In general, medication is started when blood sugar is not controlled well by diet or exercise. Depending on your glycemic control, you may only take oral hypoglycemics, or you may use a combination of medications and insulin injections or only injections alone. However, even if you start medication, you must have a combination of diet and exercise.
Types and Actions of Oral Glucose Lowering Agents
Commonly used oral hypoglycemic drugs can be classified into five types according to the mechanism of action. Insulin secretagogues that act on the beta-cells of the pancreas, metformin, which inhibits sugar production in the liver, glitazone-based drugs that improve insulin resistance, and alpha glucosidase, which inhibits carbohydrate absorption by inhibiting carbohydrates from being digested into monosaccharides in the small intestine Inhibitors, and recently developed and used DPP4 inhibitor drugs.
The main mechanism of action of oral hypoglycemic agents
1. Selection of drugs
In type 2 diabetes, oral hypoglycemic agents should be considered when glycated hemoglobin levels are above 7%. Of course, while taking medication, exercise and diet should be used together.
The choice of oral hypoglycemic drugs depends on the age or weight of the patient and the accompanying disease or health risks. In addition, by combining two or three kinds of drugs of different mechanisms, a method of reducing side effects of drugs and increasing blood sugar strengthening effect is commonly used.
In general, the first use of sulfonurea or metformin alone, the two drugs are often used together, there is no significant difference in blood sugar lowering effect. However, metformin is a drug that is considered as a priority because it has a lower risk of hypoglycemia and no weight gain than sulfone urea. Alphaglucosidase inhibitors (acarbose) are effective in reducing postprandial blood sugar by inhibiting the absorption of carbohydrates after eating.
2. Insulin Secretagogue
Insulin secretagogues include sulfone urea and non-sulfonurea and recently developed meglitinides.
Sulfonate is the most widely used drug in the treatment of type 2 diabetes, which lowers blood sugar by promoting insulin secretion from the beta cells of the pancreas. Sulfon urea is effective when there is a lack of insulin in the blood but sufficient insulin secretion remains in the pancreatic cells. Therefore, it is effective against relatively newly diagnosed type 2 diabetes and the longer the period of diabetes, the less effective the drug.
Because of the differences in half-life, daily dose, daily dose, and excretion position between each sulfonate agent, the patient’s characteristics should be selected.
Most sulfone urea drugs start at about half a grain and are increased in half every 1 to 2 weeks. If your blood sugar is not well controlled with sulfone urea, use up to half the maximum dose of sulfone urea, rather than increasing it to the maximum, and if ineffective, add metformin, glitazone or alpha glucosidase inhibitors to reduce side effects and effectively lower can.
The most important side effect of using sulfone urea is hypoglycemia. Therefore, you should be aware of any symptoms of hypoglycemia, such as tremors, palpitations, nausea, dizziness, and headaches. To avoid hypoglycemia, start at the lowest possible dose, increase in stages, and avoid skipping meals after taking medication. And sulfonate may increase your weight slightly after taking it, so you should manage your weight more thoroughly.
Among the insulin secretagogues, meglitinide-based drugs have the same effect of lowering blood sugar as sulfone urea, but they are absorbed rapidly and the effect is fast (time to reach the highest blood level: 42 minutes). It has fewer side effects than hypoglycemia and effectively lowers postprandial blood sugar, especially with fasting blood sugar. On the other hand, meglitinide is a recently developed drug that is more expensive than sulfone urea and has less clinical experience and data.
3. Biguanide (Metformin)
Metformin lowers blood sugar by inhibiting the production of sugar in the liver and increasing the absorption and utilization of sugar in the muscles. Metformin does not promote insulin secretion, so it does not cause hypoglycemia when used alone. Metformin also has anti-inflammatory and antihyperlipidemic effects. Metformin is therefore useful for diabetics with obesity or metabolic syndrome.
Metformin is rapidly absorbed from the gastrointestinal tract, the plasma half-life is 1.5-4 hours and peak plasma concentrations are reached 1-3 hours after absorption. It is excreted in the urine 24 to 36 hours after taking it.
Metformin starts with 500 mg once daily and is taken with meals to reduce gastrointestinal side effects. 500 mg in 1 to 2 week intervals, with a maximum dose of 2,500 mg per day. The most common side effects are gastrointestinal symptoms such as bloating, nausea and diarrhea. In this case, reducing the dose usually alleviates the symptoms, but in about 10% of patients, medications are discontinued due to side effects.
The most important thing to consider when using metformin is lactic acidosis. Although the incidence rate is very small, about three per 100,000 people a year, care should be taken because the mortality rate is over 30%. Most lactic acidosis is manifested by improper use and rarely in normal use.
The most important contraindication is a decrease in renal function. If your blood creatinine concentration is more than 1.5 mg / dL, we recommend that you use another medication. It should also be avoided for severe liver disease, alcoholism, heart failure (myocardial infarction, heart failure, shock), and hypoxia (pulmonary disease). You should also temporarily stop taking metformin when you need to use intravenous contrast agents for imaging tests, such as CT or MRI.
4. Alpha Glucosidase Inhibitors
Alpha glucosidase inhibitors reduce post-prandial hyperglycemia by inhibiting disaccharide degrading enzymes in the small intestine, delaying carbohydrate absorption in the intestine. In type 2 diabetes, alpha-glucosidase inhibitors are particularly useful in patients with uncontrolled post-prandial blood sugar, since elevated blood sugar levels are closely related to the development of cardiovascular disease. In addition, the drug does not cause weight gain and some studies have reported an effect on lowering triglycerides in the blood. And in a high-risk group of diabetics with impaired glucose tolerance, acarbose can reduce the incidence of diabetes. The drug is absorbed in extremely small amounts after oral administration and acts locally in the small intestine, so there is little systemic action by the drug.
Alpha glucosidase inhibitors should be taken just before or with a meal. The most common side effects are gastrointestinal symptoms such as abdominal pain, diarrhea, gas in the abdomen, and farts. These side effects are proportional to the dose, so start with small doses and gradually increase. For acarbose, the maximum dose is 100 mg three times a day. And at high doses, the level of liver function sometimes increases, so hepatic function tests should be done periodically when using the maximum dose. If liver function levels rise, doses should be reduced until levels reach normal ranges. Acarbose does not usually cause hypoglycemia, but care should be taken because congestion of sulfone urea tends to increase the frequency of hypoglycemia. If you have low blood sugar, you should take glucose solution because common methods like juice or candy are not effective.
The main mechanism of action of this drug is to stimulate peroxisome proliferators-activated receptror γ (PPAR γ), a nuclear receptor, which enhances the sensitivity of insulin in the body. Troglitazone was first introduced and used in 1997, but three years later it was banned because it caused lethal idiopathic hepatotoxicity. The use of rosiglitazone was subsequently restricted due to controversy over cardiovascular side effects. Pioglitazone and lobeglitazone are currently used, and these drugs have not been observed to date. It is effective in diabetics who have insulin resistance but have lower blood sugar lowering effects than sulfone urea or metformin. In addition, this drug has anti-inflammatory effect, improves blood lipids and lowers blood pressure, which is expected to have a positive effect on the prevention of cardiovascular diseases.
The most important side effects of this drug are edema and weight gain. It can also lead to anemia. Therefore, heart failure is contraindicated in heart failure and should not be used in active liver disease. Patients using insulin should be careful because they can increase the incidence of heart failure. Robeglitazone should not be used if lactose intolerance is caused by poor milk consumption. In addition, liver function should be measured periodically and should be discontinued when liver enzyme levels rise above 2.5 times normal levels. In addition, the maximum effect does not appear until two to three months after taking the drug, so this should be taken into account when used with concomitant medications.
6. DPP-4 Inhibitors
Recently, oral DPP4 inhibitors have been used for the treatment of type 2 diabetes, which is known to be a relatively safe drug that acts on the various mechanisms required for blood sugar control in our body, resulting in a hypoglycemic effect. The drug lowers blood sugar by inhibiting the breakdown of glucagon-like peptides in the body, increasing insulin secretion and suppressing post-prandial glucagon secretion.
Citagliptin, Bildagliptin, Saxagliptin, Linagliptin, Gemigliptin, Allogliptin, Teneregliptin, etc. are used. It is taken once a day except for bilagliptin. Mainly used with metformin. These drugs are effective if you have high blood sugar after meals.
Insulin injection therapy is an essential drug for type 1 diabetes, characterized by damage to the pancreatic beta cells. In addition, type 2 diabetes may be administered when the target blood glucose level is not reached even though the oral hypoglycemic agent is administered alone or in combination. In this case, sustained oral hypoglycemic agents, with persistent insulin or insulin analogues once daily, have a good effect on glycemic control.
Insulin Injection and Glycemic Control
Insulin or insulin analogues are categorized into fast-acting, intermediate, and sustained forms according to the duration of action (Table 5). Fast-acting forms are administered either pre or postprandially, to prevent elevated blood sugar levels after meals. Is used to maintain a constant insulin level throughout the day. You can also use products that have a mix of fast-acting and sustained forms. Insulins can be used several times a day, including sustained, mixed or intermediate insulin, twice a day mixed insulin, continuous and fast-acting insulin at mealtime and before bedtime. There are many ways to inject and choose according to the patient’s condition.
An important side effect of insulin is hypoglycemia. In addition, localized hypertrophy can occur when an injection is made in the same area. Fat hypertrophy occurs in many patients, and it is not only cosmetically bad, but it also requires careful attention because of poor blood sugar control due to obstructed absorption of insulin. In addition, insulin can increase your weight, so make sure you do your best to avoid weight gain through diet and exercise.
Precautions for Drug Therapy
1. Medication and meal therapy require regular habits.
Irregular eating habits make it difficult to control blood sugar, and depending on the drug, it can increase side effects such as hypoglycemia.
2. Regularly measuring and recording blood glucose is the data to confirm the efficacy.
Proper blood glucose measurement and recording is an important source of information to help determine whether your blood sugar is controlled and why it can’t be controlled and to help doctors choose the right medications and dosages.
3. If you forget to take your medicine, take it immediately.
However, if the next dose is close, do not forget and eat according to the next dose. (Don’t take two doses at a time) For drugs that control post-prandial blood sugar, it is recommended to combine with regular meals to prevent hypoglycemia.
4. Adverse reactions (side effects) should be discussed with your doctor or pharmacist.
If you experience any adverse reactions (adverse events) that occur during the initial or continuation of your medication, do not stop taking it yourself and consult your healthcare provider.
Other information: hypoglycemia
Hypoglycemia often refers to a phenomenon in which blood sugar falls below the required amount of energy metabolism after administration of insulin or oral hypoglycemic agents. Usually, it means that the blood sugar is 45 ~ 50 mg / dL or less, but the blood sugar level that causes the hypoglycemic symptoms is large and individual differences are not diagnosed only by the blood sugar level. Therefore, when the symptoms of hypoglycemia, the measurement of hypoglycemia on blood tests, and the administration of sugar, symptoms of loss of symptoms, etc. are comprehensively diagnosed. Hypoglycemia is an important condition that can lead to severe loss of life, so patients receiving diabetes should be aware of the symptoms of hypoglycemia and be able to take corrective action.
Hypoglycemia often causes symptoms such as sweating, shaking hands, rapid pulse, feeling of fasting and poor concentration. Hypoglycemia manifests itself when people skip food, eat too little food, eat too much insulin, or eat heavy exercise or alcohol. If you have low blood sugar, eat candy, chocolate, juice, biscuits, and other carbohydrates, such as bread and rice, for quick sugar intake. After taking food or sugar, you should have a liver blood glucose test 10 to 20 minutes later to record your blood sugar and consult your doctor. If a patient becomes unconscious and it is difficult to consume oral food, the patient should be taken immediately to a nearby emergency room and given intravenous glucose solution.