Patients with type 2 diabetes (T2D) had significantly greater reductions in glycated hemoglobin (HbA1c) and body weight with semaglutide vs dulaglutide, according to results published in the Journal of Clinical Endocrinology & Metabolism. Both are glucagon-like peptide-1 receptor agonists (GLP-1 RAs), drugs which are often used as a treatment option in people with T2D.

Investigators conducted a multilevel network meta-regression in an indirect treatment comparison of the efficacy of semaglutide 2.0 mg vs dulaglutide 3.0 mg and 4.5 mg based on aggregate and individual patient data from the SUSTAIN FORTE and SUSTAIN 7 trials and published aggregate data from AWARD-11.

A total of 1842 patients (mean aged 57.1 years; 48.8% female; 86% White) were randomly assigned to dulaglutide in AWARD-11 (3.0 mg, n = 616; 4.5 mg, n = 614; 1.5 mg, n = 612).


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In SUSTAIN 7, 599 patients (mean aged 55.6 years; 44.4% female; 77% White) of 1199 patients were randomly assigned to semaglutide (1.0 mg, n = 300) or dulaglutide (1.5 mg, n = 299).

For SUSTAIN FORTE, 961 patients (mean age, 58.0 years; 41.4% female; 88% White) were randomly assigned to either semaglutide (1.0 mg, n = 481) or 2.0 mg (n = 480).

The main analysis showed that semaglutide 2.0 mg was more effective in lowering HbA1c from baseline vs dulaglutide 3.0 mg and 4.5 mg, with estimated treatment differences (ETDs) of –0.44% (95% credible interval [CrI], –0.68, –0.19) and –0.28% (95% CrI, –0.52, –0.03), respectively.

In addition, semaglutide 2.0 mg was  more effective for reducing body weight vs dulaglutide 3.0 mg and 4.5 mg, with ETDs of –3.29 kg (95% CrI, –4.62, −1.96) and   –2.57 kg (95% CrI, –3.90, –1.24), respectively.

The proportion of patients who had an HbA1c <7.0% was greater in those who received semaglutide 2.0 mg vs those who received dulaglutide 3.0 mg, with an odds ratio (OR) of 2.23 (95% CrI, 1.16, 3.90), although it did not reach significance for semaglutide 2.0 mg vs dulaglutide 4.5 mg (OR, 1.58; 95% CrI, 0.82, 2.78). Sensitivity analyses supported the main analysis results.

The study was limited by the comparison of estimands across trials, as small differences were involved in the handling of intercurrent events, and different criteria were used for initiation of rescue medication, noted the researchers. Also, it was not possible to conduct an analysis based on results of the treatment policy estimand in SUSTAIN FORTE and SUSTAIN 7 similar to the treatment-regimen estimand in AWARD-11, which included efficacy data for patients regardless of treatment discontinuation or rescue medication.

“The findings of this study, and particularly the results provided in different trial populations, provide important comparative effectiveness information until randomized head-to-head studies become available,” the investigators stated.

Disclosure: This study was supported by Novo Nordisk A/S, makers of Ozempic® (semaglutide). Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Lingvay I, Bauer R, Baker-Knight J, Lawson J, Pratley R. An indirect treatment comparison of semaglutide 2.0 mg vs dulaglutide 3.0 mg and 4.5 mg using multilevel network meta-regression. J Clin Endocrinol Metab. Published online December 18, 2021. doi:10.1210/clinem/dgab905