Evaluation of the Glucoregulatory Effects of Glucagon-like Peptide-1 Receptor (GLP-1 Receptor) Activation in Participants With Type 2 Diabetes Mellitus (MK-0000-222)
Summary
This was a four-period crossover study to assess the glycemic effects of a single dose of oxyntomodulin (OXM) on the glucose levels in participants with Type 2 diabetes mellitus (T2DM). Participants were randomly assigned to 1 of 6 treatment sequences consisting of 4 treatment periods, with a 7-day wash-out between each treatment period. The primary hypothesis was that during graded glucose infusion (GGI) oxyntomodulin (OXM) is neutral or better than placebo (Pbo) at lowering ambient plasma glucose levels, and at significantly enhancing insulin secretion.
Timeline
- Start
- 2011-06
- Primary completion
- 2011-07
- Completion
- 2011-07
Outcome
Met primary endpoint
registry Oxyntomodulin vs Placebo; p = 0.024; Geometric Mean Ratio 0.87 (90% CI 0.77 to 0.98); t-test, 1 sided NCT01373450 ↗
registry Oxyntomodulin vs Placebo; p = 0.004; Geometric Mean Ratio 0.77 (90% CI 0.66 to 0.90); t-test, 1 sided NCT01373450 ↗
registry Oxyntomodulin vs Placebo; p <0.001; Least Square Mean Difference 0.014 (90% CI 0.008 to 0.019); t-test, 1 sided NCT01373450 ↗
Publications
- Shankar SS, Shankar RR, Mixson LA, Miller DL, Pramanik B, O'Dowd AK, Williams DM, Frederick CB, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Native Oxyntomodulin Has Significant Glucoregulatory Effects Independent of Weight Loss in Obese Humans With and Without Type 2 Diabetes. Diabetes. 2018 Jun;67(6):1105-1112. doi: 10.2337/db17-1331. Epub 2018 Mar 15.
- Shankar SS, Shankar RR, Mixson LA, Miller DL, Chung C, Cilissen C, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Linearity of beta-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series. Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E865-73. doi: 10.1152/ajpendo.00527.2015. Epub 2016 Apr 12.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Liraglutide | Peptide | 0.6 mg | Subcutaneous |
| Subject | Liraglutide | Peptide | 1.2 mg | Subcutaneous |
| Subject | Oxyntomodulin | Protein / enzyme biologic | 3 unknown | Intravenous |