Pots, T. (Thijs) (2015) GLP-1 receptor agonists and Diabetes Mellitus Type 2 : The use of GLP-1 receptor agonists in clinical practice : An explorative study at factors influencing drug survival. thesis, Medicine.
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Abstract
Background: Obesity increases the degree of insulin resistance in patients with diabetes mellitus type 2 (DM2), thereby worsening glycemic control. Exogenous insulin is often the only alternative, but is not desirable because of adverse weight gain and hypoglycemia. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a new class of antihyperglycemic agents, which appear to reduce weight without increasing the risk of hypoglycemia. However, little is known about the usage of GLP-1R agonists on the long term and in clinical practice. Objective: The primary objective in this study is to evaluate the usage of GLP-1R agonists by determining its median time to, predictors and reasons for discontinuation. The secondary objective is to evaluate effectiveness and safety on the long term. Material and methods: A retrospective cohort study was carried out under all patients with DM2, prescribed with a GLP-1R agonist within hospital group Twente, between 1 January 2010 and 30 June 2014. Demographic information, medical history, medication use, blood pressure, kidney function, cholesterol, glycated hemoglobin (HbA1c), body weight, and notifications of adverse effects were obtained from the patient files and analyzed. Missing data was retrieved from the general practitioner after patient’s approval. Results: GLP-1R agonist usage was evaluated in 482 patients, of which 258 (53.5%) discontinued, with a median time to discontinuation of 30.5 months (95% CI 24.9-36.0). Insufficient (68.6%) and adverse effects (20.9%) were the main reasons for discontinuation. HbA1c at baseline (mean 68.3 mmol/mol, SD14.5) increased the likelihood of discontinuation significantly with 2% for each mmol/mol rise (P<0.001). Insulin usage prior to GLP-1R agonist treatment (HR 1.72, 95% CI 1.34-2.19; P<0.001) and the need for applying the maximum recommended dose in the first year (HR 1.86, 95% CI 1.28-2.70; P=0,001) also increased the risk for discontinuation. In patients who did not discontinue, the mean HbA1c and BMI had decreased significantly at 6 months (P<0.001), increasing the proportion of patients achieving the glycemic target of ≤53.0 mmol/mol in this group from 14.4% to 56.3%. After 4 years, 28.9% of the continuers maintained a HbA1c ≤53.0 mmol/mol. Discussion and conclusion: The median time to discontinuation of GLP-1R agonist treatment is relatively short for patients, who need an effective therapy for the long term. GLP-1R agonists appear unable to achieve and sustain the general recommended glycemic target in most therapy-resistant patients with obesity and a high HbA1c. Therefore, we recommend that in the selection and follow-up of eligible patients predictors for discontinuation are taken into account and it should be reconsidered to extend the target population for GLP-1R agonists, to patients with a lower BMI and HbA1c, instead of saving this therapy for the therapy-resistant patients.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Faculty supervisor and Laverman, Dr. G.D. and Research location Hospital Group Twente, Department of inter |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:50 |
| Last Modified: | 25 Jun 2020 10:50 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1075 |
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