{"id":12210,"date":"2010-11-29T03:06:39","date_gmt":"2010-11-29T08:06:39","guid":{"rendered":"http:\/\/asweetlife.org\/?p=12210"},"modified":"2016-01-04T10:39:44","modified_gmt":"2016-01-04T15:39:44","slug":"type-2-diabetes-medication-understanding-the-basics","status":"publish","type":"post","link":"https:\/\/asweetlife.org\/?p=12210","title":{"rendered":"Type 2 Diabetes Medication: Understanding The Basics"},"content":{"rendered":"

\"\"<\/a>If you’re being treated for type 2 diabetes, you may have been prescribed any number of drugs over the course of your treatment.\u00a0 The good news here is that there are so many effective ways to treat diabetes.\u00a0 The bad news is that if you’re not a doctor or health care professional, it can be difficult to keep track of all the drugs, what they do, and what kind of side-effects they may bring.\u00a0 Ever catch yourself wondering… What’s a sulfonylurea?\u00a0 What’s a GLP-1 inhibitor?<\/em><\/p>\n

One of the most powerful tools a patient has is information, and here you’ll find an overview of medications to help you understand more about the treatment of type 2 diabetes.\u00a0 This list is intended as information only and is not medical advice.<\/p>\n

——————————————————————————————————<\/p>\n

Currently, there are ten classes of pharmacological agents available to treat type 2 diabetes: sulfonylureas, meglitinides, metformin (a biguanide), thiazolidinediones, alpha-glucosidase inhibitors,\u00a0dipeptidyl peptidase IV (DPP-IV) inhibitors,\u00a0GLP-1 agonists (glucagon like peptide agonist), bile acid sequestrants, dopamine agonists, and amylin analogue.\u00a0 Of these, GLP-1 agonists and amylin analogues are taken by injection, while the rest can be taken as pills.\u00a0 In addition to these medications, there are many forms of insulin used to treat type 2 diabetes.\u00a0 Very frequently, diabetes needs to be treated with a combination of these drugs.\u00a0 These combinations usually aim to take advantage of the differing mechanisms of action of each drug.<\/p>\n

Biguanides: Metformin<\/strong><\/h2>\n

Metformin is the only drug of this class currently available. It has been available in Europe for decades, although it was only approved by the FDA for use in the United States in 1995. Its primary effect is to inhibit the liver’s production of glucose and, possibly, to stimulate the process of transporting glucose into muscle, a process which requires insulin. Exactly how metformin works is not well understood.<\/p>\n

Metformin is often recommended as a first line of therapy. It is useful for patients who are obese because it does not cause the weight gain seen with sulfonylureas; it may even bring about some degree of weight loss. Metformin is also as capable as are the sulfonylureas in reducing HbA1c(1.5-2%). Just like with sulfonylurea treatment, the overall magnitude of response to metformin is directly related to the starting fasting plasma glucose concentration.<\/p>\n

Side effects can be a problem with metformin. Up to 30% of patients develop gastrointestinal complaints, though these may be mild and temporary, especially if the drug is started at low doses and increased slowly. The largest concern with metformin is the potential to produce a build up of lactic acid. However, this is a very rare side effect of the drug, particularly if the drug is not prescribed when it is contraindicated. Contraindications for this drug include evidence of kidney disease, significant liver disease, chronic alcoholism or congestive heart failure. The big advantage of metformin is that it does not generally cause hypoglycemia and, again, it does not lead to weight gain.<\/p>\n

Sulfonylureas<\/strong><\/h2>\n

This class of drugs stimulates the body to produce or secrete more insulin. Other beneficial effects of the sulfonylurea class of drugs include suppression of glucose production in the liver and enhancement of the body’s ability to dispose of excess glucose into fat and muscle tissue.<\/p>\n

The most commonly prescribed sulfonylureas today are glyburide, glipizide and glimepiride.<\/p>\n

Sulfonylureas remain the most popular group of medications today. This may be in part a function of physicians’ habits, but an important factor is their low cost. Many types of sulfonylureas are now generic and are among the cheapest medications available for the treatment of diabetes.<\/p>\n

The clinical efficacy of sulfonylureas in patients with type 2 diabetes is related to the pre-treatment levels of fasting plasma glucose and HbA1c. The higher the fasting glucose level, the greater the effect will be. In patients with a pre-treatment glucose level of approximately 200 mg\/dl, sulfonylureas typically will reduce glucose by 60-70 mg\/dl and HbA1c by 1.5-2%.\u00a0 A drawback of sulfonylureas is that, on average, they lose effectiveness for 44% of patients within six years from the beginning of their use. Some individual patients may have a more prolonged course of successful sulfonylurea treatment and others may need to add other diabetic drugs within less than six years. Failure occurs more rapidly in younger, more hyperglycemic individuals and in those with lower insulin secretion at the start of treatment.<\/p>\n

Hypoglycemia and weight gain are the two most frequent side effects of these drugs. An early study, the UGDP (University Group Diabetes Program), published in the 1970s, also raised the possibility that sulfonylureas might make heart disease worse. However, the large UKPDS study, found that sulfonylureas are no more likely to increase coronary artery disease than any of the other agents tested (insulin and metformin), so the jury is out with respect to heart disease. We do know, however, that sulfonylureas have little or no effect on blood lipid concentrations.<\/p>\n

Meglitinides:\u00a0 Repaglinide and Nateglinide <\/strong><\/h2>\n

The meglitinides are a class of medications that also cause an increase in insulin secretion, but work in a slightly different way than sulfonylureas.\u00a0 They are characterized by a very rapid onset and short duration of action. Repaglinide (Prandin) was introduced in 1998, and Nateglinide (Starlix) was introduced to the market in 2001. Because they are rapidly absorbed and quickly metabolized in the body, these drugs usually need to be taken three times a day. This could be considered an inconvenience for some.\u00a0 For others with erratic lifestyles that lead them to occasionally miss meals, skipping repaglinide at the same time appears to be very effective.<\/p>\n

The efficacy of these medications seems to be similar to that of sulfonylureas.<\/p>\n

Like sulfonylureas, this class of drugs can cause hypoglycemia and weight gain, though the weight gain might be slightly less.<\/p>\n

Thiazolidinediones: Pioglitazone and Rosiglitazone<\/strong><\/h2>\n

The thiazolidinediones (TZDs) enhance insulin action in muscle, fat and other tissues and are known as insulin sensitizers.\u00a0 This results in a reduction of fasting plasma glucose, insulin, and free fatty acids. TZDs are effective in reducing HbA1c. They are also effective in combination with either sulfonylureas or metformin.\u00a0 When starting these drugs it is important to keep in mind that it takes a TZD longer than most drugs to reach its maximal biological effect, about 4-12 weeks. About 25% of patients do not respond to TZDs.<\/p>\n

The major side effects of TZDs are weight gain and fluid retention. The weight gain may be anywhere from 2 to 20 pounds. The fluid retention may be minimal to whole body swelling, and it is not very treatable with diuretics. TZDs are not indicated if the patient has a history of heart trouble, especially heart failure.<\/p>\n

The two available drugs in the TZD class on the market are pioglitazone (Actos) and rosiglitazone (Avandia). Rosiglitazone has been in the spotlight since 2007, when a\u00a0meta-analysis by Nissen and Wolski concluded that rosiglitazone was associated with a significant increase in the risk of heart attacks and with an increased risk of death from cardiovascular causes.\u00a0 The significance of these findings was very debatable and the study was thought to have significant limitations.\u00a0 Since then, other studies have shown variable results. In September 2010, the FDA announced it would significantly restrict the use of Avandia. \u00a0In Europe, the\u00a0European Medicines Agency<\/a> recommended in September 2010 that the drug be suspended from the European market.<\/p>\n

None of the studies with pioglitazone seem to show an increase in cardiovascular events. In fact, it may even be associated with a significantly lower risk of death, heart attack, or stroke compared with any of the alternative regimens. The increased risk of heart failure, however, seems to be true for both drugs.<\/p>\n

Another concerning side effect with TZDs is the potential association with increased risk of bone fractures. This remains to be further clarified.<\/p>\n

A major advantage of TZDs is that they do not cause hypoglycemia when used alone and that pioglitazone also decreases LDL cholesterol and triglycerides, while raising HDL cholesterol.<\/p>\n

Glucosidase Inhibitors: Acarbose and Miglitol<\/strong><\/h2>\n

Glucosidase inhibitors named acarbose (Precose, Glucobay) and miglitol (Glycet) act in the intestine to block the action of enzymes that are responsible for breaking down complex carbohydrates into simple sugars. This delayed breakdown of carbohydrates helps slow down their absorption into the bloodstream, and thus slow down the increase in blood glucose levels after a meal.<\/p>\n

These medicines are not usually used for primary therapy unless a patient appears to have large increases in blood glucose after meals (“postprandial”). Glucosidase inhibitors are most useful in combination with other drugs.<\/p>\n

Gastrointestinal side effects are common, affecting up to 30% of patients. Bloating, flatulence, diarrhea and abdominal discomfort and pain are the major complaints. However, these side effects can be reduced by reducing carbohydrates intake.<\/p>\n

Weight gain does not occur with these drugs.<\/p>\n

Incretins: GLP-1 and DPP-4 inhibitors<\/strong><\/h2>\n

The incretins are a group of hormones secreted by the L cells found in the ileum, (the last segment of the small intestine) and the colon.\u00a0 The most relevant one is the hormone GLP-1 (glucagon like peptide agonist). The main action of GLP-1 is that it inhibits glucagon (a hormone that signals the liver to release glucose and is usually elevated in people with type 2 diabetes).\u00a0 It also increases insulin<\/a> secretion from the pancreas and it decreases gastric emptying (which is paradoxically increased in diabetics). GLP-1 might also enhance the survival and growth of pancreatic beta cells.<\/p>\n

The problem is that GLP-1 is active for a very short time in the blood. This is because it is broken down quickly by an enzyme called dipeptidyl peptidase 4, or DPP-4.<\/p>\n

Two classes of agents have been developed to take advantage of GLP-1<\/p>\n

1) The incretin mimetics, such as exenatide and liraglutide<\/p>\n

2) \u00a0The DPP-IV inhibitors, compounds that increase the concentration of GLP-1 by limiting its breakdown by DPP-IV.<\/p>\n

Incretin mimetics<\/span><\/h3>\n

Exenatide and Liraglutide are the two synthetic GLP-1 agonists. Exenatide is a synthetic version of exendin-4, a peptide originally identified in the saliva of the Gila monster (Heloderma suspectum), and secreted upon ingestion of nutrients. It received regulatory approval in 2005. \u00a0\u00a0Exenatide is administered via a pre-filled injection twice a day.\u00a0 The most commonly reported side effect is nausea, which is worse when people start using the drug, and generally subsides. There was no increase in the risk of hypoglycemia when exenatide was administered in combination with metformin.<\/p>\n

Liraglutide is a once-daily GLP-1 receptor agonist approved for clinical use by the FDA in January 2010.\u00a0 In clinical trials it achieves significantly greater reductions in HbA1c than sulfonylurea therapy and also seems to lead to significant weight loss\u20131.0 to\u20133.2 kg depending on the dose.<\/p>\n

Dipeptidyl Peptidase IV (DPP-IV) Inhibitors<\/span><\/h3>\n

As described above, DPP-IV inhibitors are compounds that increase the concentration of GLP-1, by limiting its breakdown by DPP-IV. This is an alternative that can be given orally to elevate circulating GLP-1 levels.<\/p>\n

There are a few DPP-4 inhibitors. Sitagliptin (Januvia) received regulatory approval in the US\u00a0in 2006. Saxagliptin (Ongyza) was approved by the FDA in 2009.\u00a0 Approval of Vildagliptin (Galvus) has been delayed by the FDA pending further data on people with kidney disease, but was approved in Europe in 2007. Another drug in the same family, alogliptin, was recently tested in large, Phase III trials, but has not yet received FDA approval.<\/p>\n

In sitagliptin monotherapy studies HbA1c was reduced from baseline slightly less than the sulfonylureas and metformin.\u00a0 Benefits, however, are that it does not lead to weight gain, gastrointestinal events rarely occur, and it rarely causes hypoglycemia. It is associated with a somewhat higher rate of hypoglycemia when used in combination with other drugs, especially with a sulfonylurea.<\/p>\n

Bile Acid Sequestrant: Colesevelam<\/strong><\/h2>\n

Colesevelam hydrochloride (WelCHOL) is a non-absorbed oral drug that lowers lipids and glucose. While it is known that it binds bile acids, the actual glucose lowering mechanism is still being investigated.<\/p>\n

As colesevelam is minimally absorbed from the gastrointestinal tract, few systemic adverse events occur after oral administration, although studies showed that constipation might be an issue.<\/p>\n

Dopamine Agonist: Bromocriptine<\/strong><\/p>\n

Bromocriptine is a medication that has been available for many decades, but in 2009 it was approved for use with diet and exercise to improve sugar control in adults with type 2 diabetes. The drug specifically approved\u00a0was a quick-release preparation under the trade name Cycloset.\u00a0 Bromocriptine,\u00a0 a dopamine D2 receptor agonist, is traditionally used to treat hyperprolactinemia, acromegaly and Parkinson’s disease, but it was noted that migrating birds develop seasonal insulin resistance and dopamine plays a role in it.<\/p>\n

It is still unclear how this drug may work, but some possible mechanisms by which bromocriptine reduces glucose levels include suppression of endogenous glucose production and\/or increased splanchnic glucose uptake after glucose ingestion.<\/p>\n

The most common adverse events associated with bromocriptine are nausea, fatigue, dizziness, vomiting and headache. The drug is also known to be associated with nasal stuffiness, nausea, headache, constrictive pericarditis,\u00a0 neuroleptic malignant syndrome,\u00a0 and hypotension. \u00a0\u00a0The incidence of hypoglycemia was 6.9% among bromocriptine treated patients compared with 5.3% of patients receiving placebo.<\/p>\n

Amylin analogue: Pramlintide<\/strong><\/h2>\n

The hormone\u00a0amylin is secreted along with insulin by the pancreatic beta cells in response to food.\u00a0\u00a0 Patients with type 1 diabetes may develop an absolute deficiency of both insulin and amylin, and those with type 2 diabetes have impaired secretion of amylin in response to a meal. Amylin suppresses glucagon secretion after meals (glucagon increases blood sugars), slows gastric emptying time, enhances satiety, and reduces food intake. Pramlintide was developed as an injectable drug and it is very similar in structure to the hormone amylin.<\/p>\n

When added to meal time insulin, pramlintide improves glucose control and promotes weight loss in patients with both type 1 and type 2 diabetes.\u00a0\u00a0 However, effects on HbA1c reduction are only modest, with 52 week net reduction of .27% at 1 year.<\/p>\n

Pramlintide has also been used alone, given before\u00a0 meals without insulin in type 2 diabetes.\u00a0 In preliminary studies, when compared to patients receiving insulin with meals, these patients were able to achieve similar glucose control with less hypoglycemia and without the weight gain seen with insulin given at meals.<\/p>\n

In both patients with type 1 and type 2 diabetes, side effects are mostly nausea, vomiting, and anorexia.\u00a0 Some reports suggest nausea occurs in up to 25% of patients. Most of the symptoms seem to be transient, gone within the first 4-8 weeks of treatment.<\/p>\n

Symlin (pramlintide acetate),\u00a0 Amylin Pharmaceuticals’ synthetic analog of human amylin, was approved by the FDA, for use by Type 1 and Type 2 Diabetics who use insulin in 2005.<\/p>\n

Insulin<\/strong><\/h2>\n

\"\"<\/a>Most people with type 2 diabetes who start insulin do so in addition to an oral medication, such as metformin<\/a>.\u00a0\u00a0 However, there are instances when type 2 diabetic patients are treated only with insulin. People taking insulin alone often require two injections of intermediate-acting insulin or one injection of long-acting insulin per day.<\/p>\n

If a long-acting insulin or a twice daily injection of intermediate-acting insulin is not adequate to control blood sugar levels, a more intensive insulin treatment regimen may be recommended, such as is used in type 1 diabetes patients. \u00a0Intensive insulin treatment in a patient with type 2 diabetes requires at least two injections of insulin per day, usually including a rapid-acting and long-acting insulin, or very rarely use of an insulin pump. It also requires that the person monitor their blood sugar levels several times per day.<\/strong><\/p>\n

Types of insulin <\/strong><\/h3>\n

There are several types of insulin and they are classified according to how quickly they begin to work:<\/p>\n

    \n
  • Rapid-acting (insulin lispro (Humalog\u00ae), insulin aspart (Novolog\u00ae), and\u00a0insulin glulisine (Apidra\u00ae))<\/li>\n
  • Short-acting (eg,\u00a0insulin regular)<\/li>\n
  • Intermediate-acting (eg,\u00a0insulin NPH)<\/li>\n
  • Long-acting (eg,\u00a0insulin glargine (Lantus\u00ae),\u00a0insulin detemir (Levemir\u00ae))<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"

    One of the most powerful tools a patient has is information, and here you’ll find an overview of medications to help you understand more about the treatment of type 2 diabetes…<\/p>\n","protected":false},"author":19,"featured_media":10737,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[1443,1441,1442],"tags":[],"yoast_head":"\nType 2 Diabetes Medication: Understanding The Basics<\/title>\n<meta name=\"description\" content=\"What's a sulfonylurea? What's a GLP-1 inhibitor? 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