礼来公司

The ICH E17 guideline is intended to promote the effective and efficient use of multi-regional clinical trials in simultaneous global medicines development, contributing to faster patient access. However, its uptake has been slower than hoped, and some regulators often require local (national) clinical trial data for regulatory submissions. This review examines the extent of ethnic (country of origin) influences on pharmacokinetic (PK) or pharmacodynamic (PD) profile of drugs, with a focus on East Asian countries. We conclude that clinically significant ethnic differences are likely to be less common for many newer therapeutics than older drugs, especially those older small-molecule drugs with low therapeutic indices. Major source of ethnic differences in drug PK or PD are due to differences in the allelic frequencies of particular genes for metabolizing enzymes and other drug targets or receptors, respectively. The default approach for conducting clinical trials for products intended for global markets should be to assess safety and efficacy through multi-regional clinical trials and requirements for country-specific enrolment in trials infrequently justifiable only on scientific grounds.

Continuous glucose monitoring (CGM) is widely used in type 1 diabetes management. Although less common in type 2 diabetes (T2D), its application is increasing, especially among patients with T2D on insulin therapy. CGM provides detailed, continuous glucose data that reveal daily glycemic fluctuations and help mitigate hyper- and hypoglycemic episodes. However, missing information on meal size and timing complicates the interpretation of data. To address these challenges, we propose a pharmacometric modeling approach that describes blood glucose profiles in patients with T2D receiving basal insulin in the absence of exact meal inputs. In this study, 73 individuals with T2D receiving insulin glargine plus oral antidiabetic medications (OAMs) underwent CGM assessments at four visits (Visit 3 on OAMs alone; Visits 13, 16, 20 on OAMs + insulin). Building upon the existing Integrated Glucose-Insulin (IGI) model, we incorporated a population meal model and an insulin glargine pharmacokinetic model, creating a comprehensive "meal–IGI–insulin" framework. The model identified three daily meal intakes, modeled as the sum of a surge function and a maximum bioavailable glucose amount of 7.83 g/hour. The model evaluation indicated adequate performance in predicting fasting blood glucose and HbA1c, though some discrepancies arose in forecasting hypoglycemic events. The developed modeling framework can facilitate prospective simulations of diverse meal patterns and insulin regimens, potentially accelerating antidiabetic drug development, simplify closed-loop automated insulin delivery algorithms, and optimize clinical strategies for patients with T2D.

Galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide, has shown efficacy in migraine prevention in clinical trials and has been included in clinical guidelines. Nonetheless, data on its real-world effectiveness are limited. TRIUMPH [Europe], an ongoing prospective study, enrolled patients ≥ 18 years old with migraine from Germany, Italy, Spain, and the UK who were initiating or switching to galcanezumab or traditional oral migraine preventive medications (TOMPs) between June 2020 and February 2023. The primary end point at 3 months was the percentage of patients achieving a response in monthly headache days (MHDs) as defined by a percentage reduction of ≥ 50

Approximately one fifth of the population of Saudi Arabia had obesity in 2019. Due to the considerable personal and societal cost of obesity in Saudi Arabia, a national initiative to reduce the prevalence of obesity is underway. This study describes the characteristics of people with obesity (PwO) and the impact of obesity on spending, work productivity and health-related quality of life (HRQoL) in Saudi Arabia to help further advance the management of overweight and obesity in this country. Data were from the multinational cross-sectional survey Adelphi Obesity Disease Specific Programme™. Physicians responsible for obesity management decisions completed online questionnaires for up to five consecutive qualifying adult PwO attending their clinic. PwO with physician-completed forms were invited to complete a separate questionnaire. Analyses were descriptive. Overall, 40 physicians provided physician-completed forms for 200 PwO; of these, 90 PwO completed a self-report form. For the 200 PwO, mean time since diagnosis was 23.0 months. A mean of 1.6 comorbidities were reported, most commonly hypothyroidism, depression and type 2 diabetes. Current weight loss approaches included diet, exercise and medication. Other than weight loss, improving HRQoL of PwO was the most common goal reported by physicians (for 70.0

QuestionWhat is the association between tirzepatide and weight reduction among patients with overweight or obesity who initiated concomitant weight-inducing medications?FindingsIn this post hoc analysis of participants in the SURMOUNT-1, -3, and -4 trials receiving at least 1 concomitant weight-inducing medication (17.3%-20.0%), tirzepatide treatment was associated with comparable weight loss to the primary study results.MeaningThis study suggests that clinically meaningful weight reduction with tirzepatide may be able to be achieved among people with overweight or obesity who require treatment with weight-inducing medications. ImportanceGiven the common use of weight-inducing (WI) medications, it is crucial to understand the potential association of these medications with the effectiveness of obesity treatments.ObjectiveTo assess the association between tirzepatide and weight reduction among participants with overweight or obesity who initiated WI medications during the SURMOUNT-1, -3, and -4 trials.Design, Setting, and ParticipantsThis post hoc analysis of the phase 3 randomized clinical trials SURMOUNT-1 (December 4, 2019, to April 1, 2022), SURMOUNT-3 (March 29, 2021, to May 12, 2023), and SURMOUNT-4 (March 29, 2021, to May 18, 2023) assessed the association between tirzepatide and weight reduction among participants taking concomitant WI medications. Randomized participants (lead-in and randomized treatment period data) who started taking 1 or more WI medications for 3 or more months (>= 1 week for oral corticosteroids) during the trial were included in the analysis. Statistical analysis was performed from July to December 2025 in the modified intent-to-treat population.Main Outcomes and MeasuresWI medication use was summarized for all treatment arms from weeks 0 to 72 (SURMOUNT-1 and SURMOUNT-3) or weeks 0 to 88 (SURMOUNT-4). A mixed model of repeated measures was used to assess percentage change in weight from week 0 to week 72 or week 88 in the efficacy analysis sets (excluding off-treatment data), with 1 or more postbaseline weight measures.ResultsThis post hoc analysis comprised the WI medication subgroups of SURMOUNT-1 participants (N = 442; mean [SD] age, 48.0 [12.5] years; 325 women [73.5%]; mean [SD] body weight, 105.9 [22.4] kg), SURMOUNT-3 participants (N = 100; mean [SD] age, 49.5 [12.0] years; 75 women [75.0%]; mean [SD] body weight, 102.7 [23.5] kg), and SURMOUNT-4 participants (N = 134; mean [SD] age, 51.8 [11.9] years; 91 women [67.9%]; mean [SD] body weight, 111.8 [23.7] kg). Approximately one-fifth of participants used 1 or more WI medications (SURMOUNT-1, 17.4% [442 of 2539]; SURMOUNT-3, 17.3% [100 of 579]; and SURMOUNT-4, 20.0% [134 of 670]). Among them, 72.9% in SURMOUNT-1 (322 of 442), 68.0% in SURMOUNT-3 (68 of 100), and 64.9% in SURMOUNT-4 (87 of 134) were taking 1 nonsteroid WI medication, with 2.0% in SURMOUNT-1 (9 of 442), 3.0% in SURMOUNT-3 (3 of 100), and 2.2% in SURMOUNT-4 (3 of 134) using 3 or more medications. The mean (SD) duration of treatment with nonsteroid WI medications was 50.9 (28.8) weeks in SURMOUNT-1, 50.9 (29.3) weeks in SURMOUNT-3, and 58.1 (34.9) weeks in SURMOUNT-4. The mean percentage weight change compared with placebo from randomization to 72 weeks for those treated with tirzepatide and using WI medication was -13.3% (95% CI, -16.0% to -10.7%) for 5 mg to -21.3% (95% CI, -23.9% to -18.7%) for 15 mg in SURMOUNT-1 and -26.1% (95% CI, -30.0% to -22.3%) for the maximum tolerated dose in SURMOUNT-3, and from randomization to 88 weeks, it was -18.6% (95% CI, -20.9% to -16.3%) for the maximum tolerated dose in SURMOUNT-4.Conclusions and RelevanceIn this post hoc analysis of 3 randomized clinical trials for participants taking at least 1 concomitant WI medication, tirzepatide treatment was associated with weight loss comparable with the primary study results. These findings suggest that people with overweight or obesity who require treatment with WI medications may be able to achieve clinically meaningful weight reduction with tirzepatide.Trial RegistrationClinicalTrials.gov Identifiers: NCT04184622, NCT04657016, NCT04660643 This post hoc analysis of the SURMOUNT-1, -3, and -4 trials evaluates the association between tirzepatide and weight reduction among participants with overweight or obesity who initiated weight-inducing medications.