Optimization of Exenatide plus Detemir Treatment for Morbid Obese Patients with Insulin Dependent Diabetes Resistant to Conventional Treatment. Effect of Exenatide on Patients with Mellitus Diabetes Type 2 — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Optimization of Exenatide plus Detemir Treatment for Morbid Obese Patients with Insulin Dependent Diabetes Resistant to Conventional Treatment. Effect of Exenatide on Patients with Mellitus Diabetes Type 2
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
,
Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
1 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
2 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
3 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
4 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
5 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
6 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
7 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
8 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
9 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
10 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
11 Unidad de Diabetes y Obesidad del área VII Murcia Este, Hospital General Universitario Reina Sofía de Murcia, Murcia, España
The purpose of this study was to analyze the effects of the treatment with Exenatide joint to insulin detemir. The study was carried out with obese patients with type 2 diabetes mellitus (DM2) and deficient control, despite intensive insulin therapy combined with oral antidiabetics. A longitudinal study was made with 15 patients controlled by the Endocrinology and Nutrition Section of the Reina Sofía University Hospital, Murcia. These patients were treated with Exenatide joint to insulin during 3, 6 and 12 months. Statistically meaningful differences (p < 0.05) were observed in the reduction of HbA1c in the 3 and 6 months treatment groups (initial HbA1c: 9.55% ± 1.086%, weight: 119.94 kg, insulin requirement: 0.71 IU/kg/day; after 3 months: HbA1c: 7.77% ± 1.164%, weight: 98.13 kg, insulin requirement: 0.59 IU/kg/day; after 6 months: HbA1c: 7.21%, weight: 97.93 kg, insulin requirement: 0.55 IU/kg/day). It was observed that the association of Exenatide and insulin promotes an improvement in several indicators such as weight, body mass index (BMI), systolic pressure (SP), diastolic pressure (DP), triglycerides (TG), cLDL, cHDL and total cholesterol (TC), in patients with diabetes resistant to conventional therapy. However, these improvements were statistically no significant (p < 0.05). It is possible to talk of a reduction of cardiovascular risk factors in patients with Exenatide, being thus a suitable option for this kind of individuals. It is important to emphasize the fact that our study showed bigger body-weight reductions results after 6 and 12 months, as compared to the researches quoted.
KeywordsType 2 Diabetes MellitusExenatideCardiovascular RiskPhysical and Biochemical Parameters
National Health Service (NHS) (2007) Exenatide. New Drug Evaluation, 84.
Centro Andaluz de Información de Medicamentos (CADIME) (2009) Exenatida (DCI). Ficha de Novedad Terapéutica 2.
Campoamor, F. (2008) Exenatida en la diabetes mellitus tipo 2. Comisión de Evaluación de Medicamentos, Islas Baleares.
Verzegnassi, F. and Chinello, M. (2010) Exenatide in Type 2 Diabetes. Lancet, 376, 1052-1053. http://dx.doi.org/10.1016/S0140-6736(10)61485-7
Peters, A. (2010) Incretin-Based Therapies: Review of Current Clinical Trial Data. American Journal of Medicine, 123, S28-S37. http://dx.doi.org/10.1016/j.amjmed.2009.12.007
Wajcberg, E. and Tavaria, A. (2009) Exenatide: Clinical Aspects of the First Incretin-Mimetic for the Treatment of Type 2 Diabetes Mellitus. Expert Opinion on Pharmacotherapy, 10, 135-142. http://dx.doi.org/10.1517/14656560802611832
Segal, J.B., Dy, S.M., Millman, E.A., Herbert, R., Bass, E.B. and Wu, A. (2007) Diffusion into Use of Exenatide for Glucose Control in Diabetes Mellitus: A Retrospective Cohort Study of a New Therapy. Clinical Therapeutics, 29, 1784-1794. http://dx.doi.org/10.1016/j.clinthera.2007.08.021
Philippe, J. (2009) Role and Indication of GLP-1 Analogues in the Treatment of Type 2 Diabetes. Revue Médicale Suisse, 5, 1260-1262, 1264-1265.
Reuter, H. and Erdmann, E. (2007) Exenatide—An Incretin-Mimetic Agent for the Treatment of Type 2 Diabetes Mellitus. Deutsche Medizinische Wochenschrift, 132, 571-574. http://dx.doi.org/10.1055/s-2007-970380
Gill, A., Hoogwerf, B.J., Burger, J., Bruce, S., Macconell, L., Yan, P., et al. (2010) Effect of Exenatide on Heart Rate and Blood Pressure in Subjects with Type 2 Diabetes Mellitus: A Double-Blind, Placebo-Controlled, Randomized Pilot Study. Cardiovascular Diabetology, 9, 6. http://dx.doi.org/10.1186/1475-2840-9-6
Moretto, T.J., Milton, D.R., Ridge, T.D., Macconell, L.A., Okerson, T., Wolka, A.M., et al. (2008) Efficacy and Tolerability of Exenatidemonotherapy over 24 Weeks in Antidiabetic Drug-Naive Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study. Clinical Therapeutics, 30, 1448-1460. http://dx.doi.org/10.1016/j.clinthera.2008.08.006
Klonoff, D.C., Buse, J.B., Nielsen, L.L., Guan, X., Bowlus, C.L., Holcombe, J.H., et al. (2008) Exenatide Effects on Diabetes, Obesity, Cardiovascular Risk Factors and Hepatic Biomarkers in Patients with Type 2 Diabetes Treated for at Least 3 Years. Current Medical Research and Opinion, 24, 275-286.
Drucker, D.J., Buse, J.B., Taylor, K., Kendall, D.M., Trautmann, M., Zhuang, D., DURATION-1 Study Group, et al. (2008) Exenatide Once Weekly versus Twice Daily for the Treatment of Type 2 Diabetes: A Randomised, Open-Label, Non-Inferiority Study. Lancet, 372, 1240-1250. http://dx.doi.org/10.1016/S0140-6736(08)61206-4
Okerson, T., Yan, P., Stonehouse, A., Brodows, R. and Bhole, D. (2008) Exenatide Improved Systolic Blood Pressure Compared to Insulin or Placebo in Patients with Type 2 Diabetes. Diabetologia, 51, S350.
Bergenstal, R., Kim, T., Yan, P., Darsow, T., Walsh, B., Okerson, T., et al. (2009) Exenatide Once Weekly Improved Cardiometabolic Risk Factors in Subjects with Type 2 Diabetes during One Year of Treatment. Diabetes, 58, A43.
Bhushan, R., Elkind-Hirsch, K.E., Bhushan, M., Butler, W.J., Duncan, K. and Marrioneaux, O. (2009) Improved Glycemic Control and Reduction of Cardiometabolic Risk Factors in Subjects with Type 2 Diabetes and Metabolic Syndrome Treated with Exenatide in a Clinical Practice Setting. Diabetes Technology & Therapeutics, 11, 353-359. http://dx.doi.org/10.1089/dia.2008.0090
Kothare, P.A., Linnebjerg, H., Isaka, Y., Uenaka, K., Yamamura, A., Yeo, K.P., de la Peña, A., Teng, C.H., Mace, K., Fineman, M., Shigeta, H., Sakata, Y. and Irie, S. (2008) Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of Exenatide in Japanese Patients with Type 2 Diabetes Mellitus. Journal of Clinical Pharmacology, 48, 1389-1399. http://dx.doi.org/10.1177/0091270008323750
Linnebjerg, H., Kothare, P., Park, S., Mace, K. and Mitchell, M. (2009) The Effect of Exenatide on Lisinopril Pharmacodynamics and Pharmacokinetics in Patients with Hypertension. International Journal of Clinical Pharmacology and Therapeutics, 47, 651-658. http://dx.doi.org/10.5414/CPP47651
Menéndez Torre, E., Lafita Tejedor, J., Artola Menéndez, S., Millán Núñez-Cortés, J., Alonso García, á., Puig Domingo, M., García Solans, J.R., álvarez Guisasola, F., García Alegría, J., Mediavilla Bravo, J., Fernández-Santos, C.M. and Romero González, R. (2010) Recomendaciones para el tratamiento farmacológico de la hiperglucemia en la diabetes tipo 2. Avances en Diabetología, 26, 331-338. http://dx.doi.org/10.1016/S1134-3230(10)65006-5
Svec, F. (2010) Incretin Physiology and Its Role in Type 2 Diabetes Mellitus. Journal of the American Osteopathic Association, 110, eS20-eS24.
Sudhakaran, C., Fathima, M., Anjana, R.M., Unnikrishnan, R.I. and Mohan, V. (2010) Effectiveness of Exenatide in Asian Indians in a Clinical Care Setting. Diabetes Technology & Therapeutics, 12, 613-618. http://dx.doi.org/10.1089/dia.2010.0033
Diamant, M., Van Gaal, L., Stranks, S., Northrup, J., Cao, D., Taylor, K. and Trautmann, M. (2010) Once Weekly Exenatide Compared with Insulin Glargine Titrated to Target in Patients with Type 2 Diabetes (DURATION-3): An Open-Label Randomised Trial. Lancet, 375, 2234-2243. http://dx.doi.org/10.1016/S0140-6736(10)60406-0
Bergenstal, R.M., Wysham, C., Macconell, L., Malloy, J., Walsh, B., Yan, P., Wilhelm, K., Malone, J., Porter, L.E. and DURATION-2 Study Group (2010) Efficacy and Safety of Exenatide Once Weekly versus Sitagliptin or Pioglitazone as an Adjunct to Metformin for Treatment of Type 2 Diabetes (DURATION-2): A Randomised Trial. Lancet, 376, 431-439. http://dx.doi.org/10.1016/S0140-6736(10)60590-9
Blevins, T., Han, J., Nicewarner, D., Chen, S., Oliveira, J.H. and Aronoff, S. (2010) Exenatide Is Non-Inferior to Insulin in Reducing HbA1c: An Integrated Analysis of 1423 Patients with Type 2 Diabetes. Postgraduate Medicine, 122, 118-128. http://dx.doi.org/10.3810/pgm.2010.05.2149
Natarajan, B., Edavalath, M., Davies, J., Jenkins, L., Marshall-Richards, N., Evans, D., Price, D.E. and Stephens, J.W. (2010) Clinical Experience with Exenatide in a Routine Secondary Care Diabetes Clinic. Primary Care Diabetes, 4, 57-60. http://dx.doi.org/10.1016/j.pcd.2009.11.001
Yoon, N.M., Cavaghan, M.K., Brunelle, R.L. and Roach, P. (2009) Exenatide Added to Insulin Therapy: A Retrospective Review of Clinical Practice over Two Years in an Academic Endocrinology Outpatient Setting. Clinical Therapeutics, 31, 1511-1523. http://dx.doi.org/10.1016/j.clinthera.2009.07.021
Drucker, D.J., Buse, J.B., Taylor, K., Kendall, D.M., Trautmann, M., Zhuang, D., Porter, L. and DURATION-1 Study Group (2008) Exenatide Once Weekly versus Twice Daily for the Treatment of Type 2 Diabetes: A Randomised, Open-Label, Non-Inferiority Study. Lancet, 372, 1240-1250. http://dx.doi.org/10.1016/S0140-6736(08)61206-4
Forti, A., Garcia, E.G., Yu, M.B., Jimenez, M.C., Brodows, R.G. and Oliveira, J.H. (2008) Efficacy and Safety of Exenatide Administered before the Two Largest Daily Meals of Latin American Patients with Type 2 Diabetes. Current Medical Research and Opinion, 24, 2437-2447. http://dx.doi.org/10.1185/03007990802282398
Nyström, T., Gutniak, M.K., Zhang, Q., Zhang, F., Holst, J.J., Ahrén, B. and Sjöholm, Å. (2004) Effects of Glucagon-Like Peptide-1 on Endothelial Function in Type 2 Diabetes Patients with Stable Coronary Artery Disease. American Journal of Physiology-Endocrinology and Metabolism, 287, E1209-E1215. http://dx.doi.org/10.1152/ajpendo.00237.2004
Thrainsdottir, I., Malmberg, K., Olsson, A., Gutniak, M. and Rydén, L. (2004) Initial Experience with GLP-1 Treatment on Metabolic Control and Myocardial Function in Patients with Type 2 Diabetes Mellitus and Heart Failure. Diabetes and Vascular Disease Research, 1, 40-43. http://dx.doi.org/10.3132/dvdr.2004.005
Sokos, G.G., Nikolaidis, L.A., Mankad, S., Elahi, D. and Shannon, R.P. (2006) Glucagon-Like Peptide-1 Infusion Improves Left Ventricular Ejection Fraction and Functional Status in Patients with Chronic Heart Failure. Journal of Cardiac Failure, 12, 694-699. http://dx.doi.org/10.1016/j.cardfail.2006.08.211
Bunck, M.C., Diamant, M., Eliasson, B., Cornér, A., Shaginian, R.M., Heine, R.J., et al. (2010) Exenatide Affects Circulating Cardiovascular Risk Biomarkers Independently of Changes in Body Composition. Diabetes Care, 33, 1734-1737. http://dx.doi.org/10.2337/dc09-2361
Buse, J.B., Bergenstal, R.M., Glass, L.C., Heilmann, C.R., Lewis, M.S., Kwan, A.Y., Hoogwerf, B.J. and Rosenstock, J. (2010) Use of Twice-Daily Exenatide in Basal Insulin-Treated Patients with Type 2 Diabetes: A Randomized, Controlled Trial. Annals of Internal Medicine, 154, 1-12.
Kolterman, O.G., Buse, J.B., Fineman, M.S., Gaines, E., Heintz, S., Bicsak, T.A., Taylor, K., Kim, D., Aisporna, M., Wang, Y. and Baron, A.D. (2003) Synthetic Exendin-4 (Exenatide) Significantly Reduces Postprandial and Fasting Plasma Glucose in Subjects with Type 2 Diabetes. Journal of Clinical Endocrinology & Metabolism, 88, 3082-3089. http://dx.doi.org/10.1210/jc.2002-021545
Arnolds, S., Dellweg, S., Clair, J., Dain, M.P., Nauck, M.A., Rave, K. and Kapitza, C. (2010) Further Improvement in Postprandial Glucose Control with Addition of Exenatide or Sitagliptin to Combination Therapy with Insulin Glargine and Metformin: A Proof-of-Concept Study. Diabetes Care, 33, 1509-1515. http://dx.doi.org/10.2337/dc09-2191
Yoon, N.M., Cavaghan, M.K., Brunelle, R.L. and Roach, P. (2009) Exenatide Added to Insulin Therapy: A Retrospective Review of Clinical Practice over Two Years in an Academic Endocrinology Outpatient Setting. Clinical Therapeutics, 31, 1511-1523. http://dx.doi.org/10.1016/j.clinthera.2009.07.021
Sheffield, C.A., Kane, M.P., Busch, R.S., Bakst, G., Abelseth, J.M. and Hamilton, R.A. (2008) Safety and Efficacy of Exenatide in Combination with Insulin in Patients with Type 2 Diabetes Mellitus. Endocrine Practice, 14, 285-292. http://dx.doi.org/10.4158/EP.14.3.285
Nayak, U.A., Govindan, J., Baskar, V., Kalupahana, D. and Singh, B.M. (2010) Exenatide Therapy in Insulin-Treated Type 2 Diabetes and Obesity. QJM, 103, 687-694. http://dx.doi.org/10.1093/qjmed/hcq112
Nathan, D.M., Buse, J.B., Davidson, M.B., Heine, R.J., Holman, R.R., Sherwin, R., et al. (2006) Management of Hyperglycaemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 29, 1963-1972. http://dx.doi.org/10.2337/dc06-9912
Schernthaner, G., Barnett, A.H., Betteridge, D.J., Carmena, R., Ceriello, A., Charbonnel, B., et al. (2010) Is the ADA/EASD Algorithm for the Management of Type 2 Diabetes (January 2009) Based on Evidence or Opinion? A Critical Analysis. Diabetologia, 53, 1258-1269. http://dx.doi.org/10.1007/s00125-010-1702-3
German Diabetes Association, Matthaei, S., Bierwirth, R., Fritsche, A., Gallwitz, B., Häring, H.U., et al. (2009) Medical Antihyperglycaemic Treatment of Type 2 Diabetes Mellitus: Update of the Evidence-Based Guideline of the German Diabetes Association. Experimental and Clinical Endocrinology & Diabetes, 117, 522-557. http://dx.doi.org/10.1055/s-0029-1239559
Apovian, C.M., Bergenstal, R.M., Cuddihy, R.M., Qu, Y., Lenox, S., Lewis, M.S., et al. (2010) Effects of Exenatide Combined with Lifestyle Modification in Patients with Type 2 Diabetes. American Journal of Medicine, 123, 468.e9-17.
Robles, G.I. and Singh-Franco, D. (2009) A Review of Exenatide as Adjunctive Therapy in Patients with Type 2 Diabetes. Drug Design, Development and Therapy, 3, 219-240. http://dx.doi.org/10.2147/DDDT.S3321