Patients with diabetes suffer often suffer from many health problems including but not limited to elevated blood glucose, insufficient pancreatic insulin production, reduced tissue insulin sensitivity, inflammation, obesity, high blood pressure, high blood triglycerides, high blood LDL, low blood HDL. In some, but not all, this progresses to diabetic nephropathy, chronic kidney disease, dialysis and end stage renal disease. No one drug can address all of these issues.

Apabetalone addresses some, but not all of these. From post-hoc analysis of SUSTAIN and ASSURE, we learned that apabetalone reduces 5-point MACE and this effect is even greater in diabetics. We also learned that fasting glucose is significantly lowered in diabetic treated with apabetalone. However, these patients were already on some kind of glucose/insulin therapy already, so very unlikely that apabetalone will ever replace these other standard of care glucose control agents. As I wrote in my previous post, effects of apabetalone on glucose/insulin paramenters and glucose kinetics were very modest in the 5 week Austrailian study. And as noted in the 2014 news release, effects of apabetalone on gluocse in diabetics didn't appear until after 12 weeks of treatment. So apabetalone is not going to be an acute glucose control/insulin sensitizing agent. Apabetalone has been shown to have effects to reduce inflammation. Apabetalone has been shown to elevate apoAI/HDL, especially in those with low-HDL at start of treatment.

The effects of apabetalone on alkaline phosphatase (ALP) not only occur in diabetics, but in all patients. Elevated ALP is associated with mortality and increased MACE in the general population. However, especially in chronic kidney disease (CKD) patients elevated ALP is associated with increased vascular calcification and reduced kidney function (reduced eGFR). CKD is a late stage diabetes condition and CKD can occur without diabetes. Therefore, reductions of ALP by apabetalone is not so much a general diabetes treatment, but more relevant to improving kidney function and reducing MACE.

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