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

Artemis Kyriakidou; Angeliki V Kyriazou; Theocharis Koufakis; Yiannis Vasilopoulos; Maria Grammatiki; Xanthippi Tsekmekidou; Iakovos Avramidis; Stefanos Baltagiannis; Dimitrios G Goulis; Pantelis Zebekakis; Kalliopi Kotsa

doi:10.3390/jpm12030424

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

J Pers Med. 2022 Mar 9;12(3):424. doi: 10.3390/jpm12030424.

Affiliations

¹ Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 1 St. Kiriakidi Street, 54636 Thessaloniki, Greece.
² Department of Biology, Section of Genetics, Cell Biology and Development, University of Patras, 26500 Patras, Greece.
³ Diabetes Center, Department of Internal Medicine, G. Papanikolaou General Hospital, 57010 Thessaloniki, Greece.
⁴ Diabetes Outpatient Clinic, General Hospital of Kastoria, 52100 Kastoria, Greece.
⁵ Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, 56429 Thessaloniki, Greece.

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.

Keywords: CTRB1/2; GLP-1 RA; liraglutide; personalized medicine; pharmacogenetics; type 2 diabetes mellitus.

Grants and funding

133935/2014/Novo Nordisk (Greece)