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Could Liver-Targeted Insulin Be the Way forward for Type 1 Diabetes Care?

This content originally appeared on diaTribe. Republished with permission.



By April Hopcroft

Led by Dr. Jeremy Pettus, researchers at UC San Diego are investigating liver-targeted insulin in type 1 diabetes. Explore how this novel insulin could significantly improve glycemic control and reduce hypoglycemia risk.

In 2021, the world celebrated the one hundredth anniversary of the discovery of insulin. The invention of insulin transformed diabetes from a grave disease to a condition that may very well be managed with medications and blood glucose monitoring.

Indeed, diabetes treatment has come a good distance since 1921, particularly with the appearance of recent technologies like continuous glucose monitoring (CGM) and the event of newer therapies.

Nonetheless, insulin therapy still has many downsides, from hypoglycemia to weight gain to the necessity to bolus before meals. Although automated insulin delivery (AID) systems can address a few of these issues, more work stays to be done. Certainly one of the important thing challenges of insulin therapy is that the insulin coming from the pancreas acts mainly on the liver, but individuals with diabetes must inject insulin subcutaneously.

Dr. Jeremy Pettus, associate professor of medication at UC San Diego Health who also has type 1 diabetes, is leading research on insulin that acts directly on the liver. Researchers consider that liver-targeted insulin could higher mimic the hormone’s natural motion, helping individuals with diabetes improve glucose control and overall health outcomes.

Why are researchers developing liver-targeted insulin?

Simply put, liver-targeted insulin is required since the insulin injected subcutaneously isn’t an ideal copy of the hormone produced naturally within the body.

Whenever you inject insulin into your skin, your body absorbs it slowly. This results in low amounts within the liver and islet cells of the pancreas, and high amounts of insulin circulating within the bloodstream and in other tissues.

“This is strictly the alternative of normal physiology where concentrations are highest within the islets, then liver, then the periphery,” Pettus said.

Consequently of low insulin within the liver, the organ releases excess glucose, leading to high blood sugar.

“This is especially problematic after meals,” Pettus said. “As anyone with type 1 will let you know, controlling the ‘spike’ after meals is sort of not possible. This is basically resulting from our inferior way of delivering insulin.”

How does liver-targeted insulin work and who may benefit?

The corporate Diasome is investigating a novel technology to deliver insulin on to the liver. Diasome’s approach, which will not be yet approved by the FDA, involves attaching small molecules to insulin to direct it specifically to the liver in an try and mimic normal physiology.

The technology has been designed for use with any commercially available insulin and any delivery option, including pump systems.

With more insulin within the liver, people should experience higher glucose control after meals and fewer hypoglycemia, Pettus said. Some consider liver-targeted insulin could also prevent weight gain.

Research goals to uncover the mechanism of liver-targeted insulin

Pettus and his team will soon begin a small trial to exhibit how liver-targeted insulin works in individuals with type 1 diabetes. Researchers will infuse participants with different amounts of the brand new insulin type and measure how their bodies respond.

“The concept is that with increasing amounts of the technology, we will show that the liver is producing less glucose,” Pettus said. “In other words, with the identical amount of insulin, the liver is ‘seeing’ more of the insulin.”

To this point, studies have shown promising leads to reducing A1C and minimizing low blood sugar episodes:

  • 26-week study in individuals with type 1 diabetes found that the novel insulin led to similar reductions in A1C in comparison with Humalog, a rapid-acting insulin. Participants with higher starting A1C (8.5% or higher) who received this insulin appeared to learn most, experiencing a 25% reduction in bolus insulin and 73% reduction in time below range (lower than 54 mg/dL).
  • 24-week study in individuals with type 1 diabetes treated with multiple every day injections showed that adding liver-targeted insulin to mealtime insulin reduced hypoglycemic events. Nocturnal hypoglycemia fell by nearly 50% amongst participants receiving the brand new insulin. Amongst 61 participants, A1C decreased from 7.3% to six.9% by the top of the study.

The underside line

This research will help scientists higher understand how liver-targeted insulin works within the bodies of individuals with type 1 diabetes. If successful, Pettus’ study may lead to larger trials and future FDA approval.

There’s the potential for liver-targeted insulin to be further explored in pumps, type 2 diabetes, and other populations. For instance, a small clinical trial examining liver-targeted insulin in individuals with type 2 diabetes found that given along with oral glucose-lowering medications, the novel insulin led to significant decreases in average post-meal blood glucose levels.

“All in all, the sector has been working on liver-directed insulin for a very long time and that is an exciting latest approach to make it occur,” said Pettus.

Learn more in regards to the way forward for insulin therapy: 

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