Matteo Monami1, Ilaria Dicembrini2, Besmir Nreu2, Francesco Andreozzi3, Giorgio Sesti3, Edoardo Mannucci2. 1. Diabetology, Careggi Teaching Hospital, Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50141, Florence, Italy. mmonami11@gmail.com. 2. Diabetology, Careggi Teaching Hospital, Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50141, Florence, Italy. 3. Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Abstract
AIMS: The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: A Medline and Embase search for "exenatide" OR "liraglutide" OR "albiglutide" OR "dulaglutide" OR "lixisenatide" was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs. Furthermore, unpublished studies were searched in the www.clinicaltrials.gov register. For meta-analyses, the outcome considered were 24- and 52-week HbA1c. Separate analyses were performed, whenever possible, for subgroups of trials based on several inclusion criteria. In addition, meta-regression analyses were performed for comparisons for which 10 or more trails were available. RESULTS: A total of 92 trials fulfilling the inclusion criteria were identified. In placebo-controlled trials (n = 41), the 24-week mean reduction of HbA1c with GLP-1 RA was - 0.75 [- 0.87; - 0.63]%. Shorter-acting molecules appear to be more effective in patients with lower fasting glucose, whereas longer-acting agents in patients with higher fasting hyperglycaemia. Obesity and duration of diabetes do not seem to moderate the efficacy of GLP-1 RA, whereas in non-Caucasians and older patients liraglutide could be less effective. At 52 weeks, only 9 placebo-controlled trials were available for preventing any reliable analyses. CONCLUSIONS: Using a variety of approaches (meta-analyses of subgroup of trials, meta-regression, systematic review of subgroup analyses in individual trials, and meta-analyses of subgroups of patients), we identified some putative predictors of efficacy of GLP-1 RA, which deserve further investigation.
AIMS: The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: A Medline and Embase search for "exenatide" OR "liraglutide" OR "albiglutide" OR "dulaglutide" OR "lixisenatide" was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs. Furthermore, unpublished studies were searched in the www.clinicaltrials.gov register. For meta-analyses, the outcome considered were 24- and 52-week HbA1c. Separate analyses were performed, whenever possible, for subgroups of trials based on several inclusion criteria. In addition, meta-regression analyses were performed for comparisons for which 10 or more trails were available. RESULTS: A total of 92 trials fulfilling the inclusion criteria were identified. In placebo-controlled trials (n = 41), the 24-week mean reduction of HbA1c with GLP-1 RA was - 0.75 [- 0.87; - 0.63]%. Shorter-acting molecules appear to be more effective in patients with lower fasting glucose, whereas longer-acting agents in patients with higher fasting hyperglycaemia. Obesity and duration of diabetes do not seem to moderate the efficacy of GLP-1 RA, whereas in non-Caucasians and older patients liraglutide could be less effective. At 52 weeks, only 9 placebo-controlled trials were available for preventing any reliable analyses. CONCLUSIONS: Using a variety of approaches (meta-analyses of subgroup of trials, meta-regression, systematic review of subgroup analyses in individual trials, and meta-analyses of subgroups of patients), we identified some putative predictors of efficacy of GLP-1 RA, which deserve further investigation.
Entities:
Keywords:
Incretins; Systematic review; Type 2 diabetes mellitus
Authors: Jae Hyun Bae; Hyung Jin Choi; Kang Ik Kevin Cho; Lee Kyung Kim; Jun Soo Kwon; Young Min Cho Journal: Diabetes Metab J Date: 2019-11-04 Impact factor: 5.376
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