Glucagon like peptide-1 is responsible for the incretin effect after a meal or an oral glucose load. Patients with type 2 diabetes mellitus have impairment of secretion and action of glucagon like peptide-1. This impairment can be overcome through pharmacological doses of glucagon like peptide-1 analogues. Aim of the Study: This study aimed at evaluation of the effect of treatment with glucagon like peptide-1 analogues; liraglutide and dulaglutide, in Emirati patients with type 2 diabetes mellitus. Glycemic control was the primary end point while the secondary end point was the effect on body mass index, blood pressure, heart rate, serum creatinine, lipid profile and estimated glomerular filtration rate. Patients & Methods: This is a retrospective study including 54 patients with type 2 diabetes mellitus. Patients used Liraglutide or Dulaglutide as add on therapy to oral antidiabetic medications for one year. Thirty-four patients used liraglutide 1.8 mg once daily and 20 patients used dulaglutide 1.5 mg once weekly. All patients were older than 18 years and had estimated glomerular filtration rate (>90 ml/min/1.73 m2). Body mass index, sitting blood pressure and heart rate were collected. Fasting plasma glucose, HbA1c, lipid panel and other biochemical parameters were also collected. Data were analysed before and at 6 and 12 months of glucagon like peptide-1 analogue treatment. Results: At 12 months of treatment, liraglutide significantly reduced fasting plasma glucose (11.3 ± 4 vs 7 ± 1.7, p < 0.001), HbA1c (8.55 ± 1.6 vs 7.18 ± 1.04, p < 0.001) and body mass index (39.4 ± 6.4 vs 37.6 ± 6.7, p < 0.0005). Dulaglutide did not significantly reduce fasting plasma glucose (15.4 ± 3.5 vs 9.5 ± 5.4 mmol/L, p = 0.053), significantly reduced HbA1c (8.84 ± 1.8 vs 7.5 ± 0.79, p = 0.007), body mass index (38.8 ± 6.8 vs 37.2 ± 6.6, p = 0.004) and estimated glomerular filtration rate (123.6 ± 60 vs 104 ± 47.3, p = 0.008). Dulaglutide was more effective in reduction of body mass index than liraglutide. Both drugs did not show significant effect on blood pressure, heart rate or lipid profile. Conclusion: Over a period of one year, liraglutide and dulaglutide produced comparable reduction of HbA1c and hence diabetes control. Both drugs significantly reduced body mass index but this effect was more pronounced with Dulaglutide. Only liraglutide significantly reduced fasting plasma
References
[1]
Scheen, A.J. (2013) GLP-1 Receptor Agonists or DPP-4 Inhibitors: How to Guide the Clinician? Annales d’Endocrinologie (Paris), 74, 515-522. https://doi.org/10.1016/j.ando.2012.06.002
[2]
Drab, S.R. (2010) Incretin-Based Therapies for Type 2 Diabetes Mellitus: Current Status and Future Prospects. Pharmacotherapy, 30, 609-624. https://doi.org/10.1592/phco.30.6.609
[3]
Lorenz, M., Evers, A. and Wagner, M. (2013) Recent Progress and Future Options in the Development of GLP-1 Receptor Agonists for the Treatment of Diabesity. Bioorganic & Medicinal Chemistry Letters, 23, 4011-4018. https://doi.org/10.1016/j.bmcl.2013.05.022
[4]
Blind, E., Janssen, H., Dunder, K. and de Graeff, P.A. (2018) The European Medicines Agency’s Approval of New Medicines for Type 2 Diabetes. Diabetes, Obesity and Metabolism, 20, 2059-2063. https://doi.org/10.1111/dom.13349
[5]
Grunberger, G., Chang, A., Garcia Soria, G., Botros, F.T., Bsharat, R. and Milicevic, Z. (2012) 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 Randomized, Double-Blind, Placebo-Controlled Study. Diabetic Medicine, 29, 1260-1267. https://doi.org/10.1111/j.1464-5491.2012.03745.x
[6]
Nauck, M., Weinstock, R.S., Umpierrez, G.E., Guerci, B., Skivanek, Z. and Milicevic, Z. (2014) Efficacy and Safety of Dulaglutide versus Sitagliptin after 52 Weeks in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-5). Diabetes Care, 37, 2149-2158. https://doi.org/10.2337/dc13-2761
[7]
Umpierrez, G.E., Blevins, T., Rosenstock, J., et al. (2011) The Effects of LY2189265, a Long-Acting Glucagon-Like Peptide-1 Analogue, in a Randomized, Placebo Controlled, Double-Blind Study of Overweight/Obese Patients with Type 2 Diabetes: The EGO Study. Diabetes, Obesity and Metabolism, 13, 418-425. https://doi.org/10.1111/j.1463-1326.2011.01366.x
[8]
Umpierrez, G., Tofé Povedano, S., Pérez Manghi, F., Shurzinske, L. and Pechtner, V. (2014) Efficacy and Safety of Dulaglutide Monotherapy versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-3). Diabetes Care, 37, 2168-2176. https://doi.org/10.2337/dc13-2759
[9]
Inzucchi, S.E., Bergenstal, R.M., Buse, J.B., et al. (2015) Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 38, 140-149. https://doi.org/10.2337/dc14-2441
[10]
St Onge, E., Miller, S., Clements, E., Celauro, L. and Barnes, K. (2017) The Role of Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Type 2 Diabetes. Journal of Translational Internal Medicine, 5, 79-89. https://doi.org/10.1515/jtim-2017-0015
[11]
American Diabetes Association (2018) Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2018. Diabetes Care, 41, S73-S85. https://doi.org/10.2337/dc18-S008
[12]
Sfairopoulos, D., Liatis, S., Tigas, S. and Liberopoulos, E. (2018) Clinical Pharmacology of Glucagon-Like Peptide-1 Receptor Agonists. Hormones (Athens), 17, 333-350. https://doi.org/10.1007/s42000-018-0038-0
[13]
Sun, F., Chai, S., Li, L., et al. (2015) Effects of Glucagon-Like Peptide-1 Receptor Agonists on Weight Loss in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis. Journal of Diabetes Research, 2015, Article ID: 157201. https://doi.org/10.1155/2015/157201
[14]
Garber, A., Henry, R., Ratner, R., et al. (2009) LEAD-3 (Mono) Study Group Liraglutide versus Glimepiride Monotherapy for Type 2 Diabetes (LEAD-3 Mono): A Randomised, 52-Week, Phase III, Double-Blind, Parallel-Treatment Trial. The Lancet, 373, 473-481. https://doi.org/10.1016/S0140-6736(08)61246-5
[15]
Gallwitz, B., Dagogo-Jack, S., Thieu, V., et al. (2018) Effect of Once-Weekly Dulaglutide on Glycated Haemoglobin (HbA1c) and Fasting Blood Glucose in Patient Subpopulations by Gender, Duration of Diabetes and Baseline HbA1c. Diabetes, Obesity and Metabolism, 20, 409-418. https://doi.org/10.1111/dom.13086
[16]
Romera, I., Cebrián-Cuenca, A., álvarez-Guisasola, F., Gomez-Peralta, F. and Reviriego, J. (2019) A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes. Diabetes Therapy, 10, 5-19. https://doi.org/10.1007/s13300-018-0535-9
[17]
Marso, S.P., Daniels, G.H., Brown-Frandsen, K., et al. (2016) Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. The New England Journal of Medicine, 375, 311-322. https://doi.org/10.1056/NEJMoa1603827
[18]
Bethel, M.A., Patel, R.A., Merrill, P., et al. (2018) Cardiovascular Outcomes with Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Meta-Analysis. The Lancet Diabetes & Endocrinology, 6, 105-113. https://doi.org/10.1016/S2213-8587(17)30412-6
[19]
Li, L., Li, S., Liu, J., et al. (2016) Glucagon-Like Peptide-1 Receptor Agonists and Heart Failure in Type 2 Diabetes: Systematic Review and Meta-Analysis of Randomized and Observational Studies. BMC Cardiovascular Disorders, 16, 91. https://doi.org/10.1186/s12872-016-0260-0
[20]
Matza, L.S., Boye, K.S., Currie, B.M., et al. (2018) Patient Perceptions of Injection Devices Used with Dulaglutide and Liraglutide for Treatment of Type 2 Diabetes. Current Medical Research and Opinion, 34, 1457-1464. https://doi.org/10.1080/03007995.2018.1465903
[21]
Reid, T.S. (2013) Practical Use of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Primary Care. Clinical Diabetes, 31, 148-157. https://doi.org/10.2337/diaclin.31.4.148
[22]
Levey, A.S., Coresh, J., Greene, T., et al. (2006) Chronic Kidney Disease Epidemiology Collaboration. Before, Then at 6 and 12 Months of Treatment. Using Standardized Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate. Annals of Internal Medicine, 145, 247-254. https://doi.org/10.7326/0003-4819-145-4-200608150-00004
[23]
Warnick, G.R., Knopp, R.H., Fitzpatrick, V. and Branson, L. (1990) Estimating Low-Density Lipoprotein Cholesterol by the Friedewald Equation Is Adequate for Classifying Patients on the Basis of Nationally Recommended Cutpoints. Clinical Chemistry, 36, 15-19. https://doi.org/10.1093/clinchem/36.1.15
[24]
Trinder, P. (1969) Determination of Glucose in Blood Using Glucosenoxidase with an Alternative Oxygen Acceptor. Annals of Clinical Biochemistry, 6, 24-27. https://doi.org/10.1177/000456326900600108
[25]
Genc, S., Omer, B., Gurdol, F., Aycan-Ustyol, E., Ince, N. and Bal, F. (2012) Evaluation of Turbidimetric Inhibition Immunoassay (TINIA) and HPLC Methods for Glycated Haemoglobin Determination. Journal of Clinical Laboratory Analysis, 26, 481-485. https://doi.org/10.1002/jcla.21550
[26]
Bolinder, J., Ljunggren, O. and Kullberg, J. (2012) Effects of Dapagliflozin on Body Weight, Total Fat Mass, and Regional Adipose Tissue Distribution in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Metformin. The Journal of Clinical Endocrinology and Metabolism, 97, 1020-1031. https://doi.org/10.1210/jc.2011-2260
[27]
Merovci, A., Solis-Herrera, C., Daniele, G., et al. (2014) Dapagliflozin Improves Muscle Insulin Sensitivity but Enhances Endogenous Glucose Production. Journal of Clinical Investigation, 124, 509-514. https://doi.org/10.1172/JCI70704
[28]
Dungan, K.M., Povedano, S.T., Forst, T., et al. (2014) 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. The Lancet, 384, 1349-1357. https://doi.org/10.1016/S0140-6736(14)60976-4
[29]
Meier, J.J. (2012) GLP-1 Receptor Agonists for Individualized Treatment of Type 2 Diabetes Mellitus. Nature Reviews Endocrinology, 8, 728-742. https://doi.org/10.1038/nrendo.2012.140
[30]
Gallwitz, B., Dagogo-Jack, S., Thieu, V., Garcia-Perez, L.-E., Pavo, I., Yu, M., Robertson, K.E., Zhang, N. and Giorgino, F. (2018) Effect of Once-Weekly Dulaglutide on Glycated Haemoglobin (HbA1c) and Fasting Blood Glucose in Patient Subpopulations by Gender, Duration of Diabetes and Baseline HbA1c. Diabetes, Obesity and Metabolism, 20, 409-418. https://doi.org/10.1111/dom.13086
[31]
Ludvik, B., Frías, J.P., Tinahones, F.J., Wainstein, J., Jiang, H., Robertson, K.E., García-Pérez, L.E., Woodward, D.B. and Milicevic, Z. (2018) 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. The Lancet Diabetes & Endocrinology, 6, 370-381. https://doi.org/10.1016/S2213-8587(18)30023-8
[32]
Mathieu, C., Botros, F.T., Thieu, V., Jia, N., Zhang, N. and Garcia-Perez, L. (2018) Effect of Once Weekly Dulaglutide by Baseline β-Cell Function in the AWARD Program. Diabetes, Obesity and Metabolism, 20, 2023-2028. https://doi.org/10.1111/dom.13313
[33]
Vázquez, L.A., Jódar, E., Trescoli, C., Nicolay, C., Reviriego, J. and Gentilella, R. (2015) Improvement in HbA1c in Patients with Type 2 Diabetes Mellitus Treated with Once Weekly Dulaglutide across Baseline Body Mass Index (BMI) Subgroups at 26 or 52 Weeks. Diabetologia, 1, S376.
[34]
Umpierrez, G.E., Pantalone, K.M., Kwan, A.Y.M., Zimmermann, A.G., Zhang, N. and Fernandez Lando, L. (2016) Relationship between Weight Change and Glycaemic Control in Patients with Type 2 Diabetes Receiving Once-Weekly Dulaglutide Treatment. Diabetes, Obesity and Metabolism, 18, 615-622. https://doi.org/10.1111/dom.12660
[35]
Pencek, R., Blickensderfer, A., Li, Y., Brunell, S.C. and Anderson, P.W. (2012) Exenatide Twice Daily: Analysis of Effectiveness and Safety Data Stratified by Age, Sex, Race, Duration of Diabetes, and Body Mass Index. Postgraduate Medicine, 124, 21-32. https://doi.org/10.3810/pgm.2012.07.2567
[36]
Seufert, J., Bailey, T., Barkholt Christensen, S. and Nauck, M.A. (2016) Impact of Diabetes Duration on Achieved Reductions in Glycated Haemoglobin, Fasting Plasma Glucose and Body Weight with Liraglutide Treatment for Up to 28 Weeks: A Meta-Analysis of Seven Phase III Trials. Diabetes, Obesity and Metabolism, 18, 721-724. https://doi.org/10.1111/dom.12623
[37]
Home, P., Miller, D. and Carr, M.C. (2015) Albiglutide Provides Effective Glycaemic Lowering across Diabetes Duration Subgroups. Diabetologia, 58, S378.
[38]
Onishi, Y., Oura, T., Matsui, A., Matsuura, J. and Iwamoto, N. (2017) Analysis of Efficacy and Safety of Dulaglutide 0.75 mg Stratified by Sex in Patients with Type 2 Diabetes in 2 Randomized, Controlled Phase 3 Studies in Japan. Endocrine Journal, 64, 553-560. https://doi.org/10.1507/endocrj.EJ16-0552
[39]
Waldrop, G., Zhong, J., Peters, M., et al. (2018) Incretin-Based Therapy in Type 2 Diabetes: An Evidence Based Systematic Review and Meta-Analysis. Journal of Diabetic Complications, 32, 113-122. https://doi.org/10.1016/j.jdiacomp.2016.08.018
[40]
Trujillo, J.M., Nuffer, W. and Ellis, S.L. (2015) GLP-1 Receptor Agonists: A Review of Head-to-Head Clinical Studies. Therapeutic Advances in Endocrinology and Metabolism, 6, 19-28. https://doi.org/10.1177/2042018814559725
[41]
Wysham, C., Blevins, T., Arakaki, R., Colon, G., Garcia, P., Atisso, C., et al. (2014) 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, 2159-2167. https://doi.org/10.2337/dc13-2760
[42]
DeFranzo, R.A., Ratner, R.E., Han, J., Kim, D.D., Fineman, M.S. and Baron, A.D. (2005) Effects of Exenatide (Exendin-4) on Glycemic Control and Weight over 30 Weeks in Metformin-Treated Patients with Type 2 Diabetes. Diabetes Care, 28, 1092-1100. https://doi.org/10.2337/diacare.28.5.1092
[43]
Buse, J.B., Henry, R.R., Han, J., et al. (2004) Effects of Exenatide (Exendin-4) on Glycemic Control over 30 Weeks in Sulfonylurea-Treated Patients with Type 2 Diabetes. Diabetes Care, 27, 2628-2635. https://doi.org/10.2337/diacare.27.11.2628
[44]
Garber, A., Henry, R.R., Ratner, R., Hale, P., Chang, C.T. and Bode, B. (2011) Liraglutide, a Once-Daily Human Glucagon-Like Peptide-1 Analogue, Provides Sustained Improvements in Glycaemic Control and Weight for 2 Years as Monotherapy Compared with Glimepiride in Patients with Type 2 Diabetes. Diabetes, Obesity and Metabolism, 13, 348-356. https://doi.org/10.1111/j.1463-1326.2010.01356.x
[45]
Zinman, B., Gerich, J., Buse, J.B., et al. (2009) Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination with Metformin and Thiazolidinedione in Patients with Type 2 Diabetes (LEAD-4 Met + TZD). Diabetes Care, 32, 1224-1230. https://doi.org/10.2337/dc08-2124
[46]
Russell-Jones, D., Vaag, A., Schmitz, O., et al. (2009) Liraglutide vs Insulin Glargine and Placebo in Combination with Metformin and Sulfonylurea Therapy in Type 2 Diabetes Mellitus (LEAD-5 Met + SU): A Randomised Controlled Trial. Diabetologia, 52, 2046-2055. https://doi.org/10.1007/s00125-009-1472-y
[47]
Ghosal, S. and Sinha, B. (2018) Liraglutide and Dulaglutide Therapy in Addition to SGLT-2 Inhibitor and Metformin Treatment in Indian Type 2 Diabetics: A Real World Retrospective Observational Study. Clinical Diabetes and Endocrinology, 4, 11. https://doi.org/10.1186/s40842-018-0061-8
[48]
Odawara, M., Miyagawa, J., Iwamoto, N., Takita, Y., Imaoka, T. and Takamura, T. (2016) Once-Weekly Glucagon-Like Peptide-1 Receptor Agonist Dulaglutide Significantly Decreases Glycated Haemoglobin Compared with Once-Daily Liraglutide in Japanese Patients with Type 2 Diabetes: 52 Weeks of Treatment in a Randomized Phase III Study. Diabetes, Obesity & Metabolism, 18, 249-257. https://doi.org/10.1111/dom.12602
[49]
Cooney, M.T., Vartiainen, E., Laatikainen, T., Juolevi, A., Dudina, A. and Graham, I.M. (2010) Elevated Resting Heart Rate Is an Independent Risk Factor for Cardiovascular Disease in Healthy Men and Women. American Heart Journal, 159, 612-619. https://doi.org/10.1016/j.ahj.2009.12.029
[50]
Robinson, L.E., Holt, T.A., Rees, K., Randeva, H.S. and O’Hare, J.P. (2013) Effects of Exenatide and Liraglutide on Heart Rate, Blood Pressure and Body Weight: Systematic Review and Meta-Analysis. BMJ Open, 3, e001986. https://doi.org/10.1136/bmjopen-2012-001986
[51]
Ferdinand, K.C., White, W.B., Calhoun, D.A., et al. (2014) Effects of the Once-Weekly Glucagon-Like Peptide-1 Receptor Agonist Dulaglutide on Ambulatory Blood Pressure and Heart Rate in Patients with Type 2 Diabetes Mellitus. Hypertension, 64, 731-737. https://doi.org/10.1161/HYPERTENSIONAHA.114.03062
[52]
Fonseca, V.A., DeVries, J.H., Henry, R.R., et al. (2014) Reductions in Systolic Blood Pressure with Liraglutide in Patients with Type 2 Diabetes: Insights from a Patient-Level Pooled Analysis of Six Randomized Clinical Trials. Journal of Diabetic Complications, 28, 399-405. https://doi.org/10.1016/j.jdiacomp.2014.01.009
[53]
Hillis, G.S., Hata, J., Woodward, M., et al. (2012) Resting Heart Rate and the Risk of Microvascular Complications in Patients with Type 2 Diabetes Mellitus. Journal of the American Heart Association, 1, e002832. https://doi.org/10.1161/JAHA.112.002832
[54]
Plutzky, J., Garber, A.J., Falahati, A., Toft, A.D. and Poulter, N.R. (2009) The Once-Daily Human GLP-1 Analogue, Liraglutide, Significantly Reduces Markers of Cardiovascular Risk in Type 2 Diabetes: A Meta-Analysis of Six Clinical Trials. European Heart Journal, 30, 917.
[55]
Peradze, N., Farr, O.M., Perakakis, N., et al. (2019) Short-Term Treatment with High Dose Liraglutide Improves Lipid and Lipoprotein Profile and Changes Hormonal Mediators of Lipid Metabolism in Obese Patients with No Overt Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled, Cross-Over, Double-Blind Clinical Trial. Cardiovascular Diabetology, 18, 141. https://doi.org/10.1186/s12933-019-0945-7
[56]
Diabetes Control and Complications Trial Research Group (1993) The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. The New England Journal of Medicine, 329, 977-986. https://doi.org/10.1056/NEJM199309303291401
[57]
United Kingdom Prospective Diabetes Study Group (1998) United Kingdom Prospective Diabetes Study 24: A 6-Year, Randomized, Controlled Trial Comparing Sulfonylurea, Insulin, and Metformin Therapy in Patients with Newly Diagnosed Type 2 Diabetes That Could Not Be Controlled with Diet Therapy. Annals of Internal Medicine, 128, 165-175. https://doi.org/10.7326/0003-4819-128-3-199802010-00001
[58]
Kim, H.J., Park, S.O., Ko, S.H., et al. (2017) Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association. Diabetes & Metabolism Journal, 41, 423-429. https://doi.org/10.4093/dmj.2017.41.6.423
[59]
Katherine, R.T., Mark, C.L., Jorge, L.G., et al. (2018) Dulaglutide versus Glargine, both Combined with Lispro, Mitigated Estimated Glomerular Filtration Rate Decline in Patients with Type 2 Diabetes and Moderate-to-Severe Chronic Kidney Disease (AWARD-7). The Lancet Diabetes & Endocrinology, 6, 605-617. https://doi.org/10.1016/S2213-8587(18)30104-9
[60]
Cherney, D.Z.I., Verma, S. and Parker, J.D. (2018) Dulaglutide and Renal Protection in Type 2 Diabetes. The Lancet Diabetes & Endocrinology, 6, 588-590. https://doi.org/10.1016/S2213-8587(18)30125-6
[61]
Dabia, P.K. (2010) Renal Function in Diabetic Nephropathy. World Journal of Diabetes, 1, 48-56. https://doi.org/10.4239/wjd.v1.i2.48
