Dulaglutide — clinical evidence
Assessed outcomes with certainty ratings, contributing trials and the reasoning for each rating.
§3Clinical evidence
§3.1Atherosclerotic cardiovascular disease and cardiovascular risk reduction
Anchor outcome. Three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke).
Effect as recorded. MACE hazard ratio 0.88 in a population with a majority without established cardiovascular disease; HR 0.88 (95 % CI 0.79 to 0.99); 12.0 % versus 13.4 % over median 5.4 years.[1,2]
Certainty. High certainty The only large GLP-1 outcome trial enrolling a majority in primary prevention, which the Institute regards as an important distinguishing feature of this evidence base.
Contributing trials. REWIND. Full structured abstracts are published for each.
Full evidence extract for atherosclerotic cardiovascular disease and cardiovascular risk reduction · Indication assessment
§3.2Type 2 diabetes mellitus
Anchor outcome. Change in HbA1c (%, mmol/mol).
Effect as recorded. −1.1 to −1.9 % HbA1c across the AWARD programme; 4.5 mg gave −1.9 % in AWARD-11; AWARD-11 difference of 4.5 mg versus 1.5 mg −0.24 % (95 % CI −0.36 to −0.11).[2,3]
Certainty. High certainty Eleven-trial programme with active comparators.
Contributing trials. AWARD-1 · AWARD-5 · AWARD-6 · AWARD-11 · SUSTAIN-7. Full structured abstracts are published for each.
Full evidence extract for type 2 diabetes mellitus · Indication assessment
§3.3Obesity and overweight in adults
Anchor outcome. Percentage change in body weight from baseline.
Effect as recorded. −4.6 kg at 4.5 mg over 52 weeks in type 2 diabetes; difference versus 1.5 mg −1.9 kg (95 % CI −2.4 to −1.4).[3,4]
Certainty. Moderate certainty No dedicated obesity programme; weight effect is modest relative to the acylated analogues.
Contributing trials. AWARD-11. Full structured abstracts are published for each.
Full evidence extract for obesity and overweight in adults · Indication assessment
§3.4Chronic kidney disease in type 2 diabetes
Anchor outcome. Composite kidney outcome (kidney failure, sustained ≥50 % eGFR decline, kidney or cardiovascular death).
Effect as recorded. Slower eGFR decline versus insulin glargine in moderate-to-severe chronic kidney disease; eGFR difference at 52 weeks approximately 1.9 mL/min/1.73 m².[4,5]
Certainty. Low certainty Renal endpoints were secondary and the trial was not event-driven.
Contributing trials. AWARD-7. Full structured abstracts are published for each.
Full evidence extract for chronic kidney disease in type 2 diabetes · Indication assessment
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet 2019;394(10193):121–130. doi:10.1016/S0140-6736(19)31149-3 · PMID 31189511
- Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. The Lancet Diabetes & Endocrinology 2018;6(4):275–286. doi:10.1016/S2213-8587(18)30024-X · PMID 29397376
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. ICH Harmonised Tripartite Guideline 1999;Step 4 version. identifier not held by the Institute
- Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metabolism 2018;27(4):740–756. doi:10.1016/j.cmet.2018.03.001 · PMID 29617641
- Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes — state-of-the-art. Molecular Metabolism 2021;46:101102. doi:10.1016/j.molmet.2020.101102 · PMID 33068776
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