glucagon
Sources réglementaires consultées
Indications approuvées
- Traitement de l’hypoglycémie sévère chez les personnes diabétiques traitées par insuline ; inhibition diagnostique de la motilité gastro-intestinale chez l’adulte.
Contre-indications
Absolues
- Phéochromocytome ou hypersensibilité.
Mises en garde cliniques
- Mise en garde majeure · Il ne sera pas efficace si le glycogène hépatique est épuisé par un jeûne prolongé, une insuffisance surrénalienne, une hypoglycémie chronique ou l’alcool ; utiliser du glucose dans ces situations. — CIMA/AEMPS, ficha técnica 59327
- Mise en garde majeure · En cas d’insulinome, il peut provoquer une hypoglycémie rebond ; en cas de phéochromocytome, une crise hypertensive. — CIMA/AEMPS, ficha técnica 59327
Interactions médicamenteuses
- ModéréeWarfarine
Mécanisme: Le glucagon peut augmenter l’effet anticoagulant.
Recommandation: Surveiller l’INR après un usage diagnostique ou répété.
CIMA/AEMPS, ficha técnica 59327
- ModéréeIndométacine et bêtabloquants
Mécanisme: L’indométacine peut abolir la réponse glycémique ; les bêtabloquants peuvent accentuer l’augmentation transitoire du pouls et de la pression.
Recommandation: Surveiller la glycémie et la réponse cardiovasculaire ; utiliser du glucose IV en l’absence de réponse.
CIMA/AEMPS, ficha técnica 59327
Effets indésirables
Communs (≥1%)
Nausées, vomissements et douleur abdominale
Rares mais graves
Anaphylaxie, coma hypoglycémique et crise hypertensive
Grossesse et allaitement
Le glucagon ne traverse pas significativement le placenta et peut être utilisé lorsqu’il est indiqué. Il peut être utilisé pendant l’allaitement.
Bibliographie récente (PubMed)
Research on Glucagon-like peptide 1 receptor agonist (GLP-1RA) has mainly focused on the efficacy of weight loss and not the long-term efficacy of weight loss maintenance. This systematic review and meta-analysis aims to evaluate the sustainability of weight loss of patients taking GLP-1RAs following the discontinuation of the drug. EBSCOhost was used to simultaneously search Academic Search Premier, CINHAL Ultimate, Cochrane Central Register of Controlled Trials, MEDLINE with full text, Cochrane Database of Systematic Reviews, and separate PubMed search was systematically investigated using a predetermined search strategy from inception to February 1st, 2024. The authors extracted data regarding body weight change from baseline on treatment and off treatment, change in waist circumference from baseline on and off treatment, and change in BMI from baseline on and off treatment. Meta-analysis was conducted using RevMan (version 5.4) to calculate pooled mean differences using a Der Simonian-Laird Random Effects model. ResultsThe initial search yielded 497 relevant articles and, after screening, retained 8 randomized controlled trials comprised of 2372 participants, all with a BMI ≥ 27 kg/m2. After discontinuing GLP-1RA therapy, weight regain was proportional to the original weight loss. Participants who took liraglutide regained 2.20 kg (95% CI 1.69 to 2.70, P < 0.00001), and participants taking semaglutide/tirzepatide regained 9.69 kg (95% CI 5.78 to 13.60, P < 0.00001). This systematic review and meta-analysis show that significant weight is regained after discontinuing GLP-1RA treatment, which should be discussed when stopping therapy. PRACTITIONER POINTS: Question: Does discontinuation of Glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment lead to significant weight gain? Findings: In this systematic review and meta-analysis, discontinuing GLP-1RA treatment led to a pooled overall mean weight regain of 2.20 kg in participants taking liraglutide and 9.69 k
While glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively reduce body weight, their impact on lean mass remains uncertain. This meta-analysis evaluated the effects of GLP-1RAs and GLP-1/GIP receptor dual agonists (GLP-1/GIP-RAs) on body composition, focusing on total weight, fat mass, and lean mass in adults with diabetes and/or overweight/obesity. A systematic search of Medline, Embase, and the Cochrane Library was conducted through November 12, 2024. Data were analyzed using random-effects pairwise and network meta-analyses to compare interventions with placebo or active comparators. Twenty-two randomized controlled trials (2258 participants) were included. GLP-1RAs significantly reduced total body weight (MD -3.55 kg, 95 %-CI [-4.81, -2.29]), fat mass (MD -2.95 kg, 95 %-CI [-4.11, -1.79]), and lean mass (MD -0.86 kg, 95 %-CI [-1.30, -0.42]), with lean mass loss comprising approximately 25 % of the total weight loss. However, the relative lean mass, defined as percentage change from baseline, was unaffected. Liraglutide, at 3.0 mg weekly or 1.8 mg daily, was the only GLP-1RA to achieve significant weight reduction without significantly reducing lean mass. Tirzepatide (15 mg weekly) and semaglutide (2.4 mg weekly) were the most effective for weight and fat mass reduction but were among the least effective in preserving lean mass. Potent GLP-1 RAs, such as tirzepatide and semaglutide, demonstrate greater overall weight loss but are associated with a significant reduction in lean mass.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity. To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes. This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models. Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects. The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2 diabetes, and more recently, for weight loss. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial. To evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to explore risk factors for these associations. MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library (inception to June 30, 2021), websites of clinical trial registries (July 10, 2021), and reference lists. There were no language restrictions. Randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non-GLP-1 RA drugs in adults. Two reviewers independently extracted data according to the PRISMA recommendations and assessed the quality of each study with the Cochrane Collaboration risk-of-bias tool. Pooled relative risks (RRs) were calculated using random or fixed-effects models, as appropriate. The quality of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. The primary outcome was the composite of gallbladder or biliary diseases. Secondary outcomes were biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis. Data analyses were performed from August 5, 2021, to September 3, 2021. A total of 76 RCTs involving 103 371 patients (mean [SD] age, 57.8 (6.2) years; 41 868 [40.5%] women) were included. Among all included trials, randomization to GLP-1 RA treatment was associated with increased risks of gallbladder or biliary diseases (RR, 1.37; 95% CI, 1.23-1.52); specifically, cholelithiasis (RR, 1.27; 95% CI, 1.10-1.47), cholecystitis (RR, 1.36; 95% CI, 1.14-1.62), and biliary disease (RR, 1.55; 95% CI, 1.08-2.22). Use of GLP-1 RAs was also associated with increased risk of gallbladder or biliary diseases in trials for weight loss
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for glycemic control or weight management in patients with type 2 diabetes mellitus or overweight/obesity. However, there are concerns regarding their association with serious gastrointestinal adverse events, although findings have been inconsistent. We systematically searched 5 databases for placebo-controlled randomized controlled trials assessing GLP-1RAs in patients with type 2 diabetes mellitus, overweight/obesity, or metabolic dysfunction-associated steatohepatitis/metabolic dysfunction-associated steatotic liver disease. We included trials that reported cholecystitis, cholelithiasis, cholangitis, cholestasis, pancreatitis, gastroesophageal reflux disease (GERD), gastritis, esophagitis, gastrointestinal ischemia, gastrointestinal hemorrhage, intestinal obstruction, paralytic ileus, gastrointestinal ulceration, gastrointestinal perforation, or gastroparesis. Meta-analyses were performed using a random-effects model, with subgroup analyses evaluating risks based on patient population, GLP-1RA vs dual-agonist formulation, weight-loss profile, dosing, and duration of action. We included 55 randomized controlled trials involving 106,395 participants. GLP-1RAs increased the risk of cholelithiasis (risk ratio [RR], 1.46; 95% CI, 1.09-1.97; 2 more cases per 1000) and probably increased the risk of GERD (RR, 2.19; 95% CI, 1.48-3.25; 4 more cases per 1000) compared with placebo. GLP-1RAs probably have little or no effect on the risk of other gastrointestinal or biliary events. Subgroup analyses showed that the increased risks of cholelithiasis and GERD were more pronounced in trials including individuals with overweight/obesity or metabolic dysfunction-associated steatohepatitis/metabolic dysfunction-associated steatotic liver disease, weight-loss-inducing GLP-1RAs, or high-dose formulations, although these subgroup effects were not statistically significant. GLP-1RAs are associated with an increased r