Clinical and Genetic Predictors of Glycemic Control and Weight Loss Response to Liraglutide in Patients with Type 2 Diabetes

Abstract

Background: Evidence suggests a heterogeneous response to therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to identify the genetic and clinical factors that relate to glycemic control and weight loss response to liraglutide among patients with T2DM. Methods: The medical records of 116 adults with T2DM (51% female, mean body mass index 35.4 ± 6.4 kg/m2), who had been on treatment with liraglutide for at least 6 months and were genotyped for CTRB1/2 rs7202877 (T > G) polymorphism, were evaluated. Clinical and laboratory parameters were measured at baseline, 3, and 6 months after initiating liraglutide treatment. The good glycemic response was defined as one of the following: (i) achievement of glycated hemoglobin (HbA1c) < 7% (ii) reduction of the baseline HbA1c by ≥1%, and (iii) maintenance of HbA1c < 7% that a patient already had before switching to liraglutide. Weight loss responders were defined as subjects who lost ≥3% of their baseline weight. Results: Minor allele frequency was 16%. Individuals were classified as glycemic control and weight loss responders (81 (70%) and 77 (66%), respectively). Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.4, 3.8, p = 0.69) and weight loss (OR: 1.12, 95% CI: 0.4, 3.2, p = 0.84). In the multivariable analysis, higher baseline HbA1c (adjusted OR: 1.45, 95% CI: 1.05, 2.1, p = 0.04) and lower baseline weight (adjusted OR: 0.97, 95% CI: 0.94, 0.99, p = 0.01) were associated with better glycemic response to liraglutide, while higher baseline weight was associated with worse weight response (adjusted OR: 0.97, 95% CI: 0.95, 0.99, p = 0.02). Conclusions: Specific patient features can predict glycemic and weight loss response to liraglutide in individuals with T2DM.

Pharmakogenetik neuer Glukosespiegelsenker: eine Chance für die Präzisionsmedizin?

“…Nach 48-wöchiger Therapie zeigte sich eine stärkere Senkung des HbA1c und der Nüchternglukosekonzentration bei vorliegendem T-Allel. Die Genvariante rs7202877 in der Nähe des Gens CTRB1/2 zeigte in Bezug auf eine Liraglutidtherapie über 6 Monate keinen Unterschied im Erreichen der HbA1c-Zielwerte zwischen verschiedenen Polymorphismen [31].…”

“…Bisher wurden Alter, Geschlecht, Ethnizität, anthropometrische Parameter, Ernährungsgewohnheiten, körperliche Aktivität, Dauer des Diabetes, Ausgangswerte von Blutglukose und HbA1c (Glykohämoglobin), klinische Marker der Insulinresistenz, Komorbiditäten (u. a. Fettleber, Niereninsuffizienz) und Umweltfaktoren (z. B. endokrine Disruptoren, Luftschadstoffe) als Einflussfaktoren identifiziert [1,8,22,28,31,40,49].…”

Genetic aspects of type 1 glucagon peptide agonists clinical efficacy: A review

“…У лиц, не являющихся носителями аллеля А, наблюдалась нормализация уровня холестерина после снижения массы тела [17]. Носители G-аллеля rs7202877 в CTRB1/2 не показали лучшего ответа на лечение лираглутидом с точки зрения гликемического контроля и снижения веса [39]. Authors' contribution.…”

Genetic Evidence for Distinct Biological Mechanisms That Link Adiposity to Type 2 Diabetes: Toward Precision Medicine

“…This complexity leads to variations in insulin resistance, production, and fat accumulation in ectopic places (liver, skeletal muscles, and pancreas) ( 2 ), making tailored weight management for diabetes challenging ( 3 , 4 ). While weight loss benefits glycemic control and health, responses vary among individuals ( 5 , 6 ), underscoring the need for personalized interventions.…”