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One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial
- Bunck, M. C. (author)
- Diamant, M. (author)
- Corner, A. (author)
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- Malloy, J. L. (author)
- Shaginian, R. M. (author)
- Deng, W. (author)
- Kendall, D. M. (author)
- Taskinen, M. R. (author)
- Yki-Jarvinen, H. (author)
- Heine, R. J. (author)
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- (creator_code:org_t)
- 2009
- 2009
- English.
- In: Diabetes Care. - 1935-5548. ; 32:5, s. 762-8
- Journal article (peer-reviewed)
Abstract
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- OBJECTIVE: Traditional blood glucose-lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients. Preclinical studies with exenatide have suggested sustained improvements in beta-cell function. We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp-derived measures of beta-cell function, glycemic control, and body weight. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). beta-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period. Additional end points included effects on glycemic control, body weight, and safety. RESULTS: Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09-2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: -0.8 +/- 0.1 and -0.7 +/- 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference -4.6 kg, P < 0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, beta-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.
Keyword
- Arginine/pharmacology
- Blood Glucose/metabolism
- Body Mass Index
- C-Peptide/blood
- Diabetes Mellitus
- Type 2/blood/*drug therapy/physiopathology
- Female
- Hemoglobin A
- Glycosylated/metabolism
- Humans
- Hypoglycemic Agents/*therapeutic use
- Insulin/*analogs & derivatives/*secretion/therapeutic use
- Insulin-Secreting Cells/drug effects/*physiology
- Kinetics
- Male
- Metformin/*therapeutic use
- Middle Aged
- Peptides/*therapeutic use
- Venoms/*therapeutic use
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- ref (subject category)
- art (subject category)
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- Bunck, M. C.
- Diamant, M.
- Corner, A.
- Eliasson, Björn, ...
- Malloy, J. L.
- Shaginian, R. M.
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- Deng, W.
- Kendall, D. M.
- Taskinen, M. R.
- Smith, Ulf, 1943
- Yki-Jarvinen, H.
- Heine, R. J.
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- Diabetes Care
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- University of Gothenburg
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