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Pill bottleUpdated September 16, 2013

Treatment of Diabetes

The goal of diabetes treatment is the prevention of damage to human tissues. Diabetes cannot be successfully treated in a vacuum. Other risk factors, such as elevated blood pressure and blood fats (cholesterol, triglycerides, etc.) must also be addressed. 

From the standpoint of blood glucose (sugar), the goal is to get it as close to normal as possible, without causing other problems such as low blood sugar (hypoglycemia).

Treatment of Type 1 diabetes.

Treatment of Type 2 diabetes.

Type 2 diabetes is treated at first with oral agents, in most cases.  However, insulin may be needed initially if the blood glucose (sugar) is very high. Type 2 diabetes occurs because available insulin from the pancreas is inadequate for metabolic needs. This is generally the result of insulin resistance and insulin lack. The largest study in type 2 diabetes, UKPDS† demonstrated that approximately half of the insulin producing capacity of the pancreas has been lost AT THE TIME OF DIAGNOSIS. This loss is progressive. Before insulin producing capacity is lost to a major extent, oral agents (pills) may be adequate for treatment. These agents generally stimulate the pancreas the produce more insulin or increase the efficiency of insulin action. The latter is frequently done through reduction of liver glucose (sugar) production; reducing the resistance to insulin in tissues; reducing the absorption of carbohydrates from the GI tract and/or reducing appetite; or some combination of these.
†United Kingdom Prospective Diabetes Study Group. UK prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes. 1995;44:1249-1258.

Pills for type 2 diabetes.

The Biguanides . Metformin (Glucophage®, Riomet® Fortamet®, Glumetza®).This medication is perhaps the most widely prescribed oral drug for diabetes in the world. It works primarily by reducing the production of glucose (sugar) of the liver.  Another, less prominent action is to increase the action of insulin in fat and muscle.  Patients with moderate to severe kidney impairment should probably not take this medication.  It can cause gastrointestinal symptoms such as diarrhea, abdominal pain and a metallic taste.  These symptoms are frequently temporary. Unlike several other medications, it does not cause low blood sugar if given alone. Metformin is available in a generic form.

The Sulfonylureas. Glyburide (Micronase®, DiaBeta®, Glibenclamide, others).
Glipizide (Glucotrol®, others). Glimepiride (Amaryl®). The sulfonylureas reduce blood glucose because they stimulate insulin release from the pancreas.  They are long acting and may cause low blood sugar.  Glyburide has been reported to cause low blood sugar in as many as 30% of users whereas glimepiride has been reported to cause this problem in only 2 -- 4% of users. Other side effects of the sulfonylureas include nausea and vomiting. Each of the above listed products are available in generic formulations.

The Meglitinides. Repaglinide (Prandin®) Nateglinide (Starlix®) These products stimulate insulin release from the pancreas much like the sulfonylureas.  The difference is that they are short acting and are generally given prior to meals. They are therefore useful in reducing high blood sugar from food. According to Wikipedia, repaglinide will be available as a generic product in March of 2009. These products are metabolized primarily by the liver and should probably not be given if there are moderate to severe liver problems.

The Thiazolidinediones (TZDs). Rosiglitazone (Avandia®). Pioglitazone (Actos®).
These products increase the efficiency of insulin by increasing sensitivity to insulin in body tissues, particularly muscle and fat.  TZDs are not effective if insulin is not present.  They have been reported to reduce A1c levels 1 - 1 .5% in patients with type 2 diabetes.  TZDs have also been reported to have positive effects on heart disease and pioglitazone has been reported to improve blood fats.  They have rarely been associated with liver problems.  The first drug in this class, troglitazone (Rezulin®) was removed from the market because of liver problems.

Alpha Glucosidase Inhibitors. Acarbose (Precose®). Miglitol (Glyset®). Alpha Glucosidase inhibitors reduce the effectiveness of enzymes that digest carbohydrates in the gastrointestinal tract.  They therefore reduce blood glucose levels after a meal.  The major side effects include flatulence, diarrhea and abdominal bloating.

Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors). Sitagliptin (Januvia™). Saxagliptin (Onglyza™) and the newest, Tradjenta™ (linagliptin).  Several others are in various stages of development. These drugs inhibit an enzyme (DPP-4) that destroys a naturally produced hormone called GLP-1. This hormone is produced in the intestine and has several beneficial effects. It stimulates the release of insulin from the pancreas and inhibits the action of substances that increase blood glucose such as glucagon among others. GLP-1 is normally destroyed rapidly by an enzyme called DPP-4. Overview of this class of medications.

STLT2 (sodium-glucose cotransporter) inhibitors.  The 1st drug in this class to be approved by the FDA for the treatment of type 2 diabetes is Invokana™(canagliflozin).  These products work in an entirely different manner.  In the normal kidney, glucose (sugar) and sodium are filtered out of the bloodstream into the tubules of the kidney.  Normally, the majority of these materials return to the blood after moving somewhat further in the kidney tubules.  Therefore, under normal circumstances the glucose and sodium in the blood stream remain relatively stable.  This movement of glucose and sodium back into the bloodstream is enabled by the sodium – glucose co-transporter.  The SGLT2 inhibiting drugs block this process to some extent.  The result is an increase in glucose and sodium in the urine and a decrease in the bloodstream.
The end result of this blockade is as follows.
A reduction in A1c as much as 1.0%.
A body weight reduction by as much as 2 – 3%.
Systolic blood pressure reduction by 3 to 4mm/Hg.


What are the downsides?
The most common side effect has been yeast infections.  Everybody has yeast on the skin, an increase in sugar in the urine promotes yeast growth.  This problem has been most common in women.  We advise ladies taking this medication to use a cleansing towel after each bathroom use.  So far, this has seemed to prevent the yeast infections.  The drug can cause dehydration, increased thirst, increased frequency of urination and a drop in blood pressure on standing in the elderly.  It should therefore be used cautiously, especially in seniors of if there is any decrease in kidney function.
Click here to see the full side effect profile of Invokana

Chuck Raine, M.D.

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INSULINinsulin_bottle

Type 1 diabetes is treated with insulin. There is generally no place for diabetic pills in type 1 diabetes. Most people with type 2 diabetes will eventually also need insulin.

Canadian researchers Banting, Best, Macleod and Collip were the first to show that animal insulin reduced blood sugar in a patient with type 1 diabetes. Currently a patient requiring insulin must give it by injection. An inhaled insulin (Exubra®) was effective but has been removed from the market. This was not for safety reasons but because it did not sell well. Another one is expected to reach the market in 2009 or 2010. Researchers are also working on insulin that can be delivered by other methods such as an insulin patch for insulin to be absorbed through the skin.

Short acting insulin. Regular Human Insulin. This is a clear insulin that generally has an onset between 30 minutes and 1hour. It peaks at around 4 (2-4) hours and has a duration of about 8 (4-8) hours. It is generally used with meals or to counteract high blood glucose. Available US brands include Humulin R®, Novolin R® and Wal-Mart ReliOn®/Novolin R ®

Rapid acting insulin. The rapid insulins are similar to regular insulin but have a faster onset and a shorter duration. These insulins generally have an onset between 15- 20 minutes with a peak between 45 minutes and two hours and a duration between 3 and 5 hours. These insulins are generally used for food and to counteract elevated blood glucose. US brands include lispro (Humalog®), aspart (Novolog®) and glulisine (Apidra®). There is evidence that glulisine (Apidra®)has a faster onset and a shorter duration in some circumstances and in some patients.

Intermediate acting insulin. The only currently available intermediate acting insulin in the US is NPH (Neutral Protamine Hagedorn). In general NPH has an onset of 1 to 3 hours, a peak in 4 to 10 hours and a duration of 10 to 18 hours. It is generally used as basal insulin. Because of a relatively short duration, it is generally given more than once daily US brands include Humulin N®, Novolin N® and Wal-Mart ReliOn®/Novolin N®.

Long acting insulins. These longer acting insulins have an onset between 1 and 3 hours and tend not to have a peak. The duration is up to 24 hours. They are used for basal insulin. Because of the slow onset of action and long-duration, other insulins or medication will generally be required to maintain good glucose control. US brands include glargine (Lantus®) with a duration of 24 or more hours and detemir (Levemir®) with a duration up to 24 hours in some circumstances.

Pre-mixed insulins. These insulins combine rapid acting insulin with long acting insulin to reduce the number of injections required. Some of them combine NPH insulin with Regular insulin and others combine rapid insulin with longer acting insulins. The onset, peak and duration are variable depending upon the mix. US brands include Human 70/30 insulin, Novolin 70/30® and Wal-Mart ReliOn®/Novolin 70/30®; Humulin Mix® 50/50;Humalog Mix® 75/25; Humalog Mix® 50/50; Novolog Mix70/30®. In general, human insulins tend to be less expensive than the analog insulins. Analog rapid insulins tend to end in “log”.

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Your Summer and Insulin

If you live in the Southern US, summer may not be official but it is HOT! People with diabetes who use insulin in pens or insulin pumps have a different issue with insulin and HEAT. First, insulin is a relatively unstable molecule. Vigorous shaking can denature the molecule and make it less potent. Exposure to high temperatures can produce the same effect.  Do not freeze insulin.

Insulin Vials

Those using insulin from a vial should store open and unopened containers in the refrigerator (recommended temperature 36-46 °F; 2-8 ° C).  According to the product information from each of the rapid acting insulins, opened vials, whether or not to refrigerated, and must be used within 28 days.  Vitals should be kept away from direct heat and light.  Temperature limitations vary, less than 77°F, 25°C (glulisine, Apidra®); 98.6°F, 37°C (aspart, Novolog® and lispro, Humalog®).

Insulin in Pumps

 The product information sheets of Humalog®, Apidra® and Novolog® recommend a pump infusion set change every 48 hours to avoid insulin degradation, loss of insulin preservative and infusion set occlusion.  We have not seen particular problems at the Diabetes Control Center with patients changing infusion sets every 72 hours.  This is subject to individual variations.  Those who spend significant time outdoors in summer weather should change infusion sets more frequently. Insulin pump users should check glucose (sugar) frequently and follow guidelines if elevations are noted.

Insulin Pens

Unopened insulin pens should be stored in the refrigerator (recommended temperature 36-46 °F; 2-8 ° C).  Once the pens have been opened (penetrated by a needle) they should NOT be returned to the refrigerator and discarded after 28 days.  Temperature limitations for  opened pens are the same as for vials.  As with other forms of insulin, pen insulin should not be frozen and should be protected from direct heat and light.  Leaving an insulin pen (or any insulin) in a vehicle in the hot summer sun is a definite no, no.

References:

Novolog® Prescribing information

Apidra® Prescribing information

Humalog® Prescribing information

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Incretin Mimetics
Relatively new classes of medication for diabetes are the incretin mimetics. Incretins are a group of hormones from the GI tract. These have several effects stability of glucose metabolism in the normal human. One of the most active of these is GLP1 (Glucagon Like Peptide -1). It is released for the small intestine, stimulated by the presence of food in the stomach. Effects are increased insulin production from the pancreas, reduced stimulation of glucose release from the liver by glucagon, slowed stomach emptying and a sensation of decreased appetite (satiety).  The result is decreased blood sugar after eating (decreased post prandial plasma glucose). GLP1 is rapidly destroyed by an enzyme (DPP4).  

Byetta has been on the market for some years. We at the Diabetes Control Center have had good success with the product. Most patients lose some weight and get better control of post meal blood glucose. Our “poster girl” patient lost 30 pounds over several months. Not all patients lose weight and not all get the desired control of post meal glucose. In our experience, about 15% do not get the desired effect.
It is important to remember that any medicine has the potential of side effects, possibly serious ones. An old maxim is:


“Any drug that has no side effects, has no beneficial effects”


As of 8/18/2008, The FDA had reviewed 36 cases of pancreatitis (an inflammation of the pancreas) in patients taking Byetta®. Click here to see the FDA report.  WE have not seen a case of pancreatitis at the Diabetes Control Center.

byetta side effects pi

Information source: Exenatide Product Information.

Liraglutide (Victoza®)

This new GLP-1 product has been approved by the FDA as an adjunct to diet and exercise for the treatment of type 2 diabetes. Like its predecessor, exenatide (Byetta®) this product is associated with significant reductions in A1c and weight loss; the most common side effect is nausea. There has been some concern by the FDA about a finding of thyroid cancers in rats with liraglutide. Click here for details.

Other Hormones

Symlin® (Pramlintide) is approved by the FDA for diabetic patients taking insulin. Pramlintide is a synthetic analog of human amylin, a naturally occurring hormone synthesized by pancreatic beta cells. It must be injected and contributes to glucose control in the post meal period. Symlin slows stomach emptying, reduces post meal glucagon elevation and increases satiety …”leading to decreased caloric intake and potential weight loss”.  Our experience at the Diabetes Control Center has been positive. Weight loss and A1c reduction may not be quite as vigorous as with Byetta. 

Symlin Side effects pi

Information source (Source Symlin Product Information).

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