Benefits diabetic patients with dual GIP/GLP-1 receptor agonist
The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 DiabetesLiterature - Frias JP, Bastyr EJ 3rd, Vignati L, et al. - Cell Metab. 2017 Aug 1;26(2):343-352.e2
- The HbA1c change from baseline was statistically significant with NNC0090-2746 compared with placebo, with estimated treatment differences (ETDs) of -0.63% (95% CI -0.93 to -0.33) at week 8 and -0.96% (95% CI -1.36 to -0.56) at week 12.
- The change from baseline in mean self-measured plasma glucose was statistically significant when comparing NNC0090-2746 with placebo (ETD week 8: -27.7 mg/dl, 95% CI -44.7 to -10.7; ETD week 12: -31.7 mg/dL, 95% CI -47.0 to -16.5).
- The change from baseline to week 12 in fasting plasma glucose was statistically significant when comparing NNC0090-2746 with placebo, with an ETD of -38.2 mg/dL (95% CI: -57.0 to -19.4).
- NNC0090-2746 improved insulin secretion compared to placebo, as the fasting C-peptide was significantly increased from baseline to week 12 with an estimated treatment ratio (ETR) of 1.29 (95% CI: 1.13-1.48).
- The fasting insulin concentration was somewhat higher for the NNC0090-2746 group than the placebo group (not significant).
- The percent change in body weight from baseline, with NNC0090-2746 compared to placebo, was significant at week 8 (ETD: -1.80%, 95% CI -3.24 to -0.37), but not at week 12 (ETD: -1.67%, 95% CI -3.43 to 0.09).
- Compared with placebo, NNC0090-2746 significantly reduced the 2-hr postprandial concentration of glucose from baseline to week 12 (ETD: -74.6 mg/dL, 95% CI 100.2 to -48.9) as well as the glucose area under the curve of (ETD: -181.3 mg*hr/dL, 95% CI -252.4 to -110.2).
- A decrease in total cholesterol (TC) levels was seen for the NNC0090-2746 group with an estimated mean value at week 13 of 169.7 mg/dL compared to 184.7 mg/dL for the placebo group. The change from baseline was significant, with a decrease of 8% to week 13 with NNC0090-2746 compared with placebo (ETR: 0.92, 95% CI 0.85-0.99).
- A trend for lowering lipids in general (LDL-C, TCs, free fatty acids and apo-B) was observed.
- The change in plasma leptin from baseline to week 12 was significant, with a reduction by 22% (ETR: 0.78, 95% CI 0.63-0.96) with NNC0090-2746 relative to placebo.
- In contrast, as also observed with some other GLP-1 receptor agonists, the open-label liraglutide arm of this trial did not exhibit any appreciable change in TC or LDL-C. The reduction in TC observed with NNC0090-2746 is driven by a reduction in LDL-C, although the LDL-C reduction was not statistically significant.
- Gastrointestinal-related adverse events were comparable to the 26-week liraglutide LEAD-2 trial (35.1 vs 44%, respectively) and to open-label liraglutide arm (31.4%). No additional safety concerns with NNC0090-2746 relative to liraglutide were observed.
In 108 T2DM patients inadequately controlled with metformin, NNC0090-2746 significantly improved glycemic control and reduced body weight, total cholesterol and leptin levels, compared with placebo. The treatment with NNC0090-2746 was generally safe and well tolerated. These data suggest that integrated GIP agonism may offer additional benefits on weight loss and total cholesterol.