The Truth about Oral Diabetes Drugs

For a summary of information about oral diabetes drugs, click HERE

Though many people find that they can bring their blood sugar back into the normal range simply by limiting their carbohydrate intake, blood sugar control is not a short term project. When you have abnormal blood sugars you will have to spend the rest of your life keeping them under control, and not everyone is willing or even able to stick with a restrictive diet for the rest of their lives.

For this reason, most doctors assume that dietary changes will not solve their patient's blood sugar problems. So immediately after diagnosing diabetes they prescribe what are known as oral anti-diabetic drugs. These drugs include Glucophage, Avandia, Actos, Glipizide, Starlix, and Prandin and though they are called "anti-diabetics" they are also occasionally prescribed for people whose blood sugars have not yet reached diabetic levels since large-scale studies have shown them to be effective for people with impaired glucose tolerance.

You may well be asking, if these drugs are effective, why bother with complex and restrictive dietary regimens?

Effective, but Not Effective Enough

Unfortunately, the catch with these drugs lies in how you define "effective." Just as research has shown that the current criteria for diagnosing diabetes ignore the blood sugar levels at which damage occurs, other research shows that none of these drugs brings blood sugar levels down to anywhere near normal levels. So while an oral anti-diabetic drug might be "effective" by the FDA definition of the term, that effect might only be to lower a diabetic person's fasting blood sugar from a dangerously high 250 mg/dl (13.8 mmol/L) to an only slightly less dangerous 180 mg/dl (10 mmol/L) --a level which is still high enough to encourage the development of serious complications. Even when prescribed for people whose blood sugar is only impaired, as we will see, these drugs may only lower the OGTT 2-hour reading by 20 or 30 mg/dl (1.1 or 1.7 mmol/L)--which still leaves their blood sugars higher than a damaging 140 mg/dl (7.8 mmol/L) most of the day.

So it's important to realize that despite the image you might see portrayed in the drug company advertisements that bombard you on TV and in your magazines, oral anti-diabetic drugs alone will not be likely to bring your blood sugars back into the normal range.

An Add-On not a Substitute for Dietary Control

But--and here's the silver lining--if you are unable to get your blood sugars back into the normal range with diet alone, but are willing to modify your diet, the addition of an oral antidiabetic drug may be able to push your blood sugar levels that last bit of the way needed to normalize them.

The Facts about These Drugs

Now let's look at some of the more popular anti-diabetic drugs to see what the lab research shows about what they do best, what they do worst, and what you need to think about if you are taking them.

Metformin

Metformin is the generic name of the drug also marketed as Glucophage. It has been used to control diabetic blood sugars since the 1970s in Europe. It has also recently been the subject of a detailed study intended to see whether it could prevent impaired glucose tolerance from progressing to actual diabetes. (1) Metformin is available in an extended release form, Metformin ER (Glucophage XR) which is supposed to be a bit easier on the digestive system.

Why Doctors Prefer Metformin

Metformin is often the first drug that a doctor will prescribe for a person with diabetes or impaired glucose tolerance. The reason for this is that, unlike the rest of the drugs we will be discussing, Metformin does not cause weight gain. Since most people with abnormal blood sugars already are overweight, and since weight loss has been shown to improve blood sugar control, doctors understandably prefer to prescribe a drug that does not push weight in the wrong direction.

Metformin Inhibits the Liver's Production of Glucose

There is some scholarly debate about what exactly it is that Metformin does, but most researchers agree that in most people Metformin suppresses the production of glucose in the liver.

If you'll remember, it is the liver's tendency to dump additional glucose into the blood stream when first phase insulin response is weak or missing that can cause blood sugar to shoot up after a meal. The liver may also dump glucose in the blood stream early in the morning when fasting insulin levels are low. (To read more on this topic, visit How Blood Sugar Deteriorates)

Metformin may lower fasting blood sugar by limiting the liver's production of glucose rather than by making cells more sensitive to insulin.

Metformin May stimulate Glucose Uptake in Muscles

Though Metformin appears to increase the amount of glucose absorbed into cells this effect is observable mostly when blood sugar is high.(2)

Recent research suggests that Metformin may stimulate glucose uptake by muscles and inhibit glucose production by the liver by activating an enzyme, AMP-activated protein kinase which is present in muscle, liver, and heart cells. This enzyme is usually activated when exercise has burnt off cellular energy stores. So in a way, Metformin seems to trick the body into thinking it has exercised. This may be why it causes a small amount of weight loss and also results in elevated levels of lactate--the substance that makes your muscles ache the day after an exercise session. (3)

How Effective is Metformin?

How much does Metformin lower blood sugar concentrations? Not much, judging from the data published both in independent research studies and from studies cited in the drug manufacturer's own prescribing information insert.

In the manufacturer's prescribing information for Metformin ER, a chart reports results of a study that showed that for 141 diabetic subjects on Metformin, average fasting plasma glucose dropped 53 mg/dl (2.9 mmol/L). However, the final fasting plasma glucose level in these subjects was still a whopping 189 mg/dl (10.5 mmol/L). However, no data is given in the prescribing information about the effect that Metformin had on their post-meal blood sugar concentrations.

The study cited above which was run by researchers at the University of Texas in 1991 (2) did administer glucose tolerance tests to 14 diabetic patients taking Metformin. They found Metformin reduced average post meal values from 360 mg/dl to 306 mg/dl--a level still dangerously high, while reducing the subjects' fasting blood sugars from an average of 207 mg/dl to 158 mg/dl again, a final level that is also still dangerously high.

Another, larger, study which compared Metformin with Avandia put 100 newly diagnosed people with diabetes on Metformin and found that their average fasting plasma glucose dropped from 223 mg/dl to a still dangerously high 173 mg/dl. That study did not measure 2-h OGTT values, but since the participants' HbA1cs dropped only to 7.1% which correlates with an average blood sugar of 175 mg/dl, they were most certainly still dangerously elevated.(4)

Metformin Does Not Really Prevent Diabetes

Though press releases published as news stories in the media made it sound like a the Diabetes Prevention Program Trials, a major study, proved that Metformin can prevent the progression of impaired glucose tolerance to diabetes, examination of the facts suggests shows that its effect was far more modest.

Metformin Makes Extremely Modest Changes in Blood Sugar for People with IGT

At the beginning of the Diabetes Prevention Program study,(1) the subjects' fasting blood sugars averaged 107 mg/dl (5.9 mmol/L) and their average 2-h OGTT results were 165 mg/dl (9.2 mmol/L). Most were overweight--the average weight of the group which was two thirds female was 207 lbs.

During the first six months of taking Metformin, the subjects who were taking it saw their average fasting plasma glucose drop by about 3 mg/dl (.17 mmol/L) -an insignificant decrease that did not help them achieve normal fasting glucose if you use the ADA's current definition of normal fasting glucose.

Over rest of the four years of the study, their fasting blood sugars rose back until they were almost identical to the starting level. The average HbA1c of the group followed a similar pattern, dropping by less than 1% during the first six months of the study to a level that is still elevated above normal and then rising over the next four years until it was very close to the 6.0% usually considered the HbA1c cutoff for diagnosing diabetes.

When presenting the statistics for the various groups, the DPPT researchers did not include data for the change in the 2-h OGTT results of the study participants, though this data was collected. Given the rise in the HbA1c, they probably showed a steady and depressing rise in post-challenge blood sugar levels.

Despite these results which should have been discouraging to anyone who was hoping to be able to attain normal blood sugar levels through the use of drug therapy alone, the researchers interpreted their results to mean that Metformin could prevent diabetes, since people in the Metformin intervention group became diabetic by the 1998 ADA criteria at a rate that was 31% less than those in the placebo group.

Once Off the Drug Many Participants Immediately Became Diabetic

The conclusion that the use of Metformin alone without changes in diet might prevent diabetes was undercut by a follow-up study which found that within weeks of going off the drug, a quarter of that apparent risk reduction disappeared, when a surprising number of people in the Metformin group developed diabetic blood sugar levels as soon as they came off the drug. This suggested that the drug had no effect on the underlying process leading to diabetes, but had only suppressed peoples' blood sugar levels while the underlying mechanism of damage went on unchecked. Unlike the original finding that Metformin appeared to prevent diabetes, this later finding received no play in the media and many doctors are still unaware of it.

So the fact seems to be that taking Metformin might slow the progress of blood sugar deterioration by a very small amount, but it does not bring blood sugars down to the normal level that might truly prevent diabetes or prevent the damage done by abnormally high blood sugars.

The reason for this is made clear by the findings of the university of Texas researchers: The big problem with Metformin is that it works best when blood sugars are high--and in people who are obese. In people of near-normal weight the UT researchers found that at normal blood sugar levels Metformin actually decreased rather than enhanced glucose uptake. This is in line with the finding that the primary way in which Metformin appears to work to lower fasting blood sugars is by limiting the production of glucose by the liver--a phenomenon more likely to occur in people whose fasting blood sugar is high--much closer to the ADA diabetes diagnostic cutoff than to normal.

That this is true was made clear by the note in the published report on the Diabetes Prevention Program study that "The effect of Metformin was less with a lower body-mass index or a lower fasting glucose concentration than with higher values for those variables."

So the conclusion has to be that for people who are not obese and whose fasting blood sugar is still relatively under control, Metformin will only have a moderate effect.

There's No Research Data about the Effect of Combining Metformin with Carb Restriction

Unfortunately, all studies of Metformin published to date have been performed with people who were encouraged to eat a high carbohydrate diet. So there is no definitive information about what happens when Metformin is combined with a low carbohydrate diet.

Anecdotal Evidence

Postings on newsgroups suggest that people who have a lot of weight to lose who stall out above their desired weight while on a long-term low carb diet often start losing again when they add Metformin to their diet regimen, if they continue to keep their carbohydrate intake low.

Women with PCOS have also found that the addition of Metformin to their regimen may improve both weight loss and fertility.

My own experience taking Metformin while at a normal weight for my height is that it makes a small improvement in my post-meal blood sugar levels if I eat slightly more carbohydrate per meal but it has no impact on my fasting blood sugars. It does apparently make it a bit easier to maintain my weight loss without having to watch every single calorie. Over a three month period Metformin decreased my triglycerides by 33%, from the top of the normal level (near 150) to a healthier level (near 100). I attribute these effects to the fact that it is making a small but helpful difference in my insulin resistance.

In contrast to my own experience, I have heard from other people who take Metformin while low carbing who have found that it lowers their fasting blood sugars but not their post-meal numbers.

Dosage and Time to Take Effect

Metformin takes about 3 days to kick in and 3 weeks to achieve its maximum effect. Because it can cause intense gastric problems, it's advisable to start out with a low dose and work up. Most people don't see an effect on blood sugars until they are taking between 1,000 and 1,500 mg a day. Lowering your carbohydrate intake while you take Metformin can help you avoid some of the more unpleasant gastric effects.

Side Effects

Gastric Distress

The most common side effects of Metformin are nausea, diarrhea, heartburn and gas. That's why it's been nicknamed "metfartin" by people who post on Web bulletin boards. These unpleasant digestive system symptoms often go away after a few weeks, but not always. Some people are unable to take Metformin because of the persistence of these symptoms.

Can Metformin Cause Low Blood Sugar?

Metformin is not supposed to cause dangerous hypos. A very few people have found that it causes their blood sugar to drop low enough to make them uncomfortable. This may be because of the phenomenon called False Hypo. You can read about false hypos HERE.

Lactic Acidosis?

Metformin is chemically similar to an earlier drug, Phenformin which was taken off the market because it caused a fatal side effect, lactic acidosis. There is some debate about whether or not Metformin also causes this symptom.

An epidemiological study in Canada found 10 cases of hospitalization for lactic acidosis in a population of 11,797 patients who had been prescribed Metformin. (5)

One review of data from published studies suggests that this frequency is a normal incidence in all populations and perhaps not related to taking the drug. (6)

The symptoms of lactic acidosis include malaise, muscle aches, and gastric distress that comes on after a person has gotten over the initial problems associated with taking Metformin. It is possible that the incidence of lactic acidosis is higher than the statistics suggest because doctors are aware of it and take patients off the drug if they begin to exhibit symptoms. There are a few anecdotal reports on newsgroups posted by people who say they have developed lactic acidosis while on Metformin.

Because they are more likely to developed lactic acidosis, people with kidney damage, liver damage, or congestive heart failure should not take Metformin. It can also occur with dehydration in people who have otherwise normal kidney and liver function. People on Metformin should discontinue taking it before having an x-ray procedure that uses dye, since these procedures can affect kidney function and increase the risk of developing lactic acidosis.

Because of a fear that alcohol intake may enhance the risk of lactic acidosis, people taking Metformin are advised not to drink more than a very small amount of alcohol.

Metformin Depletes Vitamin B-12 and Folate

Metformin has one more significant side effect. It depletes Vitamin B-12 and Folate and increases homocysteine, a blood chemical associated with increased heart attack risk.(7) This makes it important that anyone taking Metformin take supplemental vitamin B-12 and Folic Acid. Because a low carb diet may not provide enough of these important vitamins, extra supplementation is advisable for people on a low carb diet. If you have been taking Metformin for a while, you should ask your doctor to test your blood vitamin B-12 level.

Low vitamin B-12 is associated with increased neuropathy and exhaustion.

Citations

1 Diabetes Prevention Program Research Group; Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. New England Journal of Medicine, Volume 346:393-403 February 7, 2002 Number 6

http://content.nejm.org/cgi/content/short/346/6/393

2 DeFronzo RA, Barzilai N, Simonson DC. Mechanism of Metformin action in obese and lean noninsulin-dependent diabetic subjects.J Clin Endocrinol Metab. 1991 Dec;73(6):1294-301

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1955512&dopt=Abstract

3 Nicolas Musi, Michael F. Hirshman, Jonas Nygren, Monika Svanfeldt, Peter Bavenholm, Olav Rooyackers, Gaochao Zhou, Joanne M. Williamson, Olle Ljunqvist, Suad Efendic, David E. Moller, Anders Thorell, and Laurie J. Goodyear; Metformin Increases AMP-Activated Protein Kinase Activity in Skeletal Muscle of Subjects With Type 2 Diabetes. Diabetes 51: 2074-2081

http://diabetes.diabetesjournals.org/cgi/content/full/51/7/2074

4 Imre Pavo, György Jermendy, Tamas T. Varkonyi, Zsuzsa Kerenyi, Andras Gyimesi, Sergej Shoustov, Marina Shestakova, Matthias Herz, Don Johns, Belinda J. Schluchter, Andreas Festa and Meng H. Tan; Effect of Pioglitazone Compared with Metformin on Glycemic Control and Indicators of Insulin Sensitivity in Recently Diagnosed Patients with Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 4 1637-1645

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12679450&dopt=Abstract

5 Stang M, Wysowski DK, Butler-Jones D. Incidence of lactic acidosis in Metformin users. Diabetes Care (United States), Jun 1999, 22(6) p925-7

http://care.diabetesjournals.org/cgi/content/abstract/22/6/925

6 Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with Metformin use in type 2 diabetes mellitus: systematic review and meta-analysis. Arch Intern Med. 2003 Nov 24;163(21):2594-602.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12076461&dopt=Abstract

7 Wulffele MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJ, Stehouwer CD. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial.J Intern Med. 2003 Nov;254(5):455-63.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14535967

Acarbose - The Overlooked Diabetes Drug

Acarbose, sold under the brand name Precose, is the most neglected and the most useful drug available for controlling blood sugar. Like Metformin, it has also received industrial-strength testing to see if it can prevent subjects from progressing from impaired glucose tolerance to full-fledged diabetes. Though it has long been prescribed in Europe it is rarely used in the United States and many doctors are unaware of how helpful it can be to people with both diabetes and impaired glucose tolerance.

How Acarbose Works

Acarbose, works by blocking alpha-glucosidase, the enzyme that chops up starches and complex sugars into their component glucose molecules. This results in starches and complex sugars passing largely undigested through the stomach and portions the small intestine rather than entering the bloodstream as glucose soon after eating.

However, Acarbose is not that mythical substance so beloved by health scammers the "starch blocker." That is because the starches and sugars whose digestion is temporarily blocked by Acarbose do, eventually, get broken down as they pass through the intestine where they are digested by the bacteria that live in the gut. So the glucose contained in these foods does, eventually reach the bloodstream. However, because the process is slowed down, that glucose reaches it in dribs and drabs rather than in one big blood-sugar-spiking dump.

How Much Improvement Does Acarbose Make in Blood Sugar?

The Prescribing Information provided by Bayer, the manufacturer of Precose, reports that in clinical trials Precose lowered the post-meal blood sugar numbers by 25 mg/dl to 83 mg/dl (1.4 to 4.6 mmol/L)depending on dosage. However, at the commonly prescribed dose, the change was a drop of 46 mg/dl (2.6 mmol/L). The same prescribing information insert also reports that in another study, subjects taking 100 mg of Precose over four months experienced an average drop in one-hour-post-meal numbers of 42.6 mg/dl (2.4 mmol/L).

Unfortunately, none of these studies reported the amount of carbohydrate that patients ate when they achieved these improvements. The baseline one-hour-post-meal blood sugar listed in the study cited by the manufacturer was 299.1 mg/dl, so even with the Precose, study subjects were running blood sugars that were dangerously high and it is likely that they were eating 60 to 100 grams per meal.

Adding Precose to Metformin only achieved an additional 31 mg/dl drop from a 283 mg/dl baseline post-meal blood sugar. However, unlike the case with Metformin, Precose appears to be equally effective for people who maintain healtly low blood sugar levels. I find that taking it allows me to add an additional 15 to 20 grams of carbohydrate to my meal without seeing a dangerous spike.

Animal studies conducted throughout the 1990s suggested that even though this reduction in blood sugar was modest, Acarbose also decreased protein glycation and appeared to delay or prevent heart attacks and the other diabetic complications caused by elevated blood sugars.(1)

Does Acarbose Prevent the Development of Diabetes?

To see if Acarbose could be used to prevent the progression of impaired glucose tolerance to daibetes the multiple-research centers participating in the STOP-NIDDM Trial administered 100 mg of Acarbose three times a day to 714 subjects while giving another 715 subjects a placebo. At the end of three years the study a smaller percentage of the group taking Acarbose had developed diabetes than of the controls. This the researchers concluded meant that Acarbose could significantly decrease the progress of IGT to diabetes. (2)

In addition, they appeared to have half as great a risk of cardiovascular events (heart attack, death, heart failure, stroke or peripheral vascular disease) as controls. They also had less new cass of hypertension.(3)

The Study Gets a Hostile Critique

However, the validity of this data was called into question in a published review by T. Kaiser and P. T. Sawicki of the Institute for Evidence Based Medicine in Cologne, Germany.(4)

They pointed out in the critique they published in the respected journal Diabetologia that the impartiality claimed for the STOP-NIDDM study was tarnished by the fact that 5 of the 11 members of the study steering committee were employees of Bayer, the manufacturer of Acarbose and that they heavily participated in the study design, a fact not mentioned in the STOP-NIDDM publications which had specifically claimed that the main sponsor had no role in the study design.

The critiquers point out that another explanation for the study's findings might be that data supplied with the study made it clear that the people in the placebo group had worse blood sugar profiles than those in the Acarbose group at the beginning of the study--a difference that is similar to the eventual difference in the amount of diabetes that appeared in each group. That this might be the real explanation is bolstered by the fact that in their publications the researchers did not present the post-meal blood sugar levels or the HbA1c numbers of the two groups, though the study design had originally called for these to be measured. For a study of a drug that reduces post-meal blood sugars, this is a rather striking ommision.

Another explanation for the apparent benefit of Acarbose, according to Kaiser and Sawicki, was the fact that the placebo group were followed for three months longer than the Acarbose group giving them a longer time to develop diabetes. When the number of people who developed diabetes during the three month "washout" phase during which the drug was discontinued was included in the study results, a further 15.4% of the Acarbose subjects developed diabetes. Since the original finding was that 32% of patients randomized to Acarbose and 42% of patients randomized to placebo developed diabetes as measured by OGTT the addition of that extra 15.4% of the Acarbose group that developed diabetes when the drug was discontinued wipes out any real advantage the drug might have conferred.

When discussing the supposed improvement in cardiovascular risk, the critiquers make the point that the criteria for assessing whether or not a cardiovascular event occurred were changed during the course of the study, suggesting that the researchers redefined "cardiovascular event" in a way that made the drug group's results look better.

The original authors responded to this critique by claiming that reanalyzing their data showed it was not true but the critiquers countered that the response did not address most of the issues they had raised.

The Critiquers Miss the Point!

Once again, the point that seems to have been missed by everyone reviewing this study is that there is no information about the post-meal blood sugar levels that the participants maintained. Since they appear to have been on a high carbohydrate diet, it is almost certain that those blood sugar levels, even with Acarbose, were high enough to damage organs and beta cells. It is possible that if Acarbose is used along with carbohydrate restriction to keep blood sugars under 140 mg/dl at all times, it may help halt the progression of impaired glucose tolerance and of type 2 diabetes.

Acarbose and a Low Carb Diet

Unfortunately, as usual, there are no studies that look at what happens when people who control their carbohydrate intake use Acarbose to achieve healthy blood sugar targets.

The Anecdotal Evidence

When used to allow an occasional indulgence while following a low carb diet, Acarbose worked very well for me. Iused it along with a low carb diet for for several years and my blood sugar response did not deteriorate at all during that time. I find that when I am eating a mostly low carb diet, taking 50 to 100 mg of Acarbose with a meal will allow me to add an additional fifteen or twenty grams of carbohydrate without seeing a spike that lifts my blood sugar into the dangerous range. However, Acarbose does not allow of total pig-outs. A "bagel tolerance test" taken along with Acarbose will still rise well over the 140 mg/dl level that I consider safe.

My endocrinologist reports that several of her other patients have experienced similar results with Acarbose and have told her that it is the best drug they have tried.

On the other hand, I have also spoken with people who felt that Acarbose only pushed their blood sugar spike further into the future. The people who report this tend to be those who produce less insulin and who are farther along in the process of type 2 diabetes.

From this I conclude that Acarbose works best for people who have lost their first phase insulin response but still have a functional second phase response. That is because by slowing down the release of glucose from food, Acarbose delays the release of most glucose until the second phase insulin response kicks in. (For more on the phases of insulin response, visit this page).

Acarbose Does Not Block Simple Sugars like Fructose and Glucose

If you are using Acarbose it is important to understand that Acarbose does not slow the digestion of simple sugars such as fructose or glucose because they do not require digestion but are absorbed from the stomach as soon as they are eaten.

The carbohydrates from foods like corn syrup, maple syrup, or candies containing dextrose will go straight into your blood stream, whether you have taken Acarbose or not. Acarbose works well with sucrose (table sugar) and starches like wheat flour, rice, and beans.

Dosing and Time to Take Effect

You should start out taking the lowest dose of Acarbose available and then work up. This will help you avoid gastric side effects. You take Acarbose with your first bite of food and it begins to work immediately.

Unlike other drugs, Precose does not get into your body in any significant amounts. It exerts its effect within the digestive tract and is not absorbed.

Side Effects

Gas - The Killer Side Effect of Acarbose

Fully 24% of the people assigned to the Acarbose group in the STOP-NIDDM study dropped out of the study long before it completed. There's a reason for that, and the reason is this: remember how we said that when undigested carbohydrate gets further down in your digestive tract the so-called friendly bacteria can digest it? Well, that digestion also goes by the name of "fermentation" and one of its byproducts is gas.

This means that the more carbohydrates you eat with Acarbose, the greater the amount of gas will be produced in your gut. The resulting gas production can be such that it limits your social life or gets you cutting down on your carbohydrate intake very steeply because you quickly learn to associate carbohydrate dinners with hours of post-meal flatulence.

That, by the way, is why the drug manufacturer stopped marketing Precose in the US. Most Patients eating a typical high carbohydrate American diet were unable to tolerate it.

However, if you use Acarbose while eating at a more modest level of carbohydrate intake Acarbose can be useful. I have found that it works best if I only use it at one meal a day and if I limit my carbohydrate intake at that one meal 30 grams or less. I also find that foods containing wheat cause more gastric symptoms than other starchy or sugary foods. Using this kind of moderation makes it possible to occasionally eat foods that would otherwise be completely forbidden on my low carb diet without blowing away my blood sugar.

Combining Acarbose and Metformin

I have found that adding Acarbose to Metformin achieves even better blood sugar control. However, I have also found it is better to use a lower dose of Metformin (500 mg/day) along with a lower dose of Precose (50 mg), since both of these drugs can cause gastric miseries. Taking both drugs at a high dose simultaneously can result in acute stomach distress!

CITATIONS

1 Creutzfeldt W. Effects of the alpha-glucosidase inhibitor acarbose on the development of long-term complications in diabetic animals: pathophysioloical and therapeutic implications. Diabetes Metab Res rev. 1999 15(4):289-96

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10495478

2 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trail Research Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002 Jun 15;359(9323):2072-7.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12086760

3 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003 Jul 23;290(4):486-94.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12876091

4 Kaiser T, Sawicki PT. Acarbose for prevention of diabetes, hypertension and cardiovascular events? A critical analysis of the STOP-NIDDM data. Diabetologia. 2004 Mar;47(3):575-80. Epub 2004 Jan 16.

http://www.di-em.de/data/diabetologia_2004_47_575.pdf

Drugs that Force the Pancreas to Produce (or Over-produce) Insulin

The drugs we've discussed up until now either blocked the input of glucose into the blood stream by slowing the digestion of carbohydrates, shutting down liver production of glucose, or else enhance the uptake of glucose by cells. There is however, one last group of oral antidiabetic drugs which lower blood sugar by forcing the beta cells to produce more insulin.

There are two families of these drugs: the sulfonylurea drugs, which include Glyburide, Glimepiride, and Glipizide and the newer family of "glinide" drugs which include Stalix (natalinide) and Prandin (repaglinide).

Too Much Insulin Can Lead to Dangerous Hypos

These drugs can lower post meal blood sugars significantly. However, they do this at a cost. The sulfonylureas force the body to produce high amounts of insulin whether or not there is glucose in the bloodstream, so these drugs can cause low blood sugar attacks severe enough to cause unconsciousness or even death. This means that people who take these drugs must keep their carbohydrate consumption high to avoid dangerous hypoglycemic episodes. Since our goal is to lower blood sugar, that rules these drugs out as useful tools since they require that patients maintain their blood sugar at levels far above 140 mg/dl in order to avoid hypos.

The "glinide" drugs supposedly will not stimulate insulin production unless there is an elevated level of glucose in the bloodstream, but even so, users of these drugs report that they are still capable of causing reactive low blood sugar attacks.

More Insulin Means More Insulin Resistance

In addition, because both these families of drugs pour more insulin into the bloodstream they will exacerbate insulin resistance rather than improve it. If you already have higher than normal insulin levels, the addition of extra insulin to your system is likely to have a negative effect on your cardiovascular system and may also promote the growth of cancers.

Some Sulfonylurea Drugs Increase The Risk of Heart Attack

This problem is been mentioned in a warning in the PDR Prescribing Information for Amaryl and other sulonylurea drugs. A recently published study came up with the finding that the more sulfonylurea a person took, the higher the risk for a cardiac "event (i.e. heart attack). This is probably because these drugs not only stimulate the pancreas beta cells, they also stimulate a receptor in the heart. Prandin was also associated with more cardiac deaths.

The doctor commenting on this research recommends using only those Sulfonylureas that have less effect on the receptor in the heart--Amaryl, Gliclizide, and Starlix. However, there has not been research done with these drugs that guarantees they are safer. So they should be approached with caution.

"Do sulfonylurea drugs increase the risk of cardiac events?"
David S.H. Bell

http://www.cmaj.ca/cgi/content/full/174/2/185

Do These Drugs Cause Beta Cell Burn-out?

There is some question about the wisdom of forcing exhausted and already dysfunctional beta cells to produce yet more insulin. Dr. Richard K. Bernstein www.diabetes-normalsugars.com/ is a firm believer that these kinds of drugs cause beta cells to die and counsels people with diabetes to avoid them. However, there is little experimental data available to evaluate this possibility.

Some argue that since the UKPDS data shows a similar decrease in blood sugar control in patients taking sulfonylurea drugs and Metformin, the sulfonylurea did not cause additional damage to beta cells.

More Insulin Means More Weight Gain

These drugs, too, are associated with weight gain since they produce more insulin and higher levels of circulating insulin are known to cause weight gain.

Special Concerns about Diabetes Drugs in the Eldery

Here's a sheet, prepared by pharmacist, that discusses some concerns that doctors should be aware of when prescribing diabetes drugs to the elderly. The definition of "elderly" used here is "65 and over."

http://www.diabetesincontrol.com/issues/Issue%20362/DiabetesinElderlyProduction.pdf

As we get older, our metabololisms slow down and a "normal" dose of a drug may have a stronger effect on our bodies since it doesn't get eliminated the way it would be in a younger person. According to this author, this can cause problems with low blood sugar in people who take drugs that stimulate the pancreas.

A Weird End Note

Sulfonylureas have another use besides stimulating the beta cells to produce insulin. They are also used as weed killers!
http://www.monitor.net/monitor/10-9-95/herbicide.html

Discussion of Avandia and Actos Has Been Moved

Because these drugs are now known to be dangerous,they are discussed separately from the drugs which are still legitimate treatments for diabetes.

The new page can be found here:
Avandia and Actos