June 11, 2014

Why Insulin Plus Metformin May be Associated with Higher Mortality

I have not been posting much as there is more than enough on my web site to help visitors understand how to control their diabetes and retain their health.  But today's news featured a diabetes-related headline so toxic, I had to break my silence.

The headline, which differs depending on which publication reported the study, states something like:

Insulin-Metformin Combo Tied to Poorer Survival

The finding of this study, which analyzed a pool of greatly oversimplified medical records, was that people with Type 2 diabetes who took metformin with a sulfonylurea drug had better survival rates than those who took metformin with insulin.

It is quite possible this is true. But to believe that this implies that taking insulin and metformin will cause you bodily harm would be a huge mistake--albeit one that I am almost certain most family doctors will make and one that will, over the long term, lead to them giving their patients even poorer diabetes care than they get now--if that is possible.

But the logic behind the conclusion that the metformin/insulin combo will kill you is similar to the logic that says that living on New York City's Fifth Avenue will make you rich since people living their are richer than people living in other city neighborhoods.

To understand this finding you need only consider who the patients are who get put on an insulin and metformin regimen. Number one, they are almost all patients treated by family doctors, since only a very small sliver of people with Type 2 have access to endocrinologists and those tend to be wealthier, more highly educated patients who have the kinds of jobs that give them premium health insurance. The rest of the older, retired, unemployed, or middle income people who have gotten diabetes during the period of the study would have been very lucky to have any health insurance at all, and the costs of seeing an endo would have been beyond their ability to pay.

So once you realize the majority of these patients were treated by family doctors, you have to add to that the knowledge that family doctors will go to great lengths to avoid prescribing insulin to patients because it requires a lot of time and hand-holding to get insulin working safely. This is time that the family doctors do not get reimbursed for, since insurers and medicare do not reimburse physicians for diabetes education.

Therefore, family doctors will put their Type 2 patients on every single oral drug available before they turn to insulin. The sulfonylurea drugs, glibenclamide, glyburide, etc., which provided better outcomes according to the study used to be the first drugs prescribed to people with diabetes, as they are very cheap, but with the advent of the newer, far more expensive incretin drugs, Januvia, Onglyza, Byetta, Victoza this is no longer true.

But here's the crux of the matter. Both the sulfonylureas and the newer drugs work by coaxing beta cells to secrete more insulin. So none of them will do a thing for a person with Type 2 diabetes who no longer has functioning beta cless. And the people with Type 2 beta cells are those whose beta cells have died after years of exposure to dangerously high blood sugars--the very high blood sugars that study after study shows are maintained by the majority of patients who are put on the newer drugs. (Over 140 mg/dl all the time and over 200 mg/dl for hours after each meal.)

So what happens is that after diagnosing someone with Type 2 diabetes  the family  doctor puts them on one drug for 6 months that leaves them with damagingly high blood sugars that kills off beta cells. When the patient comes back to the office with a still-terrible A1c the doctor prescribes a second oral drug which makes a slight decrease in the blood sugar, perhaps, but still leaves them with an A1c closer to 8 than 5.

This goes on for years, with the A1c creeping up to the 10% range and higher. The patient develops heart disease, retinal damage, kidney damage.  Only five or perhaps ten years after being put on the oral drug cocktail do they get to the stage where they are producing no insulin at all and the doctor is forced to put them on insulin.

But remember, family doctors aren't trained in dosing insulin and don't get paid for working with patients to dose insulin and most insurers don't pay for the kind of diabetes education given people with Type 1 diabetes for the hordes with Type 2. So  when family doctors put people "on insulin" they generally give them doses that are low enough that the patient, who has no understanding of how to use insulin, won't give themselves lots of dangerous hypos. These are eneric doses of basal insulin which may lower the fasting blood sugar from 250 mg/dl to 180 mg/dl, but do almost nothing to lower post-meal blood sugars which may easily be reaching into the 400 mg/dl level or higher after every meal.

So yes, the people put on metformin and insulin prescribed like that WILL die at higher rates, because they have been running dangerously high blood sugars for years and continue running them after having been given insulin.

In contrast, people with Type 2 who are put on sulfonylureas at diagnosis and respond with a dramatic drop in their blood sugars are the people who have inherited the specific diabetes genes that cause a flaw in insulin secretion that sulfonylurea drugs can correct.  There are several of these genes prevalent in the population diagnosed with Type 2 diabetes.

These people WILL get much better blood sugars taking with those drugs and having better blood sugar levels means they are far less likely to develop the fatal damage to their arteries and nerves that kill the people who did not respond to these drugs--the people who after long delays, put on insulin.

But get this straight: There is absolutely NOTHING about the insulin/metformin combo that is damaging in itself. Good research has shown that if people with Type 2 diabetes are put on insulin shortly after diagnosis, many years after they stop using insulin, even if they have stopped the insulin after a short period of use, they do better than other people with Type 2.

You can read more about what research has learned about using insulin for Type 2 diabetes HERE.