Wednesday, January 27, 2010

More problems with insulin

I have previously blogged about my concerns with the use of insulin therapy in patients with type 2 diabetes (The Problem With Insulin and The Problem with Insulin- Part 2). Several studies show new concerns using insulin to treat type 2 diabetes. The most notable is the ACCORD study which investigated intensive diabetes treatment and was stopped early because patients in the intensive treatment group had more heart attacks and death. Many experts suspect that even though controlled blood sugar is desirable, blood sugar that is too low may cause problems. This seems to be especially true for insulin, most likely because insulin causes hypoglycemia, or blood sugar that is too low. Hypoglycemia can be dangerous and may explain the excess deaths seen in the ACCORD and other studies. One of the main reasons for my concern is that some recent recommendations from worldwide experts in diabetes suggest that we are not using insulin enough! These guidelines dismiss or leave out altogether newer and potentially safer agents, suggesting that the older (all be it cheaper) diabetes pills which are known to fail over time continued to be used with advancement to insulin once they have failed.
However, a new study from the Lancet gives further evidence to more cautious use of insulin in type 2 diabetes. This UK study looked at two groups of diabetics. One group of about
28,000 patients were already on a diabetes pill (metformin or sulfonylurea) and had their regimen adjusted by adding another pill (metformin plus sulfonylurea). In the second group of about 20,000 patients, patients on one pill that were not under control were either switched to insulin alone, or insulin was added to their diabetes pill. The chart is below, but as you can see the higher your A1c (high A1c means that diabetes is under poor control) is, the greater your chance of death (and heart attack, seen in similar graphs), EXCEPT when your A1c is too low (under 7) and you have a greater risk of death. This is known as a U shaped curve, which means that treatment works, but you need to be careful because over-treatment can cause harm. Both groups saw this effect, but the effect was much greater in the second group that got insulin. In other words, similar to what waas seen in the ACCORD study, if you are on a diabetes pill and you need to get to a goal of below 7, you should probably reserve insulin as a last resort, since it will increase the likelihood of killing you compared to a diabetes pill. In addition, one of the side effects of sulfonylureas is hypoglycemia. It would be very interesting to see how these curves look when non-sulfonylurea drugs such as the TZD's (Avandia, Actos), DPP4 inhibitors (Januvia, Onglyza) or even incretin mimetics (Byetta and just approved Victoza) that DON"T cause hypoglycemia were used. I would suspect the difference would be even greater.
Again, this study lends further evidence that insulin should be used cautiously and other agents should be considered to get diabetes under control before going to insulin. This is in stark contrast to the recently released consensus as mentioned above. I have previously speculated ( here, here, here, and here) why certain experts continue to recommend older drugs and insulin when evidence continues to point to the benefit of some of the newer drugs


Anonymous said...

The cross-over of treatment regimens between type 1 and type 2 is blurring in both directions. Some Doctors are now prescribing oral agents to insulin-dependent type 1 just as they are prescribing insulin for type 2.

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