Comparison of Efficacy and Safety of Commercially Available Fixed-Ratio Combinations of Insulin Degludec/Liraglutide and Insulin Glargine/Lixisenatide: A Network Meta-analysis

Our aim in this study was to compare the efficacy and safety of commercially available fixed-ratio combinations (FRCs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and basal insulins by a network meta-analysis of randomized controlled trials (RCTs) of people with type 2 diabetes. We prese...

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Bibliographic Details
Published in:Canadian journal of diabetes 2023-06, Vol.47 (4), p.368-377
Main Authors: Visolyi, Gergely Á., Domján, Beatrix A., Svébis, Márk M., Péterfi, Anna, Lovász, Barbara D., Mészáros, Szilvia, Horváth, Viktor J., Tabák, Ádám G.
Format: Article
Language:English
Subjects:
agoniste du GLP-1
basal insulin
Blood Glucose
Diabetes Mellitus, Type 2 - drug therapy
Drug Combinations
GLP-1 receptor agonist
Glycated Hemoglobin
Humans
Hypoglycemia - chemically induced
Hypoglycemia - prevention & control
Hypoglycemic Agents - therapeutic use
insulin degludec
insulin glargine
Insulin Glargine - therapeutic use
insuline basale
insuline dégludec
insuline glargine
liraglutide
Liraglutide - adverse effects
lixisenatide
lixisénatide
méta-analyse en réseau
Network Meta-Analysis
Randomized Controlled Trials as Topic
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Summary:Our aim in this study was to compare the efficacy and safety of commercially available fixed-ratio combinations (FRCs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and basal insulins by a network meta-analysis of randomized controlled trials (RCTs) of people with type 2 diabetes. We present a systematic review and network meta-analyses of RCTs of individuals with type 2 diabetes randomized to FRCs or to their components for ≥24 weeks. All reports were obtained from PubMed or ClinicalTrials.gov up to February 28, 2022. The primary outcome was glycated hemoglobin (A1C) level attained. Secondary outcomes included fasting plasma glucose, change in body weight, and incident hypoglycemia. Treatment effects were estimated as mean difference (MD) and standard error (SE), or as odds ratio (OR) with 95% confidence interval (CI) using the fixed combination of insulin glargine 100 IU/mL and lixisenatide (iGlarLixi) as reference. We included 29 RCTs from among the 1,404 articles identified. No direct comparisons between FRCs were found. After excluding some insulin-capped trials to reach model consistency, both FRCs were more efficacious regarding A1C than their components, but no difference between FRCs was found (MD, −0.10%; SE, 0.10%). The effect of the fixed combination of insulin degludec and liraglutide (IDegLira) (MD, −0.47 mmol/L; SE, 0.24 mmol/L) and basal insulins was similar to that of iGlarLixi (reference) on fasting glucose, whereas GLP-1RAs had lower efficacy than iGlarLixi. Weight gain was lower with GLP-1RAs and IDegLira (MD, −0.72 kg; SE, 0.32 kg) than with iGlarLixi (reference) and higher with basal insulins. Incident hypoglycemia (based on different definitions) was least frequent with GLP-1RAs, followed by IDegLira (OR, 0.78; 95% CI, 0.39 to 1.57), iGlarLixi (reference), and basal insulins. For A1C, both FRCs were more efficacious over their individual components, with similar efficacies of the 2 FRCs. L’objectif de notre étude était de comparer l’efficacité et l’innocuité des combinaisons, à ratio fixe (CRF), commercialisées d’agonistes du récepteur GLP-1 (de l’anglais glucagon-like peptide-1) (ARGLP-1) et d’insuline basales d’après une méta-analyse en réseau d’essais comparatifs à répartition aléatoire (ECRA) de patients atteints du diabète de type 2. Nous présentons une revue systématique et des méta-analyses en réseau d’ECRA de patients atteints du diabète de type 2 répartis de façon aléatoire aux CRF ou à leurs composants durant ≥24
ISSN:1499-2671
2352-3840
DOI:10.1016/j.jcjd.2023.03.002