Dataset Information

Orally Administered Semaglutide Versus GLP-1 RAs in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Antidiabetics: Systematic Review and Network Meta-Analysis.

ABSTRACT:

Introduction

Orally administered semaglutide is the first glucagon-like peptide 1 receptor agonist (GLP-1 RA) for oral administration. As head-to-head trials assessing orally administered semaglutide as an add-on to 1-2 oral antidiabetic drugs (OADs) vs other GLP-1 RAs are limited, a network meta-analysis (NMA) was performed to assess the relative efficacy and safety of orally administered semaglutide 14 mg once-daily (QD) vs injectable GLP-1 RAs in patients with type 2 diabetes inadequately controlled on 1-2 OADs.

Methods

A systematic literature review was conducted to identify randomised controlled trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA_1c), weight, HbA_1c target levels (< 7.0% and ≤ 6.5%), blood pressure, and any gastrointestinal adverse events specified in system organ class. Data were synthesised using NMA and a Bayesian framework.

Results

In total, 27 studies were included in the analyses. Orally administered semaglutide 14 mg QD was associated with significantly greater reductions in HbA_1c vs most comparators, and numerically greater reductions vs semaglutide 0.5 mg once-weekly (QW), dulaglutide 1.5 mg QW and liraglutide 1.8 mg QD. HbA_1c reductions with semaglutide 1 mg QW were numerically greater than those with orally administered semaglutide 14 mg QD. Reductions in body weight for orally administered semaglutide 14 mg QD were significantly greater than all comparators except semaglutide QW (both doses). Orally administered semaglutide QD 14 mg was associated with statistically similar odds of experiencing gastrointestinal adverse events vs injectable GLP-1 RAs.

Conclusion

Orally administered semaglutide 14 mg QD as an add-on to 1-2 OADs is one of the most efficacious GLP-1 RAs for reducing HbA_1c and body weight at 26 ± 4 weeks. Orally administered semaglutide 14 mg QD is well tolerated, with a safety profile in line with the GLP-1 RA class.

Funding

Novo Nordisk.

SUBMITTER: Nuhoho S

PROVIDER: S-EPMC6848399 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionThe superior efficacy and safety of semaglutide once-weekly (QW), compared with dulaglutide, liraglutide, or exenatide QW, have been demonstrated in the SUSTAIN trials. This study assessed treatment persistence and adherence to semaglutide QW versus dulaglutide, liraglutide, or exenatide QW in a real-world setting.MethodsThis retrospective, database study used Optum's de-identified Clinformatics® Data Mart Database to identify glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment-naïve adult patients with type 2 diabetes (T2D) initiating semaglutide QW, dulaglutide, liraglutide, or exenatide QW between January 1, 2018 and April 30, 2019. Persistence (time remaining on treatment) was assessed with Kaplan-Meier survival estimates and Cox proportional hazard models. Adherence was assessed using proportion of days covered (PDC) and proportion of patients with PDC > 80%.ResultsOf 56,715 patients included, 3279 received semaglutide QW, 27,891 dulaglutide, 17,186 liraglutide, and 8359 exenatide QW. Patients initiating semaglutide QW were younger and with lower percentage of Medicare coverage than patients initiating the comparators. Persistence at 360 days was significantly higher for semaglutide QW (67.0%) versus dulaglutide (56.0%), liraglutide (40.4%), and exenatide QW (35.5%); p < 0.001 for all comparisons. Compared with semaglutide QW, the discontinuation rate was significantly higher for dulaglutide (hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.13, 1.32; p < 0.001), liraglutide (HR 1.80; 95% CI 1.66, 1.95; p < 0.001), and exenatide QW (HR 2.12; 95% CI 1.96, 2.30; p < 0.001). Adherence to semaglutide QW versus liraglutide at 360 days and to exenatide QW was 39.1% versus 30.0% [p = 0.07] and 27.7% [p = 0.02], respectively. Adherence to dulaglutide at 360 days was numerically higher than semaglutide QW (43.2% versus 39.1%; p = 0.45) but did not reach statistical significance.ConclusionPersistence with semaglutide QW was significantly greater than comparators, while adherence was comparable or greater. Together with earlier results from double-blind clinical studies, these data support semaglutide QW use for treatment of patients with T2D.

Project description:IntroductionOnce-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin.MethodsA systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework.ResultsIn total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c (- 0.88% to - 1.39% vs comparators) and weight (- 1.49 to - 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA1c vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators.ConclusionOnce-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA1c and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs.FundingNovo Nordisk.

Project description:IntroductionIn the randomized Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 10 trial, once-daily orally administered semaglutide-the first oral glucagon-like peptide 1 receptor agonist (GLP-1RA)-was similarly tolerated with comparable (at 7 mg) or better (at 14 mg) efficacy versus the injectable GLP-1RA dulaglutide 0.75 mg. Health-related quality of life (HRQoL) in PIONEER 10 was assessed using the Japanese-specific Diabetes Therapy-Related Quality of Life (DTR-QoL) questionnaire.MethodsThe DTR-QoL comprises 29 questions, providing four domain and total scores. Answers were converted to a score between 0 and 100, with higher scores indicating greater HRQoL. Two estimands were prespecified: treatment policy (regardless of treatment discontinuation or rescue medication use) and trial product (assuming on treatment without rescue medication) in all randomized patients. Outcomes were assessed at weeks 26 and 52.ResultsMean baseline DTR-QoL domain scores were similar between treatment arms and were generally lower (giving more scope for improvement) for "anxiety and dissatisfaction with treatment" (62.1-65.3) and "satisfaction with treatment" (53.9-57.9) than "burden on social activities and daily activities" (76.5-77.7) and "hypoglycemia" (83.5-88.2). Using the treatment policy estimand, orally administered semaglutide 7 and 14 mg improved HRQoL versus dulaglutide 0.75 mg for the total score (estimated mean change from baseline [CfB] 7.3 and 8.1 vs 3.3; estimated treatment difference [ETD] 3.9 and 4.8) and the "anxiety and dissatisfaction with treatment" domain (CfB 9.7 and 10.9 vs 3.7; ETD 6.0 and 7.2) at week 52. Orally administered semaglutide 14 mg improved the "satisfaction with treatment" domain versus dulaglutide 0.75 mg (CFB 13.8 vs 5.7; ETD 8.1). DTR-QoL scores for orally administered semaglutide tended to be more durable (sustained over time) than for dulaglutide. Outcomes for the trial product estimand were similar.ConclusionOrally administered semaglutide 7 and 14 mg improved the patients' HRQoL measured by the Japanese-specific DTR-QoL instrument versus dulaglutide 0.75 mg at week 52.Trial registrationClinicalTrials.gov NCT03015220.

Project description:About 2-3 % of the population participates in blood donation programmes. Each whole blood donation or ten apheresis donations cause a loss of 200-250 mg of iron. As a result, one of the most common risks of regular blood donors is iron deficiency. Although this has been known for decades, in most countries, iron status is currently not assessed or treated in this population. Premenopausal women are particularly affected, as they have lower iron reserves and higher daily requirements. Besides anaemia, iron deficiency may lead to fatigue and impaired cognitive and physical performance. Current iron preparations for intravenous administration are well tolerated and allow for application of large doses up to 1 g in one visit. Our hypothesis is that in blood donors with iron deficiency, intravenously administered iron is more efficient and as safe as oral iron supplementation. Since anaemia is one of the most frequent reasons for permanent or intermittent donor deferral, maintaining an iron-replete donor pool may help to prevent shortages in blood supply and to avoid iron deficiency-related comorbidities.In this randomised clinical trial we include male and female blood donors aged ?18 and ?65 years with a ferritin value of ?30 ng/ml. Stratified by gender, participants are randomized with a web-based randomisation tool in a 1:1 ratio to either 1 g of intravenously administered ferric carboxymaltose or 10 g of iron fumarate supplements at one to two daily doses of 100 mg each. Eight to 12 weeks after the first visit, iron status, blood count and symptoms are assessed in both groups. The primary endpoint is the difference in transferrin saturation (%) following the intervention between both groups. Secondary endpoints include other parameters of iron metabolism and red blood cell count, the number of patients with drug-related adverse events, and subjective symptoms including those of the restless legs syndrome, quality of life, and fatigue.Iron supplementation administered intravenously in non-anaemic but iron-deficient blood donors could represent an effective strategy to protect blood donors from comorbidities related with iron deficiency and therefore improve blood donor wellbeing. Furthermore, iron supplementation will help to maintain an iron-replete blood donor pool.EudraCT: 2013-000327-14, Clinical Trials Identifier: NCT01787526 . Registered on 6 February 2013.