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.
Highlights
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs that have been recently added to the pharmacological armory against type 2 diabetes mellitus (T2DM)
The aim of the present study is to identify genetic and clinical factors related to glycemic control and weight reduction secondary to treatment with the GLP-1 RA liraglutide among patients with T2DM
78% were treated with oral hypoglycemic agents (OHAs) before the initiation of liraglutide
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs that have been recently added to the pharmacological armory against type 2 diabetes mellitus (T2DM). In addition to exhibiting strong glucose-lowering actions with minimal risk of causing hypoglycemia, they effectively reduce cardiovascular risk through their anti-atherosclerotic and anti-inflammatory properties They promote weight loss and manifest favorable effects on common diabetes and obesity comorbidities, such as fatty liver [1]. In the LEADER trial, liraglutide was associated with a lower risk of major adverse CV events, CV death, and death from any cause compared with placebo [4] It has been approved for the pharmacological management of overweight and obesity independently of the presence of diabetes since administration at the dose of 3 mg, in addition to lifestyle measures, has been linked to clinically meaningful reductions in body weight. 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. Carriers of the rs7202877 polymorphic allele had similar responses to liraglutide treatment in terms of glycemic control (odds ratio (OR): 1.25, 95%
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