Efficacy Of Glucagon-like Peptide-1 Receptor Agonists Research Articles

Effects of Glucagon-Like Peptide1 Receptor Agonists on Atrial Fibrillation Recurrence After Catheter Ablation: A Systematic Review and Meta-analysis.

Despite the technological advancements in catheter ablation strategies, the recurrence of atrial fibrillation (AF) post-ablation remains a concern that requires further investigation. Glucagon-like peptide1 (GLP-1) receptor agonists have shown a significant effect on weight reduction, which in turn is associated with freedom from AF recurrence in both patients who are obese and not obese undergoing ablation. Therefore, we aimed to summarize the available evidence on the efficacy of GLP-1 receptor agonists in maintaining sinus rhythm post-ablation. Medline, Cochrane Library, and Scopus were searched until June 9, 2024. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled using DerSimonian-Laird random effects meta-analysis. Three propensity score-matched studies (n = 6031 participants) were analyzed. Over a 12-months follow-up, the use of GLP-1 receptor agonists was associated with a significant reduction in AF recurrence compared to controls, hazard ratio (HR) = 0.549, 95% confidence interval (CI) = [0.315, 0.956], P = 0.034; I2 = 57%. No significant heterogeneity was observed (Qstatistic = 4.6, heterogeneity P = 0.1). The use of GLP-1 receptor agonists is associated with a lower risk of AF recurrence in patients receiving AF ablation therapy. Further large-scale randomized trials are necessary to explore the efficacy of GLP-1 receptor agonists in maintaining ablation outcomes over the long term.

Real-world effectiveness of GLP-1 receptor agonist-based treatment strategies on "time in range" in patients with type 2 diabetes.

Background: Diabetes affects millions of people worldwide annually, and several methods, including medications, are used for its management; glucagon-like peptide-1 receptor agonists (GLP-1RAs) are one such class of medications. The efficacy and safety of GLP-1RAs in treating type 2 diabetes mellitus (T2DM) have been assessed and have been shown to significantly improve time in range (TIR) in several clinical trials. However, presently, there is a lack of real-world evidence on the efficacy of GLP-1RAs in improving TIR. To address this, we investigated the effect of GLP-1RA-based treatment strategies on TIR among patients with T2DM in real-world clinical practice. Methods: This multicenter, retrospective, real-world study included patients with T2DM who had previously used a continuous glucose monitoring (CGM) system and received treatment with GLP-1RAs or oral antidiabetic drugs (OADs). Patients who received OADs served as controls and were matched in a 1:1 ratio to their GLP-1RA counterparts by propensity score matching. The primary endpoint was the TIR after 3-6 months of treatment. Results: According to propensity score matching, 202 patients were equally divided between the GLP-1RA and OAD groups. After 3-6 months of treatment, the TIR values for the GLP-1RA and OAD groups were 76.0% and 65.7%, respectively (p < 0.001). The GLP-1RA group displayed significantly lower time above range (TAR) and mean glucose values than the OAD group (p < 0.001). Subgroup analysis revealed that, compared with the administration of liraglutide, the administration of semaglutide and polyethylene glycol loxenatide (PEG-Loxe) significantly improved TIR over 3-6 months of treatment (p < 0.05). Conclusion: These real-world findings indicate that GLP-1RA-based treatment strategies could be superior to oral treatment strategies for improving TIR among patients with T2DM and that once-weekly GLP-1RA may be more effective than a once-daily GLP-1RA. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html, identifier number ChiCTR2300073697.

Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis.

Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12months (interquartile range 6-23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD -0.07ml/min/1.73m2 (95% CI -0.64-0.50)] or creatinine [SMD -0.08mg/dl (95% CI -0.44-0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD -0.47 (95% CI -0.77 to -0.18)] and haemoglobin A1c levels [MD -0.85% (95% CI -1.41 to -0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD -0.43ng/ml (95% CI -0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%). GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.

Safety and Efficacy of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus with Advanced and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Background and Objectives: Limited evidence exists regarding the safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD). Thus, we conducted a systematic review and meta-analysis to assess the safety and efficacy of GLP-1RAs in T2DM patients with advanced CKD and ESKD. Materials and Methods: We performed a systematic literature search in MEDLINE, EMBASE, and Cochrane database until 25 October 2023. Included were clinical trials and cohort studies reporting outcomes of GLP-1RAs in adult patients with T2DM and advanced CKD. Outcome measures encompassed mortality, cardiovascular parameters, blood glucose, and weight. Safety was assessed for adverse events. The differences in effects were expressed as odds ratios with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference or standardized mean difference (SMD) with 95% confidence intervals for continuous outcomes. The Risk of Bias In Non-randomized Studies-of Interventions (ROBIN-I) tool was used in cohort and non-randomized controlled studies, and the Cochrane Risk of Bias (RoB 2) tool was used in randomized controlled trials (RCTs). The review protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023398452) and received no external funding. Results: Eight studies (five trials and three cohort studies) consisting of 27,639 patients were included in this meta-analysis. No difference was observed in one-year mortality. However, GLP-1RAs significantly reduced cardiothoracic ratio (SMD of -1.2%; 95% CI -2.0, -0.4) and pro-BNP (SMD -335.9 pmol/L; 95% CI -438.9, -232.8). There was no significant decrease in systolic blood pressure. Moreover, GLP-1RAs significantly reduced mean blood glucose (SMD -1.1 mg/dL; 95% CI -1.8, -0.3) and increased weight loss (SMD -2.2 kg; 95% CI -2.9, -1.5). In terms of safety, GLP-1RAs were associated with a 3.8- and 35.7-time higher risk of nausea and vomiting, respectively, but were not significantly associated with a higher risk of hypoglycemia. Conclusions: Despite the limited number of studies in each analysis, our study provides evidence supporting the safety and efficacy of GLP-1RAs among T2DM patients with advanced CKD and ESKD. While gastrointestinal side effects may occur, GLP-1RAs demonstrate significant improvements in blood glucose control, weight reduction, and potential benefit in cardiovascular outcomes.

The Impact of GLP1 Agonists on Bone Metabolism: A Systematic Review.

Background and Objectives: The association between diabetes mellitus and increased risk of bone fractures has led to the investigation of the impact of antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP1RAs) are a relatively novel and promising class of anti-hyperglycemic drugs. In addition to their blood glucose lowering action, GLP1RAs seem to have additional pleiotropic properties such as a beneficial skeletal effect; although the underlying mechanisms are not completely understood. The present systematic review summarizes current evidence about GLP1RAs and their effects on bone metabolism and fracture. Methods: An extensive literature search was conducted based on electronic databases namely, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL) through October 2019 to January 2020 for articles related to bone mineral density, diabetes mellitus and GLP1RAs. We included articles published in English. Finally, we included four randomized controlled trials, three meta-analyses, a case-control study and a population-based cohort analysis. Results: Based on the articles included, the animal studies indicated the salutary skeletal effects of GLP1RAs in opposition to what has been commonly observed in human studies, showing that these agents have no impact on bone mineral density (BMD) and the turnover markers. Moreover, it was demonstrated that GLP1 was not associated with fracture risk as compared to other anti-hyperglycemic drugs. Conclusions: Findings from this systematic review have demonstrated the neutral impact of GLP1RAs on BMD. Moreover, further double-blind randomized controlled trials are needed to draw more meaningful and significant conclusions on the efficacy of GLP1RAs on BMD.

Prescribing by Ethnicity: (Im)precision Medicine?

The right drug, for the right patient, at the right time. Who wouldn’t want this? For diabetologists, after decades of domination by biguanides and sulfonylureas, only briefly punctuated by thiazolidinediones, the choice of early-stage glucose-lowering agents has recently more than doubled, now including glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP-4) and sodium–glucose cotransporter 2 (SGLT2) inhibitors. Armed with this greater choice, can we now fulfill the promise of precision medicine? Half of the 500 million people in the world with diabetes live in either China or the Indian subcontinent (1). Aside from simple demographics, these huge numbers are largely due to the greater diabetes susceptibility experienced by both populations. In this issue, Gan and associates (2) hypothesize that pathophysiological differences contributing to this greater susceptibility may be associated with different glycemic responses to diabetes medication. This is not unreasonable; 20% of new drug approvals show differences in exposure or response by ethnicity (3). They performed a systematic review and meta-analysis of published randomized clinical trials comparing absolute change in HbA1c from baseline to either 24 or 52 weeks in studies that recruited predominantly (>70%) Asians versus studies that recruited predominantly (>70%) whites. They report that SGLT2 and, possibly, DPP-4 inhibitors are more effective in lowering HbA1c in Asians than in whites. There was no ethnic difference in efficacy of GLP-1 receptor agonists. Their findings are somewhat at odds with previous work. The most striking observation, of an ∼0.3% lower HbA1c in Asians than in whites in response to SGLT2 inhibitors, contrasts with a previous meta-analysis reporting no ethnic difference (4), though an agent-specific analysis did show modest superiority of dapagliflozin (0.16%) in Asians versus non-Asians. Gan et al. …

Activation of GLP-1 receptors attenuates oxycodone taking and seeking without compromising the antinociceptive effects of oxycodone in rats.

Despite the effectiveness of current medications to treat opioid use disorder, there is still a high rate of relapse following detoxification. Thus, there is critical need for innovative studies aimed at identifying novel neurobiological mechanisms that could be targeted to treat opioid use disorder. A growing body of preclinical evidence indicates that glucagon-like peptide-1 (GLP-1) receptor agonists reduce drug reinforcement. However, the efficacy of GLP-1 receptor agonists in attenuating opioid-mediated behaviors has not been thoroughly investigated. Using recently established models of opioid-taking and -seeking behaviors, we showed that systemic administration of the GLP-1 receptor agonist exendin-4 reduced oxycodone self-administration and the reinstatement of oxycodone-seeking behavior in rats. We also identified behaviorally selective doses of exendin-4 that reduced opioid-taking and -seeking behaviors and did not produce adverse feeding effects in oxycodone-experienced rats. To identify a central site of action, we showed that systemic exendin-4 penetrated the brain and bound putative GLP-1 receptors on dopamine D1 receptor- and dopamine D2 receptor-expressing medium spiny neurons in the nucleus accumbens shell. Consistent with our systemic studies, infusions of exendin-4 directly into the accumbens shell attenuated oxycodone self-administration and the reinstatement of oxycodone-seeking behavior without affecting ad libitum food intake. Finally, exendin-4 did not alter the analgesic effects of oxycodone, suggesting that activation of GLP-1 receptors attenuated opioid reinforcement without reducing the thermal antinociceptive effects of oxycodone. Taken together, these findings suggest that GLP-1 receptors could serve as potential molecular targets for pharmacotherapies aimed at reducing opioid use disorder.

GLP-1 receptor agonists and cardiovascular outcomes: an updated synthesis

In The Lancet Diabetes & Endocrinology, Søren Kristensen and colleagues present a new, up-to-date systematic review and meta-analysis 1 Kristensen SL Rørth R Jhund PS et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019; (published online Aug 14.)http://dx.doi.org/10.1016/S2213-8587(19)30249-9 Summary Full Text Full Text PDF PubMed Scopus (323) Google Scholar of cardiovascular outcome trials evaluating glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes—a timely update after the recent reporting of the primary results from the REWIND trial of dulaglutide 2 Gerstein HC Colhoun HM Dagenais GR et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019; 394: 121-130 Summary Full Text Full Text PDF PubMed Scopus (674) Google Scholar , 3 Gerstein HC Colhoun HM Dagenais GR et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019; 394: 131-138 Summary Full Text Full Text PDF PubMed Scopus (164) Google Scholar and the PIONEER 6 trial of oral semaglutide. 4 Husain M Birkenfeld AL Donsmark M et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019; (published online June 11.)DOI:10.1056/NEJMoa1901118 Crossref PubMed Scopus (391) Google Scholar Incorporating these new trials means that the new meta-analysis includes data from seven trials with a total of 56 004 patients and, of those with available data for the primary outcome of major adverse cardiovascular events (MACE), includes a minority of 12 983 patients who did not have established cardiovascular disease but rather had multiple cardiovascular risk factors (thus being considered primary prevention patients) and 10 773 patients with an estimated glomerular filtration rate of less than 60 mL/min per 1·73 m2. The findings from the meta-analysis thereby contribute useful evidence concerning the cardiovascular safety and efficacy of GLP-1 receptor agonists across a range of patient populations. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trialsTreatment with GLP-1 receptor agonists has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes. Full-Text PDF

Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide. In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) for cardiovascular efficacy outcomes and odds ratios for key safety outcomes. Of 12 articles identified in our search and screened for eligibility, four trials of cardiovascular outcomes of GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide). Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke; HR 0·90, 95% CI 0·82-0·99; p=0·033), a 13% RRR in cardiovascular mortality (0·87, 0·79-0·96; p=0·007), and a 12% relative risk reduction in all-cause mortality (0·88, 0·81-0·95; p=0·002), with low-to-moderate between-trial statistical heterogeneity. No significant effect of GLP-1 receptor agonists was identified on fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure. Overall, no significant differences were seen in severe hypoglycaemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer reported between GLP-1 receptor agonist treatment and placebo. Our findings show cardiovascular safety across all GLP-1 receptor agonist cardiovascular outcome trials and suggest that drugs in this class can reduce three-point major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality risk, albeit to varying degrees for individual drugs, without significant safety concerns. GLP-1 receptor agonists have a favourable risk-benefit balance overall, which should allow the choice of drug to be individualised to each patient's needs. Amylin Pharmaceuticals (AstraZeneca).

Evaluating the Long-Term Cost-Effectiveness of Daily Administered GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes in the United Kingdom.

IntroductionThe glucagon-like peptide-1 (GLP-1) receptor agonist class has grown in the last decade, with several agents available in the UK. However there is currently a paucity of evidence regarding the relative cost-effectiveness of liraglutide 1.2 mg versus other daily administered GLP-1 receptor agonists, due to a lack of head-to-head trial data. Therefore the present analysis was performed, using results from a network meta-analysis (NMA), to compare the cost-effectiveness of three currently available daily administered GLP-1 receptor agonists for treatment of diabetes in the UK setting.MethodsA validated and published diabetes model was used to make long-term projections of clinical outcomes and direct costs (2015 GBP) for patients receiving liraglutide 1.2 mg once-daily, exenatide 10 μg twice daily and lixisenatide 20 μg once-daily. Treatment effects were taken from an NMA evaluating the efficacy of GLP-1 receptor agonists and were applied in a cohort based on the Liraglutide Effect and Action in Diabetes 6 (LEAD-6) trial. Costs and utilities were based on published sources.ResultsLiraglutide 1.2 mg was associated with improved quality-adjusted life expectancy versus exenatide [9.19 versus 9.17 quality-adjusted life years (QALYs)] and lixisenatide (9.19 versus 9.12 QALYs). Improvements were driven by benefits in glycemic control, leading to a reduced incidence of diabetes-related complications. Liraglutide 1.2 mg was associated with reduced costs versus exenatide (GBP 36,394 versus GBP 36,547) and lixisenatide (GBP 36,394 versus GBP 36,496), with cost savings as a result of complications avoided entirely offsetting increased acquisition costs. Based on the projected outcomes, liraglutide was found to be dominant over both exenatide and lixisenatide.ConclusionLiraglutide 1.2 mg is likely to be considered cost-effective versus alternative daily administered GLP-1 receptor agonists for treatment of type 2 diabetes in the UK.

Glucagon-Like Peptide-1 Receptor Agonist Treatment for Pediatric Obesity.

Obesity is a complex and retractable disease for which effective and durable treatments are elusive. Successful treatment of severe obesity with lifestyle modification therapy alone is highly unlikely, particularly for adolescents. Pharmacotherapy, if appropriately prescribed, can be an effective tool to use in conjunction with lifestyle modification therapy to achieve better weight loss outcomes. Only a few obesity medications have been evaluated in children and adolescents with results suggesting modest efficacy. However, a new pipeline of obesity drugs has been recently approved for use among adults. Among these, glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment appears to have reasonable weight loss efficacy along with other beneficial pleiotropic effects. Although larger trials will be required to confirm the results, two small pediatric clinical trials have suggested that GLP-1RA treatment may be useful in adolescents with severe obesity. Once sufficient evidence is generated supporting the safety and efficacy of GLP-1RAs and other obesity medications in youth, the pediatric medical community needs to become less resistant to the use of pharmacotherapy. Otherwise, poor outcomes will continue to be the norm.

Efectos de los agonistas del receptor de GLP-1 sobre el control del metabolismo hidrocarbonado

Glucagon-like peptide-1 (GLP-1) receptor agonists are a new group of drugs for the treatment of type 2 diabetes mellitus (DM2). In the present article, we review the available evidence on the efficacy of GLP-1 receptor agonists as glucose-lowering agents, their place in therapeutic algorithms, and the clinical factors associated with a favorable treatment response. Finally, we describe the clinical characteristics of patients who may benefit from these drugs.

Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet.

Leptin may reduce pancreatic lipid deposition, which increases with progression of obesity and can impair β-cell function. The insulinotropic effect of glucagon-like peptide-1 (GLP-1) and the efficacy of GLP-1 receptor agonist are reduced associated with impaired β-cell function. In this study, we examined whether leptin could restore the efficacy of exenatide, a GLP-1 receptor agonist, in type 2 diabetes with increased adiposity. We chronically administered leptin (500 μg·kg⁻¹·day⁻¹) and/or exenatide (20 μg·kg⁻¹·day⁻¹) for 2 wk in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (STZ/HFD mice). The STZ/HFD mice exhibited hyperglycemia, overweight, increased pancreatic triglyceride level, and reduced glucose-stimulated insulin secretion (GSIS); moreover, the insulinotropic effect of exenatide was reduced. However, leptin significantly reduced pancreatic triglyceride level, and adding leptin to exenatide (LEP/EX) remarkably enhanced GSIS. These results suggested that the leptin treatment restored the insulinotropic effect of exenatide in the mice. In addition, LEP/EX reduced food intake, body weight, and triglyceride levels in the skeletal muscle and liver, and corrected hyperglycemia to a greater extent than either monotherapy. The pair-feeding experiment indicated that the marked reduction of pancreatic triglyceride level and enhancement of GSIS by LEP/EX occurred via mechanisms other than calorie restriction. These results suggest that leptin treatment may restore the insulinotropic effect of exenatide associated with the reduction of pancreatic lipid deposition in type 2 diabetes with increased adiposity. Combination therapy with leptin and exenatide could be an effective treatment for patients with type 2 diabetes with increased adiposity.

Glucagon-like peptide-1 receptor agonists as add-on therapy to basal insulin in patients with type 2 diabetes: a systematic review

The prevalence of obesity and diabetes continues to rise in the US. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is an effective treatment option for type 2 diabetes mellitus (T2DM) that promotes weight loss. Common and effective treatment options added to metformin therapy (basal insulin, sulfonylureas, and pioglitazone) contribute to weight gain, which makes the addition of GLP-1RAs advantageous. Exenatide was the first agent in this class and has recently been approved for use in combination with insulin glargine by the US Food and Drug Administration and the European Medicines Agency. Until recently, there was a lack of data examining basal insulin combined with these agents. The main purpose of this article is to review the prospective interventional data on the safety and efficacy of GLP-1RAs (exenatide, liraglutide, albiglutide, lixisenatide) combined with basal insulin therapy in nonpregnant adults with T2DM. Databases searched were PubMed, Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews (inception to January 2012). s presented at relevant diabetes and endocrine meetings from 2009 to 2011 were also reviewed, as were reference lists of identified publications. A total of five studies met the criteria and were included in the review. Data from these studies demonstrated that this combination therapy offers advantages for the treatment of diabetes, such as additional lowering of A1c without major risk for hypoglycemia, lower basal insulin requirements, decreased postprandial glucose levels (with or without fasting plasma glucose decreases), and weight loss, or at the very least, less weight gain. However, the gastrointestinal side effects and high cost of these agents may limit their use. This review demonstrates that adding a GLP-1RA to an existing basal insulin regimen is a reasonable treatment strategy in nonpregnant adult patients with T2DM.

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

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/m2. Considering the average BMI at baseline (32.4 kg/m2) 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.

Liraglutide: can it make a difference in the treatment of type 2 diabetes?

Despite advances in the management of type 2 diabetes, glycaemic control remains suboptimal for many patients because of the complexities of disease progression and the need to balance improved glycaemic control against adverse treatment effects, particularly weight gain and hypoglycaemia. Thus, the development of new antidiabetes therapies continues in earnest. Incretin hormones have been the recent focus of research, as they account for up to 70% of the insulin response following a meal. There is also a high concordance between the physiological actions of one hormone, glucagon-like peptide-1 (GLP-1), and the therapeutic needs of patients. As native human GLP-1 has a half life of only approximately 2 min, researchers have developed molecules that act as GLP-1 receptor agonists or inhibit the enzyme responsible for GLP-1 degradation (dipeptidyl peptidase-4). Liraglutide, a human GLP-1 analogue sharing 97% of its amino acid sequence identity with native GLP-1, has been approved for use as monotherapy (not in Europe) and in combination with selected oral agents. In this supplement, we summarise key liraglutide data, offer practical insight into what we might expect of liraglutide in clinical use and examine selected case studies. For reasons of the safety and efficacy of GLP-1 receptor agonists, many thought leaders believe that these will become background therapy for majority of patients in the coming years. This supplement will serve as a resource from which readers can extract information concerning the potential benefits for patients who are overweight, losing pancreatic beta-cell function and drifting towards the ravaging effects of chronic hyperglycaemia.