Department of Endocrinology, Diabetes and Metabolism
Permanent URI for this collection
Browse
Recent Submissions
Item Improved health-related quality of life with tirzepatide versus semaglutide in adults with obesity or overweight from the SURMOUNT-5 trialShukla, A.P.; Dunn, J.P.; Gomez Valderas, E.; Fraseur Brumm, J.; Karanikas, C.A.; Hunter Gibble, T. (Wiley, 2025-11-04)AIMS: In SURMOUNT-5, tirzepatide led to greater body weight (BW) reduction versus semaglutide in adults with obesity without T2D. Health-related quality of life (HRQoL) with tirzepatide versus semaglutide in SURMOUNT-5 was evaluated. MATERIALS AND METHODS: This analysis included on-treatment data from participants who received ‚â•1 dose of tirzepatide or semaglutide at their maximum tolerated dose. Changes in prespecified Short Form-36 Health Survey Version 2 (SF-36v2) norm-based scores for the Physical Component Summary (PCS), Mental Component Summary (MCS), and each domain, Patient Health Questionnaire-9, and Patient Global Impression of Status for Physical Activity scores were assessed at Week 72. Post hoc analysis of changes in SF-36v2 scores in participants with limited baseline physical function and by BW reduction thresholds was assessed at Week 72. RESULTS: Baseline scores were similar between treatments and among BW reduction categories. At Week 72, PCS scores improved from baseline with both treatments (p < 0.001). However, MCS scores did not show significant improvements from baseline (p > 0.05 for both treatment arms). All domain scores improved (p ‚⧠0.008), with greater improvements in General Health (GH) with tirzepatide versus semaglutide (5.45 vs. 4.20; p = 0.003). Participants with limited physical function improved in PCS, Physical Functioning (PF), and GH with tirzepatide versus semaglutide (p ‚⧠0.025). Higher BW reductions were associated with more improvement in PCS, PF, Role-Physical, Bodily Pain (BP), GH, and Vitality scores with tirzepatide and semaglutide (pooled). CONCLUSIONS: HRQoL improved with tirzepatide and semaglutide, with greater improvement in GH with tirzepatide, especially in participants with limited baseline physical function. Participants who lost the most BW showed the greatest improvements in PF, BP, and GH.Item Tirzepatide Heralds the Hope of Chronic Disease EradicationTchang, B.G.; Barenbaum, S.; Aronne, L.J. (Oxford University Press, 2025-08-04)Item scRNA-seq reveals transcriptional plasticity of var gene expression in Plasmodium falciparum for host immune avoidance.Florini, F.; Visone, J.E.; Hadjimichael, E.; Malpotra, S.; Nötzel, C.; Kafsack, B.F.C.; Deitsch, K.W. (Nature Research, 2025-05-16)Plasmodium falciparum evades antibody recognition through transcriptional switching between members of the var gene family, which encodes the major virulence factor and surface antigen on infected red blood cells. Previous work with clonal P. falciparum populations revealed var gene expression profiles inconsistent with uniform single var gene expression. However, the mechanisms underpinning this and how it might contribute to chronic infections were unclear. Here, using single-cell transcriptomics employing enrichment probes and a portable microwell system, we analysed var gene expression in clonal 3D7 and IT4 parasite lines. We show that in addition to mono-allelic var gene expression, individual parasites can simultaneously express multiple var genes or enter a state in which little or no var gene expression is detectable. Reduced var gene expression resulted in greatly decreased antibody recognition of infected cells. This transcriptional flexibility provides parasites with greater adaptive capacity and could explain the antigenically 'invisible' parasites observed in chronic asymptomatic infections.Item Body weight reduction in women treated with tirzepatide by reproductive stage: a post hoc analysis from the SURMOUNT program.Tchang, B.G.; Mihai, A.C.; Stefanski, A.; García-Pérez, L.E.; Mojdami, D.; Jouravskaya, I.; Gurbuz, S.; Taylor, R.; Karanikas, C.A.; Dunn, J.P. (Wiley, 3/12/25)OBJECTIVE: Increases in adiposity and adverse changes in adipose distribution commonly occur in women during midlife and with the onset of menopause. This post hoc analysis assessed body weight changes with tirzepatide by reproductive stage. METHODS: Women participants from SURMOUNT-1, -3, and -4 randomized to tirzepatide (15 mg or maximum tolerated dose) or placebo were retrospectively categorized as being in the pre-, peri-, or post-menopause stages. Body weight and waist circumference changes, the proportion of participants achieving body weight-reduction thresholds, and waist to height ratio (WHtR) category shift among those with baseline BMI < 35 kg/m2 were assessed at end of study treatment. RESULTS: In SURMOUNT-1, significantly greater body weight reductions from baseline were observed with tirzepatide versus placebo in women in the premenopause (26% vs. 2%), perimenopause (23% vs. 3%), and postmenopause stages (23% vs. 3%; p < 0.001). Greater waist circumference reductions were also observed with tirzepatide across the subgroups (22 vs. 4 cm, 20 vs. 5 cm, and 20 vs. 4 cm, respectively; p < 0.001). Across the reproductive stage subgroups, 97% to 98% of participants achieved body weight reductions that were ‚â•5% with tirzepatide versus 29% to 33% with placebo. Furthermore, 30% to 52% of women among the reproductive stage subgroups who had baseline BMI < 35 kg/m2 reached WHtR ‚⧠0.49 (low central adiposity) with tirzepatide. Similar results were observed in SURMOUNT-3 and -4. CONCLUSIONS: In this post hoc analysis, tirzepatide treatment was associated with significant body weight, waist circumference, and WHtR reductions versus placebo in women living with obesity or overweight and without type 2 diabetes, irrespective of reproductive stage.Item Effect of semaglutide 2.4 mg on use of antihypertensive and lipid-lowering treatment in five randomized controlled STEP trials.Tchang, B. G.; Knight, M. G.; Adelborg, K.; Clements, J. N.; Iversen, A. T.; Traina, A. (1/5/25)OBJECTIVE: The objective of this study was to assess antihypertensive and lipid-lowering treatment changes in participants receiving semaglutide 2.4 mg versus placebo across pooled populations from five Semaglutide Treatment Effect in People with Obesity (STEP) trials. METHODS: Efficacy and safety of semaglutide 2.4 mg were evaluated in the STEP clinical trials. In this post hoc analysis, STEP 1, 3, 6, and 8 (which included people with overweight or obesity) and, separately, STEP 2 and 6 (which included people with overweight or obesity and type 2 diabetes) were pooled for analysis. Changes in antihypertensive or lipid-lowering treatment intensity from randomization to end of treatment were evaluated. RESULTS: In both pooled samples, a higher proportion of participants in the semaglutide 2.4 mg group versus placebo underwent antihypertensive or lipid-lowering treatment intensity reduction by end of treatment. A smaller proportion underwent antihypertensive or lipid-lowering treatment intensification by end of treatment in the semaglutide 2.4 mg group of both samples versus placebo. In participants receiving antihypertensive or lipid-lowering medications in both samples, greater numeric reductions in body weight were observed in the semaglutide 2.4 mg group versus placebo. CONCLUSIONS: These results support a relationship between semaglutide 2.4 mg treatment of overweight and obesity and reduced need for antihypertensive and lipid-lowering treatment, facilitating treatment intensity reduction/discontinuation and abating treatment intensification.