To assess the efficacy and safety of once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) dulaglutide for the treatment of type 2 diabetes mellitus (T2DM).
Materials and methods
We searched PubMed, Embase, and Cochrane Library from inception to August 18, 2019. Revman5.3 and Stata13.0 software were used for meta-analysis.
Twenty-one trials including 20,367 patients were analyzed. Compared with control group, hemoglobin A1c (HbA1c) in 0.75 mg dulaglutide group and 1.5 mg dulaglutide group were reduced by 0.29% and 0.55%, respectively. More patients treated with 0.75 mg dulaglutide [RR 1.24, 95% CI (1.08, 1.42), p = 0.002] and 1.5 mg dulaglutide [RR 1.66, 95% CI (1.40, 1.99), p < 0.00001] had reached the target of HbA1c 7.0%. In patients with T2DM, 0.75 mg dulaglutide and 1.5 mg dulaglutide had a statistically higher adverse events (AEs) incidence than control, whereas the risk of hypoglycaemia was lower in 0.75 mg dulaglutide group and 1.5 mg dulaglutide group than in control group.
Based on the current evidence, 0.75 and 1.5 mg dulaglutide are associated with better glycemic control and lower rate of hypoglycemia in patients with T2DM.
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D. Sun, X. Zhang, X.X. Hou, Effects of insulin treatment with Glargine or Premixed Insulin Lispro Programs in Type 2 diabetes mellitus patients: a meta-analysis of randomized clinical trials. Diabetes Technol. Ther. 20(9), 622–627 (2018)
International Diabetes Federation. IDF Diabetes Atlas, 9th edn. (International Diabetes Federation, Brussels, Belgium, 2019)
World Health Organization. World Health Organization Global Report on Diabetes. Available from: http://www.who.int/diabetes/global-report (2016)
American Diabetes Association, 8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2018. Diabetes Care 41(Suppl 1), S73–S85 (2018)
V. Mogre, N.A. Johnson, F. Tzelepis, J.E. Shaw, C. Paul, A systematic review of adherence to diabetes self-care behaviours: evidence from low- and middle-income countries. J. Adv. Nurs. 2019. https://doi.org/10.1111/jan.14190
Q. Dong, J. Huang, S. Liu, L. Yang, J. Li, B. Li, X. Zhao, Z. Li, L. Wu, A survey on glycemic control rate of type 2 diabetes mellitus with different therapies and patients’ satisfaction in China. Patient Prefer. Adherence 13, 1303–1310 (2019)
A.C. Almeida, M.E. Leandro, M.G. Pereira, Adherence and glycemic control in adolescents with type 1 diabetes: the moderating role of age, gender, and family support. J. Clin. Psychol. Med. Settings 2019. https://doi.org/10.1007/s10880-019-09662-y
B.M. Mishriky, R.J. Tanenberg, K.A. Sewell, D.M. Cummings, Comparing SGLT-2 inhibitors to DPP-4 inhibitors as an add-on therapy to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Metab. 44(2), 112–120 (2018)
Trulicity [Prescribing Information]. Indianapolis ILU, LLC. 2014, http://pi.lilly.com/us/trulicity-uspi.pdf. Accessed 23 Sept 2019
J.L. Fahrbach, H. Fu, L. Shurzinske, Z. Skrivanek, S. Martin, Network meta-analysis accurately predicted the outcome of a subsequent randomised trial comparing once weekly dulaglutide 1.5 mg and once daily liraglutide 1.8 mg. Int. J. Clin. Pract. 70(3), 218–221 (2016)
N. Hawkins, A. Padhiar, J. Thompson, D.A. Scott, J.N. Eaton, N. Varol, K. Norrbacka, K.S. Boye, C. Nicolay, Assessing consistency in a network meta-analysis to compare once weekly dulaglutide versus other Glp-1 receptor agonists in patients with type 2 diabetes. Value Health 17, A335 (2014)
K.C. Ferdinand, F.T. Botros, C.M. Atisso, P.T. Sager, Cardiovascular safety for once-weekly dulaglutide in type 2 diabetes: a pre-specified meta-analysis of prospectively adjudicated cardiovascular events. Cardiovasc. Diabetol. 15, 38 (2016)
L. Zhang, M. Zhang, Y. Zhang, N. Tong, Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review. Sci. Rep. 6, 18904 (2016)
R.E. Pratley, V.R. Aroda, I. Lingvay, J. Lüdemann, C. Andreassen, A. Navarria, A. Viljoen, SUSTAIN 7 investigators, Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet. Diabetes Endocrinol. 6, 275–286 (2018)
W. Wang, L. Nevárez, E. Filippova, K.H. Song, B. Tao, L. Gu, F. Wang, P. Li, J. Yang, 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. 21(2), 234–243 (2019)
Y.H. Chen, C.N. Huang, Y.M. Cho, P. Li, L. Gu, F. Wang, J. Yang, W.Q. Wang, Efficacy and safety of dulaglutide monotherapy compared with glimepiride in East-Asian patients with type 2 diabetes in a multicentre, double-blind, randomized, parallel-arm, active comparator, phase III trial. Diabetes Obes. Metab. 20, 2121–2130 (2018)
K.R. Tuttle, M.C. Lakshmanan, B. Rayner, R.S. Busch, A.G. Zimmermann, D.B. Woodward, F.T. Botros, 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. 6(8), 605–617 (2018)
K.M. Dungan, R. Weitgasser, F. Perez Manghi, E. Pintilei, J.L. Fahrbach, H.H. Jiang, J. Shell, K.E. Robertson, 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. 18(5), 475–482 (2016)
P. Pozzilli, P. Norwood, E. Jódar, M.J. Davies, T. Ivanyi, H. Jiang, D.B. Woodward, Z. Milicevic, 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. 19(7), 1024–1031 (2017)
B. Ludvik, J.P. Frías, F.J. Tinahones, J. Wainstein, H. Jiang, K.E. Robertson, L.E. García-Pérez, D.B. Woodward, Z. Milicevic, 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. 6(5), 370–381 (2018)
J.P. Frias, M.A. Nauck, J. Van, M.E. Kutner, X. Cui, C. Benson, S. Urva, R.E. Gimeno, Z. Milicevic, D. Robins, A. Haupt, Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet 392(10160), 2180–2193 (2018)
J.P. Frias, A.G. Wynne, B. Matyjaszek-Matuszek, D. Bartaskova, D.A. Cox, B. Woodward, Y.G. Li, L.S. Tham, Z. Milicevic, Efficacy and safety of an expanded dulaglutide dose range: a phase 2, placebo-controlled trial in patients with type 2 diabetes using metformin. Diabetes Obes. Metab. 21(9), 2048–2057 (2019)
H.C. Gerstein, H.M. Colhoun, G.R. Dagenais, R. Diaz, M. Lakshmanan, P. Pais, J. Probstfield, J.S. Riesmeyer, M.C. Riddle, L. Rydén, D. Xavier, C.M. Atisso, L. Dyal, S. Hall, P. Rao-Melacini, G. Wong, A. Avezum, J. Basile, N. Chung, I. Conget, W.C. Cushman, E. Franek, N. Hancu, M. Hanefeld, S. Holt, P. Jansky, M. Keltai, F. Lanas, L.A. Leiter, P. Lopez-Jaramillo, E.G. Cardona Munoz, V. Pirags, N. Pogosova, P.J. Raubenheimer, J.E. Shaw, W.H. Sheu, T. Temelkova-Kurktschiev, REWIND investigators, dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 394(10193), 121–130 (2019)
D. Moher, A. Liberati, J. Tetzlaff, D.G. Altman; PRISMA Group., Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339, b2535 (2009)
A. Liberati, D.G. Altman, J. Tetzlaff, C. Mulrow, P.C. Gøtzsche, J.P. Ioannidis, M. Clarke, P.J. Devereaux, J. Kleijnen, D. Moher, The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339, b2700 (2009)
J.P.T Higgins, J. Thomas, J. Chandler, M. Cumpston, T. Li, M.J . Page, V.A. Welch (eds). Cochrane Handbook for Systematic Reviews of Interventions. 2nd edn. (John Wiley & Sons, Chichester, UK, 2019)
E. Araki, N. Inagaki, Y. Tanizawa, T. Oura, M. Takeuchi, T. Imaoka, Efficacy and safety of once-weekly dulaglutide in combination with sulphonylurea and/or biguanide compared with once-daily insulin glargine in Japanese patients with type 2 diabetes: a randomized, open-label, phase III, non-inferiority study. Diabetes Obes. Metab. 17(10), 994–1002 (2015)
C. Wysham, T. Blevins, R. Arakaki, G. Colon, P. Garcia, C. Atisso, D. Kuhstoss, M. Lakshmanan, Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care 37(8), 2159–2167 (2014)
F. Giorgino, M. Benroubi, J.H. Sun, A.G. Zimmermann, V. Pechtner, Efficacy and safety of once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2). Diabetes Care 38(12), 2241–2249 (2015)
G. Umpierrez, S. Tofé Povedano, F. Pérez Manghi, L. Shurzinske, V. Pechtner, Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 37(8), 2168–2176 (2014)
L. Blonde, J. Jendle, J. Gross, V. Woo, H. Jiang, J.L. Fahrbach, Z. Milicevic, 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 385(9982), 2057–2066 (2015)
M. Nauck, R.S. Weinstock, G.E. Umpierrez, B. Guerci, Z. Skrivanek, Z. Milicevic, Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 37(8), 2149–2158 (2014)
K.M. Dungan, S.T. Povedano, T. Forst, J.G. González, C. Atisso, W. Sealls, J.L. Fahrbach, 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 384(9951), 1349–1357 (2014)
G. Grunberger, A. Chang, G. Garcia Soria, F.T. Botros, R. Bsharat, Z. Milicevic, Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose-dependent effects on glycaemic control in a randomized, double-blind, placebo-controlled study. Diabet. Med. 29(10), 1260–1267 (2012)
J. Miyagawa, M. Odawara, T. Takamura, N. Iwamoto, Y. Takita, T. Imaoka, Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide is non-inferior to once-daily liraglutide and superior to placebo in Japanese patients with type 2 diabetes: a 26-week randomized phase III study. Diabetes Obes. Metab. 17(10), 974–983 (2015)
Y. Terauchi, Y. Satoi, M. Takeuchi, T. Imaoka, Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients with type 2 diabetes: dose-dependent effects on glycaemic control in a randomised, double-blind, placebo-controlled study. Endocr. J. 61(10), 949–959 (2014)
ClinicalTrials.gov. ProMED-mail Web site. https://www.clinicaltrials.gov/ct2/show/NCT02973100?term=NCT02973100&rank=1. Accessed 23 Sept 2019
M. Castellana, A. Cignarelli, F. Brescia, L. Laviola, F. Giorgino, GLP-1 receptor agonist added to insulin versus basal-plus or basal-bolus insulin therapy in type 2 diabetes mellitus. A systematic review and meta-analysis. Diabetes Metab. Res. Rev. 35(1), e3082 (2019)
A. López-Suárez, Burden of cancer attributable to obesity, type 2 diabetes and associated risk factors. Metabolism 92, 136–146 (2019)
R.P. Bogers, W.J. Bemelmans, R.T. Hoogenveen, H.C. Boshuizen, M. Woodward, P. Knekt, R.M. van Dam, F.B. Hu, T.L. Visscher, A. Menotti, R.J. Thorpe Jr, K. Jamrozik, S. Calling, B.H. Strand, M.J. Shipley, BMI-CHD Collaboration Investigators, Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300000 persons. Arch. Intern. Med. 167, 1720–1728 (2007)
American Diabetes Association, Standard of medical care in diabetes-2018. Diabetes Care 41(Suppl 1), S1–S159 (2018)
S.P. Marso, S.C. Bain, A. Consoli, F.G. Eliaschewitz, E. Jódar, L.A. Leiter, I. Lingvay, J. Rosenstock, J. Seufert, M.L. Warren, V. Woo, O. Hansen, A.G. Holst, J. Pettersson, T. Vilsbøll, SUSTAIN-6 investigators, semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 375(19), 1834–1844 (2016)
B. Zinman, C. Wanner, J.M. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O.E. Johansen, H.J. Woerle, U.C. Broedl, S.E. Inzucchi, EMPA-REG OUTCOME investigators, empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N. Engl. J. Med. 373, 2117–2128 (2015)
R. Mody, Q, Huang, M. Yu, R. Zhao, H. Patel, M. Grabner, L.F. Landó, Adherence, persistence, glycemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide QW at 12 months follow-up in a US real-world setting. Diabetes Obes. Metab. 2018. https://doi.org/10.1111/dom.13603
T. Takase, A. Nakamura, C. Yamamoto, H. Nomoto, A. Miya, M. Dannoura, K.Y. Cho, Y. Kurihara, N. Manda, S. Aoki, T. Atsumi, H. Miyoshi, Improvement in treatment satisfaction after switching from liraglutide to dulaglutide in patients with type 2 diabetes: a randomized controlled trial. J. Diabetes Investig. 10(3), 699–705 (2019)
M.S. Abd El Aziz, M. Kahle, J.J. Meier, M.A. Nauck, 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. 19(2), 216–227 (2017)
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Qie, S., Li, X., Wang, X. et al. Efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide in patients with type 2 diabetes: a systematic review and meta-analysis of 21 randomized controlled trials. Endocrine (2020) doi:10.1007/s12020-020-02193-9
- Type 2 diabetes mellitus
- Systematic review