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The use of exenatide in islet transplant recipients with chronic allograft dysfunction: safety, efficacy, and metabolic effects.
- Source :
-
Transplantation [Transplantation] 2008 Jul 15; Vol. 86 (1), pp. 36-45. - Publication Year :
- 2008
-
Abstract
- Background: A current limitation of islet transplantation is reduced long-term graft function. The glucagon-like peptide-1 receptor agonist, exenatide (Byetta, Amylin Pharmaceuticals, CA) has properties that could improve existing islet function, prevent further loss of islet mass and possibly even stimulate islet regeneration.<br />Methods: This prospective study evaluated the safety, efficacy, and metabolic effects of exenatide in subjects with type 1 diabetes mellitus and islet allograft dysfunction requiring exogenous insulin.<br />Results: Sixteen subjects commenced exenatide, 12 continue (follow-up 214+/-57 days; range 108-287), four (25%) discontinued medication because of side effects. At 6 months, exogenous insulin was significantly reduced with stable glycemic control (0.15+/-0.02 vs. 0.11+/-0.025 U/kg per day; P<0.0001); three subjects discontinued insulin from 4, 5, and 9 U/day, respectively, two sustained insulin independence with A1c reduction below graft dysfunction criteria. Postprandial capillary blood glucose was significantly decreased (129.4+/-3.8 vs. 118.7+/-4.6 mg/dL; P<0.001), C-peptide and C-peptide-to-glucose ratio increased significantly by 5th and 6th months of treatment (ratio, 1.09+/-0.15 vs. 1.52+/-0.18; P<0.05). Weight loss more than 3 kg occurred in 8 of 12 (67%) subjects. Stimulation testing demonstrated improved glucose disposal and C-peptide secretion (glucose area under the curve 52,332+/-3,219 vs. 42,072+/-1,965; P=0.002 mg x min x dL, mixed meal stimulation index 0.50+/-0.06 vs. 0.66+/-0.09; P=0.03 pmol x mL), with marked suppression of glucagon secretion and progressive increase in amylin secretion. Side effects were more frequent and severe compared with published reports in type 2 diabetes, tolerated doses were lower.<br />Conclusions: Exenatide was tolerated in this patient population after appropriate dose titration and there appeared to be gradual but sustained positive effects on glycemic control and islet graft function.
- Subjects :
- Adult
Amyloid blood
Blood Glucose drug effects
C-Peptide blood
Diabetes Mellitus, Type 1 metabolism
Diabetes Mellitus, Type 1 surgery
Exenatide
Feasibility Studies
Glucagon blood
Graft Rejection metabolism
Humans
Hypoglycemic Agents adverse effects
Immunosuppressive Agents therapeutic use
Insulin therapeutic use
Islet Amyloid Polypeptide
Islets of Langerhans Transplantation
Middle Aged
Peptides adverse effects
Prospective Studies
Time Factors
Transplantation, Homologous
Treatment Outcome
Venoms adverse effects
Diabetes Mellitus, Type 1 drug therapy
Graft Rejection prevention & control
Graft Survival drug effects
Hypoglycemic Agents therapeutic use
Peptides therapeutic use
Venoms therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 86
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 18622276
- Full Text :
- https://doi.org/10.1097/TP.0b013e31817c4ab3