The factors predicting glucose and weight response to injectable semaglutide (Ozempic): real-world data from the Association of British Clinical Diabetologists’ audit programme

Authors

  • Tom Crabtree University Hospitals of Derby and Burton NHS Trust
  • Karen Adamson St John’s Hospital, Livingston, UK
  • Alex Bickerton Yeovil District Hospital, Yeovil District Hospital NHS Foundation Trust, Yeovil, UK
  • Alison Evans Gloucestershire Royal Hospital, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
  • Suzanne Phillips Gloucestershire Royal Hospital, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
  • Alison Gallagher Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK
  • Niels Larsen Royal Derby Hospital, University Hospitals of Derby and Burton NHS Trust, UK
  • Dennis Barnes Tunbridge Wells Hospital, Maidstone and Tunbridge Wells NHS Trust, UK
  • Ketan Dhatariya The Norfolk and Norwich Hospital, Norfolk and Norwich University Hospitals NHS Trust and Norwich Medical School, University of East Anglia
  • Benjamin CT Field  Department of Clinical and Experimental Medicine, University of Surrey, Guildford and Department of Diabetes and Endocrinology, Surrey and Sussex Healthcare NHS Trust, Redhill
  • Iskander Idris Royal Derby Hospital, University Hospitals of Derby and Burton NHS Trust and Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham
  • Robert EJ Ryder City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK

DOI:

https://doi.org/10.15277/bjd.2023.418

Keywords:

Semaglutide, audit, real-world

Abstract

Background: Previous randomised controlled trials have observed individual differences in response to Glucagon-Like Peptide-1 Receptor Agonists (GLP1RA) according to baseline characteristics such as glycated haemoglobin (HbA1c) and weight. The Association of British Clinical Diabetologists (ABCD) launched a nationwide UK audit in January 2019 to assess the clinical utility, efficacy and safety of injectable semaglutide in routine practice. The aim of this analysis was to investigate associations between baseline characteristics and HbA1c and weight reductions with semaglutide in real-world use.

Methods: Data were extracted from the secure online tool and individuals who had baseline and follow-up data available within a defined 6 (3-9) month window were included. Variables were assessed as both continuous variables and categorical variables in a multivariate regression model. Missing data were multiply imputed.

Results: In total, 620 individuals were included. Baseline characteristics: (mean±SD) age was 58.7±10.7 years, HbA1c 81.6±18.5 mmol/mol (9.5±1.7%), weight 108.2±24.2 kg and body mass index (BMI) 37.6±7.6 kg/m2. Median diabetes duration was 11.2 years (IQR 6.6-16) and 50.5% (313/620) of subjects were male. The median follow-up time was 0.5 years. HbA1c reduced by 14.9 mmol/mol (95% CI 13.5, 16.1) [-1.4% (95% CI - 1.2, -1.5)]; p<0.001; and weight reduced by 4.2kg (95% CI 3.6, 4.8; p<0.001). Higher HbA1c, younger age and GLP1RA naïvety were associated with larger HbA1c reduction. Higher baseline weight/BMI and GP1RA naïvety were associated with larger weight reduction.

Conclusion: In this real-world study, baseline HbA1c and weightwere important predictors of HbA1c and weight reduction outcomes following initiation of semaglutide in routine clinical practice. Our data mirror existing randomised controlled trial data, but further evidence is being collected over a longer follow-up period.

References

International Diabetes Federation. Diabetes Atlas, 2023. Accessed 27/06/2023. Available from: https://diabetesatlas.org/

Ong KL, Stafford LK, McLaughlin SA, et al; GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2023;402:203-34. https://doi.org/10.1016/S0140-6736(23)01301-6

NHS Digital. National Diabetes Audit Core Report 1: Target 2021-22. 2023 [cited 2023 05/01/2022]; Available from: https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-audit/nda-core-21-22/nda-core-21-22-data.

Ahlqvist E, Storm P, Karajamaki A, et al. Novel subgroups of adult- onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol 2018; 6(5):361-9. https://doi.org/10.1016/S221308587(18)30051-2

Misra S, Wagner R, Ozkan B, et al. Systematic review of precision subclassification of type 2 diabetes. medRxiv https://doi.org/2023.04.19.23288577.

Dennis JM. Precision medicine in type 2 diabetes: using individualized prediction models to optimize selection of treatment. Diabetes 2020;69:2075-85. https://doi.org/10.2337/dbi20-0002

Dennis JM, Shields BM, Henley WE, et al. Disease progression and treatment response in data-driven subgroups of type 2 diabetes compared with models based on simple clinical features: an analysis using clinical trial data. Lancet Diabetes Endocrinol 2019;7(6):442-51. https://doi.org/10.1016/S2213-8587(19)30087-7

Malandrino N, Smith RJ. Personalized medicine in diabetes. Clinical Chemistry 2011;57(2):231-40. https://doi.org/10.1373/clinchem.2010.156901

National Institute for Health and Care Excellence. Type 2 diabetes in adults: management. NICE guideline 28 2015, updated 2022.

National institute for Health and Care Excellence. NG28 Patient Decision Aid on type 2 diabetes, 2022 [cited 2023 16/01/2023]; Available from: https://www.nice.org.uk/guidance/ng28/resources/patient-decision-aid-pdf-2187281198

Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45(11):2753-86. https://doi.org/10.2337/dci22-0034

Anderson SL, Beutel TR, Trujillo JM. Oral semaglutide in type 2 diabetes. J Diabetes Complications 2020;34(4):107520. https://doi.org/10.1016/j.jdiacomp.2019.107520

Andreadis P, Karagiannis T, Malandris k, et al. Semaglutide for type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes, Obes Metab 2018;20(9):2255-63. https://doi.org/10.1111/dom.13361

Husain M, Bain SC, Holst AG, et al. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol 2020;19(1):156. https://doi.org/10.1186/s12933-01106-4

Husain M, Bain SC, Jeppesen OK, et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab 2020;22(3):442-51. https://doi.org/10.1111/dom.13955

Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New Engl J Med 2016; 375(19):1834-44. https://doi.org/10.1056/NEJMoa1607141

Wang F, Mao Y, Wang H, et al. Semaglutide and diabetic retinopathy risk in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Clin Drug Investig 2022;42:17-28. https://doi.org/10.1007/s40261-021-01110-w

Health Research Authority. FOCUS – semaglutide effect on diabetic retinopathy, 2023. Accessed 04/07/2023. Available from: https://hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/focus-semaglutide-effect-on-diabetic-retinopathy/

Davies M, Pieber TR, Hartoft-Nielsen M-L, et al. Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA 2017318(15):1460-70. https://doi.org/10.1001/jama.2017.14752

Lingvay I, Catarig A-M, Frias JP, et al. Efficacy and safety of once- weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. Lancet Diabetes Endocrinol 2019; 7(11):834-44. https://doi.org/10.1016/S2213-8587(19)30311-0

Marzullo P, Daffara T, Mele C, et al. Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients. J Endocrinol Invest 2022;45(8):1587-98. https://doi.org/10.1007/s40618-022-01799-2

Crabtree TSJ, Adamson K, Reid H, et al. Injectable semaglutide and reductions in HbA1c and weight in the real world in people switched from alternative glucagon-like peptide-1 receptor agonists. Diabetes Obes Metab 2022;24(7):1398-401. https://doi.org/10.1111/dom.14701

DeSouza C, Cariou B, Garg S, et al. Efficacy and safety of semaglutide for type 2 diabetes by race and ethnicity: a post hoc analysis of the SUSTAIN trials. The Journal of Clinical Endocrinology & Metabolism 2020;105(2):543-56. https://doi.org/10.1210/clinem/dgz072

Marshall A, Altman DG, Holder RL, et al. Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines. BMC Med Res Methodology 2009; 9:57. https://doi.org/10.1186/1471-2288-9-57

Health Research Authority. Confidentiality Advisory Group. 2021 [cited 2022 02/03/2022]. Available from: https://www.hra.nhs.uk/approvals-amendments/what-approvals-do-i-need/confidentiality-advisory-group/

Department of Health and Social Care, Medicines Supply Notification – MSN/2022/08 Semaglutide (Ozempic®) 1mg/0.74ml solution for injection 3ml pre-filled disposable device 2022: gov.uk

Downloads

Published

2023-12-18

Issue

Section

Original Research

Most read articles by the same author(s)

1 2 3 4 > >>