The NASH Tsunami in Diabetes: Getting Ahead of the Rising Tide is a four-part series focusing on what front-line providers treating patients with Type 2 diabetes and obesity can do to help their patients avoid the serious consequences of severe, progressive Fatty Liver disease. This episode looks at drug choices prescribers can make TODAY for patients with Type 2 Diabetes Mellitus and obesity that have positive impact on Fatty Liver disease. In addition to co-hosts Dr. Ken Cusi and Roger Green, panelists for this discussion include endocrinologist Dr. Scott Isaacs, second author of the recent AACE guidelines, and hepatologist Dr. Naim Alkhouri.
Diabetes Drug Choices With Benefits For NAFLD
Ken and Roger introduce the conversation by previewing the episode. KEY POINT: Ken notes that we are living in a period where the paradigm around treating chronic metabolic conditions is shifting. In a world where one in five patients with T2DM lives with clinically significant fibrosis, Ken states providers can no longer ignore the liver when making treatment decisions about diabetes. He also suggests that hepatologists need to become more comfortable using medications that were previously reserved for diabetes.
At this point, Naim and Scott join the conversation. Naim kicks off the conversation by discussing EDICT, a trial that compared the standard T2DM regimen of the day (metformin, followed by the sulfonylurea glipizide, and then insulin) to a first-line combination therapy of metformin, the GLP-1 agonist exenatide and the PPAR pioglitazone. At the end of this six-year period, the researchers found meaningful, statistically significant differences in three key Fatty Liver parameters: prevalence of NAFLD (69% vs. 31%); clinically significant fibrosis (26% vs. 7%); and percentage fat in the liver (12.5% vs. 8.5%). It also found that patients achieved a lower HbA1c level (6.0% with the combination, vs. 6.8% in the standard treatment group).
In response to a question from Roger, Ken identifies three majors lessons of the last 10 years:
7 of 10 Americans with T2D have a fatty liver; those with NAFLD but not T2D see their chances of becoming diabetic and , separately, developing cardiovascular disease double.
15-20% of Americans with T2D also exhibit moderate-to-advanced cirrhosis.
GLP-1s, as a class, address multiple factors of chronic metabolic disease. They reduced HbA1c, promote and maintain significant weight loss, and slow progression of fibrosis.
Now, Ken adds, he newer class of GLP-1/GIP dual agonists promote more weight loss, which might suggest a stronger effect against NASH.
Naim expresses a concern that many doctors treating patients with T2D do not consider NASH. A Cleveland Clinic assessment of ICD-10 codes demonstrated that only 5% of T2D patients were coded for NAFLD. This means the 2/3 of the T2D patients in that system have fatty livers and were never evaluated! Similarly, ~2/3 of the patients who present with cirrhosis in his clinic were never told that they had NAFLD. In Naim’s view, NAFLD should be a disease for primary care and endocrinology to treat, while it should be hepatologists that treat NASH.
Roger raises a paradox: primary care and endocrinology avoid Fatty Liver disease because they fear having to treat cirrhosis, but this avoidance leads to a large number of cirrhosis cases that might have been avoidable. Scott agrees and says one reason is that physicians hear “there is nothing to be done.” Scott disagrees with the last point, noting that drugs are available and the prescription of diet and exercise can be “incredibly motivating.”
The rest of the discussion centers around why primary care, endocrinologists and hepatologists do not treat the combined metabolic package more aggressively and what Fatty Liver advocates can do to drive earlier, more aggressive treatment.