The online version of this article (https://doi.org/10.1007/s13300-019-00709-9) contains supplementary material, which is available to authorized users.
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The ADA-EASD consensus report recommends using glucagon-like peptide-1 receptor agonists (GLP-1RAs) as the first injectable therapy prior to basal insulin in most patients with type 2 diabetes (T2D) not at glycemic goals after oral anti-hyperglycemia medications (OH). The objective of this analysis was to assess the glycemic efficacy of once-weekly dulaglutide 1.5 mg in patients with T2D when added on a background of commonly used OH regimens.
Patients from seven phase 3 AWARD [Assessment of Weekly AdministRation of LY2189265 (Dulaglutide) in Diabetes] trials, where once-weekly dulaglutide 1.5 mg was added to OHs, were pooled into the following categories based on OH regimens: metformin (MET), sulfonylurea (SU), MET + SU, MET + pioglitazone, and MET + SGLT2i. Change from baseline in glycated hemoglobin A1c (HbA1c), fasting serum glucose and body weight, proportion of patients reaching target HbA1c < 7%, and safety parameters were assessed.
A total of 1784 patients treated with once-weekly dulaglutide 1.5 mg were included in this analysis. Baseline characteristics of the overall population were (mean ± standard deviation): age, 55.4 ± 9.8 years, HbA1c: 8.2 ± 1.0%, body mass index: 31.4 ± 5.4 kg/m2, duration of diabetes: 8.0 ± 5.6 years, and 878 (49.2%) were female. At 6 months, the addition of once-weekly dulaglutide 1.5 mg to various OH regimens significantly reduced HbA1c (− 1.3 to − 1.6%) and fasting blood glucose (− 29 to − 45 mg/dl) from baseline in all groups (p < 0.001), with 39–61% and 52–76% of these patients achieving HbA1c targets of ≤ 6.5% and < 7%, respectively. Significant reductions in body weight (− 0.8 to − 2.9 kg) were also observed in all groups (p < 0.001). Nausea, vomiting, and diarrhea were reported by 10–35%, 4–19%, and 6–28% of patients, respectively. Severe hypoglycemia occurred in one patient (MET + SU).
The addition of a once-weekly GLP-1RA, dulaglutide, demonstrated clinically meaningful HbA1c reduction in patients with T2D on different background OH regimens, making it an effective first injectable option.
Eli Lilly and Company.
Supplementary material 1 (DOCX 18 kb)13300_2019_709_MOESM1_ESM.docx
American Diabetes Association. Standards of medical care in diabetes-2019. Diabetes Care. 2019;42(Suppl 1):S1–193.
Brod M, Kongsø JH, Lessard S, Christensen TL. Psychological insulin resistance: patient beliefs and implications for diabetes management. Qual Life Res. 2009;18(1):23–32. CrossRef
Brod M, Alolga SL, Meneghini L. Barriers to initiating insulin in type 2 diabetes patients: development of a new patient education tool to address myths, misconceptions and clinical realities. Patient. 2014;7(4):437–50. CrossRef
Khunti K, Millar-Jones D. Clinical inertia to insulin initiation and intensification in the UK: a focused literature review. Prim Care Diabetes. 2017;11(1):3–12. CrossRef
Carls G, Huynh J, Tuttle E, Yee J, Edelman SV. Achievement of glycated hemoglobin goals in the us remains unchanged through 2014. Diabetes Ther. 2017;8(4):863–73. CrossRef
Mocarski M, Yeaw J, Divino V, et al. Slow titration and delayed intensification of basal insulin among patients with type 2 diabetes. J Manag Care Spec Pharm. 2018;24(4):390–400. PubMed
Yu M, Mody R, Landó LF, et al. Characteristics associated with the choice of first injectable therapy among us patients with type 2 diabetes. Clin Ther. 2017;39(12):2399–408. CrossRef
van Bloemendaal L, IJzerman RG, Ten Kulve JS, et al. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes. 2014;63(12):4186–96. CrossRef
Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord. 2014;15(3):181–7. CrossRef
Marso SP, Bain SC, Consoli A. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44. CrossRef
Marso SP, Daniels GH, Brown-Frandsen K. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. CrossRef
Hernandez AF, Green JB, Janmohamed S. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018;392(10157):1519–29. CrossRef
Gerstein HC, Colhoun HM, Dagenais GR. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121–30. CrossRef
Bettge K, Kahle M, Abd El Aziz MS, Meier JJ, Nauck MA. Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: a systematic analysis of published clinical trials. Diabetes Obes Metab. 2017;19(3):336–47. CrossRef
Abd El Aziz MS, Kahle M, Meier JJ, Nauck MA. A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients. Diabetes Obes Metab. 2017;19(2):216–27. CrossRef
Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm 2018 executive summary. Endocr Pract. 2018;24(1):91–120. CrossRef
Trulicity (2019) Rev Jan 2019. Indianapolis, IN: Lilly USA, LLC; 2019. http://uspl.lilly.com/trulicity/trulicity.html#pi Accessed 14 May 2019.
Trulicity (2018) Houten, The Netherlands: Eli Lilly and Company; 2018. https://www.ema.europa.eu/documents/product-information/trulicity-epar-product-information_en.pdf Accessed 4 Feb 2019.
Blonde L, Jendle J, Gross J, et al. Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study. Lancet. 2015;385(9982):2057–66. CrossRef
Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet. 2014;384(9951):1349–57. CrossRef
Dungan KM, Weitgasser R, Perez Manghi F, et al. A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (AWARD-8). Diabetes Obes Metab. 2016;18(5):475–82. CrossRef
Giorgino F, Benroubi M, Sun JH, Zimmermann AG, Pechtner V. Efficacy and safety of once weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2). Diabetes Care. 2015;38(12):2241–9. CrossRef
Ludvik B, Frías JP, Tinahones FJ. Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2018;6(5):370–81. CrossRef
Pozzilli P, Norwood P, Jódar E, et al. Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD-9). Diabetes Obes Metab. 2017;19(7):1024–31. CrossRef
Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605–17. CrossRef
Umpierrez G, Tofé Povedano S, Pérez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care. 2014;37(8):2168–76. CrossRef
Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added on to pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care. 2014;37(8):2159–67. CrossRef
Weinstock RS, Guerci B, Umpierrez G, Nauck MA, Skrivanek Z, Milicevic Z. Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes (AWARD-5): a randomized, phase III study. Diabetes Obes Metab. 2015;17(9):849–58. CrossRef
Trulicity (2018) Indianapolis, IN: Lilly USA, LLC; 2018. http://pi.lilly.com/us/trulicity-highdose-ai-ifu.pdf. Accessed 14 Feb 2019.
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(5):1071–9. CrossRef
Wang W, Nevárez L, Filippova E, et al. Efficacy and safety of once-weekly dulaglutide versus insulin glargine in mainly Asian patients with type 2 diabetes mellitus on metformin and/or a sulphonylurea: a 52-week open-label, randomized phase III trial. Diabetes Obes Metab. 2019;21(2):234–43. CrossRef
Meloni AR, DeYoung MB, Lowe C, Parkes DG. GLP-1 receptor activated insulin secretion from pancreatic β-cells: mechanism and glucose dependence. Diabetes Obes Metab. 2012;15(1):15–27. CrossRef
Lebovitz HE, Banerji MA. Insulin resistance and its treatment by thiazolidinediones. Recent Prog Horm Res. 2001;56:194–265. CrossRef
Fonseca V. Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med. 2003;115(Suppl 8A):42S–8S. CrossRef
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):341–54. CrossRef
Cosentino F, Grant PJ, Aboyans V, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Eur Heart J. 2019. https://doi.org/10.1093/eurheartj/ehz486. CrossRefPubMed
Frías JP, Guja C, Hardy E, et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4(12):1004–16. CrossRef
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):356–67. CrossRef
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. CrossRef
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57. CrossRef
- Efficacy of Dulaglutide as a First Injectable Option for Patients with Type 2 Diabetes: A Post-Hoc Pooled Analysis
Chrisanthi A. Karanikas
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