Diabetes and its treatment by FDA Approved Drugs

Diabetes and its treatment by 4 FDA Approved Drugs

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Last edited and updated on: by Sagar Aryal

Diabetes is a set of condition that occurs due to disruptions in metabolism which is described by high blood sugar level that results from the deficiency of secretion of insulin, action of insulin, or both of the phenomenon is called diabetes [1]. Here in this, I will be discussing diabetes and its treatment by FDA Approved Drugs.

Diabetes and its treatment by FDA Approved Drugs

Types of diabetes

Two major categories of diabetes mellitus (DM) are present namely; type 1 & type 2. There is a lack of production of insulin as well as deterioration of the pancreatic beta cells in type 1 diabetes (T1D).

However, the release of insulin is impaired and the insensitivity of insulin is enhanced also the tissues cease to respond towards insulin in type 2 diabetes (T2D) [2-4].

Prevalence

The International Diabetes Federation projects that the prevalence of diabetes will expand from the present estimation of 415 million to 642 million people by 2040, of which greater than 90% have type 2 diabetes [5]. Contributing to the prevalence of diabetes, it has become the need of the time to get the treatment of diabetes by FDA Approved drugs.

  • Approximately 68% of individuals of more than 65 years of age with DM (diabetes mellitus) expire due to heart diseases in the USA [6].
  • It is greatly understood that type 2 diabetes mellitus (T2DM) builds the possibility of cardiovascular disease (CVD) two to three times more [7].
  • DM amplifies the possibility of heart failure [8] and antagonistically influences the results among patients with HF [6].

Glucose Lowering Products

The glucose-lowering products when given orally or injected in the body, alteration in taking diet and regular exercise can lead to the treatment of diabetes to a great extent.

  • The lowering of the level of glucose in the blood up to the normal levels is the ultimate goal of the therapies that manage T2D [9].
  • The growth, as well as progress of the complication of diabetes, can be reduced by maintaining the levels of glucose toward normal range [10].
  • There is little question that most of the pharmacologic treatments for normal disorders have a fundamentally limited the problem of the ailment and improve the personal satisfaction for people that are affected by the disease [9].

Treatment by FDA Approved Drugs

Numerous medications are available in the pharmacies for diabetes. Our main focus is the FDA approved drugs for the treatment of diabetes [11].

T2D is also treated pharmacologically with medicines that are ratified.

  • α-glucosidase inhibitors, sulfonylureas, thiazolidinediones, insulin with similar compounds, meglitinides, and biguanides come under the heading of such medicines [9].

A lot of questions have been raised for the effectiveness of the treatment of diabetes in recent years by the administration of numerous medications [11, 12].

Following are the FDA approved drugs that are widely used for the treatment of diabetes:

1. Sulfonylureas

  • Sulfonylureas are one of the most widely used classes of oral hypoglycemic agents.
  • The 1st generation, as well as the 2nd generation sulfonylureas, is present in the category of the insulin-secreting agents that treat diabetes.
  • The K+ channels present in beta cells of the pancreas are closed which stimulates the release of insulin thereby treating T2D [13, 14].
  • The receptors present in the plasma membrane which have a high attraction binds the pancreatic the β-cells, as a result insulin is released.
  • Potassium channels that depend upon ATP have a connection with these receptors. Due to this boundary, the closing of K+ channels occurs.

Through this contact, the efflux of potassium is inhibited and the plasma membrane is depolarized then the channels of calcium get opened. The inflow of Ca2+ with the increased levels of calcium results in the insulin release from the β-cells [9].

2. Metformin

  • In the presence of insulin, metformin regulates the levels of glucose through the reduction of the absorbed glucose from the alimentary tract, decline in the synthesis of glucose as well as decreased insensitivity towards insulin [14, 15].
  • The molecular mechanisms that are fundamental for the action of metformin began by means of the activation of the AMPK through a drug.
  • Through this, the production of glucose is repressed by means of gluconeogenesis and the elevated uptake of glucose from the peripheral tissues [16, 17].
  • The synthesis of glucose in the hepatic tissues is inhibited by metformin through the control of SHP which is dependent on AMPK. This is precarious to lower the glucose through metformin affecting in the liver [18, 19].
  • Meglitinides characterize a novel type of insulin-secreting agent that is not related to sulfonylureas in structure due to its quick beginning as well as a short time of reaction [20].
  • The glucose-lowering action is reduced by the stimulation of the secretion of insulin by meglitinides [14].

3. Thiazolidinediones

  • Glucose, as well as lipid degrading action, is stimulated by thiazolidinediones which act as sensitive agents of insulin the insensitivity of insulin is reduced and the reaction toward insulin is increased because TZDs act as the protagonist towards PPAR-γ [14].
  • Nuclear receptor PPAR consists of three types namely PPAR-α, PPAR-γ, as well as PPAR-δ [21]. PPARG2 has a protagonist which is known as TZDs, which is mainly articulated in adipose tissue, and it does not have a significant action on other types of PPAR [22].
  • TZD stimulation of PPARG2 is stimulated by TZD which results in the elevated levels of the differentiation of the adipose cells along with the decline in the high sugar levels of the patients suffering from T2D [23].
  • TZDs have various other influences that do not depend upon adipose tissues [9, 24].

4. Alpha-glucosidase inhibitors

  • Diabetes was controlled by the use of α-glucosidase inhibitors (AGIs) through the suppression of glucose which is being released from carbohydrates [25].
  • AGIs act similarly but not identically [26].
  • AGIs bind with the regions of α-glucosidase enzymes.
  • Hence, the competition of binding with enzyme between oligosaccharides and AGIs takes place which hinders with their attachment with monosaccharides [27].

References

  1. Association, A.D., Diagnosis and classification of diabetes mellitus. Diabetes care, 2014. 37(Supplement 1): p. S81-S90.
  2. Burcelin, R., et al., Encapsulated, Genetically Engineered Cells, Secreting Glucagon‐like Peptide‐1 for the Treatment of Non‐insulin‐dependent Diabetes Mellitus. Annals of the New York Academy of Sciences, 1999. 875(1): p. 277-285.
  3. Kaushik, G., et al., Commonly consumed Indian plant food materials in the management of diabetes mellitus. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2010. 4(1): p. 21-40.
  4. Balbaa, M., Diabetes and Cell Signaling. Biochem Physiol, 2016. 5: p. e151.
  5. Han Cho, N., International Diabetes Federation. IDF Diabetes Atlas, 7th ed. Brussels, Belgium: International Diabetes Federation, 2015: p. 10-60.
  6. Mozaffarian, D., et al., Executive summary: heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation, 2016. 133(4): p. 447-454.
  7. Fox, C.S., et al., Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation, 2007. 115(12): p. 1544-1550.
  8. Geisler, S., et al., PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nature cell biology, 2010. 12(2): p. 119.
  9. DiStefano, J.K. and R.M. Watanabe, Pharmacogenetics of anti-diabetes drugs. Pharmaceuticals, 2010. 3(8): p. 2610-2646.
  10. Holman, R.R., et al., 10-year follow-up of intensive glucose control in type 2 diabetes. New England Journal of Medicine, 2008. 359(15): p. 1577-1589.
  11. Modi, P., Diabetes beyond insulin: review of new drugs for treatment of diabetes mellitus. Current drug discovery technologies, 2007. 4(1): p. 39-47.
  12. Federation, I.D., Clinical Guidelines Task Force. Global guideline for type 2 diabetes. Brussels: International Diabetes Federation, 2005.
  13. Groop, L.C., Sulfonylureas in NIDDM. Diabetes care, 1992. 15(6): p. 737-754.
  14. Huang, Q. and Z.-q. Liu, Pharmacogenetics for T2DM and Anti-Diabetic Drugs, in Recent Advances in the Pathogenesis, Prevention and Management of Type 2 Diabetes and its Complications. 2011, IntechOpen.
  15. Kirpichnikov, D., S.I. McFarlane, and J.R. Sowers, Metformin: an update. Annals of internal medicine, 2002. 137(1): p. 25-33.
  16. Abbud, W., et al., Stimulation of AMP-activated protein kinase (AMPK) is associated with enhancement of Glut1-mediated glucose transport. Archives of biochemistry and biophysics, 2000. 380(2): p. 347-352.
  17. Zhou, G., et al., Role of AMP-activated protein kinase in mechanism of metformin action. The Journal of clinical investigation, 2001. 108(8): p. 1167-1174.
  18. Kim, Y.D., et al., Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase–dependent regulation of the orphan nuclear receptor SHP. Diabetes, 2008. 57(2): p. 306-314.
  19. Shaw, R.J., et al., The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science, 2005. 310(5754): p. 1642-1646.
  20. Glamočlija, U. and A. Jevrić-Čaušević, Genetic polymorphisms in diabetes: Influence on therapy with oral antidiabetics. Acta Pharmaceutica, 2010. 60(4): p. 387-406.
  21. Braissant, O., et al., Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha,-beta, and-gamma in the adult rat. Endocrinology, 1996. 137(1): p. 354-366.
  22. Spiegelman, B.M., PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes, 1998. 47(4): p. 507-514.
  23. Scherbaum, W., et al., Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study. Hormone and metabolic research, 2002. 34(10): p. 589-595.
  24. Diani, A., et al., Pioglitazone preserves pancreatic islet structure and insulin secretory function in three murine models of type 2 diabetes. American Journal of Physiology-Endocrinology and Metabolism, 2004. 286(1): p. E116-E122.
  25. Hanefeld, M. and F. Schaper, The role of alpha-glucosidase inhibitors (acarbose), in Pharmacotherapy of Diabetes: New Developments. 2007, Springer. p. 143-152.
  26. Puls, W., Pharmacology of glucosidase inhibitors, in Oral Antidiabetics. 1996, Springer. p. 497-534.
  27. Lebovitz, H.E., Alpha-glucosidase inhibitors. Endocrinology and metabolism clinics of North America, 1997. 26(3): p. 539-551.
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