BALANCE: Olezarsen for Familial Chylomicronemia Syndrome

Olezarsen is an investigational drug that tackles triglycerides by blocking the production of apolipoprotein C-III (apoC3). ApoC3 normally hinders the liver’s ability to remove triglycerides from the blood. By reducing apoC3, Olezarsen allows the liver to work more effectively, lowering triglyceride levels. This can significantly reduce the risk of pancreatitis, a dangerous condition caused by high triglyceride levels in the blood.

What is the Endocrine Feedback Loop?

As an endocrinologist, a clear understanding of endocrine feedback loops is paramount. These loops play a vital role in visualizing the endocrine system and, more importantly, in practicing endocrinology correctly.

From obesity and triglycerides to pancreatitis

Obesity rates are rising worldwide. Acute pancreatitis is also on the rise. The authors of the current study followed prospectively about 120,000 individuals. As expected, they found a high correlation between BMI and acute pancreatitis events. Investigators also observed that hypertriglyceridemia could explain about 22-30% of the relationship between obesity and pancreatitis.

The results of the study, although not new, confirm prior research and knowledge that obesity leads to insulin resistance, which in turn elevates blood triglyceride concentration. Hypertriglyceridemia is a well-known specific cause of acute pancreatitis, especially when triglyceride measurements are above 500 mg/dL.

Clinically, it is essential to screen obesity patients for hypertriglyceridemia. A fasting lipid panel is a simple and inexpensive laboratory test that can provide significant insights into the patient’s risk of insulin resistance and pancreatitis.

GT

Adaptive artificial pancreas shows good results

Semi artificial pancreas (AP) from Medtronic was FDA approved in 2016. The quest for full automated insulin pump continues. Current study evaluated the adaptive artificial pancreas technology in 30 adults with type 1 diabetes over a 12 week period.

By the end of the study, adaptive AP lowered A1c down to 6.7% from 7.0%. Day-time and night-time hypoglycemia also improved significantly.  Software adaptations were manually overwritten 10% of the time.

Overall these are great advances toward user-independent artificial-intelligence pancreas. There will be more to come on the subject.

GT

Saxenda/victoza, lipase & acute pancreatitis (part 2)

Dr. Steinberg’s secondary analyses of SCALE trial show that saxenda/liraglutide raises reversibly the blood levels of amalyse and lipase. The incidence of acute pancreatitis was rare, but more common in those receiving liraglutide (n=12, 0.3%) than placebo (n=1, 0.1%). About 5,000 participants were followed for one year.

Roughly 50% of acute pancreatitis cases were felt to be gallstone-mediated. No correlation between amylase/lipase levels, gallstone formation and anticipation of pancreatitis was seen. Findings suggest no need of measuring pancreatic markers in patients receiving liraglutide 1.8 or 3.0 mg daily.

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Saxenda/victoza, lipase & acute pancreatitis (part 1)

Dr. Steinberg’s work shows that serum lipase is increased in about one-fourth of diabetes patients treated with victoza/liraglutide. Lipase elevation was seen at 6 months of treatment and remained so till the end of study. 

Importantly however, victoza use or the lipase rise were not found to anticipate or cause future events of acute pancreatitis. A group of about 9,000 participants were followed for 4 years. 

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Bihormonal Bionic Pancreas – using both insulin and glucagon

This study demonstrates a great advancement in the field of type 1 diabetes. A full artificial pancreas, called “bihormonal bionic” shows superior results compared to the traditional CGM-assisted insulin pump.

The bihormonal system utilizes both insulin and glucagon to maintain steady blood glucose levels, resulting in better glycemic control with less hypoglycemia. No carbohydrate counting is needed by the patient. Although of short duration, 11 days, the results are very promising.

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Semi-artificial pancreas shows positive outcomes.

Although of short duration, this well designed study shows that semi-artificial pancreas helps in reducing A1c and preventing hypoglycemia more than the usual insulin pump. A group of 29 individuals with type 1 diabetes and A1c < 7.5% were randomized to receive hybrid closed-loop system or the traditional pump therapy. Participants were followed for 4 weeks and then crossed over for another 4 weeks.

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Diabetes drug, risk of pancreatitis and pancreatic cancer

Initial analysis of TECOS trial showed that Januvia/Sitagliptin does not increase the risk of cardiovascular disease, heart failure and death from any cause. 

Further investigation, just published in Diabetes Care reveals that Januvia has slight tendency to protect from pancreatic cancer but cause more pancreatitis, although these contributions were not statistically convincing. Important to be aware that baseline pancreatic cancer or pancreatitis are rare and multifactorial. 

About 15,000 patients with type 2 diabetes and cardiovascular disease were randomized to receive Sitagliptin or placebo for 3 years.

GT