Comparison of the injection-site experience of the starting doses with semaglutide and dulaglutide: A randomized, double-blind trial in healthy subjects

Søren Snitker, Andreas Andersen, Birgitte Berg, Sjoerd van Marle, Thomas Sparre, Søren Snitker, Andreas Andersen, Birgitte Berg, Sjoerd van Marle, Thomas Sparre

Abstract

This double-blind, randomized, single-site, crossover trial compared the injection-site experience with the starting doses of semaglutide and dulaglutide. Healthy subjects (aged 18-75 years; body mass index ≥ 25 kg/m2 ; n = 104) were randomized 1:1, using a pregenerated list, to semaglutide 0.25 mg as the first injection and dulaglutide 0.75 mg as the second injection or vice versa; each was administered using their proprietary pen-injectors, according to instructions for use. The primary endpoint was intensity of injection-site pain, measured using a visual analogue scale (VAS; 0 mm = no pain, 100 mm = unbearable pain). Exploratory endpoints included intensity category, duration and quality of injection-site pain, and comparative assessment of injection-site pain with the two injections. The point estimate of the VAS score for injection-site pain intensity was 11.5 mm with dulaglutide versus 5.6 mm with semaglutide; mean (95% confidence interval) estimated treatment difference 5.9 (3.6; 8.2) mm; p < .0001. Other endpoints corroborated a less painful injection experience with semaglutide versus dulaglutide. Safety was consistent with reported data for the drugs. In conclusion, the injection-site experience with semaglutide was rated as less painful than that with dulaglutide.

Keywords: GLP-1 analogue; antidiabetic drug; clinical trial.

Conflict of interest statement

SS, AA, BB and TS are employees of Novo Nordisk A/S; BB and TS own Novo Nordisk A/S stock. SvM is an employee of PRA Health Sciences, which was funded by Novo Nordisk A/S to conduct this trial.

© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Trial design
FIGURE 2
FIGURE 2
(A) Distribution of visual analogue scale (VAS) scores for injection‐site pain intensity; (B) distribution of within‐subject VAS score differences between dulaglutide and semaglutide (dulaglutide – semaglutide); (C) mean VAS score for injection‐site pain intensity (0 = ‘no pain’ and 100 = ‘unbearable pain’); (D) categorical assessment of injection‐site pain intensity (n = 104 for each treatment); (E) assessment of pain qualities using the modified short‐form McGill Pain Questionnaire‐2 inventory (n = 104 for each treatment; subjects could select more than one quality); and (F) comparison of injection‐site pain. CI, confidence interval; ETD, estimated treatment difference. In Figure 2C, values are least squares means estimates

References

    1. Williams DM, Nawaz A, Evans M. Drug therapy in obesity: a review of current and emerging treatments. Diabetes Ther. 2020;11:1199‐1216.
    1. American Diabetes Association . 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2021. Diabetes Care. 2021;44:S111‐S124.
    1. Chudleigh RA, Platts J, Bain SC. Comparative effectiveness of long‐acting GLP‐1 receptor agonists in type 2 diabetes: a short review on the emerging data. Diabetes Metab Syndr Obes. 2020;13:433‐438.
    1. Sikirica MV, Martin AA, Wood R, Leith A, Piercy J, Higgins V. Reasons for discontinuation of GLP1 receptor agonists: data from a real‐world cross‐sectional survey of physicians and their patients with type 2 diabetes. Diabetes Metab Syndr Obes. 2017;10:403‐412.
    1. Novo Nordisk . Ozempic (semaglutide) injection, for subcutaneous use ‐ highlights of prescribing information. . Accessed May 5, 2020.
    1. Matfin G, Van Brunt K, Zimmermann AG, Threlkeld R, Ignaut DA. Safe and effective use of the once weekly dulaglutide single‐dose pen in injection naïve patients with type 2 diabetes. J Diabetes Sci Technol. 2015;9:1071‐1079.
    1. Dworkin RH, Turk DC, Revicki DA, et al. Development and initial validation of an expanded and revised version of the short‐form McGill pain questionnaire (SF‐MPQ‐2). Pain. 2009;144:35‐42.
    1. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med. 1996;27:485‐489.
    1. Robb DM, Kanji Z. Comparison of two needle sizes for subcutaneous administration of enoxaparin: effects on size of hematomas and pain on injection. Pharmacotherapy. 2002;22:1105‐1109.
    1. Coley RM, Butler CD, Beck BI, Mullane JP. Effect of needle size on pain and hematoma formation with subcutaneous injection of heparin sodium. Clin Pharm. 1987;6:725‐727.
    1. Arendt‐Nielsen L, Egekvist H, Bjerring P. Pain following controlled cutaneous insertion of needles with different diameters. Somatosens Mot Res. 2006;23:37‐43.
    1. European Medicines Agency . Ozempic: summary of product characteristics. . Accessed June 2, 2020.
    1. United States Food and Drug Administration . OZEMPIC (semaglutide) injection, for subcutaneous use. . Accessed June 2, 2020.
    1. European Medicines Agency . Trulicity: summary of product characteristics. . Accessed June 2, 2020.
    1. United States Food and Drug Administration . Trulicity: highlights of prescribing information. . Accessed June 2, 2020.
    1. Heise T, Nosek L, Dellweg S, et al. Impact of injection speed and volume on perceived pain during subcutaneous injections into the abdomen and thigh: a single‐centre, randomized controlled trial. Diabetes Obes Metab. 2014;16:971‐976.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere