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: 4.33). 05/2012; 2012:672658. DOI: 10.1155/2012/672658
Source: PubMed


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.

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    • "It might be because body fat distribution differs across ethnic background, Chinese and South Asian cohorts had relatively greater amount of abdominal adipose tissue, and this difference was more pronounced in VAT [28]. It is possible that liraglutide exhibited its utmost effectiveness on weight reduction merely due to genetic differences, confirming the hypothesis of one recent study from Japanese in which liraglutide administrated 0.9 mg once-daily achieved about 10% of body weight reduction after 6 months, the result was also much greater than those mainly done in Caucasians [13,29], however the Japanese study failed to observe the reductions in body fat tissue, and the present study using DXA and CT to assess the changes in liraglutide-induced body compositions only performed in Chinese obese T2D. Therefore, the excellent results of liraglutide-induced reductions in fat tissue should be supported in the future in a double-blind placebo-controlled clinical trial across ethnic groups. "
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    ABSTRACT: Background and aims: Liraglutide treatment can improve glycemic control with a concomitant weight loss, but the underlying mechanism on weight loss is not completely understood. Cardiac natriuretic peptides (NPs) can resist body fat accumulation through increasing adipocytes lypolysis. In this study, we tested the hypothesis that liraglutide-induced weight loss was associated with increased plasma NPs concentrations. Thirty-one outpatients with type 2 diabetes (T2D) treated with metformin and other oral antidiabetic drugs except for thiazolidinediones (TZDs) were subcutaneously administered with liraglutide for 12 weeks. Body composition, abdominal visceral adipose tissue areas (VAT) and subcutaneous adipose tissue areas (SAT) were assessed at pre- and post-treatment by dual-energy X-ray absorptiometry (DXA) scanning and abdominal computerized tomography (CT). Plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) concentrations were tested by commercial ELISA Kit quantitatively. Following 12-week liraglutide treatment, body weight, waist circumference, total fat and lean mass, fat percentage, SAT and VAT areas were significantly reduced from baseline. Concurrently, plasma ANP and BNP levels were significantly increased following 12-week liraglutide treatment. There were significant correlations between the reductions in body compositions and the increases in both plasma ANP and BNP levels. There were significant correlations between increases in both plasma ANP and BNP levels and changes in liraglutide-induced body composition. Our data implied that increases in plasma NPs may add a novel dimension to explain how liraglutide induces weight loss.
    Full-text · Article · Feb 2014 · Cardiovascular Diabetology
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    • "However, insulin therapy is often associated with bodyweight gain and hypoglycemia3, and antidiabetic therapies that circumvent these problems have long been sought. GLP‐1 receptor agonists, such as liraglutide, are gaining attention because they can ameliorate glycemic control with lower risk of hypoglycemia, and have the ability to reduce bodyweight as well28. Head‐to‐head trials comparing GLP‐1 receptor agonists with insulin glargine or biphasic insulin demonstrated that GLP‐1 receptor agonists show similar or slightly improved HbA1c reduction with significant bodyweight reduction11. "
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    ABSTRACT: Aims/IntroductionThe safety and efficacy of insulin-to-liraglutide switch in type 2 diabetes has not been studied adequately. Here, we retrospectively characterize clinical parameters that might predict insulin-to-liraglutide treatment switch without termination due to hyperglycemia, and examine the effects of switching the therapies on glycated hemoglobin (HbA1c) and bodyweight in Japanese type 2 diabetes. Materials and Methods Japanese type 2 diabetes patients who underwent the switch of therapy were evaluated for their clinical data including β-cell function-related indices, such as increment of serum C-peptide during glucagon stimulation test (GST-ΔCPR). HbA1c and bodyweight were analyzed in patients continuing with liraglutide after switching from insulin for 12 weeks. ResultsOf 147 patients, 28 failed in the switch due to hyperglycemia, nine failed because of other reasons and 110 continued with liraglutide for the 12-week period. Patients failing in the switch due to hyperglycemia showed longer duration and higher daily insulin dose, as well as lower GST-ΔCPR. Receiver–operating characteristic analysis showed that GST-ΔCPR of 1.34 ng/mL is a cut-off point for insulin-to-liraglutide switch without termination due to hyperglycemia. In patients continuing liraglutide for 12 weeks, the switch significantly reduced HbA1c and bodyweight with no severe hypoglycemia, irrespective of sulfonylurea co-administration, body mass index, duration and total daily insulin dose. The switch also significantly reduced the percentage of body fat and visceral fat areas. Conclusions Insulin-to-liraglutide switch can improve glycemic control and reduce bodyweight in Japanese type 2 diabetes patients. However, caution must be taken with the switch in patients with reduced insulin secretory capacity as predicted by GST-ΔCPR.
    Full-text · Article · Nov 2013 · Journal of Diabetes Investigation
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    • "Les données sont similaires avec la sitagliptine. Pour les analogues du GLP-1 la baisse d'HbA1c peut être très importante, À1,5 à À2 %, chez certains patients très hyperglycémiques au départ (HbA1c > 8,5 à > 10 %) et en fort surpoids (IMC > 35 kg/m 2 ), donc en l'absence de signe de carence insulinique marquée [24] [25] [26] [27]. "
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    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.
    Full-text · Article · May 2013 · La Presse Médicale
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