Diabetes Treatment

Drug treatment depends on the type of diabetes: Type 1 diabetes (also known as Insulin Dependent Diabetes Mellitus (IDDM)) is where the body does not produce insulin, so replacement insulin must be delivered by injection or pump. Type 2 diabetes (or Non Insulin Dependent Diabetes Mellitus (NIDDM)) patients may be able to control their blood glucose levels by carefully following a diet and exercise program and losing excess weight. If this first-line treatment does not control blood sugar levels effectively, an oral medication can be added to the treatment plan. In certain circumstances, patients with Type 2 diabetes may also need insulin injections. Many patients with diabetes also need to take medicine to control their blood pressure and cholesterol levels. Weight loss medications such as Xenical can help with the management of obesity.

Insulin
Injected insulin acts similar to endogenous insulin to lower blood glucose levels. There are more than 20 different types of insulin available in the United States. The various types of insulin differ in several ways: in the source (animal, human, or genetically engineered), in the time for the insulin to take effect and in the length of time the insulin remains working. Variations of insulin have been developed to satisfy the needs of individual patients. For example, zinc suspension insulin is an intermediate acting insulin that starts working within 1 to 1-1/2 hours and lasts approximately 24 hours. Insulin combined with zinc and protamine is a longer acting insulin that takes effect within 4 to 6 hours and lasts up to 36 hours. The time and course of action may vary considerably in different individuals or at different times in the same individual.

Insulin is classified according to how it works in the body:

Onset - how soon the insulin starts working Peak - when it is working most effectively Duration - how long the insulin lasts in the body

Classifications of Insulin
Rapid Acting Insulin - Insulin Lispro, Insulin Aspart and Insulin Glulisine Brand Name Apidra Humalog Generic Name insulin glulisine insulin lispro Onset 10 to 20 mins 15 mins Peak 55 mins 1 to 1.5 hours Duration 3 hours 2 to 5 hours

NovoLog

insulin aspart

10 to 20 mins

1 to 3 hours

3 to 5 hours

Short Acting - Insulin Regular (R) is also known as Soluble Insulin Brand Name Humulin R, Novolin R Generic Name insulin regular Onset 30-60 mins Peak 2 - 5 hours Duration 6 - 8 hours

Insulin regular used to be manufactured from beef and pork pancreas but is now available as human recombinant insulin. All brands of insulin from beef or pork origin have now been discontinued.

Discontinued Brands of Insulin Regular

y Regular Iletin II (insulin purified beef) y Iletin II, Regular Iletin II (Pork) (insulin purified pork) y Velosulin BR (insulin recombinant human) y Velosulin BR Human (insulin recombinant purified human) Intermediate Acting - Insulin Isophane (N), Insulin Zinc (also known as Lente (L) insulin)

Brand Name Humulin N, Novolin N

Generic Name insulin isophane

Onset 1 to 1.5 hours

Peak 6 to 12 hours

Duration 15 to 24 hours

Discontinued Brands of Insulin Isophane

y y y y y

Insulated NPH Human (insulin suspension isophane semisynthetic purified human) Insulin Insulated NPH Nordisk, NPH Iltein II (Pork) (insulin suspension isophane purified pork) NPH Iletin I (Beef-Pork) (insulin suspension isophane beef/pork) NPH Iletin II (insulin suspension isophane purified beef) NPH Insulin (insulin suspension isophane beef

Discontinued Brands of Insulin Zinc

y Humulin L, Novolin L (insulin zinc) y Lentard (insulin zinc Suspension Purified Beef/Pork) y Lente, Lente Iletin II (Pork) (insulin zinc suspension purified pork) y Lente Iletin II (insulin zinc suspension purified beef) y Lente Insulin (insulin zinc suspension beef) y Semilente (insulin zinc suspension prompt purified pork) y Semilente Insulin (insulin zinc suspension prompt beef) Long Acting - Insulin Zinc Extended (also known as Ultralente (U) insulin). All these brands have now been discontinued.

Humulin U (insulin zinc extended) Ultralente (insulin zinc suspension extended purified beef) y Ultralente Insulin (insulin zinc suspension extended beef) Very Long Acting - Insulin Glargine and Insulin Detemir
y

Insulin glargine is a recombinant human insulin analog that is a man made form of the natural hormone. It is very long acting, and is slightly different from other forms of insulin that are not manmade. Due to its long duration of action it is injected just once a day. It should be clear and colorless and should not contain particles or be discolored. It should not be diluted or mixed with any other insulin. Insulin detemir is a man-made form of insulin. It may be used in combination with another type of insulin or with an oral diabetes medicine to keep blood sugar under control. Brand Name Lantus Levemir Generic Name insulin glargine insulin detemir Onset 1 hour 3 to 4 hours Peak peakless 6 to 8 hours Duration 24 hours 24 hours

Inhaled Insulin
Exubera is a rapid-acting form of human insulin that is inhaled through the mouth. It works by lowering levels of glucose (sugar) in the blood. Exubera was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal. Brand Name Exubera (withdrawn 2007) Generic Name insulin inhalation

Premixed Insulin
Premixed insulin has two types of insulin mixed together in one vial. These are called biphasic insulin. This makes it easier to inject two different types of insulin at the same time. Profile of the premixed insulin depends on the combination. Normally, one insulin will be rapid or short acting and the other one has a longer duration of action. Insulin lispro protamine and Insulin aspart protamine are suspensions of crystals produced from combining insulin lispro and protamine sulfate, and insulin aspart and protamine sulfate, respectively, under appropriate conditions for crystal formation. The addition of protamine makes insulin lispro and insulin aspart, which are rapid acting insulin, into intermediate acting insulin. Brand Name Humalog Mix 50/50 Humalog Mix 75/25 Humulin 50/50 Humulin 70/30 Novolin 70/30 Generic Name insulin lispro/insulin lispro protamine insulin lispro/insulin lispro protamine insulin isophane/insulin regular insulin isophane/insulin regular insulin isophane/insulin regular

Novolog Mix 70/30

insulin aspart/insulin aspart protamine

Discontinued Brands of Premixed Insulin

Insulin Nordisk Mixtard (Pork) (insulin purified pork/Insulin susp isophane purified pork) Mixtard Human 70/30 (insulin recombinant purified human/Insulin suspension isophane semisynthetic purified human) WARNING: Hypoglycemia can be a dangerous complication of insulin treatment, and it must be treated promptly.
y y

Oral Antidiabetic Medicines

Oral medications are used in the treatment of Type 2 diabetes. The first line treatment for Type 2 diabetes is usually diet and exercise and sometimes these measures alone are sufficient to bring blood glucose levels back to the normal range. If these measures do not effectively control blood glucose levels, one or a combination of oral medications may be necessary to control hyperglycemia. Oral medication either makes the pancreas produce more insulin, helps decrease insulin requirements by the body or reduces gluconeogenesis by the liver.

Sulfonylureas
Sulfonylureas work by stimulating the pancreas to release more insulin and are only effective when there is some pancreatic beta-cell activity still present. Non-obese patients with Type 2 diabetes are usually started on sulfonylureas. A common side effect is hypoglycemia. It may cause weight gain and is therefore not suitable for obese patients.

First Generation Sulfonylureas

Brand Name Dymelor (discontinued) Diabinese, Glucamide (discontinued) Orinase (discontinued) Tolinase Generic Name acetohexamide chlorpropamide tolbutamide tolazamide

Second Generation Sulfonylureas

Brand Name Amaryl DiaBeta, Glynase Pres-Tab, Micronase Generic Name glimepiride glyburide (also known as glibenclamide)

Glucotrol, Glucotrol XL Diamicron

glipizide gliclazide (not commercially available in the U.S.)

Biguanides
Metformin is the only available biguanide. It inhibits the amount of glucose produced by the liver, increases the insulin-receptor binding and stimulates tissue uptake of glucose. Metformin does not stimulate the pancreas to make or release more insulin. It does not cause hypoglycaemia or weight gain therefore obese patients with Type 2 diabetes are usually started on biguanides. Common side effects include abdominal discomfort, diarrhea, nausea or vomiting, loss of appetite, and metallic taste. Brand Name Fortamet, Glucophage, Glucopahge XR, Glumetza, Riomet Generic Name metformin

Alpha-Glucosidase Inhibitors
Alpha-Glucosidase inhibitors slow the digestion of carbohydrates and delay glucose absorption. They work by inhibiting intestinal enzymes that digest carbohydrates, thereby reducing carbohydrate digestion after a meal, which lowers postprandial blood glucose elevation in diabetics. Common side effects include abdominal pain, diarrhea and flatulence. Brand Name Glyset Precose Generic Name miglitol acarbose

Thiazolidinediones
Thiazolidinediones (also called glitazones) work by making the body's cells more sensitive to insulin, so less insulin is needed to move glucose from the blood into the cells. This leads to a reduction of blood glucose levels. They should be taken in combination with metformin or a sulphonylurea. Brand Name Actos Avandia Prelay (discontinued), Rezulin (discontinued) Generic Name pioglitazone rosiglitazone troglitazone (withdrawn March 2000)

Meglitinides
Meglitinides works by stimulating the pancreas to release insulin in response to a meal. Hypoglycemia is a common side effect. Brand Name Prandin Starlix Generic Name repaglinide nateglinide

Drugs Combinations
Several drug combinations have become available to treat Type 2 diabetes. These drugs would have been given together so combining them into one tablet may help encourage patient compliance. Brand Name Actoplus Met Avandamet Avandaryl Duetact Glucovance Janumet Metaglip Prandimet Generic Name metformin and pioglitazone metformin and rosglitazone glimepiride and rosglitazone glimepiride and pioglitazone glyburide and metformin metformin and sitagliptin glipizide and metformin metformin and repaglinide

Miscellaneous Antidiabetic Agents Incretin Mimetics - Exenatide

Exenatide is an injectable diabetes medicine that helps control blood sugar levels. It helps the pancreas to produce insulin more efficiently. Exenatide is used to treat Type 2 (non-insulin dependent) diabetes. Other diabetes medicines are sometimes used in combination with exenatide if needed. It is not indicated for the treatment of Type 1 (insulin-dependent) diabetes or for diabetic ketoacidosis. Brand Name Generic Name

Byetta

exenatide

Dipeptidyl Peptidase 4 Inhibitors - Sitagliptin

Sitagliptin is an oral diabetes medicine that helps control blood sugar levels. It works by regulating the levels of insulin the body produces after a meal. Sitagliptin is for people with Type 2 diabetes (non-insulin-dependent) diabetes, and is sometimes used in combination with other diabetes medication. It is not for treating Type 1 diabetes. Brand Name Januvia Generic Name sitagliptin

Amylin Analogs - Pramlintide

Pramlintide is an injectable medicine for adults with Type 1 and Type 2 diabetes to control blood sugar. It slows down the movement of food through your stomach. This affects how fast sugar enters your blood after eating. Pramlintide is always used with insulin to help lower blood sugar during the 3 hours after meals. Even when pramlintide is carefully added to your mealtime insulin therapy, your blood sugar may drop too low, especially if you have Type 1 diabetes. If this low blood sugar (severe hypoglycemia) happens, it is generally seen within 3 hours after a pramlintide injection. Severe low blood sugar makes it hard to think clearly, drive a car, use heavy machinery or do other risky activities where you could hurt yourself or others. Pramlintide should only be used by people with type 1 or type 2 diabetes who already use their insulin as prescribed but still need better blood sugar control. Never mix pramlintide and insulin. You must use different syringes for pramlintide and insulin because insulin can affect pramlintide when the two are mixed together. Brand Name Symlin Generic Name pramlintide