Article

Effects of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight: A Meta-Analysis

Geriatric Cardiology, Careggi Teaching Hospital and University of Florence, 50141 Florence, Italy.
Experimental Diabetes Research (Impact Factor: 3.54). 05/2012; 2012:672658. DOI: 10.1155/2012/672658
Source: PubMed

ABSTRACT Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for "exenatide," "liraglutide," "albiglutide," "semaglutide," and "lixisenatide" was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of -1.0 [-1.3; -0.6] kg/m(2). Considering the average BMI at baseline (32.4 kg/m(2)) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction.

Download full-text

Full-text

Available from: Edoardo Mannucci, Jul 05, 2015
0 Followers
 · 
254 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Once lifestyle measures implemented, if hyperglycemia persists, above individual HbA1c targets, a medication should be started in type 2 diabetic patients (T2DM). First, unless exception, an oral antidiabetic drug. Except in case of intolerance, the initial monotherapy, metformin remains the strengthening treatment. Latter, combination of two oral drugs, now offers several options, mainly the choice to associate a "conventional insulin-secretor", sulfonylureas, glinide, or a "new one" belonging the class of "incretin", more readily a gliptine (DPP-4 inhibitors) rather than injectable GLP-1 analogue which can also be sometimes chosen at this stage. These options are mostly new and have the advantage a neutral or favourable (for GLP-1) effect on body weight in obese type 2 DM patient and the absence of any hypoglycaemic risk in both classes of incretins. But this risk varies depending on the patient profile, much higher if the target HbA1c is low (6 to 6.5 or 7%), or in the elderly, fragile and/or in case of renal insufficiency. These two different situations with a high risk of hypoglycaemia, define best indications of this new class. If dual oral therapy does not achieve the goals we are faced with three options: triple oral therapy: metformin-sulfonylurea-gliptine or one of two approaches with injections, insulin or GLP-1 analogues. The use of GLP-1 analogues is often delayed today and put wrongly in balance with the transition to insulin, a use already delayed in France and insufficient. The use of incretins is new and needs to be validated by studies of sustainability on glycemic control, prevention of microvascular and macrovascular complications and after years on the market security of use, primarily on the exocrine pancreas. In short, individualization of strategies and HbA1c targets are required, the new molecules can help us in this process. This individualization can easily be done through the handy guide proposed by the experts ADA EASD statement, endorsed by the SFD, abandoning the complex algorithm recently again proposed by HAS and ANSM in 2013. A recommendation that prioritizes the costs of the strategies. An absolutely critical issue, while admitting not to have the tools to measure them in all their dimensions. Finally, we must reconsider every treatment after a maximum of 6months of use, if the results are deemed inadequate substitute rather than adding drugs.
    La Presse Médicale 05/2013; · 1.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Une fois les mesures hygiénodiététiques mises en place, si l’hyperglycémie persiste et selon les cibles d’HbA1c visées, il convient d’entreprendre un traitement médicamenteux. En premier lieu, un antidiabétique oral hormis quelques exceptions. Si la monothérapie initiale, sauf intolérance, reste la metformine, le renforcement du traitement offre maintenant plusieurs options, principalement le choix de lui associer un « insulino-sécréteur conventionnel », sulfonylurées, glinide, ou un « nouvel insulino-sécréteur » de la classe des incrétines, plus volontiers une gliptine (inhibiteurs des DPP-4) plutôt qu’un analogue du GLP-1 injectable qui peut aussi être parfois choisi dès ce stade. Ces options sont nouvelles et offrent principalement l’avantage de l’absence de risque hypoglycémique et d’un effet neutre ou favorable sur le poids. Mais ce risque est très variable selon les patients, il est d’autant plus élevé que la cible HbA1c est basse (6,5 à 7 %) ou le sujet âgé, fragile et/ou insuffisant rénal. Ici dans ces deux situations le risque hypoglycémique, selon nous, définit les meilleures indications de cette nouvelle classe. Si la bithérapie orale ne permet pas d’atteindre les objectifs on est face à trois options : une trithérapie orale, metformine–sulfonylurées–gliptine ou une des deux approches injectables, la mise à l’insuline ou l’injection de GLP-1. L’usage des analogues du GLP-1 est donc souvent aujourd’hui retardé et mis, à tort, en balance avec le passage à l’insuline, recours déjà jugé tardif et insuffisant en France. L’usage des incrétines est récent et doit être validé par des études de durabilité sur le contrôle glycémique, sur la prévention des complications micro- et macrovasculaires (en cours) et après mise sur le marché sur la sécurité d’emploi, risque pancréatique exocrine principalement. En somme l’individualisation des prescriptions s’impose, les nouvelles molécules peuvent y contribuer, une fois déterminé le « profil patient ». Cette individualisation des objectifs et moyens de traitement peut aisément se faire grâce au guide très pratique proposé par la déclaration des experts ADA EASD, endossée par la SFD, abandonnant les algorithmes complexes encore récemment proposés par la HAS et l’ANSM dans sa recommandation 2013. Une recommandation qui priorise le coût des stratégies, question absolument cruciale, tout en admettant ne pas disposer des moyens de le mesurer dans toutes ses dimensions. Enfin, on doit savoir reconsidérer la thérapeutique choisie, après six mois d’utilisation au maximum, si les résultats sont jugés insuffisants, savoir la remplacer plutôt qu’additionner les molécules.
    La Presse Médicale 05/2013; 42(5):861–870. DOI:10.1016/j.lpm.2013.04.002 · 1.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We recently reported that short-term treatment with liraglutide (20.0 ± 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics. Patients with obesity (body mass index (BMI) >25 kg/m2) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 ± 5.3 kg/m2, n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 ± 3.0 kg/m2, n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge. Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style. Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.
    Cardiovascular Diabetology 09/2012; 11(1):107. DOI:10.1186/1475-2840-11-107 · 3.71 Impact Factor