Exenatide is an incretin mimetic that improves beta cell function by mimicking the effects of a naturally occurring incretin hormone protein called glucagon-like peptide-1. Exenatide also suppresses glucagon secretion, lower concentrations of which lead to decreased hepatic glucose output. It also slows emptying of food from the stomach, reducing the rate at which meal-derived glucose appears in the circulation.
The efficacy of exenatide has been studied in three 30-week multicentre, randomised, double-blind trials. Exenatide was assessed in combination with metformin >1500mg/day (n=336)1, a sulphonylurea (n=377)2, and metformin plus sulphonylurea (n=733)3. In all three trials the primary outcome measure was glycaemic control, as assessed by HbA1c. Secondary outcome measurements included body weight.
In the exenatide versus metformin-only trial, the exenatide treatment groups (5 microgram and 10 microgram twice daily) showed significant dose-dependent reductions in HbA1c compared with placebo at week 30. The HbA1c changes from baseline were -0.78 ± 0.10 per cent in the 10 microgram group, -0.40 ± 0.11 per cent in the 5 microgram group and +0.08 ± 0.10 per cent in the placebo group.
In the exenatide versus sulphonylurea-only trial, again both exenatide groups showed significant dose-dependent reductions in HbA1c at week 30. The HbA1c change from baseline was -0.86 ± 0.11 per cent in the 10 microgram exenatide group and -0.46 ± 0.12 per cent in the 5 microgram exenatide group compared with an increase of 0.12 ± 0.09 per cent in the placebo group.
In the exenatide versus metformin-and-a-sulphonylurea trial, the exenatide groups again showed significant reductions in HbA1c compared with placebo at week 30. The HbA1c changes from baseline were -0.80 ± 0.10 per cent in the 10 microgram group, -0.60 ± 0.10 per cent in the 5 microgram group and +0.20 ± 0.10 per cent in the placebo group.
The exenatide groups showed overall progressive weight loss compared with placebo in all three trials. The most frequent adverse events were mild to moderate gastrointestinal effects. The efficacy of exenatide has also been compared to insulin glargine4 and insulin aspart5 in patients that are inadequately controlled with metformin and a sulphonylurea combination therapy. Exenatide and both insulins achieved similar improvements in overall glycaemic control. The exenatide group showed significant weight reduction compared with both insulins. There was a higher incidence of gastrointestinal adverse effects with exenatide.
1. DeFronzo R, Ratner R, Han, J et al. Effects of exenatide on glycaemic control and weight over 30 weeks in metformin treated patients with type II diabetes. Diabetes Care 2005: Vol 28 (5); 1092-1100.
2. Buse J, Henry R, Han J et al. Effects of exenatide on glycaemic control over 30 weeks in sulphonylurea treated patients with type II diabetes. Diabetes Care 2004: Vol 27 (11); 2628-2635.
3. Kendall D, Riddle M, Rosenstock J et al. Effects of exenatide on glycaemic control over 30 weeks in patients with type II diabetes treated with metformin and a sulphonylurea. Diabetes Care 2005: Vol 28 (5); 1083-1091.
4. Heine R, Gaal L, Johns D et al. Exenatide versus insulin glargine in patients with suboptimally controlled type II diabetes. Ann Internl Med 2005: 143; 559-569.
5. Nauck M, Duran S, Kim D et al. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type II diabetes who were suboptimally controlled with sulphonylurea and metformin. Diabetologica 2007: 50; 259-267.
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