Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2-4 and 10

Matthew Capehorn, Yasmin Ghani, Charlotte Hindsberger, Pierre Johansen, Esteban Jódar, Matthew Capehorn, Yasmin Ghani, Charlotte Hindsberger, Pierre Johansen, Esteban Jódar

Abstract

Introduction: Despite treatment with oral antidiabetic drugs (OADs), achieving effective glycaemic control in type 2 diabetes (T2D) remains a challenge. The objective of this post hoc analysis of data from the SUSTAIN 2, 3, 4 and 10 active-controlled trials was to assess the efficacy and safety of the once-weekly glucagon-like peptide 1 receptor agonist (GLP-1RA) semaglutide in patients on background treatment with metformin (MET), with or without a sulphonylurea (SU).

Methods: Data from the randomised phase 3 trials SUSTAIN 2, 3, 4 and 10 for subjects who received background MET alone or MET + SU were analysed. Change from baseline in HbA1c and body weight at the end of treatment visit (week 30 in SUSTAIN 4 and 10, week 56 in SUSTAIN 2 and 3), and rates of hypoglycaemia and adverse events leading to premature treatment discontinuation were assessed.

Results: In total, 3411 subjects were included in the full analysis set (3410 in the safety analysis set). Across the four trials, semaglutide significantly reduced HbA1c (estimated treatment difference [ETD] - 0.32 to - 0.79%-points for semaglutide 0.5 mg, and - 0.38 to - 1.07%-points for semaglutide 1.0 mg vs comparators; p < 0.01) in subjects receiving both MET and MET + SU. Regardless of background OAD, semaglutide significantly reduced body weight (ETD - 2.35 to - 4.72 kg for semaglutide 0.5 mg, and - 2.96 to - 6.76 kg for semaglutide 1.0 mg vs comparators; p < 0.0001). Across the trials, hypoglycaemic events were more common with background MET + SU than MET alone, in subjects receiving either semaglutide or a comparator. The rate of adverse events (AEs) leading to premature treatment discontinuations in subjects treated with semaglutide were generally consistent regardless of background therapy.

Conclusion: Semaglutide 0.5 mg and 1.0 mg significantly improve glycaemic control (HbA1c) and body weight in subjects with T2D, with a similar tolerability profile, regardless of whether they receive background MET or MET + SU.

Trial registration: Clinicaltrials.gov: NCT01930188 (SUSTAIN 2), NCT01885208 (SUSTAIN 3), NCT02128932 (SUSTAIN 4) and NCT03191396 (SUSTAIN 10).

Keywords: Diabetes care; GLP-1RA; Metformin; Oral antidiabetic agents; Randomised controlled trials; Semaglutide; Sulphonylurea; Type 2 diabetes.

Figures

Fig. 1
Fig. 1
Mean (SE) change from baseline in HbA1c (a) and body weight (b) by background oral antidiabetic drug subgroup. Mean (SE) change from baseline and ETD [95% confidence interval] for semaglutide vs comparators shown; *p < 0.0001, †p < 0.01. BW body weight, ER extended release, ETD estimated treatment difference, IGlar insulin glargine, MET metformin, SE standard error, SU sulphonylurea

References

    1. International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: IDF; 2019. . Accessed Mar 2020.
    1. Gavin JR, 3rd, Bohannon NJ. A review of the response to oral antidiabetes agents in patients with type 2 diabetes. Postgrad Med. 2010;122(3):43–51. doi: 10.3810/pgm.2010.05.2141.
    1. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care. 2018;41(12):2669–2701. doi: 10.2337/dci18-0033.
    1. American Diabetes Association 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl 1):S90–S102. doi: 10.2337/dc19-S009.
    1. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019;41(2):255–323. doi: 10.1093/eurheartj/ehz486.
    1. Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetologia. 2020;63:221–228. doi: 10.1007/s00125-019-05039-w.
    1. National Institute for Health and Care Excellence. Type 2 diabetes in adults: management [NG28] 2015. . (Updated December 2015. NICE clinical guidelines). Accessed Mar 2020.
    1. Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(4):251–260. doi: 10.1016/S2213-8587(17)30013-X.
    1. Ahrén B, Masmiquel L, Kumar H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017;5(5):341–354. doi: 10.1016/S2213-8587(17)30092-X.
    1. Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care. 2018;41(2):258–266. doi: 10.2337/dc17-0417.
    1. Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(5):355–366. doi: 10.1016/S2213-8587(17)30085-2.
    1. Rodbard HW, Lingvay I, Reed J, et al. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial. J Clin Endocrinol Metab. 2018;103(6):2291–2301. doi: 10.1210/jc.2018-00070.
    1. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–1844. doi: 10.1056/NEJMoa1607141.
    1. Pratley RE, Aroda VR, Lingvay I, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275–286. doi: 10.1016/S2213-8587(18)30024-X.
    1. Lingvay I, Catarig AM, 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):834–844. doi: 10.1016/S2213-8587(19)30311-0.
    1. Zinman B, Bhosekar V, Busch R, et al. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019;7(5):356–367. doi: 10.1016/S2213-8587(19)30066-X.
    1. Capehorn MS, Catarig AM, Furberg JK, et al. Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10) Diabetes Metab. 2019 doi: 10.1016/j.diabet.2019.101117.
    1. International Diabetes Federation Guideline Development Group Global guideline for type 2 diabetes. Diabetes Res Clin Pract. 2014;104(1):1–52. doi: 10.1016/j.diabres.2012.10.001.
    1. National Health Service. Prescribing for diabetes: England 2007/08 to 2017/18. . Accessed Mar 2020.
    1. International Conference on Harmonisation Working Group. ICH harmonised tripartite guideline: guideline for good clinical practice E6 (R1). Washington, DC: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; 1996.
    1. World Medical Association World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–2194. doi: 10.1001/jama.2013.281053.
    1. Thong K, Gupta P, Cull M, et al. GLP-1 receptor agonists in type 2 diabetes-NICE guidelines versus clinical practice. Br J Diabetes Vasc Dis. 2014;14:52–59. doi: 10.15277/bjdvd.2014.015.
    1. Patel H, Munir K, Sutherland S, Karanikas C, Konig M. Efficacy of dulaglutide as a first injectable option for patients with type 2 diabetes: a post hoc pooled analysis. Diabetes Ther. 2019;6(10):2321–2330. doi: 10.1007/s13300-019-00709-9.
    1. Blonde L, Russell-Jones D. The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies. Diabetes Obes Metab. 2009;11(Suppl 3):26–34. doi: 10.1111/j.1463-1326.2009.01075.x.
    1. Bennett WL, Maruthur NM, Singh S, et al. Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med. 2011;154(9):602–613. doi: 10.7326/0003-4819-154-9-201105030-00336.
    1. Klein-Schwartz W, Stassinos G, Isbister GK. Treatment of sulfonylurea and insulin overdose. Br J Clin Pharmacol. 2016;81(3):496–504. doi: 10.1111/bcp.12822.

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