Diabetes its tyes and treatment

Diabetes is a disorder of metabolism—the way our bodies use digested food for growth and energy. Most of the food we eat is broken down into glucose, the form of sugar in the blood. Glucose is the main source of fuel for the body.
After digestion, glucose passes into the bloodstream, where it is used by cells for growth and energy. For glucose to get into cells, insulin must be present. Insulin is a hormone produced by the pancreas, a large gland behind the stomach.
When we eat, the pancreas automatically produces the right amount of insulin to move glucose from blood into our cells. In people with diabetes, however, the pancreas either produces little or no insulin, or the cells do not respond appropriately to the insulin that is produced. Glucose builds up in the blood, overflows into the urine, and passes out of the body in the urine. Thus, the body loses its main source of fuel even though the blood contains large amounts of glucose.



What are the types of diabetes? The three main types of diabetes are

type 1 diabetes
type 2 diabetes
gestational diabetes
Type 1 Diabetes Type 1 diabetes is an autoimmune disease. An autoimmune disease results when the body’s system for fighting infection (the immune system) turns against a part of the body. In diabetes, the immune system attacks and destroys the insulin-producing beta cells in the pancreas. The pancreas then produces little or no insulin. A person who has type 1 diabetes must take insulin daily to live.
At present, scientists do not know exactly what causes the body’s immune system to attack the beta cells, but they believe that autoimmune, genetic, and environmental factors, possibly viruses, are involved. Type 1 diabetes accounts for about 5 to 10 percent of diagnosed diabetes in the United States. It develops most often in children and young adults but can appear at any age.
Symptoms of type 1 diabetes usually develop over a short period, although beta cell destruction can begin years earlier. Symptoms may include increased thirst and urination, constant hunger, weight loss, blurred vision, and extreme fatigue. If not diagnosed and treated with insulin, a person with type 1 diabetes can lapse into a life-threatening diabetic coma, also known as diabetic ketoacidosis.

Type 2 Diabetes The most common form of diabetes is type 2 diabetes. About 90 to 95 percent of people with diabetes have type 2. This form of diabetes is most often associated with older age, obesity, family history of diabetes, previous history of gestational diabetes, physical inactivity, and certain ethnicities. About 80 percent of people with type 2 diabetes are overweight.
Type 2 diabetes is increasingly being diagnosed in children and adolescents. However, nationally representative data on prevalence of type 2 diabetes in youth are not available.
When type 2 diabetes is diagnosed, the pancreas is usually producing enough insulin, but for unknown reasons the body cannot use the insulin effectively, a condition called insulin resistance. After several years, insulin production decreases. The result is the same as for type 1 diabetes—glucose builds up in the blood and the body cannot make efficient use of its main source of fuel.
The symptoms of type 2 diabetes develop gradually. Their onset is not as sudden as in type 1 diabetes. Symptoms may include fatigue, frequent urination, increased thirst and hunger, weight loss, blurred vision, and slow healing of wounds or sores. Some people have no symptoms.

Gestational Diabetes Some women develop gestational diabetes late in pregnancy. Although this form of diabetes usually disappears after the birth of the baby, women who have had gestational diabetes have a 20 to 50 percent chance of developing type 2 diabetes within 5 to 10 years. Maintaining a reasonable body weight and being physically active may help prevent development of type 2 diabetes.
About 3 to 8 percent of pregnant women in the United States develop gestational diabetes. As with type 2 diabetes, gestational diabetes occurs more often in some ethnic groups and among women with a family history of diabetes. Gestational diabetes is caused by the hormones of pregnancy or a shortage of insulin. Women with gestational diabetes may not experience any symptoms.

How is diabetes diagnosed? The fasting blood glucose test is the preferred test for diagnosing diabetes in children and nonpregnant adults. It is most reliable when done in the morning. However, a diagnosis of diabetes can be made based on any of the following test results, confirmed by retesting on a different day:

A blood glucose level of 126 milligrams per deciliter (mg/dL) or more after an 8-hour fast. This test is called the fasting blood glucose test.


A blood glucose level of 200 mg/dL or more 2 hours after drinking a beverage containing 75 grams of glucose dissolved in water. This test is called the oral glucose tolerance test (OGTT).


A random (taken at any time of day) blood glucose level of 200 mg/dL or more, along with the presence of diabetes symptoms.

Gestational diabetes is diagnosed based on blood glucose levels measured during the OGTT. Glucose levels are normally lower during pregnancy, so the cutoff levels for diagnosis of diabetes in pregnancy are lower. Blood glucose levels are measured before a woman drinks a beverage containing glucose. Then levels are checked 1, 2, and 3 hours afterward. If a woman has two blood glucose levels meeting or exceeding any of the following numbers, she has gestational diabetes: a fasting blood glucose level of 95 mg/dL, a 1-hour level of 180 mg/dL, a 2-hour level of 155 mg/dL, or a 3-hour level of 140 mg/dL.

What is pre-diabetes? People with pre-diabetes have blood glucose levels that are higher than normal but not high enough for a diagnosis of diabetes. This condition raises the risk of developing type 2 diabetes, heart disease, and stroke.
Pre-diabetes is also called impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), depending on the test used to diagnose it. Some people have both IFG and IGT.

IFG is a condition in which the blood glucose level is high (100 to 125 mg/dL) after an overnight fast, but is not high enough to be classified as diabetes. (The former definition of IFG was 110 mg/dL to 125 mg/dL.)


IGT is a condition in which the blood glucose level is high (140 to 199 mg/dL) after a 2-hour oral glucose tolerance test, but is not high enough to be classified as diabetes. Pre-diabetes is becoming more common in the United States, according to new estimates provided by the U.S. Department of Health and Human Services. About 40 percent of U.S. adults ages 40 to 74—or 41 million people—had pre-diabetes in 2000. New data suggest that at least 54 million U.S. adults had pre-diabetes in 2002. Many people with pre-diabetes go on to develop type 2 diabetes within 10 years.
The good news is that if you have pre-diabetes, you can do a lot to prevent or delay diabetes. Studies have clearly shown that you can lower your risk of developing diabetes by losing 5 to 7 percent of your body weight through diet and increased physical activity. A major study of more than 3,000 people with IGT, a form of pre-diabetes, found that diet and exercise resulting in a 5 to 7 percent weight loss—about 10 to 14 pounds in a person who weighs 200 pounds—lowered the incidence of type 2 diabetes by nearly 60 percent. Study participants lost weight by cutting fat and calories in their diet and by exercising (most chose walking) at least 30 minutes a day, 5 days a week.

What are the scope and impact of diabetes? Diabetes is widely recognized as one of the leading causes of death and disability in the United States. In 2002, it was the sixth leading cause of death. However, diabetes is likely to be underreported as the underlying cause of death on death certificates. About 65 percent of deaths among those with diabetes are attributed to heart disease and stroke.
Diabetes is associated with long-term complications that affect almost every part of the body. The disease often leads to blindness, heart and blood vessel disease, stroke, kidney failure, amputations, and nerve damage. Uncontrolled diabetes can complicate pregnancy, and birth defects are more common in babies born to women with diabetes.
In 2002, diabetes cost the United States $132 billion. Indirect costs, including disability payments, time lost from work, and premature death, totaled $40 billion; direct medical costs for diabetes care, including hospitalizations, medical care, and treatment supplies, totaled $92 billion.

Who gets diabetes? Diabetes is not contagious. People cannot “catch” it from each other. However, certain factors can increase the risk of developing diabetes.
Type 1 diabetes occurs equally among males and females but is more common in whites than in non-whites. Data from the World Health Organization’s Multinational Project for Childhood Diabetes indicate that type 1 diabetes is rare in most African, American Indian, and Asian populations. However, some northern European countries, including Finland and Sweden, have high rates of type 1 diabetes. The reasons for these differences are unknown. Type 1 diabetes develops most often in children but can occur at any age.
Type 2 diabetes is more common in older people, especially in people who are overweight, and occurs more often in African Americans, American Indians, some Asian Americans, Native Hawaiians and other Pacific Islander Americans, and Hispanics/Latinos. On average, non-Hispanic African Americans are 1.8 times as likely to have diabetes as non-Hispanic whites of the same age. Mexican Americans are 1.7 times as likely to have diabetes as non-Hispanic whites of similar age. (Data are not available for estimation of diabetes rates in other Hispanic/Latino groups.) American Indians have one of the highest rates of diabetes in the world. On average, American Indians and Alaska Natives are 2.2 times as likely to have diabetes as non-Hispanic whites of similar age. Although prevalence data for diabetes among Asian Americans and Pacific Islanders are limited, some groups, such as Native Hawaiians, Asians, and other Pacific Islanders residing in Hawaii (aged 20 or older) are more than twice as likely to have diabetes as white residents of Hawaii of similar age.
Diabetes prevalence in the United States is likely to increase for several reasons. First, a large segment of the population is aging. Also, Hispanics/Latinos and other minority groups at increased risk make up the fastest-growing segment of the U.S. population. Finally, Americans are increasingly overweight and sedentary. According to recent estimates from the Centers for Disease Control and Prevention (CDC), diabetes will affect one in three people born in 2000 in the United States. The CDC also projects the prevalence of diagnosed diabetes in the United States will increase 165 percent by 2050.


How is diabetes managed? Before the discovery of insulin in 1921, everyone with type 1 diabetes died within a few years after diagnosis. Although insulin is not considered a cure, its discovery was the first major breakthrough in diabetes treatment.
Today, healthy eating, physical activity, and taking insulin are the basic therapies for type 1 diabetes. The amount of insulin must be balanced with food intake and daily activities. Blood glucose levels must be closely monitored through frequent blood glucose checking. People with diabetes also monitor blood glucose levels several times a year with a laboratory test called the A1C. Results of the A1C test reflect average blood glucose over a 2- to 3-month period.
Healthy eating, physical activity, and blood glucose testing are the basic management tools for type 2 diabetes. In addition, many people with type 2 diabetes require oral medication, insulin, or both to control their blood glucose levels.
Adults with diabetes are at high risk for cardiovascular disease (CVD). In fact, at least 65 percent of those with diabetes die from heart disease or stroke. Managing diabetes is more than keeping blood glucose levels under control—it is also important to manage blood pressure and cholesterol levels through healthy eating, physical activity, and use of medications (if needed). By doing so, those with diabetes can lower their risk. Aspirin therapy, if recommended by the health care team, and smoking cessation can also help lower risk.
People with diabetes must take responsibility for their day-to-day care. Much of the daily care involves keeping blood glucose levels from going too low or too high. When blood glucose levels drop too low—a condition known as hypoglycemia—a person can become nervous, shaky, and confused. Judgment can be impaired, and if blood glucose falls too low, fainting can occur.
A person can also become ill if blood glucose levels rise too high, a condition known as hyperglycemia.
People with diabetes should see a health care provider who will help them learn to manage their diabetes and who will monitor their diabetes control. Most people with diabetes get care from primary care physicians—internists, family practice doctors, or pediatricians. Often, having a team of providers can improve diabetes care. A team can include

a primary care provider such as an internist, a family practice doctor, or a pediatrician


an endocrinologist (a specialist in diabetes care)


a dietitian, a nurse, and other health care providers who are certified diabetes educators—experts in providing information about managing diabetes


a podiatrist (for foot care)


an ophthalmologist or an optometrist (for eye care) and other health care providers, such as cardiologists and other specialists. In addition, the team for a pregnant woman with type 1, type 2, or gestational diabetes should include an obstetrician who specializes in caring for women with diabetes. The team can also include a pediatrician or a neonatologist with experience taking care of babies born to women with diabetes.
The goal of diabetes management is to keep levels of blood glucose, blood pressure, and cholesterol as close to the normal range as safely possible. A major study, the Diabetes Control and Complications Trial (DCCT), sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), showed that keeping blood glucose levels close to normal reduces the risk of developing major complications of type 1 diabetes.
This 10-year study, completed in 1993, included 1,441 people with type 1 diabetes. The study compared the effect of two treatment approaches—intensive management and standard management—on the development and progression of eye, kidney, nerve, and cardiovascular complications of diabetes. Intensive treatment aimed to keep A1C levels as close to normal (6 percent) as possible. Researchers found that study participants who maintained lower levels of blood glucose through intensive management had significantly lower rates of these complications. More recently, a follow-up study of DCCT participants showed that the ability of intensive control to lower the complications of diabetes has persisted more than 10 years after the trial ended.
The United Kingdom Prospective Diabetes Study, a European study completed in 1998, showed that intensive control of blood glucose and blood pressure reduced the risk of blindness, kidney disease, stroke, and heart attack in people with type 2 diabetes.


Type 1 Diabetes A number of Federally-funded research studies and clinical trials are under way. Studies focus on the prevention and causes of type 1 diabetes as well as experimental treatments such as islet transplantation.
The Environmental Determinants of Diabetes in the Young Consortium
The main mission of The Environmental Determinants of Diabetes in the Young (TEDDY) consortium, an international group of clinical centers, is to identify infectious agents, dietary factors, or other environmental factors (including psychosocial events) that trigger type 1 diabetes in those who are genetically susceptible. In addition, the consortium aims to

create a central repository of data and biological samples for use by researchers


develop novel approaches to finding the causes of type 1 diabetes


find ways to understand how the disease starts and progresses


discover new methods to prevent, delay, and reverse type 1 diabetes TEDDY is funded by the NIDDK, the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Environmental Health Sciences, the CDC, the JDRF, and the ADA. For more information


Type 2 Diabetes Diabetes Prevention Program
In 1996, NIDDK launched its Diabetes Prevention Program (DPP). The goal of this research effort was to learn how to prevent or delay type 2 diabetes in people with impaired glucose tolerance (IGT), a strong risk factor for type 2 diabetes.
The findings of the DPP, released in August 2001, showed that people at high risk for type 2 diabetes could sharply lower their chances of developing the disorder through diet and exercise. In addition, treatment with the oral diabetes drug metformin also reduced diabetes risk, though less dramatically. Metformin lowers the amount of glucose released by the liver and also fights insulin resistance, a condition in which the body doesn't use insulin properly.
Participants randomly assigned to intensive lifestyle intervention reduced their risk of getting type 2 diabetes by almost 60 percent. On average, this group maintained their physical activity at 30 minutes per day, usually with walking or other moderate intensity exercise, and lost 5 to 7 percent of their body weight. Participants randomized to treatment with metformin reduced their risk of getting type 2 diabetes by 31 percent.
Of the 3,234 participants enrolled in the DPP, 45 percent were from minority groups that suffer disproportionately from type 2 diabetes: African Americans, Hispanics/Latinos, Asian Americans and Pacific Islanders, and American Indians. The trial also recruited other groups known to be at higher risk for type 2 diabetes, including individuals aged 60 and older, women with a history of gestational diabetes, and people with a first-degree relative with type 2 diabetes. Participants are being followed to check for long-term effects of the interventions, including the effects on risk of CVD.
Type 2 Diabetes in Children and Teens
Two studies focusing on type 2 diabetes in children and teens are under way. The TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) study, a 13-site study sponsored by NIDDK, will compare treatments for type 2 diabetes in children and teens. Participants will undergo one of three treatments:

taking one diabetes medication (metformin)


taking two diabetes medications (metformin and rosiglitazone, another medication that fights insulin resistance)


taking metformin and participating in an intensive lifestyle change program designed to promote weight loss by cutting calories and increasing physical activity The main goal of the study is to determine how well each type of treatment controls blood glucose levels. The study also will evaluate how long each type of treatment is effective.
The STOPP-T2D (Studies to Treat or Prevent Pediatric Type 2 Diabetes) study, sponsored by NIDDK with support from the ADA, is exploring methods to lower risk factors for type 2 diabetes and CVD in middle-school children (grades 6 through 8) at eight sites. A 3-year program will focus on the benefits of improving nutrition, promoting physical activity, and making changes in behavior.
Preventing and Treating CVD in People with Type 2 Diabetes
CVD is the main killer of people with type 2 diabetes. For this reason, the NIH is studying the best strategies to prevent and treat CVD in people with diabetes in three major studies. These studies are all joint efforts of the NIDDK and the National Heart, Lung, and Blood Institute.
The Look AHEAD (Action for Health in Diabetes) trial is the largest clinical trial to date to examine the long-term health effects of voluntary weight loss. This multi-center, randomized clinical trial is studying the effects of a lifestyle intervention designed to achieve and maintain weight loss over the long term through decreased caloric intake and increased exercise. Look AHEAD will focus on the disorder most associated with being overweight or obese, type 2 diabetes, and on the outcome that causes the greatest morbidity and mortality in people with type 2 diabetes, CVD.
The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, a multi-center, randomized trial, is studying three approaches to preventing major cardiovascular events in individuals with type 2 diabetes. ACCORD is designed to compare current practice guidelines with more intensive glycemic control in 10,000 individuals with type 2 diabetes, including those at especially high risk for CVD events because of age, evidence of subclinical atherosclerosis, or existing clinical CVD. More intensive control of blood pressure than is called for in current guidelines and a medication to reduce triglyceride levels and raise HDL (good) cholesterol levels will also be studied in subgroups of these 10,000 volunteers. Each treatment strategy will be accompanied by standard advice regarding lifestyle choices, including diet, physical activity, and smoking cessation, appropriate for individuals with diabetes.
The primary outcome to be measured is the first occurrence of a major CVD event, specifically heart attack, stroke, or cardiovascular death. In addition, the study will investigate the impact of the treatment strategies on other cardiovascular outcomes; total mortality; limb amputation; eye, kidney, or nerve disease; health-related quality of life; and cost-effectiveness.
The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, a 5-year, multi-center clinical trial, is comparing medical versus early surgical management of patients with type 2 diabetes who also have coronary artery disease and stable angina or ischemia. At the same time, BARI 2D will study the effect of two different strategies to control blood glucose—providing insulin versus increasing the sensitivity of the body to insulin—on the risk of cardiovascular mortality and morbidity.



What is the treatment for diabetes?


The major goal in treating diabetes is to minimize any elevation of blood sugar (glucose) without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with insulin,exercise, and a diabetic diet. Type 2 diabetes is treated first with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, treatment with insulin is considered.


Adherence to a diabetic diet is an important aspect of controlling elevated blood sugar in patients with diabetes. The American Diabetes Association (ADA) has provided guidelines for a diabetic diet. The ADA diet is a balanced, nutritious diet that is low in fat, cholesterol, and simple sugars. The total daily calories are evenly divided into three meals. In the past two years, the ADA has lifted the absolute ban on simple sugars. Small amounts of simple sugars are allowed when consumed with a complex meal.


Weight reduction and exercise are important treatments for diabetes. Weight reduction and exercise increase the body's sensitivity to insulin, thus helping to control blood sugar elevations.




Medications for type 2 diabetes


WARNING: All the information below applies to patients who are not pregnant or breastfeeding. At present the only recommended way of controlling diabetes in women who are pregnant or breastfeeding is by diet, exercise and insulin therapy. You should speak with your doctor if you are taking these medications and are considering becoming pregnant or if you have become pregnant while taking these medications.


Based on what is known, medications for type 2 diabetes are designed to:
increase the insulin output by the pancreas,
decrease the amount of glucose released from the liver,
increase the sensitivity (response) of cells to insulin,
decrease the absorption of carbohydrates from the intestine, and
slow emptying of the stomach to delay the presentation of carbohydrates for digestion and absorption in the small intestine.


When selecting therapy for type 2 diabetes, consideration should be given to:
the magnitude of change in blood sugar control that each medication will provide;
other coexisting medical conditions (high blood pressure, high cholesterol, etc.);
adverse effects of the therapy;
contraindications to therapy;
issues that may affect compliance (timing of medication, frequency of dosing); and
cost to the patient and the health care system.


It's important to remember that if a drug can provide more than one benefit (lower blood sugar and have a beneficial effect on cholesterol, for example), it should be preferred. It's also important to bear in mind that the cost of drug therapy is relatively small compared to the cost of managing the long-term complications associated with poorly controlled diabetes.


Varying combinations of medications also are used to correct abnormally elevated levels of blood glucose in diabetes. As the list of medications continues to expand, treatment options for type 2 diabetes can be better tailored to meet an individuals needs. Not every patient with type 2 diabetes will benefit from every drug, and not every drug is suitable for each patient. Patients with type 2 diabetes should work closely with their physicians to achieve an approach that provides the greatest benefits while minimizing risks.


Patients with diabetes should never forget the importance of diet and exercise. The control of diabetes starts with a healthy lifestyle regardless of what medications are being used.







Drugs used in diabetes


It should be remembered that control of modifiable cardiovascular risk factors such as lipids and blood pressure are the most important interventions to be made in patients with type II diabetes.


Healthy eating should be tried first, and drug therapy added if glycaemic control is unsatisfactory after a 3 month trial of dietary restrictions and an increase in physical activity.






Dual Therapy


For patients who have not reached HbA1c <6.5% (or their agreed target) on metformin monotherapy, add in a sulphonylurea as the standard second line agent. Consider a gliptin (or a glitazone) to metformin if hypoglycaemia on a sulfonylurea is a potential problem, or if a sulphonylurea is not tolerated or contraindicated. A gliptin may be preferable to a glitazone in patients where further weight gain would be problematic, or where a glitazone is contraindicated (e.g. heart failure), not tolerated/effective. Continue either only if 0.7% reduction in HbA1c in 6 months.






Triple Therapy


For patients who have not reached HbA1c <7.5% (or their agreed target) on metformin and a sulphonylurea, consider adding a gliptin (or a glitazone). If human insulin likely to be unacceptable or ineffective (because of employment (e.g. HGV drivers), social, recreational or other personal issues, or obesity/metabolic syndrome) consider use of GLP-1 receptor agonist. Continue only if 0.7% reduction in HbA1c in 6 months. Sitagliptin is the only gliptin licensed for use in a triple combination.










6.1.1 Insulins






Patients starting on insulin should receive an insulin passport. For full details click here






6.1.1.1 Short-acting insulins






GREEN Human Actrapid®


GREEN Humulin S®





The insulin analogues have a faster onset and shorter duration of action than standard soluble insulin. They should be injected immediately before or, when necessary, shortly after a meal.





GREEN Humalog® (insulin lispro)


GREEN NovoRapid®(insulin aspart)


GREEN Apidra® (insulin glulisine) – see new drug review online - click here to acces it.








6.1.1.2 Intermediate and long-acting insulins





Intermediate


GREEN Insulatard®


GREEN Humulin I®





Long acting


Long-acting recombinant human insulin analogues should be used in accordance with NICE guidance.






GREEN Lantus® (insulin glargine)


GREEN Levemir®(insulin detemir)





Biphasic


GREEN Mixtard 30® -


GREEN Humulin M3®


GREEN Insuman Comb 25®






GREEN Humalog Mix25®, Humalog Mix50® (insulin lispro)


GREEN NovoMix 30®


Biphasic analogue insulins (e.g. Novomix, Humalog Mix) do not offer any advantage over conventional human biphasic insulins in terms of efficacy, long term outcomes or safety but cost considerably more.






The above brands of insulin are recommended for new diabetics and are available in a variety of vial, cartridge and pre-loaded pen presentations. The hospital pharmacy will keep stocks of other brands and species for established diabetics. Insulin is usually available in 3mL cartridges, 10mL vials, and 3mL disposable pens. Not all insulin cartridges fit all pens. Pens are available on prescription except OptiPen® and HumaPen®.














6.1.2 Oral antidiabetic drugs






6.1.2.1 Sulphonylureas


Act by augmenting insulin secretion. For patients who have not reached HbA1c <6.5% (or their agreed target) on metformin monotherapy, add in a sulphonylurea as the standard second line agent. Re-assess patients after 2-6 months on first line therapy, including checking concordance with therapy and asking about adverse effects. Reinforce lifestyle measures, especially weight loss.






However, sulphonylureas can also be used first line in the following situations:


the person is not overweight or


the person does not tolerate metformin (or it is contraindicated) or


a rapid response to therapy is required because of hyperglycaemic symptoms.






Prescribe a sulfonylurea with a low acquisition cost (not glibenclamide) when an sulphonylurea is indicated. When drug concordance is a problem, offer a once-daily, long-acting sulfonylurea such as glimepiride. Avoid long acting products in those at risk of severe hypoglycaemia (e.g. elderly). Educate the person about the risk of hypoglycaemia, particularly if he or she has renal impairment. Sulphonylureas can cause weight gain.






Glibenclamide and chlorpropamide are specifically not recommended and should not be used due to the greater risk of hypoglycaemia, especially in the elderly.





GREEN Gliclazide tablets 80mg


GREEN Glimepiride tablets 1mg, 2mg, 4mg


GREEN Tolbutamide tablets 500mg





6.1.2.2 Biguanides


For patients who have not reached HbA1c <6.5% (or their own target) with lifestyle interventions, use metformin as the first line choice, whether patients are overweight/obese or are not, unless contraindicated or not tolerated. Patients frequently report gastrointestinal (GI) side effects such as diarrhoea or nausea when initiated on any formulation of metformin. Such adverse effects are often transient, and can be minimised by slow dose titration.






Dose: Step up metformin over several weeks to minimise risk of gastrointestinal (GI) side effects. Give 500 mg with evening meal for at least 1 week then 500 mg with breakfast and evening meal for at least 1 week then 500 mg with breakfast and 1 gram with evening meal; usual max. 2 g daily in two divided doses






The benefits of metformin therapy should be discussed with a person with mild to moderate liver dysfunction or cardiac impairment so that:
due consideration can be given to the cardiovascular-protective effects of the drug
an informed decision can be made on whether to continue, reduce the dose or stop the metformin.






GREEN Metformin tablets 500mg, 850mg


GREEN Metformin sachets 500mg, 1000mg






Review metformin dose when serum creatinine >130 micromol/litre or eGFR <45 ml/min/1.73 m2.


Stop metformin if serum creatinine >150 micromol/litre or eGFR <30 ml/min/1.73 m2.


Prescribe metformin with caution in those at risk of sudden deterioration of kidney function, or at risk of a decline of eGFR to <45 ml/min/1.73 m2.






Meformin Sustained Release (SR) Tablets


In patients in whom slow dose titration does not reduce GI adverse effects, metformin sustained release tablets should be used ONLY where intolerance to the immediate release preparation had been clearly documented and where it prevents continuation of metformin therapy. A review of the evidence on the use of sustained release metformin preparations did not find that their use in unselected patients reduced gastro-intestinal side effects.






Metformin sustained release tablets are supported purely as an attempt to ensure the largest number of patients are able to stay on metformin therapy, hopefully delaying progression to other new drugs which often have a reduced evidence base and/or additional safety concerns.






GREEN Metformin sustained release (SR) tablets 500mg, 750mg, 1000mg





6.1.2.3 Other antidiabetic drugs






Repaglinide & Nateglinide


Repaglinide and nateglinide stimulate insulin release. They have a rapid onset of action and short duration of activity, and only need to be taken at mealtimes (shortly before each main meal). This makes them particularly useful alternatives to sulphonylureas for patients with irregular meal patterns or lifestyles (where hypoglycaemia would otherwise pose a risk).






Repaglinide may be given as monotherapy for patients who are not overweight or for those in whom metformin is contra-indicated or not tolerated, or it may be given in combination with metformin.






GREEN Nateglinide tablets 60mg, 120mg, 180mg


GREEN Repaglinide tablets 1mg, 2mg










Thiazolidinediones (Glitazones)





Dual Therapy


For patients who have not reached HbA1c <6.5% (or their agreed target) on metformin monotherapy, add in a sulphonylurea as the standard second line agent. Consider pioglitazone or a gliptin to metformin if hypoglycaemia or a sulphonylurea is a potential problem, or if a sulphonylurea is not tolerated or is contraindicated. Pioglitazone may be preferable to a gliptin in patients with evidence of metabolic syndrome, or where a gliptin is contraindicated (e.g. renal impairment), not tolerated/effective. Continue only if 0.7% reduction in HbA1c achieved in 6 months.






Triple Therapy


For patients who have not reached HbA1c <7.5% (or thier agreed target) on metformin and a sulphonylurea, consider adding pioglitazone (or a gliptin) if human insulin is likely to be unacceptable or ineffective (because of employment [e.g. HGV drivers], social/recreational or other personal issues, or obesity/metabolic syndrome). Continue only if 0.7% reduction in HbA1c achieved in 6 months.






In combination with insulin


Consider pioglitazone in combination with insulin if a glitazone has been effective previously or high-dose insulin is providing inadequate control. Consider continuing pioglitazone when starting insulin therapy when a reduction in HbA1c of >1.5% previously seen with pioglitazone. This should be done only under specialist supervision. Combining pioglitazone with insulin significantly increases the risk of heart failure. Warn the patient to discontinue pioglitazone if clinically significant fluid retention occurs, or heart failure develops.






Glitazone Safety Concerns


Pioglitazone causes weight gain and increases the risk of heart failure (especially in combination with insulin). It may also worsen existing heart failure. Do not start or continue pioglitazone if the patient has current evidence or a history or heart failure, or is at a higher risk of fracture. If prescribing pioglitazone, warn about significant oedema and tell the patient what to do if this happens. Patients should be closely monitored for signs of heart failure.






There are no restrictions on the use of pioglitazone in acute coronary syndrome, ischaemic heart disease or peripheral arterial disease. remembered that the dose of a glitazone should beaft a dose






Pioglitazone to be prescribed in accordance with NICE guidance (CG87). LFT measurements are needed prior to treatment and periodically thereafter. It should be remembered that control of modifiable cardiovascular risk factors such as smoking cessation, lipids and blood pressure are the most important interventions to be made in patients with type II diabetes.






GREEN Pioglitazone tablets 15mg, 30mg, 45mg (generic only)


GREEN Competact® tablets - Pioglitazone 15mg plus metformin 850mg






Intestinal alpha glucosidase inhibitor


Consider acarbose for a person unable to use other oral glucose-lowering medications. Delays the digestion and absorption of starch and sucrose. Timing of doses is crucial: tablets should be chewed or swallowed whole with the first mouthful of food.





GREEN Acarbose tablets 50mg, 100mg (Glucobay)






Gliptins


Sitagliptin is licensed for monotherapy, combination oral therapy (metformin, sulphonylurea and/or glitazone) and also in combination with insulin. Requires dose adjustment in patients with renal impairment (please refer to SPC for details).


Linagliptin is licensed for monotherapy and combination oral therapy (metformin and sulphonylurea), is a once daily dosage and does not require dose adjustment for patients with renal impairment.






GREEN Sitagliptin 25mg, 50mg,100mg tablets (Januvia )


GREEN Linagliptin 5mg (Trajenta)






Glucagon-like Peptide-1 agonists






Exenatide


It should be remembered that control of modifiable cardiovascular risk factors such as lipids and blood pressure are the most important interventions to be made in patients with type II diabetes.






Consider adding exenatide to metformin and a sulfonylurea if a person has:


a body mass index (BMI) ≥ 35 kg/m2 in those of European descent, with appropriate adjustment in tailoring this advice for other ethnic groups and other specific psychological or medical problems associated with high body weight


a BMI < 35 kg/m2 and for whom initiation of insulin therapy would have significant occupational implications, or where weight loss would benefit other significant comorbidities such as sleep apnoea.


Continue exenatide only if beneficial response occurs and is maintained (≥ 1.0 percentage point HbA1c reduction in 6 months and weight loss ≥ 5% at 1 year).






Exenatide is licensed for use with metformin, sulphonylurea and pioglitazone. Exenatide is not licensed for use with any other oral antidiabetic drug. Up to 50% of patients experience nausea and vomiting, and due to its effects on slowing gastric emptying, may interact with a variety of drugs including the contraceptive pill and antibiotics.






Exenatide 5mcg and 10mcg only is licensed as adjunct to basal insulin.


Exenatide 2mg is a long acting formulation administered once a week





GREEN Exenatide pre-filled pen 5 micrograms, 10 micrograms (Byetta)


Exenatide 2mg vial with solvent (Bydureon)






Liraglutide


Liraglutide is a treatment option for patients whose diabetes is not controlled with Metformin, and or sulphonylure and/or glitazone. Patients prescribed liraglutide should be regularly reviewed and treatment should be in line with the recommedations of NICE TAG203: only continue liraglutide if reduction in HbA1c of at least 1 percentage point and weight loss of at least 3% of initial body weight at 6 months. Liraglutide should only be used at a maximum dose of 1.2mg daily, the 1.8mg/day dose should not be used.






GREEN Liraglutide pre-filled pen 18mg (Victoza)










6.1.4 Treatment of hypoglycaemia


In the unconscious diabetic glucagon is an alternative to IV glucose 50%.






GREEN Glucagon injection 1 mg (GlucaGen HypoKit)