Diabetes mellitus/Anti-diabetic medication (From Wikipedia)
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Diabetes mellitus (DM) or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar. This high blood sugar produces the symptoms of frequent urination, increased thirst, andincreased hunger. Untreated, diabetes can cause many complications. Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long-term complications include heart disease, kidney failure, and damage to the eyes.
Diabetes is due to either the pancreas not producing enough insulin, or because cells of the body do not respond properly to the insulin that is produced. There are three main types of diabetes mellitus:
Prevention and treatment often involve a healthy diet, physical exercise, not using tobacco, and being a normal body weight. Blood pressure control and proper foot care are also important for people with the disease.Type 1 diabetes must be managed with insulin injections.Type 2 diabetes may be treated with medications with or without insulin. Insulin and some oral medications can cause low blood sugar, which can be dangerous. Gastric bypass surgery has been successful in many with severe obesity and type 2 DM. Gestational diabetes usually resolves after the birth of the baby.
Globally, as of 2013, an estimated 382 million people have diabetes worldwide, with type 2 diabetes making up about 90% of the cases. This is equal to 3.3% of the population, with equal rates in both women and men.In 2011 diabetes resulted in 1.4 million deaths worldwide, making it the 8th leading cause of death.The number of people with diabetes is expected to rise to 592 million by 2035.
Type 1: Diabetes mellitus type 1
Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in which a T-cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults, but was traditionally termed "juvenile diabetes" because a majority of these diabetes cases were in children.
"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.Still, type 1 diabetes can be accompanied by irregular and unpredictable hyperglycemia, frequently with ketosis, and sometimes with serious hypoglycemia. Other complications include an impaired counterregulatory response to hypoglycemia, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.
Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. There is some evidence that suggests an association between type 1 diabetes and Coxsackie B4 virus. Unlike type 2 diabetes, the onset of type 1 diabetes is unrelated to lifestyle.
Type 2 Diabetes mellitus type 2
Type 2 diabetes mellitus is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type.
In the early stage of type 2, the predominant abnormality is reduced insulin sensitivity. At this stage, hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver.
Type 2 diabetes is due primarily to lifestyle factors and genetics.A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than thirty), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60-80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.Those who are not obese often have a high waist–hip ratio.
Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.The type of fats in the diet is also important, with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating lots of white rice appears to also play a role in increasing risk. A lack of exercise is believed to cause 7% of cases.
Gestational diabetes : Gestational diabetes
Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2-10% of all pregnancies and may improve or disappear after delivery. However, after pregnancy approximately 5-10% of women with gestational diabetes are found to have diabetes mellitus, most commonly type 2.Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases insulin may be required.
Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A Caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.
Why is diabetes a concern in pregnancy? Diabetes in pregnancy can have serious consequences for the mother and the growing fetus. The severity of problems often depends on the degree of the mother's diabetic disease, especially if she has vascular (blood vessel) complications and poor blood glucose control. Diabetes that occurs in pregnancy is often listed according to White's classification:
It is very important for a mother to maintain very close control of her diabetes during pregnancy. Generally, the poorer the control of blood glucose and the more severe the disease and complications, the greater the risks for the pregnancy.
Maternal complications of diabetes on a pregnancy:Complications for the mother depend on the degree of insulin need, the severity of complications associated with diabetes, and control of blood glucose.
Most complications occur in women with pre-existing diabetes and are more likely when there is poor control of blood glucose. Women may require more frequent insulin injections. They may have very low blood glucose levels, which can be life threatening if untreated, or they may have ketoacidosis, a condition that results from high levels of blood glucose. Ketoacidosis may also be life threatening if untreated. It is not clear whether pregnancy worsens diabetic related blood vessel damage and retinal changes, or if it causes changes in kidney function.
Complications for fetus and baby:Infants of mothers with diabetes are at greater risk for several problems, especially if blood glucose levels are not carefully controlled, including the following:
Insulin is a peptide hormone, produced by beta cells in the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. It causes cells in the skeletal muscles, and fat tissue to absorb glucose from the blood.
Insulin is a very old protein that may have originated more than one billion years ago.The molecular origins of insulin go at least as far back as the simplest unicellular eukaryotes. Apart from animals, insulin-like proteins are also known to exist in Fungi and Protista kingdoms.
Insulin stops the use of fat as an energy source by inhibiting the release of glucagon. Except in the presence of the metabolic disorder diabetes mellitus and metabolic syndrome, insulin is provided within the body in a constant proportion to remove excess glucose from the blood, which otherwise would be toxic. When blood glucose levels fall below a certain level, the body begins to use stored sugar as an energy source through glycogenolysis, which breaks down the glycogen stored in the liver and muscles into glucose, which can then be utilized as an energy source. As a central metabolic control mechanism, its status is also used as a control signal to other body systems (such as amino acid uptake by body cells). In addition, it has several other anabolic effects throughout the body.
The commonly used types of insulin are:
Anti-diabetic medication
Drugs used in diabetes treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, liraglutide and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.
Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected.
Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents that increase the amount of insulin secreted by the pancreas, (2) agents that increase the sensitivity of target organs to insulin, and (3) agents that decrease the rate at which glucose is absorbed from the gastrointestinal tract.
Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.
Most anti-diabetic agents are contraindicated in pregnancy, in which insulin is preferred.
DailyMed Advanced Search Medicines Micromedex UpToDate
Diabetes mellitus (DM) or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar. This high blood sugar produces the symptoms of frequent urination, increased thirst, andincreased hunger. Untreated, diabetes can cause many complications. Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long-term complications include heart disease, kidney failure, and damage to the eyes.
Diabetes is due to either the pancreas not producing enough insulin, or because cells of the body do not respond properly to the insulin that is produced. There are three main types of diabetes mellitus:
- Type 1 DM results from the body's failure to produce insulin. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes".
- Type 2 DM results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes also with an absolute insulin deficiency. This form was previously referred to as non insulin-dependent diabetes mellitus (NIDDM) or "adult-onset diabetes".
- Gestational diabetes, is the third main form and occurs when pregnant women without a previous diagnosis of diabetes develop a high blood glucose level.
Prevention and treatment often involve a healthy diet, physical exercise, not using tobacco, and being a normal body weight. Blood pressure control and proper foot care are also important for people with the disease.Type 1 diabetes must be managed with insulin injections.Type 2 diabetes may be treated with medications with or without insulin. Insulin and some oral medications can cause low blood sugar, which can be dangerous. Gastric bypass surgery has been successful in many with severe obesity and type 2 DM. Gestational diabetes usually resolves after the birth of the baby.
Globally, as of 2013, an estimated 382 million people have diabetes worldwide, with type 2 diabetes making up about 90% of the cases. This is equal to 3.3% of the population, with equal rates in both women and men.In 2011 diabetes resulted in 1.4 million deaths worldwide, making it the 8th leading cause of death.The number of people with diabetes is expected to rise to 592 million by 2035.
Type 1: Diabetes mellitus type 1
Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated nature, in which a T-cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults, but was traditionally termed "juvenile diabetes" because a majority of these diabetes cases were in children.
"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.Still, type 1 diabetes can be accompanied by irregular and unpredictable hyperglycemia, frequently with ketosis, and sometimes with serious hypoglycemia. Other complications include an impaired counterregulatory response to hypoglycemia, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.
Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. There is some evidence that suggests an association between type 1 diabetes and Coxsackie B4 virus. Unlike type 2 diabetes, the onset of type 1 diabetes is unrelated to lifestyle.
Type 2 Diabetes mellitus type 2
Type 2 diabetes mellitus is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type.
In the early stage of type 2, the predominant abnormality is reduced insulin sensitivity. At this stage, hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver.
Type 2 diabetes is due primarily to lifestyle factors and genetics.A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than thirty), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60-80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.Those who are not obese often have a high waist–hip ratio.
Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.The type of fats in the diet is also important, with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating lots of white rice appears to also play a role in increasing risk. A lack of exercise is believed to cause 7% of cases.
Gestational diabetes : Gestational diabetes
Gestational diabetes mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2-10% of all pregnancies and may improve or disappear after delivery. However, after pregnancy approximately 5-10% of women with gestational diabetes are found to have diabetes mellitus, most commonly type 2.Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases insulin may be required.
Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A Caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.
Why is diabetes a concern in pregnancy? Diabetes in pregnancy can have serious consequences for the mother and the growing fetus. The severity of problems often depends on the degree of the mother's diabetic disease, especially if she has vascular (blood vessel) complications and poor blood glucose control. Diabetes that occurs in pregnancy is often listed according to White's classification:
- Gestational diabetes - when a mother who does not have diabetes develops a resistance to insulin because of the hormones of pregnancy.
- Non-insulin dependent - Class A1
- Insulin dependent - Class A2
- Pre-existing diabetes - women who already have insulin-dependent diabetes and become pregnant.
- Class B - diabetes developed after age 20, have had the disease less than 10 years, no vascular complications.
- Class C - diabetes developed between age 10 and 19 or have had the disease for 10-19 years, no vascular complications.
- Class D - diabetes developed before age 10, have had the disease more than 20 years, vascular complications are present.
- Class F - diabetic women with kidney disease called nephropathy.
- Class R - diabetic women with retinopathy (retinal damage).
- Class T - diabetic women who have undergone kidney transplant.
- Class H - diabetic women with coronary artery or other heart disease.
- Class B - diabetes developed after age 20, have had the disease less than 10 years, no vascular complications.
It is very important for a mother to maintain very close control of her diabetes during pregnancy. Generally, the poorer the control of blood glucose and the more severe the disease and complications, the greater the risks for the pregnancy.
Maternal complications of diabetes on a pregnancy:Complications for the mother depend on the degree of insulin need, the severity of complications associated with diabetes, and control of blood glucose.
Most complications occur in women with pre-existing diabetes and are more likely when there is poor control of blood glucose. Women may require more frequent insulin injections. They may have very low blood glucose levels, which can be life threatening if untreated, or they may have ketoacidosis, a condition that results from high levels of blood glucose. Ketoacidosis may also be life threatening if untreated. It is not clear whether pregnancy worsens diabetic related blood vessel damage and retinal changes, or if it causes changes in kidney function.
Complications for fetus and baby:Infants of mothers with diabetes are at greater risk for several problems, especially if blood glucose levels are not carefully controlled, including the following:
- birth defects
Birth defects are more likely in infants of diabetic mothers, especially insulin-dependent women who may have two to six times greater the risk of major birth defects. Some birth defects are serious enough to cause fetal death. Birth defects usually originate sometime during the first trimester of pregnancy. They are more likely in women with pre-existing diabetes, who may have changes in blood glucose during that time. Overall, major birth defects may occur in about 5 to 10 percent of infants born to insulin-dependent women. Major birth defects that may occur in infants of diabetic mothers include the following:- heart and connecting blood vessels
- brain and spine abnormalities
- urinary and kidney
- digestive tract
- stillbirth (fetal death)
Stillbirth is more likely in pregnant women with diabetes. The fetus may grow slowly in the uterus due to poor circulation or other conditions, such as high blood pressure, that can complicate diabetic pregnancy. The exact reason stillbirths occur with diabetes is unknown. The risk of stillbirth increases in women with poor blood glucose control and with blood vessel changes. - macrosomia
Macrosomia refers to a baby that is considerably larger than normal. All of the nutrients the fetus receives come directly from the mother's blood. If the maternal blood has too much glucose, the pancreas of the fetus senses the high glucose levels and produces more insulin in an attempt to use this glucose. The fetus converts the extra glucose to fat. Even when the mother has gestational diabetes, the fetus is able to produce all the insulin it needs. The combination of high blood glucose levels from the mother and high insulin levels in the fetus results in large deposits of fat that causes the fetus to grow excessively large. - birth injury
Birth injury may occur due to the baby's large size and difficulty being born. - hypoglycemia
Hypoglycemiais low levels of blood sugar in the baby immediately after delivery. This problem occurs if the mother's blood sugar levels have been consistently high causing the fetus to have a high level of insulin in its circulation. After delivery, the baby continues to have a high insulin level, but no longer has the high level of sugar from the mother, resulting in the newborn's blood sugar level becoming very low. The baby's blood sugar level is checked after birth, and if the level is too low, it may be necessary to give the baby glucose intravenously. - respiratory distress (difficulty breathing)
Too much insulin or too much glucose in a baby's system may delay lung maturation and cause respiratory difficulties in babies. This is more likely if they are born before 37 weeks of pregnancy.
Insulin is a peptide hormone, produced by beta cells in the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. It causes cells in the skeletal muscles, and fat tissue to absorb glucose from the blood.
Insulin is a very old protein that may have originated more than one billion years ago.The molecular origins of insulin go at least as far back as the simplest unicellular eukaryotes. Apart from animals, insulin-like proteins are also known to exist in Fungi and Protista kingdoms.
Insulin stops the use of fat as an energy source by inhibiting the release of glucagon. Except in the presence of the metabolic disorder diabetes mellitus and metabolic syndrome, insulin is provided within the body in a constant proportion to remove excess glucose from the blood, which otherwise would be toxic. When blood glucose levels fall below a certain level, the body begins to use stored sugar as an energy source through glycogenolysis, which breaks down the glycogen stored in the liver and muscles into glucose, which can then be utilized as an energy source. As a central metabolic control mechanism, its status is also used as a control signal to other body systems (such as amino acid uptake by body cells). In addition, it has several other anabolic effects throughout the body.
The commonly used types of insulin are:
- Fast-acting: Includes the insulin analogues aspart, lispro, and glulisine. These begin to work within 5 to 15 minutes and are active for 3 to 4 hours. Most insulins form hexamers which delay entry into the blood in active form; these analog insulins do not, but have normal insulin activity. Newer varieties are now pending regulatory approval in the U.S. which are designed to work rapidly, but retain the same genetic structure as regular human insulin.
- Short-acting: Includes regular insulin which begins working within 30 minutes and is active about 5 to 8 hours.
- Intermediate-acting: Includes NPH insulin which begins working in 1 to 3 hours and is active 16 to 24 hours.
- Long acting: Includes the analogues glargine and detemir, each of which begins working within 1 to 2 hours and continue to be active, without major peaks or dips, for about 24 hours, although this varies in many individuals.
- Ultra-long acting: Currently only includes the analogue degludec, which begins working within 30–90 minutes, and continues to be active for greater than 24 hours.
- Combination insulin products – Includes a combination of either fast-acting or short-acting insulin with a longer acting insulin, typically an NPH insulin. The combination products begin to work with the shorter acting insulin (5–15 minutes for fast-acting, and 30 minutes for short acting), and remain active for 16 to 24 hours. There are several variations with different proportions of the mixed insulins (e.g. Novolog Mix 70/30 contains 70% aspart protamine [akin to NPH], and 30% aspart.)
Anti-diabetic medication
Drugs used in diabetes treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, liraglutide and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.
Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected.
Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents that increase the amount of insulin secreted by the pancreas, (2) agents that increase the sensitivity of target organs to insulin, and (3) agents that decrease the rate at which glucose is absorbed from the gastrointestinal tract.
Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.
- 1 Insulin
- 2 Comparison
- 3 Sensitizers
- 4 Secretagogues
- 5 Alpha-glucosidase inhibitors
- 6 Peptide analogs
- 7 Glycosurics
- 8 Natural substances
- 9 Generic
- 10 References
- 11 Further reading
Most anti-diabetic agents are contraindicated in pregnancy, in which insulin is preferred.
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mechanism
Reduces glucose absorbance by acting on small intestine to cause decrease in production of enzymes needed to digest carbohydrates Acts on liver to cause decrease in insulin resistance Stimulating insulin release by pancreatic beta cells by inhibiting the KATP channel Reduce insulin resistance by activating PPAR-γ in fat and muscle |
advantages
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disadvantages
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Sensitizers Insulin sensitizers address the core problem in Type II diabetes--insulin resistance.
Biguanides Main article: Biguanide
Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Among common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain.
Typical reduction in glycated hemoglobin (A1C) values for metformin is 1.5–2.0%
- Metformin (Glucophage) may be the best choice for patients who also have heart failure, but it should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast, as patients are at an increased risk of lactic acidosis.
- Phenformin (DBI) was used from 1960s through 1980s, but was withdrawn due to lactic acidosis risk.
- Buformin also was withdrawn due to lactic acidosis risk.
Metformin is usually the first-line medication used for treatment of type 2 diabetes. In general, it is prescribed at initial diagnosis in conjunction with exercise and weight loss, as opposed to in the past, where it was prescribed after diet and exercise had failed. There is an immediate release as well as an extended-release formulation, typically reserved for patients experiencing GI side-effects. It is also available in combination with other oral diabetic medications.
Thiazolidinediones[edit]Main article: Thiazolidinedione
Thiazolidinediones (TZDs), also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on peroxysome proliferator responsive elements (PPRE).The PPREs influence insulin-sensitive genes, which enhance production of mRNAs of insulin-dependent enzymes. The final result is better use of glucose by the cells.
Typical reductions in glycated hemoglobin (A1C) values are 1.5–2.0%. Some examples are:
- rosiglitazone (Avandia): the European Medicines Agency recommended in September 2010 that it be suspended from the EU market due to elevated cardiovascular risks.
- pioglitazone (Actos)
- troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk
Concerns about the safety of rosiglitazone arose when a retrospective meta-analysis was published in the New England Journal of Medicine.There have been a significant number of publications since then, and a Food and Drug Administration panel voted, with some controversy, 20:3 that available studies "supported a signal of harm," but voted 22:1 to keep the drug on the market. The meta-analysis was not supported by an interim analysis of the trial designed to evaluate the issue, and several other reports have failed to conclude the controversy. This weak evidence for adverse effects has reduced the use of rosiglitazone, despite its important and sustained effects on glycemic control.Safety studies are continuing.
In contrast, at least one large prospective study, PROactive 05, has shown that pioglitazone may decrease the overall incidence of cardiac events in people with type 2 diabetes who have already had a heart attack.
Secretagogues. These are the drugs that increase Insulin output from Pancreas.
Sulfonylureas Main article: Sulfonylurea
Sulfonylureas were the first widely used oral anti-hyperglycaemic medications. They are insulin secretagogues, triggering insulin release by inhibiting the KATP channel of the pancreatic beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side-effects. All may cause weight gain. A 2012 study found sulfonylureas raise the risk of death compared with metformin.
Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are useful only in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old who have had diabetes mellitus for under ten years. They cannot be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side-effect is hypoglycemia.
Typical reductions in glycated hemoglobin (A1C) values for second-generation sulfonylureas are 1.0–2.0%.
- First-generation agents
- tolbutamide (Orinase, Rastinon brand name )
- acetohexamide (Dymelor)
- tolazamide (Tolinase)
- chlorpropamide (Diabinese)
- Second-generation agents
- glipizide (Glucotrol, Minidiab, Glibenese)
- glyburide or glibenclamide (Diabeta, Micronase, Glynase, Daonil, Euglycon)
- glimepiride (Amaryl)
- gliclazide (Uni Diamicron)
- glycopyramide
- gliquidone (Glurenorm)
Nonsulfonylurea secretagogues Meglitinides Main article: Meglitinide
Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues." They act on the same potassium channels as sulfonylureas, but at a different binding site. By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, thereby enhancing insulin secretion.
They are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped.
Typical reductions in glycated hemoglobin (A1C) values are 0.5–1.0%.
- repaglinide (Prandin, NovoNorm)
- nateglinide (Starlix)
Alpha-glucosidase inhibitors Main article: Alpha-glucosidase inhibitor
Alpha-glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.
Typical reductions in glycated hemoglobin (A1C) values are 0.5–1.0%.
These medications are rarely used in the United States because of the severity of their side-effects (flatulence and bloating). They are more commonly prescribed in Europe. They do have the potential to cause weight loss by lowering the amount of sugar metabolized.
Research has shown that the culinary mushroom maitake (Grifola frondosa) has a hypoglycemic effect, possibly due to the mushroom acting as a natural alpha glucosidase inhibitor.
Peptide analogs
Overview of insulin secretion
Injectable Incretin mimetics Incretins are insulin secretagogues. The two main candidate molecules that fulfill criteria for being an incretin are glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (glucose-dependent insulinotropic peptide, GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).
Injectable Glucagon-like peptide analogs and agonists Glucagon-like peptide (GLP) agonists bind to a membrane GLP receptor. As a consequence, insulin release from the pancreatic beta cells is increased. Endogenous GLP has a half-life of only a few minutes, thus an analogue of GLP would not be practical.
- Exenatide (also Exendin-4, marketed as Byetta) is the first GLP-1 agonist approved for the treatment of type 2 diabetes. Exenatide is not an analogue of GLP but rather a GLP agonist. Exenatide has only 53% homology with GLP, which increases its resistance to degradation by DPP-4 and extends its half-life. Typical reductions in A1C values are 0.5–1.0%.
- Liraglutide, a once-daily human analogue (97% homology), has been developed by Novo Nordisk under the brand name Victoza. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, and by the U.S. Food and Drug Administration (FDA) on January 25, 2010.
- Taspoglutide is presently in Phase III clinical trials with Hoffman-La Roche.
- Lixisenatide (Lyxumia) Sanofi Aventis
These agents may also cause a decrease in gastric motility, responsible for the common side-effect of nausea, and is probably the mechanism by which weight loss occurs.
Gastric inhibitory peptide analogs
- None are FDA approved
GLP-1 analogs resulted in weight loss and had more gastrointestinal side-effects, while in general DPP-4 inhibitors were weight-neutral and increased risk for infection and headache, but both classes appear to present an alternative to other antidiabetic drugs. However, weight gain and/or hypoglycaemia have been observed when DPP-4 inhibitors were used with sulfonylureas; effect on long-term health and morbidity rates are still unknown.
Dipeptidyl peptidase-4 (DPP-4) inhibitors increase blood concentration of the incretin GLP-1 by inhibiting its degradation by dipeptidyl peptidase-4.
Examples are:
- vildagliptin (Galvus) EU Approved 2008
- sitagliptin (Januvia) FDA approved Oct 2006
- saxagliptin (Onglyza) FDA Approved July 2009
- linagliptin (Tradjenta) FDA Approved May 2, 2011
- allogliptin
- septagliptin
A result in one RCT comprising 206 patients aged 65 or older (mean baseline HgbA1c of 7.8%) receiving either 50 or 100 mg/d of Sitagliptin was shown to reduce HbA1c by 0.7% (combined result of both doses). A combined result of 5 RCTs enlisting a total of 279 patients aged 65 or older (mean baseline HbA1c of 8%) receiving 5 mg/d of Saxagliptin was shown to reduce HbA1c by 0.73%. A combined result of 5 RCTs enlisting a total of 238 patients aged 65 or older (mean baseline HbA1c of 8.6%) receiving 100 mg/d ofVildagliptin was shown to reduce HbA1c by 1.2%. Another set of 6 combined RCTs involving Alogliptin (not yet approved, might be released in 2012) was shown to reduce HbA1c by 0.73% in 455 patients aged 65 or older who received 12.5 or 25 mg/d of the medication.
Injectable Amylin analogues Amylin agonist analogues slow gastric emptying and suppress glucagon. They have all the incretins actions except stimulation of insulin secretion. As of 2007, pramlintide is the only clinically available amylin analogue. Like insulin, it is administered by subcutaneous injection. The most frequent and severe adverse effect of pramlintide is nausea, which occurs mostly at the beginning of treatment and gradually reduces. Typical reductions in A1C values are 0.5–1.0%.
Glycosurics SGLT-2 inhibitors block the re-uptake of glucose in the renal tubules, promoting loss of glucose in the urine. This causes both mild weight loss, and a mild reduction in blood sugar levels with little risk of hypoglycaemia.Urinary tract infection is a common side effect. Examples of SGLT-2 inhibitors include:
- Canagliflozin (Invokana - FDA approved March 2013)
- Dapagliflozin (marketed in Europe as Forxiga)
Diabetic Related Websites
Brands and Types of Insulin: Rapid-Acting, Long-Acting, and More
Clinical Pharmacist Intervention and the Proportion of Diabetes
Insulin Comparison Chart
Insulin Chart - dLife
Images for insulin types and duration chart
Types of Insulin :: Diabetes Education Online
Insulin Comparison Chart and Insulin Education - Diabetic Supplies
Insulin Comparison Chart and Insulin Education - Diabetic Supplies
Insulin: Compare common options for insulin therapy - Mayo Clinic
Insulin Basics: American Diabetes Association®
Insulin: Types and Activity
Humulin R U-500
The Use of U-500 in Patients With Extreme Insulin Resistance
U-500 insulin: why, when and how to use in clinical practice.
Regular Insulin U-500 Dosing Guidelines
USPharmacist.com > U-500 Insulin: Not for Ordinary Use
Concentrated Insulin Human Regular (U-500) for Patients
Insulin Management - American Association of Diabetes Educators
Blood Sugar Goals and Targets | LillyDiabetes.com
Type 2 Diabetes and Glucose Control
Goals of Treatment :: Diabetes Education Online
Goals for Blood Glucose Control | Joslin Diabetes Center
Checking Your Blood Glucose: American Diabetes Association®
