Liraglutide — 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 0.87 in type 2 diabetes at high cardiovascular risk; HR 0.87 (95 % CI 0.78 to 0.97); 13.0 % versus 14.9 % over median 3.8 years.[1,2]
Certainty. High certainty Event-driven with independent adjudication; 9,340 participants.
Contributing trials. LEADER. Full structured abstracts are published for each.
Full evidence extract for atherosclerotic cardiovascular disease and cardiovascular risk reduction · Indication assessment
§3.2Obesity and overweight in adults
Anchor outcome. Percentage change in body weight from baseline.
Effect as recorded. −8.0 % body weight at 56 weeks with 3.0 mg versus −2.6 % with placebo; estimated difference −5.4 percentage points (95 % CI −5.8 to −5.0).[2,3]
Certainty. High certainty Consistent across the SCALE programme. Inferior to semaglutide 2.4 mg in a direct comparison (STEP 8).
Contributing trials. SCALE-OBESITY · STEP-8. Full structured abstracts are published for each.
Full evidence extract for obesity and overweight in adults · Indication assessment
§3.3Type 2 diabetes mellitus
Anchor outcome. Change in HbA1c (%, mmol/mol).
Effect as recorded. −1.1 to −1.5 % HbA1c at 26 weeks with 1.8 mg; LEAD-6 difference versus exenatide twice daily −0.33 % (95 % CI −0.47 to −0.18).[3,4]
Certainty. High certainty Large and reproducible.
Contributing trials. LEAD-6 · LEADER. Full structured abstracts are published for each.
Full evidence extract for type 2 diabetes mellitus · Indication assessment
§3.4Adjunctive therapy in type 1 diabetes
Anchor outcome. Change in HbA1c.
Effect as recorded. HbA1c reduction of approximately 0.2 % with increased hypoglycaemia and hyperketonaemia; small effect, adverse safety trade-off.[4,5]
Certainty. Moderate certainty The Institute records this as a programme in which a statistically detectable benefit was judged not to justify the safety signal, and no approval followed.
Contributing trials. ADJUNCT-ONE · ADJUNCT-TWO. Full structured abstracts are published for each.
Full evidence extract for adjunctive therapy in type 1 diabetes · Indication assessment
§3.5Obesity in children and adolescents
Anchor outcome. Change in BMI (%, absolute, z-score).
Effect as recorded. BMI z-score reduction of 0.22 versus 0.01 with placebo at 56 weeks; estimated difference −0.22 (95 % CI −0.37 to −0.08).[5,6]
Certainty. Moderate certainty Smaller effect than semaglutide in an equivalent population.
Contributing trials. SCALE-TEENS. Full structured abstracts are published for each.
Full evidence extract for obesity in children and adolescents · Indication assessment
§3.6Obstructive sleep apnoea with obesity
Anchor outcome. Change in apnoea–hypopnoea index (events/hour).
Effect as recorded. Apnoea–hypopnoea index reduced by 12.2 events/hour versus 6.1 with placebo at 32 weeks; estimated difference −6.1 events/hour (95 % CI −11.0 to −1.2).[6,7]
Certainty. Moderate certainty Imprecise; substantially smaller effect than reported for tirzepatide.
Contributing trials. SCALE-SLEEP-APNOEA. Full structured abstracts are published for each.
Full evidence extract for obstructive sleep apnoea with obesity · Indication assessment
§3.7Prediabetes and progression to type 2 diabetes
Anchor outcome. Incident type 2 diabetes.
Effect as recorded. Time to onset of type 2 diabetes over 160 weeks: hazard ratio 0.21; HR 0.21 (95 % CI 0.13 to 0.34).[7,8]
Certainty. Moderate certainty Downgraded for the confounding effect of treatment on the diagnostic measure itself.
Contributing trials. SCALE-PREDIABETES. Full structured abstracts are published for each.
Full evidence extract for prediabetes and progression to 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.
- Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DCW, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JPH. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine 2015;373(1):11–22. doi:10.1056/NEJMoa1411892 · PMID 26132939
- Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB. Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine 2016;375(4):311–322. doi:10.1056/NEJMoa1603827 · PMID 27295427
- Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). The Lancet 2009;374(9683):39–47. doi:10.1016/S0140-6736(09)60659-0 · PMID 19515413
- Knudsen LB, Nielsen PF, Huusfeldt PO, Johansen NL, Madsen K, Pedersen FZ, Thøgersen H, Wilken M, Agersø H. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. Journal of Medicinal Chemistry 2000;43(9):1664–1669. doi:10.1021/jm9909645 · PMID 10794683
- Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA 2022;327(2):138–150. doi:10.1001/jama.2021.23619 · PMID 35015037
- 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
- United States Food and Drug Administration. WEGOVY (semaglutide) injection, for subcutaneous use — Highlights of Prescribing Information. FDA Approved Labeling 2024;Reference ID revision 01/2024. identifier not held by the Institute
- Medicines and Healthcare products Regulatory Agency. GLP-1 receptor agonists: reminder of the risk of hypoglycaemia and of use only for licensed indications. MHRA Drug Safety Update 2023;17(3). identifier not held by the Institute
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.