ReviewCureus2026
Efficacy and Safety of Once-Weekly Semaglutide Versus Basal Insulin and Other GLP-1 Receptor Agonists in Adults With Type 2 Diabetes Uncontrolled on Oral Antidiabetic Drugs: A Systematic Review and Pairwise Meta-Analysis.
Review in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Authors and funding
2 authors.
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Abstract
Type 2 diabetes mellitus (T2DM) affects over 537 million adults worldwide. When oral antidiabetic drugs (OADs) fail, escalation to injectable therapy is required, yet no systematic review has simultaneously compared once-weekly semaglutide against basal insulin and other GLP-1 receptor agonists - specifically exenatide ER, insulin glargine, dulaglutide, and liraglutide - in insulin-naïve patients uncontrolled on OADs. This review aimed to evaluate the efficacy and safety of once-weekly semaglutide versus injectable antidiabetic therapies - specifically basal insulin (insulin glargine) and three GLP-1 receptor agonists (exenatide ER, dulaglutide, and liraglutide) - in adults with T2DM inadequately controlled on OADs, through pairwise meta-analyses of randomized controlled trials (RCTs). Five databases were searched from inception to April 2026. Eligible studies were phase 2b-4 RCTs of at least 12 weeks comparing once-weekly semaglutide against injectable therapy in insulin-naïve adults with T2DM. Two reviewers performed selection, extraction, and Cochrane Risk of Bias version 2 (RoB 2) assessment; both are co-authors with prior trial familiarity, constituting a registered protocol deviation. Random-effects pairwise meta-analyses were performed, and certainty was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Four Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) RCTs were included (n = 3,680 total; 2,705 analyzable for the primary comparison). Semaglutide 1.0 mg reduced HbA1c versus all comparators (mean difference (MD) -0.64%, 95% confidence interval (CI) -0.80 to -0.47; low certainty) and body weight (MD -4.38 kg, 95% CI -5.76 to -3.01; low certainty). Against GLP-1 RAs specifically, body weight reduction was homogeneous (MD -3.72 kg, 95% CI -4.17 to -3.28; I² = 0%; moderate certainty). Systolic BP was reduced (MD -2.32 mmHg; moderate certainty). HbA1c less than 7.0% was achieved more frequently with semaglutide (relative risk (RR) 1.60; low certainty). Hypoglycemia risk was lower versus insulin glargine (RR 0.53; moderate certainty). Gastrointestinal (GI) adverse events and treatment discontinuation were higher with semaglutide versus insulin (both low certainty). Moderate-certainty evidence supports greater body weight reduction with semaglutide versus other GLP-1 RAs and lower hypoglycemia risk versus basal insulin. Low-certainty evidence suggests HbA1c benefits versus all comparators. Certainty is limited by heterogeneity, open-label design across all included trials, and exclusive industry sponsorship by the manufacturer of semaglutide. Future independent trials are needed.
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