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Sulfonylureas May Elevate Risk in MI Survivors (MI as in myocardial infarction, aka "heart attack")
Family Practice News ^ | 1 October 2009 | BRUCE JANCIN

Posted on 10/15/2009 12:00:36 AM PDT by neverdem

Barcelona — Four widely prescribed oral sulfonylurea drugs are associated with significantly increased risk of all-cause mortality compared with metformin in type 2 diabetic patients having a history of MI, according to a comprehensive Danish national cohort study.

The study included all Danish adults with a prior MI who started on oral glucose-lowering monotherapy during 1997-2006. The conclusion: Glimepiride, glyburide, glipizide, and tolbutamide were associated with 33%-43% higher mortality risk than was metformin, Dr. Tina Ken Schramm said at the annual congress of the European Society of Cardiology.

In contrast, single-agent gliclazide and repaglinide had all-cause mortality risks similar to metformin.

“We believe that metformin in general should be part of the treatment of type 2 diabetes to reduce mortality, but gliclazide and repaglinide may be good alternatives,” said Dr. Schramm of the Heart Center at Copenhagen University National Hospital.

Metformin deserves the nod as the first-line agent on the basis of the results of the landmark United Kingdom Prospective Diabetes Study, which convincingly established the drug as the safest glucose-lowering agent available, she added.

Out of the total Danish population of roughly 4.1 million, 107,870 type 2 diabetic individuals initiated monotherapy with a glucose-lowering agent during the 9-year study period. Among them were 9,135 with a prior MI, who formed the population for this study.

Glimepiride was the most widely prescribed of the glucose-lowering medications in Denmark, being used by 43% of subjects. Next came metformin (32%), glyburide (13%), glipizide and gliclazide (7% each), tolbutamide (6%), and repaglinide (2%). Acarbose was prescribed as monotherapy in only 44 patients nationwide—far too small a number to allow meaningful results. Similarly, the thiazolidinediones were used too seldom to draw any conclusions, Dr. Schramm explained.

Metformin served as the comparator in determining all-cause mortality risks for the other oral glucose-lowering agents in a multivariate analysis. Dr. Schramm reported having no financial conflicts of interest.

TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: diabetes; myocardialinfarction; sulfonylureas; type2diabetes
In the USA, sulfonylurea drugs are chlorpropamide, glimepiride, glyburide and glipizide.

I don't believe gliclazide and tolbutamide are sold in the USA. Somebody correct me if I'm wrong.

Prandin is repaglinide. Glucophage is metformin. Both can be found in combo drugs for type 2 diabetes.

1 posted on 10/15/2009 12:00:37 AM PDT by neverdem
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To: austinmark; FreedomCalls; IslandJeff; JRochelle; MarMema; Txsleuth; Newtoidaho; texas booster; ...
FReepmail me if you want on or off the diabetes ping list.

IIRC, sulfonylureas have a black box warning or the equivalent.

2 posted on 10/15/2009 12:11:37 AM PDT by neverdem (Xin loi minh oi)
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To: neverdem

thanks for the ping.

I take glimepiride, but (am I’m reading this correctly?) the risk of taking it, that they are referring to, is only is patients with previous MI. So, as it relates to the heart, glimepiride is save otherwise?

3 posted on 10/15/2009 2:13:05 AM PDT by Kimberly GG (Sarah Palin - Supports a "path to citizenship" for illegal aliens. "path to citizenship" IS AMNESTY)
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Aren’t the sulfonylureas considered older forms of treatment? I’ve been diabetic for > 10 years and no doctor (and I go to university-affiliated endos) has ever suggested a sulfonylurea.

I’ve taken a few of the newer drugs and have decided to stay with metformin and insulin when necessary. There are just too many risks associated with any of these drugs to be on them long term. Even metformin has risks, but I think it’s better than the older drugs. What gets me is that many of the sulfonylureas cause weight gain. Well, damn, just what we want huh, more plump Type II diabetics? They make weight loss so hard, you end up taking more drugs, and the doc just blames you for not being ‘compliant.’ I know people who have gained 20 lbs with sulfonylureas. To heck with that.

4 posted on 10/15/2009 7:17:28 AM PDT by radiohead (Buy ammo, get your kids out of government schools, pray for the Republic.)
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To: neverdem

I was on Metformin & Glimepiride. 2 weeks ago we stopped the glimepiride and started Insulin. I feel much better and my blood sugar is way better.

5 posted on 10/15/2009 7:23:43 AM PDT by Petruchio (Democrats are like Slinkies... Not good for anything, but it's fun pushing 'em down the stairs.)
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To: neverdem

Thanks for posting this.

6 posted on 10/15/2009 8:29:27 AM PDT by trisham (Zen is not easy. It takes effort to attain nothingness. And then what do you have? Bupkis.)
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To: Kimberly GG; austinmark; FreedomCalls; IslandJeff; JRochelle; MarMema; Txsleuth; Newtoidaho; ...
So, as it relates to the heart, glimepiride is save otherwise?

"Oral hypoglycemic drugs, including glimepiride, have been associated with increased cardiovascular mortality. Talk to your doctor about the possible risks, benefits, and alternatives of using this drug for your condition."

Check that webpage with that quote. Consider saving it to your favorites. Do the same for the homepage of the next two links. I've found them to be reliable sources of medical information. The first, Medlineplus, is written for the general public.

I thought I remembered reading an entry that was restricted just to sulfonylureas in the 1990s in the PDR, which is just a collection of the product information slips that manufacturers submit to the FDA. Since that time Rezulin (troglitazone), an oral agent described as an insulin sensitizer, was introduced and then later withdrawn from the market. Two similar drugs, Avandia (rosiglitazone) and Actos (pioglitazone), with the same mechanism of action, but less liver toxicity, are still on the market.

Here's more information about glimepiride.

Your question highlights the problem of type 2 diabetes if it can't be controlled by diet and exercise. Type 2 diabetes is characterized by insulin resistance. The excess insulin, i.e. hyperinsulinemia, needed to get blood glucose to normal or near normal levels is now considered problematic itself, whether it is from endogenous insulin prompted by sulfonylureas' effect on the pancreas or exogenous insulin self administered by syringes.

Patient compliance is better with pills as opposed to needles. IMHO, you probably have less blindness and kidney disease, i.e. microvascular disease, using pills. As for macrovascular disease, e.g. MI and stroke, "Intensive Glycemic Control Fails to Cut Cardiovascular Risk: Focus on blood pressure, lipid changes.." IIRC, further subgroup analysis of one or both of the ACCORD and ADVANCE(entered as keywords) studies showed that if the patients only had type 2 diabetes as their initial diagnosis, their outcomes were better. Both insulin and oral agents were used.

7 posted on 10/15/2009 12:45:49 PM PDT by neverdem (Xin loi minh oi)
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To: neverdem

Lovely. I just got an Rx for Actos this week. Haven’t started to take it yet

8 posted on 10/15/2009 12:50:08 PM PDT by Calm_Cool_and_Elected (Who is John Thompson?)
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To: neverdem; austinmark; FreedomCalls; IslandJeff; JRochelle; MarMema; Txsleuth; Newtoidaho; ...

I know I have harped on this a lot, but there is no proof that the oral hypoglycemic drugs do anything but lower the numbers. They treat the surrogate measure of diabetes, but no long term studies show that they reduce the risk of major complications (heart attack, amputations, kidney disease, etc.). We all want to think that a lower A1C is significant, but it could be like getting rid of your cough and thinking your pneumonia is cured. Pharmaceutical companies have a great deal invested in pushing these drugs and in promoting constant testing and measuring blood sugar values. It is just possible that type 2 diabetics are being lulled into a false sense of comfort just because they see their numbers are down.

Also, all of these drugs have risks associated with them. If the long term (and I mean decades long!) studies are not there that show these drugs actually benefit type 2 patients in meaningful outcomes, then they are just making the drug companies rich.

If There’s No Benefit, Why Tolerate Any Risk?

I know this goes against everything that is promoted by various health organizations, but until I see some real studies, not done by drug companies, that measure the outcomes in absolute rather than relative risk, I will remain skeptical of the pill pushers.

9 posted on 10/20/2009 12:29:46 PM PDT by Pining_4_TX
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To: Pining_4_TX

I agree with you completely. Folks here may not approve of my methods, but I think I am avoiding what really kills diabetics - heart issues - by avoiding sat fat and going vegan. No blood pressure or cholesterol problems, greatly reduced insulin needs (like going from 190 units to 5-10 unless unless I eat something stupid.

Dr. McDougall ( has said that he is willing to let diabetics go w/o drugs if their am BGs are 250 or less. Most docs would pass out at those numbers, but I say if you are free of a lot of meds that are doing harm to other systems in your body, eating clean, and losing weight, you are better off than pumping yourself full of drugs. And remember the recent study that they had to call off because diabetics were dying as the researchers kept trying to keep their numbers at ‘normal’ levels with loads of drugs.

Just my opinion; not medical advice.

10 posted on 10/20/2009 4:28:00 PM PDT by radiohead (Buy ammo, get your kids out of government schools, pray for the Republic.)
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To: radiohead

Thanks for the interesting comments. I will check out that website. I am currently trying to eat far less fat than I have had in my diet. I tried Atkins for a while, and I couldn’t stay with it, and my weight loss was not that great after a couple of weeks.

I have cut out artificial sweeteners completely (a radical step for me!). If I want a little sweetness in my coffee or tea, I use real sugar or honey - I just try not to go overboard. I have only been experimenting with this for a few days, but I think the artificial sweeteners increased my appetite.

I know this could just be the placebo effect, but if it keeps me from getting so ravenously hungry in the afternoon and evening, I don’t care why it works!

11 posted on 10/24/2009 8:17:05 PM PDT by Pining_4_TX
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To: Petruchio

Have you considered Byetta?

12 posted on 10/24/2009 8:22:38 PM PDT by Captain Peter Blood
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To: Calm_Cool_and_Elected

I am a Type II and Actos is more dangerous than Metformin or Glyburide. Although I just started Byetta and hope to reduce or eliminate some of the others.

13 posted on 10/24/2009 8:25:18 PM PDT by Captain Peter Blood
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To: Captain Peter Blood

Make sure you also read:

14 posted on 10/27/2009 6:58:59 PM PDT by muawiyah (Git Out The Way)
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To: Captain Peter Blood
There are very few drugs that interact with the cell nucleus and actually rewrite code such that the right enzymes and proteins are produced to alleviate a symptom.

At this stage in their development these drugs may be a bit clunky and could precipitate MIs.

Think of what this means a few decades down the line when metaformin-like drugs can be fine-tuned to be administered daily to ward of a wide variety of cancers.

15 posted on 10/27/2009 7:01:11 PM PDT by muawiyah (Git Out The Way)
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