Anti-diabetic drug

Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, 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 or inhaled.

Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents which increase the amount of insulin secreted by the pancreas, (2) agents which increase the sensitivity of target organs to insulin, and (3) agents which 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.

Contents

Insulin

Main article: insulin

Insulin is usually given subcutaneously, either by injections or by an insulin pump. Research is underway of other routes of administration. In acute care settings, insulin may also be given intravenously. There are several types of insulin, characterized by the rate which they are metabolized by the body.

Secretagogues

Sulfonylureas

Sulfonylureas were the first widely used oral anti-hyperglycaemic medications. They are insulin secretagogues, triggering insulin release by direct action on 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.

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful 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 can not 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 A1C values for second generation sulfonylureas are 1.0-2.0%.

Meglitinides

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.[1] By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion.[2]

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 A1C values are 0.5-1.0%.

Adverse reactions include weight gain and hypoglycemia.

Sensitizers

Insulin sensitizers address the core problem in Type II diabetes—insulin resistance. Among oral hypoglycemic agents, insulin sensitizers are the largest category.[3]

Biguanides

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. Amongst common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain.

Typical reductions in A1C values for metformin is 1.5-2.0%.

Metformin is usually the first-line medication used for treatment of type-2 diabetes. It is generally prescribed at initial diagnosis in conjunction with exercise and weight loss as opposed to in the past, where Metformin was prescribed after diet and exercise had failed. Initial dosing is 500 mg once daily, then if need be increased to 500 mg twice daily up to 1000 mg twice daily. It is also available in combination with other oral diabetic medications.

There is an extended release formulation available, but it is typically reserved for patients experiencing GI side effects.

Thiazolidinediones

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 [1]). 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 A1C values are 1.5-2.0%.

As a result of multiple retrospective studies, there is a concern about rosiglitazone's safety, although it is established that the group, as a whole, has beneficial effects on diabetes. The greatest concern is an increase in the number of severe cardiac events in patients taking it. The ADOPT study showed that initial therapy with drugs of this type may prevent the progression of disease,[8] as did the DREAM trial.[9]

Concerns about the safety of rosiglitazone arose when a retrospective meta-analysis was published in the New England Journal of Medicine.[10] There have been a significant number of publications since then, and a Food and Drug Administration panel[11] 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.[12] 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 II diabetes who have already had a heart attack.[13]

Alpha-glucosidase inhibitors

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 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 the culinary mushroom Maitake (Grifola frondosa) has a hypoglycemic effect,[14][15][16][17][18][19] possibly due to the fact the mushroom naturally acts as an alpha-glucosidase inhibitor.[20]

Peptide analogs

Overview of insulin secretion

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 (aka glucose-dependent Insulinotropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).

Glucagon-like peptide (GLP) analogs and agonists

GLP agonists bind to a membrane GLP receptor.[2] As a consequence of this, 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.

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 (GIP) analogs

DPP-4 inhibitors

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase blood concentration of the incretin GLP-1 (glucagon-like peptide-1) by inhibiting its degradation by dipeptidyl peptidase-4 (DPP-4).

Typical reductions in A1C values are 0.5-1.0%.

Examples are:

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%.

Experimental agents

Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research. Others are undergoing phase I/II studies.

Alternative medicine

A recent review article presents the profiles of plants with hypoglycaemic properties, reported in the literature from 1990 to 2000 and states that "Medical plants play an important role in the management of diabetes mellitus especially in developing countries where resources are meager."[30]

The first registered use of anti-diabetic drugs was as herbal extracts used by Indians in the Amazon Basin for the treatment of type 2 diabetes, and today promoted as vegetable insulin although not formally an insulin analog.[31] The major recent development was done in Brazil around Myrcia sphaerocarpa and other Myrcia species.[32] The usual treatment is with concentrated (root) Myrcia extracts, commercialized as "Pedra hume de kaá". Phytochemical analysis of the Myrcia extracts reported kinds of flavanone glucosides (myrciacitrins) and acetophenone glucosides (myrciaphenones), and inhibitory activities on aldose reductase and alpha-glucosidase.[33]

Walnut leaf can significantly reduce fasting blood glucose levels in rats with alloxan-induced diabetes, and rats thus treates show some evidence of regeneration of the beta cells.[34] Garlic also significantly reduces fasting blood glucose levels in rats with alloxan-induced diabetes.[35]

At least two studies have shown that cinnamon can act significantly reducing some effects of diabetes. One study on people used fine ground cassia (Cinnamomum aromaticum) for oral consumption. Another study used an extract (MHCP) on laboratory rats. The study on people published in 2003 conducted in the Department of Human Nutrition, NWFP Agricultural University, Peshawar, Pakistan concluded "that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases."[36] The study on laboratory rats at Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University published in 2001 used purified hydroxychalcone (MHCP) from cinnamon. Part of the study's conclusion stated that "the MHCP is fully capable of mimicking insulin" and recommended further studies.[37][38] The Food and Drug Administration has not yet evaluated the use of cinnamon for the management of diabetes. It should be noted that the spice sold as cinnamon is often obtained from C. verum (true cinnamon), not C. aromaticum (cassia).

Research has shown the Maitake mushroom (Grifola frondosa) has a hypoglycemic effect, and may be beneficial for the management of diabetes.[14][15][16][17][18][19] The reason Maitake lowers blood sugar is due to the fact the mushroom naturally acts as an alpha glucosidase inhibitor.[2] Other mushrooms like Reishi,[39][40] Agaricus blazei,[41][42][43][44] Agrocybe cylindracea[45] and Cordyceps[46][47][48][49][50] have been noted to lower blood sugar levels to a certain extent, although the mechanism is currently unknown.

Cinnamon

Though not yet evaluated by the Food and Drug Administration, at least two studies have shown that cinnamon can act significantly reducing some effects of diabetes. One study on people used fine ground cinnamon (Cinnamomum cassia) for oral consumption. Another study used an extract (MHCP) on laboratory rats.

The study on people published in 2003 conducted in the Department of Human Nutrition, NWFP Agricultural University, Peshawar, Pakistan concluded:

The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.[51]

The study on laboratory rats at Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University published in 2001 used purified hydroxychalcone from cinnamon. The extract was named "MHCP". Part of the study's conclusion stated that "the MHCP is fully capable of mimicking insulin" and recommended further studies.[52][53]

Other studies have failed to reproduce these results, and, because large doses of cinnamon are not innocuous, some experts advise against treatment of diabetes with cinnamon.[54]

Chromium and vanadium

Chromium - Cholesterol and triglycerides are risk factors in heart disease and diabetes, and studies show that chromium lowers levels of total cholesterol, LDL cholesterol, and triglycerides.[55][56][57][58] Chromium supplements such as chromium picolinate have been shown to improve glucose tolerance in people with type 2 diabetes,[59][60][61] although other studies have not replicated this result.[62] A meta analysis of these trials concluded that chromium supplements had no beneficial effect on healthy people, but that there might be an improvement in glucose metabolism in diabetics, although the authors stated that the evidence for this effect remains weak.[63]

Vanadium - A form of vanadium, vanadyl sulfate, seems to improve glucose control in people with type 2 diabetes.[64][65][66][67][68]

A pilot study has also found evidence that Tai Chi and Qigong reduce the severity of type 2 diabetes.[69]

Benfotiamine, a pro-vitamin of vitamin B1 which has been in use in Europe as an over-the-counter medicine for alcoholic neuropathy for the past half century with no significant side-effects or toxicity, has recently been found to block the major metabolic pathways by which excess blood glucose in the body is transformed into the advanced glycation endproducts (AGEs) which cause diabetic complications.[70] Studies have shown that taking oral benfotiamine can prevent diabetic retinopathy,[71] diabetic neuropathy,[72] and diabetic nephropathy[73] independently of any affect on the blood sugar levels of the patient. In theory, taking benfotiamine might allow patients to be less scrupulous in trying to normalize blood sugar levels and thus free them from the danger of hypoglycemia and the stress of stringent blood sugar monitoring, while still protecting them against the negative effects of hyperglycemia. Research is ongoing to establish the full significance of benfotiamine in the treatment of diabetes.

Traditional plant treatments for diabetes

A study was made of the effects on glucose homeostasis in normal and streptozotocin (induced) diabetic mice of eleven plants that have been used as traditional treatments for diabetes. The mice were given diets containing dried leaves from the following plants: agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra). The study concluded that "The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice".[74]

Mushrooms
Research has shown the Maitake mushroom (Grifola frondosa) has a hypoglycemic effect, and may be beneficial for the management of diabetes.[14][15][16][17][18][19] The reason Maitake lowers blood sugar is due to the fact the mushroom naturally acts as an alpha glucosidase inhibitor.[75] Other mushrooms like Reishi,[39][40] Agaricus blazei,[41][42][43][76] Agrocybe cylindracea[77] and Cordyceps[46][47][48][49][50] have been noted to lower blood sugar levels to a certain extent, although the mechanism is currently unknown.

Aloe vera Oral administration of aloe vera might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia . Ten controlled clinical trials were found to reach that conclusion in four independent literature searches. However, caveats reported in each study led the researchers to conclude that aloe vera's clinical effectiveness was not yet sufficiently defined in 1999.[78]

Notes

  1. ↑ Rendell (2004). "Advances in diabetes for the millennium: drug therapy of type 2 diabetes.". MedGenMed : Medscape general medicine 6 (3 Suppl): 9. PMID 15647714. 
  2. ↑ 2.0 2.1 "Helping the pancreas produce insulin". HealthValue. http://www.healthvalue.net/diabetespancreasbeta.html. Retrieved 2007-09-21. 
  3. ↑ "Metabolic Syndrome." C&EN. November 22, 2004
  4. ↑ Eurich; McAlister, FA; Blackburn, DF; Majumdar, SR; Tsuyuki, RT; Varney, J; Johnson, JA (2007). "Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review.". BMJ (Clinical research ed.) 335 (7618): 497. doi:10.1136/bmj.39314.620174.80. PMID 17761999. 
  5. ↑ Fimognari; Pastorelli, R; Incalzi, RA (2006). "Phenformin-induced lactic acidosis in an older diabetic patient: a recurrent drama (phenformin and lactic acidosis).". Diabetes care 29 (4): 950–1. doi:10.2337/diacare.29.04.06.dc06-0012. PMID 16567854. http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=16567854. 
  6. ↑ Verdonck; Sangster, B; Van Heijst, AN; De Groot, G; Maes, RA (1981). "Buformin concentrations in a case of fatal lactic acidosis.". Diabetologia 20 (1): 45–6. doi:10.1007/BF01789112. PMID 7202882. 
  7. ↑ Hinterthuer, Adam (2008). "Retired Drugs: Failed Blockbusters, Homicidal Tampering, Fatal Oversights". Wired News. http://www.wired.com/medtech/drugs/multimedia/2008/10/gallery_retired_drugs?slide=6&slideView=6. Retrieved 2009-06-21. 
  8. ↑ Haffner, Steven M. (2007). "Expert Column - A Diabetes Outcome Progression Trial (ADOPT)". Medscape. http://www.medscape.com/viewarticle/552484. Retrieved 2007-09-21. 
  9. ↑ Gagnon, Louise (2007). "DREAM: Rosiglitazone Effective in Preventing Diabetes". Medscape. http://www.medscape.com/viewarticle/546503. Retrieved 2007-09-21. 
  10. ↑ Nissen; Wolski, K (2007). "Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.". The New England journal of medicine 356 (24): 2457–71. doi:10.1056/NEJMoa072761. PMID 17517853. Lay summary – Associated Press (21 May 2007). 
  11. ↑ Wood, Shelley (2007-07-31). "FDA Advisory Panels Acknowledge Signal of Risk With Rosiglitazone, but Stop Short of Recommending Its Withdrawal". Heartwire. http://www.medscape.com/viewarticle/560709. Retrieved 2007-09-21. 
  12. ↑ Ajjan; Grant, PJ (2008). "The cardiovascular safety of rosiglitazone.". Expert opinion on drug safety 7 (4): 367–76. doi:10.1517/14740338.7.4.367. PMID 18613801. 
  13. ↑ Erdmann; Dormandy, JA; Charbonnel, B; Massi-Benedetti, M; Moules, IK; Skene, AM; Proactive, Investigators (2007). "The effect of pioglitazone on recurrent myocardial infarction in 2,445 patients with type 2 diabetes and previous myocardial infarction: results from the PROactive (PROactive 05) Study.". Journal of the American College of Cardiology 49 (17): 1772–80. doi:10.1016/j.jacc.2006.12.048. PMID 17466227. 
  14. ↑ 14.0 14.1 14.2 Konno; Tortorelis, DG; Fullerton, SA; Samadi, AA; Hettiarachchi, J; Tazaki, H (2001). "A possible hypoglycaemic effect of maitake mushroom on Type 2 diabetic patients.". Diabetic medicine : a journal of the British Diabetic Association 18 (12): 1010. doi:10.1046/j.1464-5491.2001.00532-5.x. PMID 11903406. 
  15. ↑ 15.0 15.1 15.2 Hong; Xun, M; Wutong, W (2007). "Anti-diabetic effect of an alpha-glucan from fruit body of maitake (Grifola frondosa) on KK-Ay mice.". The Journal of pharmacy and pharmacology 59 (4): 575–82. doi:10.1211/jpp.59.4.0013. PMID 17430642. 
  16. ↑ 16.0 16.1 16.2 Kubo; Aoki, H; Nanba, H (1994). "Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake). I.". Biological & pharmaceutical bulletin 17 (8): 1106–10. PMID 7820117. 
  17. ↑ 17.0 17.1 17.2 Lo, HC; Hsu, TH; Chen, CY (2008). "Submerged culture mycelium and broth of Grifola frondosa improve glycemic responses in diabetic rats.". The American journal of Chinese medicine 36 (2): 265–85. doi:10.1142/S0192415X0800576X. PMID 18457360. 
  18. ↑ 18.0 18.1 18.2 Manohar; Talpur, NA; Echard, BW; Lieberman, S; Preuss, HG (2002). "Effects of a water-soluble extract of maitake mushroom on circulating glucose/insulin concentrations in KK mice.". Diabetes, obesity & metabolism 4 (1): 43–8. doi:10.1046/j.1463-1326.2002.00180.x. PMID 11874441. 
  19. ↑ 19.0 19.1 19.2 Horio; Ohtsuru, M (2001). "Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats.". Journal of nutritional science and vitaminology 47 (1): 57–63. PMID 11349892. 
  20. ↑ Matsuur; Asakawa, C; Kurimoto, M; Mizutani, J (2002). "Alpha-glucosidase inhibitor from the seeds of balsam pear (Momordica charantia) and the fruit bodies of Grifola frondosa.". Bioscience, biotechnology, and biochemistry 66 (7): 1576–8. doi:10.1271/bbb.66.1576. PMID 12224646. 
  21. ↑ Briones; Bajaj, M (2006). "Exenatide: a GLP-1 receptor agonist as novel therapy for Type 2 diabetes mellitus.". Expert opinion on pharmacotherapy 7 (8): 1055–64. doi:10.1517/14656566.7.8.1055. PMID 16722815. 
  22. ↑ Gallwitz (2006). "Exenatide in type 2 diabetes: treatment effects in clinical studies and animal study data.". International journal of clinical practice 60 (12): 1654–61. doi:10.1111/j.1742-1241.2006.01196.x. PMID 17109672. 
  23. ↑ Cvetković; Plosker, GL (2007). "Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea).". Drugs 67 (6): 935–54. doi:10.2165/00003495-200767060-00008. PMID 17428109. 
  24. ↑ http://www.drugs.com/nda/liraglutide_080530.html May 2008
  25. ↑ http://www.medicalnewstoday.com/articles/74913.php "Liraglutide Provides Significantly Better Glucose Control Than Insulin Glargine In Phase 3 Study" June 2007
  26. ↑ http://www.medicalnewstoday.com/articles/110349.php "Clinical Study Shows Liraglutide Reduced Blood Sugar, Weight, And Blood Pressure In Patients With Type 2 Diabetes" June 2008
  27. ↑ http://www.drugdevelopment-technology.com/projects/liraglutide/
  28. ↑ http://www.novonordisk.com/science/about_rd/quarterly_rd_update.asp Oct 2008 Inc results of LEAD 6 extension
  29. ↑ http://money.cnn.com/news/newsfeeds/articles/marketwire/0580389.htm January 2009
  30. ↑ Bnouham M et al. (2006). "Medicinal plants with potential antidiabetic activity - A review of ten years of herbal medicine research (1990-2000)" (PDF). Int J Diabetes & Metabolism 14: 1–25. http://ijod.uaeu.ac.ae/iss_1401/a.pdf. 
  31. ↑ Soumyanath, Amala(ed.) (2005-11-01). Traditional Medicines for Modern Times (1st ed.). Taylor & Francis. ISBN 0-415-33464-0. 
  32. ↑ McNeill, John H. (1999-02-01). Experimental Models of Diabetes (1st ed.). CRC Press. pp. 208. ISBN 0-8493-1667-7. 
  33. ↑ Matsuda, Hisashi; Nishida, Norihisa; Yoshikawa, Masayuki (2002). "Antidiabetic Principles of Natural Medicines. V. Aldose Reductase Inhibitors from Myrcia multiflora DC. (2): Structures of Myrciacitrins III, IV, and V". Chemical & Pharmaceutical Bulletin 50: 429. doi:10.1248/cpb.50.429. 
  34. ↑ Jelodar G, Sirus Sh, Mohsen M (2007). "Effect of Walnut leaf, coriander and pomegranate on blood glucose and histopathology of pancreas of alloxan induced diabetic rats". African Journal of Traditional, Complimentary and Alternative Medicines 4 (3): 299–305. http://www.bioline.org.br/request?tc07044. Retrieved 2008-05-10. 
  35. ↑ Jelodar; Maleki, M; Motadayen, MH; Sirus, S (2005). "Effect of fenugreek, onion and garlic on blood glucose and histopathology of pancreas of alloxan-induced diabetic rats.". Indian journal of medical sciences 59 (2): 64–9. doi:10.4103/0019-5359.13905. PMID 15738612. 
  36. ↑ Khan, A.; Safdar, M.; Ali Khan, M. M.; Khattak, K. N.; Anderson, R. A. (2003). "Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes". Diabetes Care 26 (12): 3215. doi:10.2337/diacare.26.12.3215. PMID 14633804. 
  37. ↑ Jarvill-Taylor, Karalee J.; Anderson, R; Graves, D (2001). "A Hydroxychalcone Derived from Cinnamon Functions as a Mimetic for Insulin in 3T3-L1 Adipocytes". Journal of the American College of Nutrition 20 (4): 327. PMID 11506060. http://www.jacn.org/cgi/content/full/20/4/327. 
  38. ↑ Richard A. Anderson, Ph.D., CNS, Cinnamon, Glucose Tolerance and Diabetes, www.ars.usda.gov, August 23, 2005, retrieved August 4, 2008
  39. ↑ 39.0 39.1 Zhang; Lin, ZB (2004). "Hypoglycemic effect of Ganoderma lucidum polysaccharides.". Acta pharmacologica Sinica 25 (2): 191–5. PMID 14769208. 
  40. ↑ 40.0 40.1 Yang; Jung, YS; Song, CH (2007). "Hypoglycemic effects of Ganoderma applanatum and Collybia confluens exo-polymers in streptozotocin-induced diabetic rats.". Phytotherapy research : PTR 21 (11): 1066–9. doi:10.1002/ptr.2214. PMID 17600864. 
  41. ↑ 41.0 41.1 Liu; Fukuwatari, Y; Okumura, K; Takeda, K; Ishibashi, KI; Furukawa, M; Ohno, N; Mori, K et al. (2008). "Immunomodulating Activity of Agaricus brasiliensis KA21 in Mice and in Human Volunteers.". Evidence-based complementary and alternative medicine : eCAM 5 (2): 205–219. doi:10.1093/ecam/nem016. PMID 18604247. 
  42. ↑ 42.0 42.1 Kim; Kim, KH; Choi, HJ; Lee, DS (2005). "Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei.". Biotechnology letters 27 (7): 483–7. doi:10.1007/s10529-005-2225-8. PMID 15928854. 
  43. ↑ 43.0 43.1 Hsu; Liao, YL; Lin, SC; Hwang, KC; Chou, P (2007). "The mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial.". Journal of alternative and complementary medicine (New York, N.Y.) 13 (1): 97–102. doi:10.1089/acm.2006.6054. PMID 17309383. 
  44. ↑ Fortes; Novaes, MR; Recôva, VL; Melo, AL (2009). "Immunological, hematological, and glycemia effects of dietary supplementation with Agaricus sylvaticus on patients' colorectal cancer.". Experimental biology and medicine (Maywood, N.J.) 234 (1): 53–62. doi:10.3181/0806-RM-193. PMID 18997106. 
  45. ↑ Kiho; Sobue, S; Ukai, S (1994). "Structural features and hypoglycemic activities of two polysaccharides from a hot-water extract of Agrocybe cylindracea.". Carbohydrate research 251: 81–7. doi:10.1016/0008-6215(94)84277-9. PMID 8149381. 
  46. ↑ 46.0 46.1 Kiho; Hui, J; Yamane, A; Ukai, S (1993). "Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of a polysaccharide from the cultural mycelium of Cordyceps sinensis.". Biological & pharmaceutical bulletin 16 (12): 1291–3. PMID 8130781. 
  47. ↑ 47.0 47.1 Kiho; Yamane, A; Hui, J; Usui, S; Ukai, S (1996). "Polysaccharides in fungi. XXXVI. Hypoglycemic activity of a polysaccharide (CS-F30) from the cultural mycelium of Cordyceps sinensis and its effect on glucose metabolism in mouse liver.". Biological & pharmaceutical bulletin 19 (2): 294–6. PMID 8850325. 
  48. ↑ 48.0 48.1 Zhao; Yin, WT; Wang, JY; Zhang, Y; Yu, H; Cooper, R; Smidt, C; Zhu, JS (2002). "CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats.". Journal of alternative and complementary medicine (New York, N.Y.) 8 (3): 309–14. doi:10.1089/10755530260127998. PMID 12165188. 
  49. ↑ 49.0 49.1 Lo; Tu, ST; Lin, KC; Lin, SC (2004). "The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin.". Life sciences 74 (23): 2897–908. doi:10.1016/j.lfs.2003.11.003. PMID 15050427. 
  50. ↑ 50.0 50.1 Li; Zhang, GH; Zeng, Q; Huang, ZG; Wang, YT; Dong, TT; Tsim, KW (2006). "Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia.". Phytomedicine : international journal of phytotherapy and phytopharmacology 13 (6): 428–33. doi:10.1016/j.phymed.2005.02.002. PMID 16716913. 
  51. ↑ Khan, A.; Safdar, M; Ali Khan, MM; Khattak, KN; Anderson, RA (2003). "Cinnamon Improves Glucose and Lipids of People With Type 2 Diabetes". Diabetes Care 26 (12): 3215. doi:10.2337/diacare.26.12.3215. PMID 14633804. 
  52. ↑ Jarvill-taylor, Karalee J; Anderson, Richard A; Graves, Donald J (2001). "A Hydroxychalcone Derived from Cinnamon Functions as a Mimetic for Insulin in 3T3-L1 Adipocytes". Journal of the American College of Nutrition 20 (4): 327. PMID 11506060. http://www.jacn.org/cgi/content/full/20/4/327. 
  53. ↑ Anderson, Richard A. (23 August 2005). "Cinnamon, Glucose Tolerance and Diabetes". Agricultural Research Service. http://www.ars.usda.gov/Research/docs.htm?docid=8877. Retrieved 2 October 2009. 
  54. ↑ White, John R. (25 December 2008). "Cinnamon: Should It Be Taken as a Diabetes Medication?". Diabetes Health. http://www.diabeteshealth.com/read/2008/12/25/5703/cinnamon-should-it-be-taken-as-a-diabetes-medication/. Retrieved 2 October 2009. 
  55. ↑ Sherman, L; Glennon, JA; Brech, WJ; Klomberg, GH; Gordon, ES (1968). "Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus". Metabolism 17 (5): 439. doi:10.1016/0026-0495(68)90066-8. PMID 4869710. 
  56. ↑ Lee, NA; Reasner, CA (1994). "Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM". Diabetes care 17 (12): 1449–52. doi:10.2337/diacare.17.12.1449. PMID 7882815. 
  57. ↑ Hermann, Janice; Chung, Hyunhee; Arquitt, Andrea; Goad, Carla; Burns, Michelle; Chan, Benjamin (1999). "Effects of Chromium or Copper Supplementation on Plasma Lipids, Plasma Glucose and Serum Insulin in Adults Over Age Fifty". Journal of Nutrition for the Elderly 18: 27. doi:10.1300/J052v18n01_03. 
  58. ↑ Press, RI; Geller, J; Evans, GW (1990). "The effect of chromium picolinate on serum cholesterol and apolipoprotein fractions in human subjects". The Western journal of medicine 152 (1): 41–5. PMID 2408233. 
  59. ↑ Evans, GW (1989). "The effect of chromium picolinate on insulin controlled parameters in humans". International Journal of Biosocial and Medical Research 11: 163–80. 
  60. ↑ Anderson, RA (1998). "Chromium, glucose intolerance and diabetes". Journal of the American College of Nutrition 17 (6): 548–55. PMID 9853533. 
  61. ↑ Anderson, RA (2000). "Chromium in the prevention and control of diabetes". Diabetes & metabolism 26 (1): 22–7. PMID 10705100. 
  62. ↑ Kleefstra, N; Houweling, ST; Bakker, SJ; Verhoeven, S; Gans, RO; Meyboom-De Jong, B; Bilo, HJ (2007). "Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial". Diabetes care 30 (5): 1092–6. doi:10.2337/dc06-2192. PMID 17303791. 
  63. ↑ Balk, EM; Tatsioni, A; Lichtenstein, AH; Lau, J; Pittas, AG (2007). "Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials". Diabetes care 30 (8): 2154–63. doi:10.2337/dc06-0996. PMID 17519436. 
  64. ↑ Halberstam, M; Cohen, N; Shlimovich, P; Rossetti, L; Shamoon, H (1996). "Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects". Diabetes 45 (5): 659–66. doi:10.2337/diabetes.45.5.659. PMID 8621019. 
  65. ↑ Boden, G; Chen, X; Ruiz, J; Van Rossum, GD; Turco, S (1996). "Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non?insulin-dependent diabetes mellitus*1". Metabolism 45 (9): 1130. doi:10.1016/S0026-0495(96)90013-X. PMID 8781301. 
  66. ↑ Goldfine, A; Patti, ME; Zuberi, L; Goldstein, BJ; Leblanc, R; Landaker, EJ; Jiang, ZY; Willsky, GR et al. (2000). "Metabolic effects of vanadyl sulfate in humans with non—insulin-dependent diabetes mellitus: In vivo and in vitro studies". Metabolism 49 (3): 400. doi:10.1016/S0026-0495(00)90418-9. PMID 10726921. 
  67. ↑ Badmaev, Vladimir; Prakash, S; Majeed, M (1999). "Vanadium: A Review of its Potential Role in the Fight Against Diabetes". The Journal of Alternative and Complementary Medicine 5 (3): 273. doi:10.1089/acm.1999.5.273. PMID 10381252. 
  68. ↑ Goldwaser, I; Li, J; Gershonov, E; Armoni, M; Karnieli, E; Fridkin, M; Shechter, Y (1999). "L-Glutamic acid gamma-monohydroxamate. A potentiator of vanadium-evoked glucose metabolism in vitro and in vivo". The Journal of biological chemistry 274 (37): 26617–24. doi:10.1074/jbc.274.37.26617. PMID 10473627. 
  69. ↑ Christiansen, Melanie (20 December 2005). "Tai Chi a promising remedy for diabetes". Australian Broadcasting Corporation. http://www.abc.net.au/pm/content/2005/s1535304.htm.  - Pilot study of qigong and T'ai Chi in diabetes sufferers.
  70. ↑ Du, X; Edelstein, D; Brownlee, M (2008). "Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes". Diabetologia 51 (10): 1930–2. doi:10.1007/s00125-008-1100-2. PMID 18663426. 
  71. ↑ Hammes, HP; Du, X; Edelstein, D; Taguchi, T; Matsumura, T; Ju, Q; Lin, J; Bierhaus, A et al. (2003). "Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy". Nature medicine 9 (3): 294–9. doi:10.1038/nm834. PMID 12592403. 
  72. ↑ Stracke, H; Gaus, W; Achenbach, U; Federlin, K; Bretzel, RG (2008). "Benfotiamine in diabetic polyneuropathy (BENDIP): results of a randomised, double blind, placebo-controlled clinical study". Experimental and clinical endocrinology & diabetes 116 (10): 600–5. doi:10.1055/s-2008-1065351. PMID 18473286. 
  73. ↑ Babaei-Jadidi, R; Karachalias, N; Ahmed, N; Battah, S; Thornalley, PJ (2003). "Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine". Diabetes 52 (8): 2110–20. doi:10.2337/diabetes.52.8.2110. PMID 12882930. 
  74. ↑ Swanston-Flatt, SK; Day, C; Bailey, CJ; Flatt, PR (1990). "Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice". Diabetologia 33 (8): 462–4. doi:10.1007/BF00405106. PMID 2210118. 
  75. ↑ Matsuur, H; Asakawa, C; Kurimoto, M; Mizutani, J (2002). "Alpha-glucosidase inhibitor from the seeds of balsam pear (Momordica charantia) and the fruit bodies of Grifola frondosa". Bioscience, biotechnology, and biochemistry 66 (7): 1576–8. doi:10.1271/bbb.66.1576. PMID 12224646. 
  76. ↑ Fortes, RC; Novaes, MR; Recôva, VL; Melo, AL (2009). "Immunological, hematological, and glycemia effects of dietary supplementation with Agaricus sylvaticus on patients' colorectal cancer". Experimental biology and medicine 234 (1): 53–62. doi:10.3181/0806-RM-193. PMID 18997106. 
  77. ↑ Kiho, T; Sobue, S; Ukai, S (1994). "Structural features and hypoglycemic activities of two polysaccharides from a hot-water extract of Agrocybe cylindracea". Carbohydrate research 251: 81–7. doi:10.1016/0008-6215(94)84277-9. PMID 8149381. 
  78. ↑ Vogler BK, Ernst E (October 1999). "Aloe vera: a systematic review of its clinical effectiveness". Br J Gen Pract 49 (447): 823–8. PMID 10885091. 

References

  • Lebovitz, Harold E. (2004). Therapy For Diabetes Mellitus and Related Disorders (4th ed.). Alexandria, VA: American Diabetes Association. ISBN 1-58040-187-2. 
  • Adams, Michael Ian; Holland, Norman Norwood (2003). Core Concepts in Pharmacology. Englewood Cliffs, NJ: Prentice Hall. ISBN 0-13-089329-3. 


Oral anti-diabetic drugs and Insulin analogs (A10)
Insulin
Biguanides
Metformin# · Buformin‡ · Phenformin‡
TZDs (PPAR)
Pioglitazone · Rivoglitazone† · Rosiglitazone · Troglitazone‡
Dual PPAR agonist
Aleglitazar† · Muraglitazar§ · Tesaglitazar§
K+ ATP
Sulfonylureas

1st generation: Acetohexamide · Carbutamide · Chlorpropamide · Gliclazide · Tolbutamide · Tolazamide

2nd generation: Glibenclamide (Glyburide)# · Glipizide · Gliquidone · Glyclopyramide

3rd generation: Glimepiride
Meglitinides/"glinides"
Nateglinide · Repaglinide · Mitiglinide
GLP-1 analogs
Exenatide · Liraglutide · Taspoglutide† · Albiglutide† · Lixisenatide
DPP-4 inhibitors
Alogliptin† · Linagliptin† · Saxagliptin · Sitagliptin · Vildagliptin
Analogs/other insulins
fast acting (Insulin lispro · Insulin aspart · Insulin glulisine) · short acting (Regular insulin) · long acting (Insulin glargine · Insulin detemir · NPH insulin) · ultralong acting (Insulin degludec†) · Inhalable Insulin Exubera‡
Other
Alpha-glucosidase inhibitors
Acarbose · Miglitol · Voglibose
Amylin analog
Pramlintide
SGLT2 inhibitors
Canagliflozin† · Dapagliflozin† · Remogliflozin† · Sergliflozin†
Other
Benfluorex · Tolrestat‡
#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III

: END

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proc, drug (A10/H1/H2//)
Pharmacology: major drug groups
Gastrointestinal tract/metabolism (A)
stomach acid (Antacids, H2 antagonists, Proton pump inhibitors) • Antiemetics • Laxatives • Antidiarrhoeals/Antipropulsives • Anti-obesity drugs • Anti-diabetics • Vitamins • Dietary minerals
Blood and blood forming organs (B)
Antithrombotics (Antiplatelets, Anticoagulants, Thrombolytics/fibrinolytics) • Antihemorrhagics (Platelets, Coagulants, Antifibrinolytics)
Cardiovascular system (C)

cardiac therapy/antianginals (Cardiac glycosides, Antiarrhythmics, Cardiac stimulants)

Antihypertensives • Diuretics • Vasodilators • Beta blockers • Calcium channel blockers • renin-angiotensin system (ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors)

Antihyperlipidemics (Statins, Fibrates, Bile acid sequestrants)
Skin (D)
Emollients • Cicatrizants • Antipruritics • Antipsoriatics • Medicated dressings
Genitourinary system (G)
Hormonal contraception • Fertility agents • SERMs • Sex hormones
Endocrine system (H)
Hypothalamic-pituitary hormones • Corticosteroids (Glucocorticoids, Mineralocorticoids) • Sex hormones • Thyroid hormones/Antithyroid agents
Infections and infestations (J, P, QI)
Antimicrobials: Antibacterials (Antimycobacterials) • Antifungals • Antivirals • Antiparasitics (Antiprotozoals, Anthelmintics, Ectoparasiticides) • IVIG • Vaccines
Malignant disease (L01-L02)
Anticancer agents (Antimetabolites, Alkylating, Spindle poisons, Antineoplastic, Topoisomerase inhibitors)
Immune disease (L03-L04)
Immunomodulators (Immunostimulants, Immunosuppressants)
Muscles, bones, and joints (M)
Anabolic steroids • Anti-inflammatories (NSAIDs) • Antirheumatics • Corticosteroids • Muscle relaxants • Bisphosphonates
Brain and nervous system (N)
Analgesics • Anesthetics (General, Local) • Anorectics • Anti-ADHD Agents • Antiaddictives • Anticonvulsants • Antidementia Agents • Antidepressants • Antimigraine Agents • Antiparkinson's Agents • Antipsychotics • Anxiolytics • Depressants • Entactogens • Entheogens • Euphoriants • Hallucinogens (Psychedelics, Dissociatives, Deliriants) • Hypnotics/Sedatives • Mood Stabilizers • Neuroprotectives • Nootropics • Neurotoxins • Orexigenics • Serenics • Stimulants • Wakefulness-Promoting Agents
Respiratory system (R)
Decongestants • Bronchodilators • Cough medicines • H1 antagonists
Sensory organs (S)
Ophthalmologicals • Otologicals
Other ATC (V)
Antidotes • Contrast media • Radiopharmaceuticals • Dressings
Diabetes (E10-E14, 250)
Types of diabetes

Prediabetes (Impaired fasting glucose, Impaired glucose tolerance)

Type 1 · Type 2 · MODY · NDM (Transient, Permanent)

Diabetes and pregnancy: Gestational diabetes
Blood tests
Blood sugar · Glycosylated hemoglobin · Glucose tolerance test · Fructosamine
Diabetes management
Diabetic diet  · Anti-diabetic drugs · Insulin therapy · Glossary of diabetes
Complications/prognosis
Diabetic comas (Diabetic hypoglycemia, Diabetic ketoacidosis, Nonketotic hyperosmolar) · Diabetic angiopathy · Diabetic myonecrosis · Diabetic nephropathy · Diabetic neuropathy · Diabetic retinopathy · Diabetic cardiomyopathy · Diabetic dermadrome (Diabetic dermopathy, Diabetic bulla, Diabetic cheiroarthropathy, Neuropathic ulcer)

: END

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