwent surgical treatment, including 45 patients in the phaco-tube group and 45 patients in the phaco-trab group. METHODS: Eligible patients were identified using current procedural terminology (CPT) codes, and their medical records were retrospectively reviewed. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of surgical failure (IOP ≤5 mmHg or >21 mmHg or reduced <20% from baseline on two consecutive study visits after 3 months, reoperations for glaucoma, or experienced loss of light perception vision). Patients who had successful surgical outcomes without use of glaucoma medications were classified as complete successes, while those that used glaucoma medications were classified as qualified successes. Secondary outcome measures were visual acuity (VA), visual field mean deviation (VFMD), intraocular pressure (IOP), glaucoma medication use, and complications. RESULTS: The cumulative probability of failure was 6.7% in the phaco-tube group and 32.8% in the phaco-trab group after 3 years (P= 0.005; Restricted Mean Survival Time = 5.9 months, 95% CI = 1.4 to 10.4 months). IOP was 13.1 ± 3.4 mmHg in the phaco-tube group and 13.3 ± 6.2 mmHg in the phaco-trab group at 3 years (P= 0.90), and the number of glaucoma medications was 2.6 ± 1.5 in the phaco-tube group and 1.7 ± 1.3 in the phaco-trab group (P= 0.015). LogMAR VA was 0.39 ± 0.58 in the phaco-tube group and 0.43 ± 0.73 in the phaco-trab group at 3 years (P= 0.82) and VFMD was -18.3 ± 9.0 dB in the phaco-tube group and -14.1 ± 7.0 dB in the phaco-trab group (P= 0.16). Postoperative complications developed in 21 patients (47%) in the phaco-tube group and 15 patients (33%) in the phaco-trab group (P= 0.28). CONCLUSIONS: Phaco-tubes had a significantly lower rate of surgical failure compared to phaco-trabs after 3 years of follow-up. However, phaco-trabs used significantly fewer glaucoma medications at multiple postoperative timepoints and had a higher proportion of complete success.

Sink-source connectivity for restocking of Pinna nobilis in the western Mediterranean Sea.

The critically endangered endemic bivalve Pinna nobilis from the Mediterranean Sea suffered a sudden population decline after a mass mortality event in early autumn 2016. Conservation efforts aimed at preventing extinction included safeguarding resistant individuals and implementing a breeding plan to contribute to the repopulation of the species. This study utilized a model combining Lagrangian dispersion and connectivity analyses to pinpoint optimal restocking sites in the Western Mediterranean. Our approach allowed to identify locations capable of sustaining and generating larvae for broader repopulation in key areas of the Western Mediterranean Sea prior to the mass mortality event. Six important repopulation locations from Murcia, Valencia and Balearic Islands were selected for reintroduction efforts. The results obtained in this study show how the network could be self-sufficient and able to self-replenish itself of recruits. Overall, our work can be used to direct the reintroduction of resistant animals in the Western Mediterranean Sea.

Chaotic vortex-induced rotation of an elliptical cylinder.

Non-linear oscillations of an elliptical cylinder, which can rotate about an axis that passes through its symmetry axle due to a torsional spring and hydrodynamic torque produced by the flow of a Newtonian fluid, were analyzed in terms of a single parameter that compares vortex shedding frequency with the torsional spring's natural frequency. The governing equations for the flow coupled with a rigid body with one degree of freedom were solved numerically using the lattice-Boltzmann method. The Reynolds number used was Re=200, which, in the absence of torsional spring, produces chaotic oscillations of the elliptical cylinder. When the torsional spring is included, we identified three branches separated by transition regions when stiffness of the restorative torque changes, as in the case of vortex-induced vibrations. However, in this case, several regions presenting chaotic dynamics were identified. Two regions with stable limit cycles were found when both torques synchronized and when stiffness of the torsional spring is big enough so that the ellipse's oscillation is small.

A serverless computing architecture for Martian aurora detection with the Emirates Mars Mission.

Remote sensing technologies are experiencing a surge in adoption for monitoring Earth's environment, demanding more efficient and scalable methods for image analysis. This paper presents a new approach for the Emirates Mars Mission (Hope probe); A serverless computing architecture designed to analyze images of Martian auroras, a key aspect in understanding the Martian atmosphere. Harnessing the power of OpenCV and machine learning algorithms, our architecture offers image classification, object detection, and segmentation in a swift and cost-effective manner. Leveraging the scalability and elasticity of cloud computing, this innovative system is capable of managing high volumes of image data, adapting to fluctuating workloads. This technology, applied to the study of Martian auroras within the HOPE Mission, not only solves a complex problem but also paves the way for future applications in the broad field of remote sensing.

Genomic and phenotypic analysis of invasive Streptococcus suis isolated in Spain reveals genetic diversification and associated virulence traits.

Streptococcus suis is a zoonotic pathogen that causes a major health problem in the pig production industry worldwide. Spain is one of the largest pig producers in the world. This work aimed to investigate the genetic and phenotypic features of invasive S. suis isolates recovered in Spain. A panel of 156 clinical isolates recovered from 13 Autonomous Communities, representing the major pig producers, were analysed. MLST and serotyping analysis revealed that most isolates (61.6%) were assigned to ST1 (26.3%), ST123 (18.6%), ST29 (9.6%), and ST3 (7.1%). Interestingly, 34 new STs were identified, indicating the emergence of novel genetic lineages. Serotypes 9 (27.6%) and 1 (21.8%) prevailed, followed by serotypes 7 (12.8%) and 2 (12.2%). Analysis of 13 virulence-associated genes showed significant associations between ST, serotype, virulence patterns, and clinical features, evidencing particular virulence traits associated with genetic clusters. The pangenome was generated, and the core genome was distributed in 7 Bayesian groups where each group included a variable set of over- and under-represented genes of different categories. The study provides comprehensive data and knowledge to improve the design of new vaccines, antimicrobial treatments, and bacterial typing approaches.

Exploring the Therapeutic Significance of microRNAs and lncRNAs in Kidney Diseases.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two crucial classes of transcripts that belong to the major group of non-coding RNAs (ncRNAs). These RNA molecules have significant influence over diverse molecular processes due to their crucial role as regulators of gene expression. However, the dysregulated expression of these ncRNAs constitutes a fundamental factor in the etiology and progression of a wide variety of multifaceted human diseases, including kidney diseases. In this context, over the past years, compelling evidence has shown that miRNAs and lncRNAs could be prospective targets for the development of next-generation drugs against kidney diseases as they participate in a number of disease-associated processes, such as podocyte and nephron death, renal fibrosis, inflammation, transition from acute kidney injury to chronic kidney disease, renal vascular changes, sepsis, pyroptosis, and apoptosis. Hence, in this current review, we critically analyze the recent findings concerning the therapeutic inferences of miRNAs and lncRNAs in the pathophysiological context of kidney diseases. Additionally, with the aim of driving advances in the formulation of ncRNA-based drugs tailored for the management of kidney diseases, we discuss some of the key challenges and future prospects that should be addressed in forthcoming investigations.

Sex hormones and the total testosterone:estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men.

BACKGROUND: The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. OBJECTIVES: To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. MATERIALS AND METHODS: This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. RESULTS: We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111 ± 89 vs. 191 ± 143 ng/dL; p < 0.001), dehydroepiandrosterone (1.69 ± 1.26 vs. 2.96 ± 2.64 ng/mL; p < 0.001), and dehydroepiandrosterone sulfate (91.72 ± 76.20 vs. 134.28 ± 98.261 µg/dL; p = 0.009), significantly higher levels of estradiol (64.61 ± 59.35 vs. 33.78 ± 13.78 pg/mL; p = 0.001), and significantly lower total testosterone:estradiol ratio (0.28 ± 0.31 vs. 0.70 ± 0.75; p < 0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p = 0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p < 0.001). DISCUSSION AND CONCLUSION: Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.

Pesticides luminescent sensing by a Tb3+-doped Zn metal-organic framework with selectivity towards parathion.

Organophosphorus pesticides (OPPs) such as parathion have extensive uses in agriculture and household applications. Chronic exposure to these pesticides can cause severe health and environmental issues. Therefore, a current ecological concern is associated with accumulating these noxious OPPs in food and water sources. In this work, a new Tb3+-doped Zn-LMOF (Zn-LMOF= (3D) {[Zn3(1,4 benzenedicarboxylate)3(EtOH)2]·(EtOH)0.6}∞) was synthesized by a solvent-free reaction between the Zn-LMOF and the salt TbCl3·6H2O using a high-speed ball milling. The Tb@Zn-LMOF was thoroughly characterized by multiple spectroscopic tools, including Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy, and studied in-depth as a luminescent sensor for a series of pesticides (parathion, malathion, methalaxil, carbofuran, iprodione, captan and glyphosate) in aqueous methanol. The Tb@Zn-LMOF is a long-lived green-emitting compound with luminescence originated by an efficient antenna effect from the excited energy levels of Zn-LMOF toward the 5D state of Tb3+ ions, as it is displayed by its strong emission bands at 488, 545, 585, and 620 nm and a lifetime of 1.01 ms upon excitation at 290 nm. Additions of pesticides to a neutral methanolic dispersion of Tb@Zn-LMOF modified its green emission intensity with a pronounced selectivity toward parathion within the micromolar concentration range. The detection limit for parathion was calculated to be 3.04 ± 0.2 µM for Tb@Zn-LMOF. Based on 31P NMR and mass spectrometry studies, it is attributed to the release of lanthanide ions from Tb@Zn-LMOF with the simultaneous formation of a Tb3+-parathion complex.

Provider perspectives on equity in use of mobile health autism screening tools.

LAY ABSTRACT: Families may find information about autism online, and health care and education providers may use online tools to screen for autism. However, we do not know if online autism screening tools are easily used by families and providers. We interviewed primary care and educational providers, asking them to review results from online tools that screen for autism. Providers had concerns about how usable and accessible these tools are for diverse families and suggested changes to make tools easier to use.

Entomopathogenic fungi for the control of larvae and adults of Aedes aegypti (Diptera: Culicidae) vector of dengue, chikungunya and Zika viruses in Mexico.

OBJECTIVE: To assess larvicide and adulticide activity of different native strains of fungi on Aedes aegypti. MATERIALS AND METHODS: Third instar larvae were exposed for 72 h at a concentration of 1x108 conidia/ml of 15 fungi; only fungi that significantly affected the larvae were evaluated against the adult phase at a concentration of 2x1010 conidia/ml. Mortality readings were performed at 24, 48, and 72 h for larvae, and every day to 30 days for adults. RESULTS: Trichoderma longibrachiatum, Aspergillus aculeatus, and Metarhizium anisopliae had the best larvicidal activity at 24 h of exposure (p<0.05), causing mortalities of 100, 72, and 62%, respectively. Adult mosquitoes were more affected by Gliocladium virens (45% mortality), M. anisopliae (30% mortality), and T. longibrachiatum (23.33% mortality). CONCLUSION: The larval stage of Ae. aegypti was more susceptible than the adult phase to the pathogenic action of native fungi, with T. longibrachiatum being with the highest virulence.

Design and Evaluation of a Sticky Attractant Trap for Intra-Domiciliary Surveillance of Aedes aegypti Populations in Mexico.

Surveillance consists of systematic data collection, analysis, and interpretation and is essential for planning and implementing control activities. The lack of success in the control and surveillance of the Ae. aegypti mosquito elsewhere demands the development of new accessible and effective strategies. This work aimed to develop and evaluate an adhesive lure trap for household indoor surveillance of Ae. aegypti. Based on a bibliographic review, four compounds that have significant attraction percentages for Ae. aegypti were considered. Our more effective blend was determined through preliminary bioassays using the high-throughput screening system (HITSS) and 90 × 90 cm mosquito cages. We designed a low-cost, pyramid-shaped, sticky cardboard trap to incorporate the selected blend. Semi-field 2 × 2 m cages and field tests were utilized to evaluate its effectiveness through mosquito capture percentages. In laboratory tests, blend number 2 presented an attraction percentage of 47.5 ± 4.8%; meanwhile, in semi-field cages, a 4-inch, 110 v powered fan was used to disperse the attractants, and then a similar capture percentage of 43.2 ± 4.0% was recorded. Results were recorded during the field evaluation of the at-house indoor environment and were compared with those recorded with the golden-standard BG-Sentinel trap, i.e., our prototype trapped an average of 6.0 ± 1.5 mosquitoes versus 10.0 ± 2.6. In most Latin American countries, there is a lack of formal and accessible strategies for monitoring adult populations of Ae. Aegypti; therefore, we must develop tools that reinforce entomological surveillance methods.

Safety of the modified posteromedial approach in complex ankle fractures: Comparative analysis versus posterolateral access.

INTRODUCTION: The aim of the study was to evaluate the safety of the modified posteromedial approach (MfPM) in the surgical management of complex ankle fractures in terms of local complications. METHODS: Retrospective multicenter review of a series of malleolar fractures surgically treated by posterior ankle approaches between 2016 and 2022. Two approaches were used. In the MfPM group patients were placed in a prone position and the incision was made 1 cm medially to the Achilles tendon. In the posterolateral access (PL) group patients were placed in a prone or lateral decubitus position and the incision was made between the lateral malleolus and the Achilles tendon. Complications evaluated were divided into wound complications, infections, neuritis, vascular alterations and others. RESULTS: 81 ankle fractures with a posterior malleolar fragment treated by open reduction and internal fixation were identified. 20 cases were approached through the MfPM approach and 61 through the PL access. The mean follow up was 18.60 months (range 4-78 months). In the MfPM group the local complication rate was 10% (2/10 patients), both corresponding to minor wound problems which required no surgical intervention. No infection or other neural or vascular complications were found. In the PL group a complication rate of 8,19% (5/61 patients) was found, all of them corresponding to minor wound problems which required no surgical intervention. No infection or other neural or vascular complications were found. There were no significant differences between the two approaches regarding postoperative local complications (z score 0.249 - P: 0.803). CONCLUSION: The MfPM approach is safe and may become as readily used as the PL due to the low incidence of postoperative local complications, especially in fractures with a large fragment and posteromedial extension in which greater access to the posterior pilon can facilitate instrumentation for anatomic reduction and fixation.

The applications of CRISPR/Cas-mediated microRNA and lncRNA editing in plant biology: shaping the future of plant non-coding RNA research.

MAIN CONCLUSION: CRISPR/Cas technology has greatly facilitated plant non-coding RNA (ncRNA) biology research, establishing itself as a promising tool for ncRNA functional characterization and ncRNA-mediated plant improvement. Throughout the last decade, the promising genome editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated proteins (Cas; CRISPR/Cas) has allowed unprecedented advances in the field of plant functional genomics and crop improvement. Even though CRISPR/Cas-mediated genome editing system has been widely used to elucidate the biological significance of a number of plant protein-coding genes, this technology has been barely applied in the functional analysis of those non-coding RNAs (ncRNAs) that modulate gene expression, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Nevertheless, compelling findings indicate that CRISPR/Cas-based ncRNA editing has remarkable potential for deciphering the biological roles of ncRNAs in plants, as well as for plant breeding. For instance, it has been demonstrated that CRISPR/Cas tool could overcome the challenges associated with other approaches employed in functional genomic studies (e.g., incomplete knockdown and off-target activity). Thus, in this review article, we discuss the current status and progress of CRISPR/Cas-mediated ncRNA editing in plant science in order to provide novel prospects for further assessment and validation of the biological activities of plant ncRNAs and to enhance the development of ncRNA-centered protocols for crop improvement.

Evaluation of the interrelated effects of slaughtering, drying, and defatting methods on the composition and properties of black soldier fly (Hermetia illucens) larvae fat.

The interrelated effect of different slaughtering, drying and defatting methods of black soldier fly larvae (BSFL) on the lipid composition and properties of the fat was studied. Blanching and freezing were compared as slaughtering methods, oven or freeze-drying as drying methods, and mechanical pressing or supercritical fluid extraction (SFE) as defatting methods. The different modes of slaughtering, drying, and defatting, along with both binary and ternary interactions caused significant effects on processes yields, lipid composition, moisture content and thermal properties. Thus, considering the defatting degree and the yield in total valued products (defatted meal plus fat), the combination of blanching, freeze-drying plus mechanical pressing was the worst option (51.2% and 87.5%, respectively). In contrast, the other combinations demonstrated better and comparable efficiency, although SFE is preferable for defatting (83.2% and 96.9%, respectively). The content of major fatty acids (lauric, palmitic and myristic acids) was significantly affected by the BSFL treatments, although with unsignificant impact on the total saturated fatty acids content. To preserve the integrity of the fat, the combination of blanching and oven-drying was preferred, as non-thermal methods of slaughtering and drying caused intense lipolysis, releasing free fatty acids (FFA) in the range of 18.6-23.5%. To achieve the lowest moisture content in the fats (≤0.1%), oven-drying with mechanical pressing were desired, regardless of the slaughtering method; while values > 1% were reached for freezing, freeze-drying and SFE. Both differences in FFA and moisture contents caused different thermal behaviors in the samples. Specially, the melting temperature was lower for samples with higher FFA and moisture contents, with a notable difference when freezing, freeze-drying and SFE were combined (14.5 °C vs 30.6 °C, as the mean value for the rest of samples). The different modes of processing did not affect the minor lipid compounds. Therefore, the modes employed for slaughtering, drying, and defatting of BSFL determine, either individually or in combination, the process yields, composition, and properties of the fat.

Combination of Dehydration and Expeller as a Novel Methodology for the Production of Olive Oil.

An alternative olive oil (OO) production process has been developed based on the combination of olive dehydration, followed by extraction with an expeller press. This procedure eliminates the utilization of water and avoids the malaxation stage. Hence, no water residues are generated. In this study, the mentioned alternative methodology was compared to conventional extraction methods. High extraction yields and oil recovery were obtained with our novel procedure. On the contrary, substantial percentages of by-products were generated with conventional methodology. The quality indexes (acidity and peroxide values) of the oils obtained by the combination of dehydration and expeller (dOO) were 0.4% of oleic acid and 3 meq O2/kg of oil, respectively. Furthermore, none of the applied processes affected the resulting OO's fatty acid composition and lipid profile. Total phenolic content was up to four times higher for dOO than for other olive oils and it showed resistance to oxidation with an oxidative stability index about five times higher than that for conventional olive oils.

Acrylates Polymerization on Covalent Plasma-Assisted Functionalized Graphene: A Route to Synthesize Hybrid Functional Materials.

The modification of the surface properties of graphene with polymers provides a method for expanding its scope into new applications as a hybrid material. Unfortunately, the chemical inertness of graphene hinders the covalent functionalization required to build them up. Developing new strategies to enhance the graphene chemical activity for efficient and stable functionalization, while preserving its electronic properties, is a major challenge. We here devise a covalent functionalization method that is clean, reproducible, scalable, and technologically relevant for the synthesis of a large-scale, substrate-supported graphene-polymer hybrid material. In a first step, hydrogen-assisted plasma activation of p-aminophenol (p-AP) linker molecules produces their stable and covalent attachment to large-area graphene. Second, an in situ radical polymerization reaction of 2-hydroxyethyl acrylate (HEA) is carried out on the functionalized surface, leading to a graphene-polymer hybrid functional material. The functionalization with a hydrophilic and soft polymer modifies the hydrophobicity of graphene and might enhance its biocompatibility. We have characterized these hybrid materials by atomic force microscopy (AFM), X-Ray photoelectron spectroscopy (XPS) and Raman spectroscopy and studied their electrical response, confirming that the graphene/p-AP/PHEA architecture is anchored covalently by the sp3 hybridization and controlled polymerization reaction on graphene, retaining its suitable electronic properties. Among all the possibilities, we assess the proof of concept of this graphene-based hybrid platform as a humidity sensor. An enhanced sensitivity is obtained in comparison with pristine graphene and related materials. This functional nanoarchitecture and the two-step strategy open up future potential applications in sensors, biomaterials, or biotechnology fields.

Glycaemic Control and Weight Reduction: A Narrative Review of New Therapies for Type 2 Diabetes.

Early and intensive treatment of type 2 diabetes (T2D) has been associated with lower risk of diabetes-related complications. Control of overweight and obesity, which are strongly associated with T2D and many of its complications, is also key in the management of the disease. New therapies allow for individualised glycaemic control targets with greater safety. Thus, in patients with a higher cardiovascular and renal risk profile, current guidelines encourage early treatment with metformin together with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit. GLP-1 RAs combine highly efficacious glucose-lowering activity with a reduced risk of hypoglycaemia. Recently, tirzepatide, a first-in-class drug that activates both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, has demonstrated very high efficacy in glycated haemoglobin (HbA1c) and weight reduction in clinical trials. Tirzepatide has the potential to help people with T2D reach recommended glycaemic and weight targets (HbA1c < 7% and > 5% weight reduction) and to allow some patients to reach HbA1c measurements close to normal physiological levels and substantial weight reduction. In 2022, tirzepatide was approved by the US Food and Drug Administration and the European Medicines Agency for treatment of people with T2D and is currently in development for chronic weight management.

In people newly diagnosed with type 2 diabetes, early and intensive treatment of the disease can help control blood sugar and reduce the risk of later complications. The need to control weight in people with obesity and diabetes has also recently become a priority. New drugs developed in recent years allow for better and more individualised management of blood sugar without the risk of blood sugar levels dropping too low. In patients at risk of kidney or heart disease, the current recommendation is early treatment with metformin and drugs with proven cardiovascular benefit. Tirzepatide is a new drug that has also demonstrated very high efficacy in reducing blood glucose and body weight. It has the potential to help people with type 2 diabetes achieve their goals and prevent other diabetes-related complications. It is likely that some patients will even be able to bring their blood glucose to normal levels and lose substantial amounts of weight. The US and European regulatory agencies approved tirzepatide in 2022 for the treatment of type 2 diabetes and it is currently being tested for chronic weight management.

Achieving Normoglycemia With Tirzepatide: Analysis of SURPASS 1-4 Trials.

OBJECTIVE: Tirzepatide is a novel single-molecule glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, which demonstrated unprecedented improvements in glycemic control and body weight reduction, in the SURPASS phase 3 program. In this exploratory analysis, we aimed to characterize tirzepatide-treated participants who achieved HbA1c <5.7% and evaluate changes in clinical markers associated with long-term cardiometabolic health. RESEARCH DESIGN AND METHODS: Baseline characteristics and change from baseline to week 40 for several efficacy and safety parameters were analyzed according to HbA1c attainment category (<5.7%, 5.7-6.5%, and >6.5%) using descriptive statistics in participants taking ≥75% of treatment doses, without rescue medication, in the SURPASS 1-4 trials (N = 3,229). Logistic regression models with tirzepatide doses adjusted as a covariate were used to obtain odds ratios and assess the impact of patient characteristics achieving an HbA1c <5.7%. RESULTS: Tirzepatide-treated participants who achieved HbA1c <5.7% were slightly younger, with a shorter duration of diabetes and lower HbA1c value at baseline compared with those who did not achieve HbA1c <5.7%. In addition, they showed greater improvements in HbA1c, body weight, waist circumference, blood pressure, liver enzymes, and lipid parameters without increasing hypoglycemia risk. CONCLUSIONS: Normoglycemia was unprecedently achieved in a significant proportion of participants in the SURPASS clinical program, without increasing hypoglycemia risk, and was associated with an overall improvement in metabolic health.