Re: PNAS - jbuffet
in response toby
Regarding the HbA1c and glucose levels.....
In the total BETonMACE population published in the BETonMACE JAMA article, baseline HbA1c was 7.4% and 7.3% in the apabetalone group [n=1202] and placebo group [n=1194], respectively. Baseline serum glucose was 152.2 mg/dL [n=1210] and 150.7 mg/dL [n=1205].
As Barsax pointed out, after 100 weeks of treatment as reported in the post AHA 2019 Corporate Update, HbA1c was 7.76% (+0.12) and 7.76% (+0.04) in the apabetalone and placebo groups, respectively, with no statistical difference between the two groups. Serum glucose at 100 weeks also rose in both groups to 161.1 mg/dL (+9.2) and 160.5 mg/dL (+10.5) in the apabetalone and placebo groups, respectively, with no statistical difference between the two groups. These values are for the total population (~1200 patients per group). So HbA1c and serum glucose increased from baseline by about the same amount in both apabetalone and placebo groups.
As Barsax pointed out, in the Nov 2 2020 news release it was stated:"The combination of apabetalone and the SGLT2 inhibitors, in addition to standard of care medicines, resulted in a significant improvement of key renal function marker eGFR compared to SGLT2 inhibitors and placebo (p=0.05). Additionally, a significant reduction of plasma Hb1Ac was also observed in patients receiving the combination of apabetalone and the SGLT2 inhibitors, on top of standard of care treatment, compared to placebo (p<0.001). Details of these findings are planned to be submitted to a leading peer review journal in the near future."
So in the ~300 patients on SGLT2 inhibitors (150 apabetalone, 148 placebo), there seems to be a statistically significant benefit of the apabetalone+SGLT2i on eGFR and HbA1c vs. those patients on placebo+SGLT2i. The magnitude to these eGFR and HbA1c changes has not been disclosed yet. However, the fact that in this SGLT2i subgroup, but not the total BETonMACE population, apabetalone elicits significant HbA1c lowering is exciting. There was a similar phenomenon for the total population vs. SGLT2i subgroup data for eGFR kidney function. At 100 weeks for the total population, the eGFR was 104.3 and 105.2 in the apabetalone and placebo groups, respectively, with a marginally significant difference (p=0.03) favoring the placebo group. Importantly, in the SGLT2i subgroup the press release indicates that apabetalone elicited "significant improvement of key renal function marker eGFR compared to SGLT2 inhibitors and placebo (p=0.05)."
So similar to the MACE data, it appears that the benefit of apabetalone on HbA1c and eGFR is amplified in the presence of SGLT2 inhibitors.
Very exciting stuff.