Content Reviewers:Yifan Xiao, MD
Hypoglycemics are used to treat high blood sugar, a condition commonly known as diabetes mellitus.
As a quick review, Type 1 diabetes mellitus, which most commonly affects children and adolescents, arises when certain cells of the pancreas known as beta cells are unable to produce enough insulin to maintain normal blood glucose levels.
In this video, however, we’ll be focusing specifically on the use of non-secretagogues in the treatment of Type 2 diabetes.
It’s important to note, however, that diet and exercise should always be the first step in managing diabetes before initiating medications, and should generally be continued while on medication as well.
It's main mechanism of action is to decrease the production of new glucose from the liver, or to inhibit hepatic gluconeogenesis.
Activated AMPK inhibits certain genes that promote gluconeogenesis such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Thus, via AMPK activation, metFORMIN results in the reduction of gluconeogenesis.
Thus, metFORMIN increases insulin sensitivity in these tissues and promotes peripheral glucose uptake, and this reduces the overall levels of glucose in the blood.
Finally, besides diabetes type II, this medication can be used to treat polycystic ovarian syndrome, or short PCOS, and antipsychotic-induced weight gain in individuals with schizophrenia or schizoaffective disorder.
The most common side effects of metFORMIN are gastrointestinal disturbances such as diarrhea, nausea, vomiting, and abdominal cramps.
Typically, lactate is taken up by the liver and utilized in the process of hepatic gluconeogenesis.
In healthy individuals this excess lactate usually does not become problematic because the kidneys are able to excrete it in the urine.
In addition, since it can cause lactic acidosis, metformin is also contraindicated in individuals with liver impairment, alcoholism, and conditions that are associated with tissue anoxia and increased lactic acid production, such as heart failure, respiratory failure, or shock.
But, in contrast to metFORMIN, these medications have a slow onset of action, meaning they might require several weeks to develop their therapeutic effect.
They work as agonists at a receptor known as the peroxisome proliferator activated receptor gamma, or PPAR gamma.
Normally, this receptor is activated when ligands such as free fatty acids bind to it, after which, it binds to DNA and another receptor known as a retinoid X receptor.
In fact, these medications have been shown to increase insulin sensitivity or glucose uptake in peripheral tissues by 30-50%.
In addition, thiazolidinediones increase adiponectin levels, which is a hormone that inhibits hepatic gluconeogenesis; and stimulates glucose uptake by skeletal muscles, consequently decreasing blood glucose levels.
Furthermore, the thiazolidinediones also increase the synthesis of proteins involved in lipid metabolism.
The end result is a decrease in triglycerides, and increase in both high density lipoprotein or HDL and low density lipoprotein or LDL.
In terms of side effects, when used as monotherapy, these medications are rarely associated with hypoglycemia.
But, it’s important to note that they can cause fluid retention and edema, which can further increase the risk of heart failure; therefore, they are contraindicated in individuals with NYHA class III or IV heart failure.
Next, thiazolidinediones are associated with weight gain and increased risk of osteopenia and fractures.
There is also some concern that these medications can increase the risk of hepatitis and liver failure, and therefore liver enzymes must be monitored closely, particularly during the first few months of initiating therapy.
Now the next two classes of medications, the alpha glucosidase inhibitors and amylin analogues act directly upon the GI tract by delaying the breakdown of food and its excretion from the body.
Alpha glucosidase is an enzyme that is found in the brush border of the intestines and it breaks down oligosaccharides and disaccharides into simpler monosaccharide units, like glucose, which is eventually absorbed through the lining of the intestine and into the blood.
Alpha glucosidase inhibitors prevent this process and reduce intestinal glucose absorption; thus they should be taken just before meals.
This ultimately lowers postprandial glucose levels; but in contrast to the previous two groups, these medications lack an effect on fasting glucose!
This results in increased bacterial fermentation and gastrointestinal disturbances like gas, bloating, and diarrhea.
Therefore, if individuals on alpha-glucosidase inhibitors experience hypoglycemia, they should not be treated with sucrose since it will promote gastrointestinal side effects; instead, they should be treated with dextrose whose absorption is not inhibited.
Hypoglycemics are used to treat type II diabetes mellitus. They include drugs like sulfonylureas, biguanides, meglitinides, alpha-glucosidase inhibitors, and thiazolidinediones. Each type of medication works in a different way to lower blood sugar levels.
For example, sulfonylureas and meglitinides are secretagogues, meaning they stimulate the pancreas to produce more insulin. Biguanides inhibit production of new glucose from the liver. Alpha-glucosidase inhibitors prevent starch from being broken down into glucose in the gastrointestinal system, whereas thiazolidinediones make tissues more sensitive to insulin.
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