Semaglutide for type 2 diabetes mellitus: A systematic review and meta‐analysis

Andréadis, P; Karagiannis, Thomas; Malandris, Konstantinos; Avgerinos, Ioannis; Liakos, Aris; Manolopoulos, Apostolos; Bekiari, Eleni; Matthews, David R.; Τσάπας, Απόστολος

doi:10.1111/dom.13361

Cited by 91 publications

(70 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, these findings were largely driven by the results of the PIONEER 6 cardiovascular outcome trial . Moreover, similar to other GLP‐1 receptor agonists, oral semaglutide slightly increased heart rate, although the clinical relevance of this finding is still unknown . Discontinuation rates caused by gastrointestinal adverse events were dose dependent and higher compared with placebo or sitagliptin but similar to other injectable GLP‐1 receptor agonists, hence a slower dose‐escalation regimen might be helpful for patients experiencing increased nausea.…”

Section: Discussionmentioning

confidence: 99%

Oral semaglutide for type 2 diabetes: A systematic review and meta‐analysis

Avgerinos

Michailidis

Liakos

et al. 2019

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

Aim To assess the efficacy and safety of oral semaglutide, a novel glucagon‐like peptide‐1 receptor agonist, for patients with type 2 diabetes. Methods We searched Medline, Embase, the Cochrane Library and grey literature sources up to July 1, 2019 for randomized controlled trials (RCTs) comparing oral semaglutide with placebo or other antidiabetic agents. The primary outcome was change from baseline in HbA1c. Secondary outcomes included change from baseline in body weight and blood pressure, cardiovascular endpoints, severe hypoglycaemia, gastrointestinal adverse events and diabetic retinopathy. We synthesized results using weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, along with 95% confidence intervals (CIs). Results We included 11 RCTs with 9890 patients in the systematic review. Compared with placebo, oral semaglutide reduced HbA1c and body weight (WMD –0.89%, 95% CI −1.07 to −0.71 and − 2.99 kg, 95% CI −3.69 to −2.30, respectively). Oral semaglutide was also superior to other active comparators (including liraglutide, empagliflozin and sitaglipitin) in terms of lowering HbA1c (WMD –0.35%, 95% CI −0.43 to −0.26) and reduction of body weight (WMD −1.48 kg, 95% CI −2.28 to −0.67), and had a favourable effect on systolic blood pressure. Compared with placebo, oral semaglutide reduced all‐cause mortality (OR 0.58, 95% CI 0.37 to 0.92) and cardiovascular mortality (OR 0.55, 95% CI 0.31 to 0.98), and had a neutral effect on myocardial infarction, stroke, severe hypoglycaemia and diabetic retinopathy. However, treatment with oral semaglutide increased the incidence of nausea, vomiting and diarrhea, while events of acute pancreatitis were rare. Conclusions Oral semaglutide can effectively and safely reduce blood glucose, body weight and systolic blood pressure. Nevertheless, it is associated with increased incidence of gastrointestinal adverse events. Further research is needed to clarify its long‐term safety and comparative effectiveness against other antidiabetic agents.

show abstract

Section: Discussionmentioning

confidence: 99%

Oral semaglutide for type 2 diabetes: A systematic review and meta‐analysis

Avgerinos

Michailidis

Liakos

et al. 2019

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

“…In REWIND, there was no increase in retinopathy complications associated with dulaglutide compared with SOC, and no increased risk of retinopathy was noted in EXSCEL 18,19 . Overall, GLP‐1 RAs as a class were not associated with an increased risk of retinopathy 49‐51 …”

Section: Resultsmentioning

confidence: 93%

Cardiovascular safety outcomes of once‐weekly GLP‐1 receptor agonists in people with type 2 diabetes

Goldman

2020

J Clin Pharm Ther

View full text Add to dashboard Cite

What is known and objective People with type 2 diabetes (T2D) are at increased risk of cardiovascular disease (CVD), which in turn is associated with increased morbidity and mortality. The impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on cardiovascular (CV) outcomes has been investigated in CV outcomes trials (CVOTs). This review aims to help pharmacists and other healthcare professionals (HCPs) gain a better understanding of such CVOTs in T2D with a primary focus on the once‐weekly (QW) GLP‐1 RAs. Methods This narrative review mainly focuses on the evaluation of the similarities and differences in the design and results of CVOTs involving currently approved and marketed QW GLP‐1 RAs—semaglutide subcutaneous, exenatide extended‐release (ER) and dulaglutide. Results from CVOTs of dipeptidyl peptidase‐4 inhibitors (DPP4is) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) are also included. Results and discussion Three CVOTs of QW GLP‐1 RAs were identified for inclusion in this review: SUSTAIN 6 (semaglutide), EXSCEL (exenatide ER) and REWIND (dulaglutide), all of which varied in terms of trial design, patient demographics and other baseline characteristics. Results from these CVOTs demonstrated the CV safety of QW GLP‐1 RAs compared with standard of care. Additionally, CV and renal benefits were demonstrated for semaglutide and dulaglutide, but not for exenatide ER. The CV safety of four DPP4is and three SGLT2is was demonstrated. None of the DPP4is had a CV or renal benefit, whereas all three SGLT2is were associated with CV and renal benefits. What is new and conclusion This article provides an overview of the results from QW GLP‐1 RA CVOTs, including the recently published results for dulaglutide, and places them within the broader T2D treatment landscape to help HCPs make informed decisions in daily practice. The QW GLP‐1 RAs with benefits reaching beyond glycaemic control can provide a comprehensive treatment option for people with T2D at high risk of CVD, with CVD or chronic kidney disease.

show abstract

“…8,9,14,24,33,34 This glycaemic control has been shown consistently across clinical trials with the three QW and other GLP-1 RAs. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] The differing half-lives and MoA appear to influence the degree of the glycaemic control. Greater and more consistent reductions in glycated haemoglobin (HbA 1c ) levels were seen with longer-acting GLP-1 RAs compared with short-acting agents.…”

Section: Mechanism Of Action Related To Glycaemic Controlmentioning

confidence: 99%

“…62 This aspect of their MoA is evident through proven efficacy for reducing body weight in people with T2D. 51,[64][65][66][67][68] Clinical studies showed changes in body weight that varied among the QW GLP-1…”

Section: Effects On Body Weightmentioning

confidence: 99%