New drugs that give hope to diabetic patients

Diabetes is a disease that can affect multiple system in the body. Since the prevalence of this disease in the community is very high and there is high chance to develop various complication if it is not controlled well lot of drug trial are going on this field. Newer drugs with different modes of action are tried to bring the blood sugar under control. Three such drugs are recently approved for treatment.

They are 

For people with type 2 diabetes drugs approved are 

1. Exenatide injection (Byetta)

2. Sitagliptin (Januvia)

3. Pramlintide acetate (Symlin)

For those with type 1 diabetes along with insulin Pramlintide acetate (Symlin) can be tried.

Why this drugs are useful in diabetes?

Insulin secretion from pancreas is stimulated by GLUCOSE. These newer drugs target the hormone incretin. Incretins potentiate this glucose stimulated insulin secretion from pancreas. As the insulin synthesizing and secreting action of GLP-1 is preserved in type 2 diabetic patients this has been developed as therapeutic agent for this disease. These are useful in treatment irrespective of the severity and duration of the disease. Diabetes is a chronic progressive disease sometime the agent that works for a period of time may become less effective and ,then we need to introduce new one.

Basic mechanism of action of these drugs.

Incretin are produced in the intestine in response to food intake. Incretin effect is mainly  mediated by two peptide hormones, they are glucose-dependent insulin releasing polypeptide(GIP), and glucagon-like peptide-1(GLP-1). Both GIP and GLP-1 are rapidly metabolized  into inactive metabolites by the action of  dipeptidyl-peptidase-IV (DPP-IV) enzyme. As the insulin synthesizing and secreting action of GLP-1 is preserved in type 2 diabetic  patients this has been developed as therapeutic agent. These are useful in treatment irrespective of the severity and duration of the disease. Thus the modulation of GLP-1 levels and GLP-1 activity by administration of the native hormone, its analogs, and mimetics or the agents that inhibit its degradation has become the chief focus of investigation for type 2 diabetes  treatment.

Advantage of this drugs in diabetes.

1. They enhance the insulin secretion.In addition to its effects on insulin secretion, GLP-1.

2. Stimulate the insulin synthesis.

3. Inhibit  the glucagon secretion ,glucagons increases the blood sugar.

4. Delays the  gastric emptying thus reduces the sugar. 

5. Reduction of food intake.

6. It has trophic effects on the pancreas. Stimulate betacell proliferation.

Drugs act on GLP1 receptor are

1. Exenatide injection (Byetta)

Indicated in those people with type 2 DM whose blood sugar fails to bring under control with oral drugs. They helps to control the blood sugar by mimicking the insulin action and slowing stomach emptying. Since the patient feel full faster and stop eating these agents will help to reduce weight. This is given as injection 2 times a day at mealtime. Special advantage of this drug is it help to reduce weight and wont produce hypoglycemia. But there is risk of hypoglycemia if taken with other agents that enhance the insulin secretion. Side effect of this drugs are nausea, inflammation of pancreas, risk of kidney disease. Exenatide should not be used in people with kidney disease. Approved for either as single therapeutic agent or in combination with other drugs. To minimize the initial side effect treatment started at lower doses, dose limiting side effect is nausea that is tendency to vomit. Exenatide extended release (Bydureon) advantage of this extended release formulations is it require injection only once a week. Action and side effects are similar to Byetta.

2. Liraglutide (Victora)

Liraglutide is other GLP 1 agonist it is injected once a day. Not used in those people with family history of medullary type of thyroid cancer.

3. Amylin agonist

Pramlintide acetate (Symlin)

Pramlintide acetate is useful for those with type 1 or type 2 diabetes who are on insulin. This is injected at mealtime,it should not be mixed with insulin in same syringe. Advantage of this drug is that it helps to achieve better control of blood sugar, mainly reduce the blood sugar spike after meals. Weight reduction is other added advantage of this drug. This is injected at mealtime. Unwanted side effects is hypoglycemia if used with insulin.

4. DPP-IV inhibitors

Sitagliptin (Januvia), saxagliptin (Onglyza), and linagliptin (Tradjenta)

All are orally active drugs taken once a day, indicated in type 2 DM, they may be combined with metformin. They wont promote weight loss. Associated with only few unwanted effects. Used with precaution in patients with kidney disease. They act by protecting the breakdown of incretin, so incretins are available for long duration for insulin stimulation.

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Why insulin is given in diabetes?

Diabetes is a state of insulin deficiency. In adult diabetes is treated with either oral anti diabetic tablets or with insulin. 

Insulin has got the following advantages

1. To stop the severe catabolic state & regain lean body mass.

2. Decreases frequent infections.

3. Reduce  fetal & maternal complications  in pregnancy.

4. Prevent & delay complications of diabetes.

5. Eliminate symptoms of hypoglycemia.

6. Prevent DKA(diabetic ketoacidosis).

Principles of insulin therapy

1. To supply  sufficient insulin throughout 24 h to cover the  basal requirements

2. To provide higher boluses of insulin to match the high glucose levels  following meals .

Treatment strategies

Appropriate insulin regimen is planned based on

1. Patient’s lifestyle.

2. Age.

3. Motivation.

4. General health.

5. Self management skills.

6. Goals of treatment.
Before initiating insulin patient should be given appropriate education & support about the care & use of insulin, detection & management of  hypoglycemia.

Treatment strategies in type 1

1. Multiple Daily Injections.

2. Twice daily injections are not recommended in Type 1 DM.

3. Complementary education & support.

4. Most newly diagnosed patients with type 1 diabetes may be started on a total daily dose of 0.2 to .0.4 u/ kg / day, most will ultimately require 0.6 to 0.7 u/ kg / day.

6. During puberty > 1 IU/kg per day insulin is given

Type 2 DM (Diabetes mellitus) 

1. Initial management does not include insulin.

2. Given for patients unable to achieve good blood sugar  control with a combination of diet, exercise and OHA.

3. Goals of insulin treatment is  similar to Type1 DM

Achronym's used
DM - Diabetes mellitus.
IU/kg - Units of Drug per Kilogram of body weight.
OHA - oral hypoglycemic agents.
DKA - diabetic ketoacidosis.

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Insulin use - Practical points

Diabetes mellitus is a progressive, metabolic disorder where there are disturbances in carbohydrate, lipid and protein metabolism. It results from insulin deficiency and / or insulin resistance. As the global burden of diabetes is increasing number of patients on insulin also increases. All those who are on insulin must know the following practical points.

Storage of insulin

1. Stored in a cool and dark place, otherwise their potency is lost (Temperature dependent).
2. Do not keep in a freezer compartment. 
3. The vial in current use can be easily kept at room temperature in a dark place without losing any potency. 
4. Cold insulin if injected is painful.

Insulin injection sites

• Absorption of insulin shows regional difference
  Absorption of insulin is maximum from abdominal region followed by upper outer arms, buttocks and upper outer thighs.
• Abdominal region > upper outer arm and buttocks > upper outer thighs
• The site of injection should be rotated within the same area.
• Depth of injection – subcutaneous with insulin syringe.
• Intravenous injection (direct injection into vein), Intravenous infusion , or Intramuscular routes (direct injection into muscle ) are used only during, emergency such as  ketoacidosis or stressful conditions.
• Same site is used for at least one month and rotation is done within the same site rather than rotating to different sites.
• Using same site decreases variability in day to day absorption. 
• Rotation within the same area prevents lipodystrophy.
• Avoid a site with open wounds or blisters.

Injection technique

• If site is clean, there is no need to clean the site with alcohol or spirit. 
• In thin or averagely built person, lift or grasp a fold of skin between thumb and index finger and inject at 45° or 90°.
• In obese person, full length injection at 90° is recommended.
• Mixing – usually available as premixed form.
• Regular insulin can be mixed with all other preparations.
• Insulin glargine should not be mixed with other insulin.

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