Effectiveness Of Anti Diabetic Drug Metformin Biology Essay

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Type 2 diabetes or non-insulin dependent diabetes mellitus usually develops in people over 40 years old so is also known as adult-onset diabetes. It is the most common form of diabetes where about 90% of diabetes patients are in this category. Type 2 diabetes is a metabolic disorder due to high blood sugar(glucose). The disease develops when body cells become resistant to insulin or the insulin secreted by the pancreas is not enough. Insulin moves blood glucose into body cells where the glucose is stored and later used for energy. Insulin resistance is a condition where body cell receptors are less sensitive to insulin and cannot use insulin effectively causing a build up of glucose in the blood and resulting in high blood glucose level. Exactly why this problem happens is not known, although obesity and inactivity seem to be one of the important factors. Since high blood sugar can cause a number of symptoms and health problems including a higher risk of heart attacks, strokes, amputations, and kidney failure, what are the treatments to protect the patients from these complications?

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Figure 1.0 : Pancreas, the organ that secretes insulin hormone.

Possible solution

Oral Anti-diabetic Drugs

The most suitable treatment for type 2 diabetes is not known but one of most effective treatment found to minimise the risks of long-term consequences of type 2 diabetes was anti-diabetic drugs. Aiming to control blood sugar level, they work either by :

increasing insulin levels in the body ,

increasing the body's sensitivity or dercreasing its resistance to insulin , or

decreasing glucose absorption in the intestines.

The drugs are divided into two types; the most commonly used drugs and new drugs. Thiazolidinediones, a-glucose inhibitors, and meglitinides are the new anti-diabetic drug groups discovered by scientists whereas sulphonylureas and biguanides are the most commonly used drug groups. Despite the presence of a wide range of drugs at present, biguanides and sulphonylureas are the most widely used drugs compared to the new drugs.

"A systematic review of randomized controlled trials found that metformin and second-generation sulfonylureas are the preferred choices for most with type 2 diabetes, especially those early in the course of the condition."

(http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2)

The oldest oral anti-diabetic drugs, Sulphonylurea such as glipizide, glyburide, and glimepiride are still prescribed today. They work by boosting the beta cells in the pancreas to produce more insulin and making the body cells more receptive towards insulin. Patients are either prescribed with sulphonylureas once or twice daily and are to be taken orally before meals. Starting with a low dose usually, which can be increased if necessary every few weeks until the patients get a good control over the body's blood sugar level. However, some drawbacks are sulphonylureas results in hypoglycemia if a good lifestyle is not maintained as it increases the level of insulin. It also causes weight gain hence it is not suitable for overweight people.

On the other hand, biguanides like metformin play the primary role of reducing the amount of glucose production by the liver. Metformin also increases the sensitivity of body cells to insulin and provokes an increase in cellular uptake of glucose in body cells. Patients are prescribed with an initial dose of 500mg twice daily or 850mg once daily. The maximum dose is 1g twice daily or 850mg three times daily. The dosage depends on the patients condition.

Diagram 2.0 : The chemical structure of metformin http://diabetesmanager.pbworks.com/f/1255202482/metformin.JPG

Between metformin and sulphonylureas, metformin has been found to be more effective in controlling blood glucose levels for a longer period compared to sulphonylureas. It remains as the first-line drug therapy for type 2 diabetes. Metformin does not induce increase in insulin production thus rarely causes hypoglycemia when taken as a monotherapy unlike sulphonylurea drugs. So, complications of the disease are lowered especially in overweight people.

However, since the drugs work differently with different mechanisms of action, some patients may be prescribed either with metformin as a monotherapy or together with sulphonylurea drugs or even sometimes with insulin injections. Anyway, patients should be examined by doctors to see which drug suits them best and the doctor should be told if a patient is under other medications to avoid complications with a combination of drugs taken by them.

Effectiveness of anti-diabetic drug metformin

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Of all the old and new drugs available for type 2 diabetes treatment, I have found metformin that can be the best solution currently. Studies as well as researches have found that metformin has been able to control blood glucose level and reduce or prevent type 2 diabetes complications for both obese and non-obese patients. It is also suitable for patients with heart failure unlike sulphonylureas which can increase the risk of heart attacks and congestive heart failures.

"Metformin does not promote weight gain and has beneficial effects on several cardiovascular risk factors. Accordingly, metformin is widely regarded as the drug of choice for most patients with type 2 diabetes."

(http://www.ncbi.nlm.nih.gov/pubmed/15669880)

To prove the effectiveness of metformin, i found evidence from an article: "Metformin vs. Sulfonylureas for Diabetes" by Salynn Boyles from WebMD Health News which was reviewed by Louise Chang, MD; date-December 4, 2009 which compared metformin and other drugs mainly with sulphonylurea drugs. Based on the article, single drug treatment with sulphonylureas was said to impose a higher risk of death compared to metformin. Second-generation sulphonylurea users also had a greater risk of congestive heart failure.

Below is the part of the findings from the research :

"Compared with metformin, single-drug treatments with first- or second-generation sulfonylureas was associated with a 24% to 61% increased risk for death from all causes.

Compared to metformin, second-generation sulfonylurea use was associated with an 18% to 30% increased risk for heart failure."

(http://www.medicinenet.com/script/main/art.asp?articlekey=109066)

The American Diabetes Association (ADA) shows the same trend in its latest recommendation like this data. Hence, the data is reliable and the authors of WebMD are medical officers or researchers who are well-versed with such health problems so can be depended upon.

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Figure 3.0 : A study showing that metformin is less risky than sulphonylureas but a combination is seen to be better. http://care.diabetesjournals.org/content/25/12/2244.full

Besides, the graph above also proves metformin is less dangerous than sulphonylureas. So, patients can consume it more safely.

Social and Ethical Implications

Social implications

Some patient with type 2 diabetes take do not take the disease seriously and refuse to take medications or treatment. They might have a wrong perception too where they think diabetes is related to consuming too much sugar so may just reduce food rich in sugar rather than taking their medications as advised by doctors. This leads to undesirable effect.

The drugs do work but also cause side effects to the patients. Besides having to cope with type 2 diabetes symptoms, they have to bare the side effects caused by anti-diabetic drugs. The drugs will reduce complications from the disease over time but some patients can suffer from problems like gastrointestinal intolerance. Thus, the patients may avoid taking

the medications as required.

Ethical implications

Using metformin for a long term or even taking higher doses has been related to vitamin B12 deficiency.

"....After adjusting for confounders, we found clinically important and statistically significant association of vitamin B12 deficiency with dose and duration of metformin use...."

(http://www.natap.org/2006/HIV/102606_10.htm)

After a long period, malabsorption of vitamin B12 can be a significant health risk. This is because vitamin B12 is essential for the proper growth and function of every cells in the body.

Moreover, metformin results in a more serious side-effect; lactic acidosis. It is a condition in the body where the blood pH falls creating an acidic environment. Lactic acidosis can build up gradually causing other symptoms and making the patients feel very ill. So, patient have to take additional different medications to treat this condition. Although it is a rare occasion, it has been seen to be fatal 50% of the time.

Benefits

Using metformin is cheaper and more effective compared to the new anti-diabetic drugs. As an ideal drug, it also promotes weight loss and reduces cardiovascular risk factors. As it does not cause increased insulin secretion but only increases insulin sensitivity, metformin is not associated with hypoglycemia. So, it is suitable for both obese and non-obese patients unlike sulphonylurea which causes weight gain and hypoglycemia. Furthermore, risks of death from all causes and risk of heart failure is lower in diabetes patient consuming metfromin oral therapy.

Risks

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Drugs can lead to adverse side-effects too. in the case using metformin, some patients face allergic reaction with the drug. If insufficient metformin is taken for proper blood sugar control, patients may face high blood sugar level with symptoms like confusion, dry mouth, and vomiting. There are side-effects, for instance gastrointestinal problems like nausea and diarrhea when its first prescribed. More serious side-effects are a drop in pulseand exertion as well as fever, flu, chills together with body aches. Besides, patients with heart failure,kidney or liver disease should not take this drug in fear of lactic acidosis. When consumed with other certain other drugs contributes to side-effects too.

"On the other hand medicines like beta-blockers, sulfa drugs, probenecid, tend to lower blood sugar levels if they are used with Metformin. Medicines like morphine, quinidine, furosemide and digoxin, tend to react with Metformin."

Many people are able control the side-effects of metformin by either taking it with meals as well as starting with small doses and raising the doses slowly whereas the rest fail to do so. So, patients should also inform their doctors if they are under other medications at the same time and only consume metformin as advised.

Alternative solutions

Duodenal Switch Surgery

An alternative for type 2 diabetes is duodenal switch surgery especially in owerweight patients. Type 2 diabetes is greatly related with obesity thus, this surgery can be a good choice of treatment too. Combined moderate intake restrictions with substantial calorie malabsorption is the benefit of this surgery. It is carried out in two stages :

Stage 1 : Restrictive stage

The stomach is modified, reshaping it into a long, narrow tube. About 70% of the stomach along the greater curvature is removed but the remaining stomach is not affected in its function. Anyway, the amount a patient can consume is restricted. However, over time, the stomach stretches allowing patients to comsume about 60% of what they did before the surgery. Unfortunately, this process is not reversible.

Stage 2 : Malabsorptive stage

A lengthy portion of the small intestine is rerouted. Two separate pathways and one common pathway is created. The digestive loop, the shorter of the two pathways carries food from stomach to large intestine whereas the bilio-pancreatic loop, the much longer pathway, transports bile from liver to the common path. The common path : a stretch of small intestine about 75-100 cm long, is where the contents of the digestive path mix with the bile from the bilio-pancreatic loop before moving into the large intestine. So, the small intestine is altered to decrease the amount of it can absorb.

Figure 2.0 : The anatomy after duodenal switch surgery

(http://www.duodenalswitch.com/procedure/procedure.html)

The metabolic effect from this surgery has been believed to be the reason for reduced needs of oral hypoglycemic agents or even insulin.

"Although this surgery is initially aimed as obesity treaments, the duodenal switch surgery procedure has seen the highest rate of type 2 diabetes cure. Type 2 diabetics have had a 98% "cure" almost immediately following surgery which is due to the metabolic effect from the intestine switch."

(http://www.dsfacts.com/benefits-of-duodenal-switch.html)

An article :Duodenal Bypass: Cure for Type 2 Diabetes? by Field Correspondent Nancy Wride on May 17, 2010 agrees with this surgery as a solution. However, it states that clinical trials are being done to find the reason why it ends up removing type 2 diabetes symptoms.

Unfortunately, this surgery is only a better choice for obese patients. Patients with normal Body Mass Index(BMI) are not suitable to opt for this surgery as it causes weight loss so will be less effective on them. But there is evidence to show that this surgery can be effective in patients who are slightly obese or overweight. As with any other surgeries, there are both short term as well as long term risks to be considered and this surgery is costly as it costs about $20,000 or more.

Nevertheless, I feel duodenal switch surgery should only be done when patients failed to respond to anti-diabetic drugs or even with insulin. Not to be ignored healthy eating and moderate exercise should be followed.

Lifestyle changes

A patient can usually reduce the blood glucose level by one of these changes to his lifestyle :

Eating a healthy balanced diet - Patients should eat a diet low in fat, calories but high in fibre with plenty of fruits and vegetables. They should limit their glucose intake. Meal plans should suit their daily lifestyle and habits. Eating a well-balanced diet are important.

2) Losing weight if you are overweight - If a patient is obese or overweight, losing weight can help reducing or controlling blood glucose level. Maintaining an ideal body weight has other health benefits also.

Doing some physical activity regularly - Patients are advised to do a minimum of 30 minutes' brisk walking at least five times a week because regular aerobic exercise lowers blood sugar level without medication and helps burn excess calories and fat so managing a patients weight. It alsodecreases insulin resistance even without weight loss.

No any single lifestyle changes is proven to be clearly effective when carried out alone. Doctors will usually advice patients to apply all these changes to their lifestlye to get a better control over their blood sugar level. Any other type of treatment is unlikely to help patients achieve long term control over the blood glucose level unless coupled with a healthy lifestlye. Both medications and surgery mentioned earlier, have to be followed with a healthy lifestyle practise to be trully helpful in avoiding the risks of type 2 diabetes. Patients should avoid unhealthy practises like smoking and alcohol consumptions too especially when they are under medications to avoid serious side effects.

Even though, complications of type 2 diabetes cannot be avoided completely from this method alone, I would still say that this is the cheapest and safest method. Patients also can prevent developing other health problems by following a healthy lifestyle.

Source evaluation

The website http://www.diabetes.org/ or known as the American Diabetes Association is aimed to give information relating to diabetes. It is a very trustable source and in my opinion the informations in this website are factual as it has various current issues related to diabetes and the current issues are based from real life situations. Officers in the management team have years of experience too. The informations based from this website are relevant with many other sources also. One of it is the WebMD :

(http://www.webmd.com/about-webmd-policies/default.htm?ss=ftr).

This web has a mixture of successful expertise in medicine, and health communication.

The book "Diabetes For Dummies" provides good information about diabetes. The disease is well explained with the proper solutions also according to the type of diabetes and the author is qualified highly. The facts in this book agree mostly with other books too like the book " Diabetes A practical guide to managing your health". For instance, it tells clearly about type 2 diabetes and its solutions. Both these books were published not long ago(2004) and the datas can be relied on.