Sulfonylureas

Sulfonylureas
Sulfonylureas, the first drug group introduced into the U.S. in 1955, stimulates the beta cells
to produce more insulin. These drugs have kept many Type 2’s off injected insulin.
Sulfonylureas will not work in those with Type 1 diabetes (except for a specific type) nor in
anyone with Type 2 whose beta cells no longer produce insulin. Loss of insulin production,
indicated by a low C-peptide level in the blood, is found in those with Type 1 diabetes, in many
who have Type 1.5 diabetes, and in many others with Type 2 diabetes for more than 6 to 15
years.
Sulfonylureas
Target Organ: Pancreas
Action: Increase insulin release
Lowers HbA1c by 1% to 2%
Taken: with or without food
Acts Dose
Drug Rel.Potency Doses/Day
Over Range
Orinase 6-10 500 -
1 2-3
(tolbutamide) hrs 3000 mg
1st Tolinase 100 -
3 1-2
Gen (tolazamide) 1000 mg
Diabinese 24-72 100 - 500
6 1-2
(chlorpropamide) hrs mg
Glucotrol 2.5 - 40
12 hrs 75 1-2
(glipizide) mg
Glucotrol XL 2.5 - 20
24 hrs 150 1
2nd (ext. rel. glipizide) mg
Gen Micronase, Diabeta 18-24 1.25 - 2.0
150 1-2
(glyburide) hrs mg
Glynase
24 hrs 3 - 12 mg 250 1-2
(micronized gly.)
3rd Amaryl
24 hrs 1 - 8 mg 350 1
Gen (glimepiride)
Side Effects: low blood sugar, bloating, nausea, heartburn, anemia, weight gain, sun
sensitivity, metallic or change in taste in 1% to 3 %
Contraindications: Type 1 diabetes, advanced liver or kidney disease, sulfa allergy
If the beta cells are able to produce insulin, this production can be increased by stimulating
beta cells with certain medications such as the sulfonylureas and rapid insulin releasers
(Prandin and Starlix). Insulin from the beta cells is released directly to the liver via the portal
vein, allowing it to work more effectively.
Sulfonylureas can cause low blood sugars, although this occurs much less often than with
insulin. Severe low blood sugars occur about 500 times more often with insulin than with
sulfonylureas. Emergency room visits for low blood sugars occurred only once for every 4,000
person-years of sulfonylurea use during a large 10 year study done in Switzerland between
1975 and 1984. Low blood sugars brought on by sulfonylureas are generally infrequent and
mild.
The original "first generation" sulfonylureas include Orinase (tolbutamide), Tolinase

(tolazamide), and Diabinese (chlorpropamide). These drugs work well in lowering the blood
sugar, but they have a major drawback. Because they bind to proteins in the blood, they can
be dislodged by other medications that bind to these same proteins. Once dislodged, their
activity can increase rapidly and lead to low blood sugars.
Diabinese lasts longer in the blood and on rare occasions can cause a severe and long-lasting
form of hypoglycemia. Its use was phased out as newer, safer sulfonylureas became available.
However, chlorpropamide, the generic form of Diabinese, can still be encountered in many
nonprescription oriental “herb mixtures” that are imported and used as over-the-counter
treatments for diabetes within the U.S. The product label is unlikely to list chlorpropamide, so
the wise approach is to avoid use of any herb mixtures for diabetes.
Second generation sulfonylureas include Glucotrol (glipizide), as well as Micronase, Diabeta,

and Glynase (all contain glyburide). A third generation called Amaryl (glimepiride) is also
available. These drugs have an advantage for those who use other medications since they do
not bind to carrier proteins in the blood. Because of this, drug interactions that may cause low
blood sugars are less likely.
Sulfonylureas work best when taken at the same time each day. Glyburide and glipizide are
shorter-acting versions. Glyburide (Micronase and Diabeta), and glipizide (Glucotrol) are
usually taken twice a day, half before breakfast and half before dinner. Sustained-release
versions called Glynase or Glucotrol XL are also available. Long-lasting versions can be taken
once a day instead of twice a day. These medications can be used once a day before the
evening meal when a person has high blood sugars at bedtime or before breakfast if care is
taken to monitor the daytime blood sugar until the safety of the dose is assured.
As well as stimulating insulin production, Amaryl (glimepiride) may cause a mild reduction in
insulin resistance and may be less likely to cause low blood sugars than other sulfonylureas. It
is also safer for people who have advanced kidney disease indicated by an elevated creatinine
level. Other sulfonylureas are usually not recommended when the creatinine level is elevated.
Glimepiride also does not block the normal relaxation of blood vessels and does not affect
coronary arteries. These unwanted side effects may occur infrequently with other
sulfonylureas.
When starting a sulfonylurea, the risk of a low blood sugar is greatest during the first few days
to first four months of use. Be careful during this time and check your blood sugar often when
you exercise, increase activity, or skip a meal. Drinking alcohol or taking certain medications
like decongestants can also increase the risk of a low. Medications, such as steroids, beta
blockers, niacin, and Retin-A may decrease the action of a sulfonylurea and cause the blood
sugar to rise.
A Recent Study
A recent study has identified a genetic mutation, called KCNJ11, that prevents insulin
producing cells from releasing insulin. Dr. Andrew Hattersley of Peninsula Medical School in
Exeter had been studying the genes of patients diagnosed with Type 1 diabetes before the
age of six months. The reported occurrence rate of this type of diabetes is about 1 in
500,000 but it may be more.
Usually, when you have an elevated blood sugar from eating, your body closes a channel in
the insulin producing cells. This causes potassium to accumulate, which triggers another
channel to open and release calcium. When the calcium flows into these cells, insulin is
released. With the mutated gene, this potassium channel does not close so insulin is not
released like it should be. However, giving a sulfonylurea medication that is normally used for
Type 2 diabetes helps correct this defect by closing the potassium channel, stimulating the
calcium release and the release of insulin.
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Sulfonylureas

The original "first generation" sulfonylureas include Orinase (tolbutamide), Tolinase

Second generation sulfonylureas include Glucotrol (glipizide), as well as Micronase, Diabeta,

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