Novel therapies based on the physiologic and pharmacologic glucoregulatory effects of incretin hormones, mimicking the effects of GLP-1 (e.g. incretin mimetics), or increasing endogenous incretin concentrations (e.g. DPP-IV inhibitors), provide new options for the treatment of type 2 diabetes. The unique ability of incretin mimetics to enhance glucose-dependent insulin secretion, slow gastric emptying, suppress glucagon secretion, decrease food intake, and even cause body weight loss (e.g. exenatide), provides new therapeutic choices for patients with type 2 diabetes. Furthermore, since these compounds have been shown to improve β-cell mass in animal studies and function in clinical studies, these compounds may potentially be able to alter the natural progression of diabetes, and associated complications.
Table 2. Summary of Randomized clinical trials with Exenatide
|
Authors |
Number of Patients |
Duration of Treatment |
Treatment groups |
Primary Endpoint |
Summary of Results |
|---|---|---|---|---|---|
|
Fineman et al.84 |
109 |
4 weeks |
Exenatide 0.08 mcg/kg bid or tid vs. placebo |
A1C |
Significant reduction in A1C with exenatide treatment. Most common side effects were nausea and hypoglycaemia. |
|
Poon et al.85 |
156 |
4 weeks |
Exenatide 2.5, 5, 7.5 and 10 mcg bid vs. placebo |
A1C |
Significant, dose-dependent, reduction in A1C with exenatide treatment. Most common side effect was dose dependent nausea. |
|
Buse et al.79 |
377 |
30 weeks |
Exenatide 5 and 10 mcg SC (bid) vs. placebo in sulfonylurea treated patients |
A1C |
Significant dose dependent reduction in A1C and body weight with exenatide treatment. Nausea and hypoglycaemia were the most common side effect. |
|
De Fronzo et al.80 |
336 |
30 weeks |
Exenatide 5 and 10 mcg SC (bid) vs. placebo in metformin treated patients |
A1C |
Significant dose dependent reduction in A1C and body weight with exenatide treatment. Nausea was the most common side effect. No increase in risk of hypoglycaemia when exenatide added with metformin. |
|
Kendall et al.81 |
733 |
30 weeks |
Exenatide 5 and 10 mcg SC (bid) vs. placebo in metformin and sulfonylurea treated patients |
A1C |
Significant dose dependent reduction in A1C and body weight with exenatide treatment. Nausea and hypoglycaemia were the most common side effect. |
Table 3. Summary of Randomized clinical trials with Liraglutide
|
Authors |
Number of Patients |
Duration of Treatment |
Treatment groups |
Primary Endpoint |
Summary of Results |
|---|---|---|---|---|---|
|
Degn et al.87 |
13 |
1 week |
Liraglutide 6 mcg/kg SC vs. placebo |
24 h plasma glucose |
Significant reduction of mean plasma glucose. |
|
Madsbad et al.91 |
193 |
12 weeks |
Liraglutide 0.045, 0.225, 0.45, 0.6 and 0.75 mg qd vs. placebo |
A1C |
Significant reduction in A1C with no weight gain. Dose dependent nausea was the most frequent adverse event. |
|
Harder et al.89 |
33 |
8 weeks |
Liraglutide 0.6 mg SC qd vs. placebo |
A1C, glucose, body composition |
Significant reduction in A1C. No difference in body weight, body composition or 24-h energy expenditure. Nausea and diarrhea were the most common adverse events. |