What is the most urgent unmet need in Type 2 diabetes management?
Guess what the most urgent problem in treating type 2 diabetes is today?
You might already have an answer because you've probably seen it happen to people around you. When someone is first diagnosed with type 2 diabetes, a low dose of first-line diabetes medication can control their blood sugar well. But after a while, they need higher doses to keep their blood sugar in check.
However, that’s not the end of the story. Gradually, even at the highest dose, the first-line diabetes medicine stops working. At that point, doctors have to switch to, or add, second-line medications. But these medicines also lose effectiveness over time, and eventually, the only option left is insulin injections.
According to a report in the New England Journal of Medicine (Ref 1), the first-line drug (Metformin) starts losing its effect after about a year and a half. Second-line drugs face the same problem (see Figure) (Ref 2).
Doctors and scientists believe this is the most urgent issue in the care of type 2 diabetes right now. Metformin is a great drug because it's affordable, effective, and has few side effects. However, when it stops working, switching to or adding drugs like Rosiglitazone increases the risk of heart disease by 43% (Ref 3). Drugs like Glyburide, a type of sulfonylurea, are even worse. While they work well at first, they stimulate insulin production in a way that overworks and eventually damages the insulin-producing beta cells in the pancreas, making blood sugar control worse in the long run (shown by the red line in the chart). Because of this, many doctors who stay up to date with new information have stopped using these kinds of drugs (Ref 4,5).
Furthermore, while drugs like DPP-4 inhibitors have few side effects and can even protect the heart, the problem is that they also stop working after about a year (Ref 6). So, they don’t solve the issue of long-term effectiveness either.
To fix this problem with drug durability, we first need to understand its root cause. Recent research shows that the function of β cells in the pancreas plays a key role in the progression of type 2 diabetes. This makes sense because a patient's blood sugar is controlled by both the insulin produced by beta cells and the medications they take. Once beta cells start to lose their ability to function, the patient needs stronger medications, which is why they notice their condition getting worse (Ref 7)
As for the detailed mechanisms, we'll discuss them in other articles.
1. https://www.nejm.org/doi/full/10.1056/NEJMoa066224
2. https://slideplayer.com/slide/14047973/ (Slide 29)
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212476/
4. https://www.nature.com/articles/s41574-023-00815-6
5. https://www.latimes.com/archives/la-xpm-2010-jul-01-la-fi-lazarus-20100702-story.html
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