作者: Haid, Mark ; Thomsen, Henrik S ; Viñuela, Ana ; Hansen, Torben ; Thomas, E Louise ; Frost, Gary ; Dawed, Adem Y ; Sharma, Sapna ; Adamski, Jerzy ; Holst, Jens J ; Holmes, Elaine ; Bell, Jimmy D ; Mari, Andrea ; Perez, Isabel Garcia ; Ridderstråle, Martin ; White, Margaret C ; Pearson, Ewan R ; Mahajan, Anubha ; Muilwijk, Mirthe ; Forgie, Ian ; Brunak, Søren ; Bizzotto, Roberto ; Eriksen, Rebeca ; Prehn, Cornelia ; McCarthy, Mark I ; Walker, Mark ; Ruetten, Hartmut ; Rutters, Femke ; Schwenk, Jochen M ; Koivula, Robert W ; Posma, Joram M ; Pavo, Imre ; Jennison, Chris ; Beulens, Joline ; Franks, Paul W ; Fernandez-Tajes, Juan ; Jones, Angus ; Hansen, Tue H ; McDonald, Timothy J ; Elders, Petra ; Tsirigos, Konstantinos D ; Kokkola, Tarja ; Blom, Marieke ; De Masi, Federico ; Giordano, Giuseppe N ; Pedersen, Oluf

AbstractContextThe role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.ObjectiveWe investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.MethodsWe analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D.ResultsOur multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes.ConclusionThese studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D.

2023-08-01·Diabetes research and clinical practice

Perspectives on weight control in diabetes - Tirzepatide.

Review

作者: Pávó, Noémi ; Pósa, Anikó ; Pavo, Imre ; Várkonyi, Tamás T

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (GIP/GLP-1 RA) improves glycemic control. Besides improvement of glycemic control, tirzepatide treatment is associated with significantly more weight loss as compared to potent selective GLP-1 receptor agonists as well as other beneficial changes in cardio-metabolic parameters, such as reduced fat mass, blood pressure, improved insulin sensitivity, lipoprotein concentrations, and circulating metabolic profile in individuals with type 2 diabetes (T2D). Some of these changes are partially associated with weight reduction. We review here the putative mechanisms of GIP receptor agonism contributing to GLP-1 receptor agonism-induced weight loss and respective findings with GIP/GLP-1 RAs, including tirzepatide in T2D preclinical models and clinical studies. Subsequently, we summarize the clinical data on weight loss and related non-glycemic metabolic changes of tirzepatide in T2D. These findings suggest that the robust weight loss and associated changes are important contributors to the clinical profile of tirzepatide for the treatment of T2D diabetes and serve as the basis for further investigations including clinical outcomes.

2022-08-01·Dermatology and Therapy

Patient Characteristics and Treatment Patterns in European Pediatric Patients with Psoriasis: A Real-World, Cross-Sectional Study

Article

作者: Sticherling, Michael ; Reed, Catherine ; Lucas, James ; de Lucas Laguna, Raúl ; Artime, Esther ; Mahé, Emmanuel ; Costanzo, Antonio ; Schuster, Christopher ; Robert, Camille ; McPherson, Tess

INTRODUCTIONThis study evaluated patient characteristics and treatment patterns according to weight in pediatric patients with psoriasis in a real-world setting.METHODSPrimary care and specialist physicians treating pediatric patients with psoriasis aged 6-17 years in five European countries were surveyed in the 2019-2020 Adelphi Real World Pediatric Psoriasis Disease Specific Programme. At least two patients with current or previous biologic use were included per physician. Patient characteristics and treatment patterns were analyzed overall and for patients weighing 25-50 kg or more than 50 kg.RESULTSData from 772 patients weighing 25-50 kg and 1147 weighing more than 50 kg were analyzed. Median age at diagnosis was significantly less in lighter than heavier patients (10.0 vs. 14.0 years; p < 0.001), as was median disease duration (2.2 vs. 3.0 years; p < 0.001). Topical treatments were prescribed in 59.0% of patients overall (70.3% of lighter and 51.4% of heavier patients; p < 0.001), and were used to treat mild rather than moderate-to-severe psoriasis. Conventional systemic use was low (10.8% of patients overall) and predominantly for moderate-to-severe psoriasis. In this biologic-enriched sample, most biologics (78.2%) were prescribed in older (> 13 years) patients. Biologic use increased with line of therapy (6.6% of first-line, 18.0% of second-line, 33.7% of third-line, 44.7% of fourth-line treatments).CONCLUSIONBiologics are predominantly prescribed in older (> 13 years) and heavier (> 50 kg) patients, with little first- or second-line use. The low use of biologics in European pediatric patients with psoriasis may represent an unmet treatment need, as topical or conventional systemic agents remain the main treatment option for moderate or severe psoriasis in these patients through the treatment pathway.

100 项与 Eli Lilly Regional Operations GmbH 相关的药物交易

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