The influence of 6-months treatment with exenatide on type 2 diabetes mellitus compensation, anthropometric and biochemical parameters

Czech version

Authors: T. Roubíček ¹; M. Mráz ¹; M. Bártlová ¹; P. Kaválková ¹; D. Haluzíková ^1,2; P. Trachta ¹; J. Housová ¹; M. Matoulek ¹; Š. Svačina ¹; M. Haluzík ¹
Authors‘ workplace: III. interní klinika 1. lékařské fakulty UK a VFN Praha, přednosta prof. MUDr. Štěpán Svačina, DrSc., MBA ¹; Ústav tělovýchovného lékařství 1. lékařské fakulty UK a VFN Praha, přednosta doc. MUDr. Zdeněk Vilikus, CSc. ²
Published in: Vnitř Lék 2010; 56(1): 15-20
Category: Original Contributions

Overview

Objectives:
Exenatide, a synthetic GLP‑1 analogue, is a new antidiabetic agent from the group of incretine mimetics coming into the daily clinical practice. In our study we evaluated the effect of 6-months treatment with exenatide on diabetes compensation, anthropometric and biochemical parameters in the patients with poorly controlled type 2 diabetes mellitus and obesity.

Method:
We included 18 patients with poorly controlled diabetes (mean HbA_1c 8.5 ± 0.3%) treated with diet and peroral antidiabetic agents (4 patients were treated with insulin in the past). Exenatide was administered via subcutaneous injection twice daily for 6 months. Patients were examined after 1 month, when the dose of exenatide was increased from 5 μg twice daily to 10 μg twice daily and after 3 and 6 months. We evaluated the diabetes compensation, biochemical parameters, body weight changes and side effects of exenatide.

Results:
6-months exenatide treatment significant decreased body weight (baseline vs 6 month treatment 107.3 ± 4.4 kg vs 103.7 ± 4.6 kg, p = 0.02), BMI (36.7 ± 1.2 kg/m² vs 35.3 ± 1.3 kg/m², p = 0.01) a HbA_1c (8.5 ± 0.3 % vs 7.4 ± 0.4%, p = 0.04) and increased HDL‑cholesterol (0.92 ± 0.1 mmol/l vs 0.98 ± 0.1 mmol/l, p = 0.02). Fasting glycemia tended to decline at the end of the study, but the difference did not reach the statistical significance. The area under the curve of glycemia levels after the standardized breakfast in the subgroup of 8 patients after the 6-months exenatide treatment was significantly lower when compared to baseline values (2,908 ± 148 vs 2,093 ± 194, p = 0.03). Concentrations of total and LDL‑cholesterol and triglycerides did not change significantly. The most frequent side effects of exenatide treatments were transient anorexia and nausea (38.5%), dyspepsia and functional gastrointestinal discomfort (38.5%) and various neuropsychical symptoms (nervosity and insomnia – 30.8%). Most of the side effects disappeared during the treatment, none of these side effects was a reason for discontinuation of a treatment. 3 minor hypoglycemic episodes occured in patients simultaneously treated with derivates of sulfonylurea, but no serious hypoglycemia occured during the entire study.

Conclusion:
Exenatide treatment in obese patients with poor diabetes control was accompanied by statistically significant decrease of body weight, improvement of diabetes control and increase in HDL‑cholesterol.

Key words:
exenatide – GLP‑1 – type 2 diabetes mellitus – body weight – obesity

Sources

1. O’rahilly S. Science, medicine, and the future. Non‑insulin dependent diabetes mellitus: the gathering storm. BMJ 1997; 314: 955–959.

2. Haffner SM, Lehto S, Ronnemaa T et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229–234.

3. Haffner SM. Pre‑diabetes, insulin resistance, inflammation and CVD risk. Diabetes Res Clin Pract 2003; 61 (Suppl 1):S9–S18.

4. Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2000; 106: 171–176.

5. Seppala‑Lindroos A, Vehkavaara S, Hakkinen AM et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002; 87: 3023–3028.

6. Wohl P, Krušinová E, Kratochvílová S et al. Inzulínová rezistence u diabetiků – metabolická inflexibilita. DMEV 2005; 8: 174–178.

7. Creutzfeldt W, Ebert R. New developments in the incretin concept. Diabetologia 1985; 28: 565–573.

8. Nauck MA, Homberger E, Siegel EG et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C‑peptide responses. J Clin Endocrinol Metab 1986; 63: 492–498.

9. Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 2003; 26: 2929–2940.

10. Nauck M, Stockmann F, Ebert R et al. Reduced incretin effect in type 2 (non‑insulin‑dependent) diabetes. Diabetologia 1986; 29: 46–52.

11. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab 2004; 287: E199–E206.

12. Nauck MA. Glucagon‑like peptide 1(GLP‑1) in the treatment of diabetes. Horm Metab Res 2004; 36: 852–858.

13. Nielsen LL, Baron AD. Pharmacology of exenatide (synthetic exendin‑4) for the treatment of type 2 diabetes. Curr Opin Investig Drugs 2003; 4: 401–405.

14. Viswanathan P, Chaudhuri A, Bhatia R et al. Exenatide therapy in obese patients with type 2 diabetes mellitus treated with insulin. Endocr Pract 2007; 13: 444–450.

15. Kendall DM, Riddle MC, Rosenstock J et al. Effects of exenatide (exendin‑4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005; 28: 1083–1091.

16. Kolterman OG, Buse JB, Fineman MS et al. Synthetic exendin‑4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003; 88: 3082–3089.

17. Gentilella R, Bianchi C, Rossi A et al. Exenatide: a review from pharmacology to clinical practice. Diabetes Obes Metab 2009; 11: 544–556.

18. Gerstein HC, Yusuf S, Bosch J et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368: 1096–1105.

19. Effect of intensive blood‑glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352: 854–865.

20. Patel A, Macmahon S, Chalmers J et al. Intensive blood glucose control and vascular outcomes in patients with type 2diabetes. N Engl J Med 2008; 358: 2560–2572.

21. Home PD, Pocock SJ, Beck‑Nielsen H et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open‑label trial. Lancet 2009; 363: 256–278.