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New Diabetes Drugs Prevent Glucose Reabsorption in the Kidney



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Diabetes mellitus is a group of common metabolic disorders characterized by increased blood glucose levels. They are caused by a complex interplay of environmental and genetic factors. In diabetes mellitus, increased blood glucose is caused by a decreased insulin (a hormone secreted by the pancreas that is necessary for glucose utilization) level, reduced glucose utilization by the tissues and increased glucose production by the liver.

Diabetes mellitus can be classified broadly into type 1 and type 2.  In type 1 diabetes, there is a complete insulin deficiency. Type 2 diabetes is characterized by variable degrees of insulin deficiency and insulin resistance by the tissues of the body.

Increased glucose levels cause various complications such as reduced immunity, eye problems, neuropathy or nerve problems, and kidney failure. Diabetes mellitus is treated with insulin and oral anti-diabetic drugs.

What are the common types of diabetes drugs besides insulin?

Anti-diabetes drugs (currently approved) act by increasing the insulin level in the body, inhibiting glucagon (a hormone responsible for increasing blood glucose) levels, decreasing glucose absorption by the gut and decreasing insulin resistance in body tissues.

Sulfonyl ureas (Gliclazide, Glibenclamide) and Meglitinides (Prandin®) work by increasing insulin secretion by the pancreas. Sitagliptin works by inhibiting the glucagon hormone in the body. Metformin works by decreasing peripheral glucose resistance. In addition, Acarbose works by decreasing glucose absorption by the gut.

New glucose reabsorption inhibitor drug class

This drug class was developed by Bristol-Myers Squibb in partnership with AstraZeneca (dapagliflozin) and GlaxoSmithkline (sergliflozin). Several clinical trials have confirmed the effectiveness of this drug class (PMID: 18996802).

How these new drugs act

Human kidneys excrete stuff in two levels. In the first level kidney blindly excretes lots of stuff and forms the glomerular filtrate. In the second level, it intelligently reabsorbs necessary chemicals from the glomerular filtrate into the blood stream and the rest goes as urine. Here glucose is reabsorbed, because it is a necessary to the body.

These new drugs inhibit the transporter necessary for this mechanism. It is called the SGLT2 transporter. By way of inhibiting the SGLT2 transporter, this drug promotes glucose excretion from the body. This results in reduced glucose levels in the body. In addition, it is not dependent on insulin. Therefore this drug acts even in the extreme insulin deficiency seen in late diabetes mellitus.

Effectiveness of this new therapy

Several phase 3 trials confirmed the effectiveness of this novel therapy (NCT00528879). It is in the final stages of development and will be released to the market after formal FDA approval.  Most of the data on side effects are also not yet finalized. However, patientville website lists some side effects of this new therapy. Most of them are not confirmed.

Conclusion

For the patients, it is a little too early to try the new therapy. It is also prudent to wait until some more data is available on this drug class before asking the doctor to prescribe it.

Sources

Harrison principles of internal Medicine 17th edition


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ARTICLE SOURCES AND CITATIONS
  • InfoBoxCallToAction ActionArrowhttp://diabetes.webmd.com/sulfonylureas-for-type-2-diabetes
  • InfoBoxCallToAction ActionArrowhttp://diabetes.webmd.com/meglitinides-for-type-2-diabetes
  • InfoBoxCallToAction ActionArrowhttp://www.nlm.nih.gov/medlineplus/druginfo/meds/a606023.html
  • InfoBoxCallToAction ActionArrowhttp://www.nlm.nih.gov/medlineplus/druginfo/meds/a696015.html
  • InfoBoxCallToAction ActionArrowhttp://ctr.bms.com/OneBmsCtd/InitTrialDetailAction.do?pnum=MB102-020
  • InfoBoxCallToAction ActionArrowhttp://jpet.aspetjournals.org/content/320/1/323.full
  • InfoBoxCallToAction ActionArrowhttp://www.ncbi.nlm.nih.gov/pubmed/18996802
  • InfoBoxCallToAction ActionArrowhttp://www.clinicaltrials.gov/ct2/show/NCT00528879?term=NCT00528879&rank=1
  • InfoBoxCallToAction ActionArrowhttp://www.patientsville.com/medication/dapagliflozin_side_effects.htm