Drug Treatment for Diabetes

• The aim of treatment is to control high blood sugar and prevent the occurrence of complications due to sustained high blood sugar. More specifically, HbA1c test should be < 7%, fasting capillary plasma glucose values measured by the common glucose meters between 70 mg/dL (3.9 mmol/L) and 130 mg/dL (7.2 mmol/L), and peak postprandial (2 hours after a meal) capillary plasma glucose less than 180 mg/dL (10 mmol/L).
• Treatment is lifetime. The patient should take his/her drugs on a daily basis.
• Treatment of type 1 diabetes is based on daily insulin injections.
• The first step upon diagnosis of type 2 diabetes in most cases includes lifestyle interventions and metformin.
• Further treatment options include (i) medicines (pills) alone, (ii) medicines plus insulin or (iii) insulin alone.
• The physician will tailor the drug treatment according to the individual patient’s characteristics (“individualized” therapy), by taking into account several factors such as the required effectiveness, the effects on weight, the risk of hypoglycemia, major side effects and cost.

There are several medicines that are commonly used to treat diabetes, and these are divided in the following broad categories according to the way they act:

Insulin sensitizers

These medications improve the body’s response to its own insulin by making tissues more sensitive to it. These include metformin and thiazolidinediones. Metformin is most often used as a first step in the treatment of newly diagnosed type 2 diabetics. Actually, all diabetics unless contraindicated or intolerable should be started on metformin immediately after diagnosis. It is usually administered twice a day, and when taken with food, side effects are less. Another effect of the medicine which is desirable in some cases is weight loss. Thiazolidinediones help insulin work better in organs like fatty tissue and muscle, making them absorb more sugar from the blood. Also they reduce glucose production in the liver. These drugs cannot be used in patients with heart failure.

Insulin secretagogues

These drugs stimulate the pancreas to produce more insulin and include sulfonylureas (they have been used for more than 50 years) and meglitinides. Insulin is produced independently from blood sugar levels, so patients receiving these medicines are more prone to hypoglycemia episodes.

Incretin mimetics

After food is ingested, a hormone called GLP-1 is released from the gastrointestinal tract. This hormone lowers blood sugar, by stimulating insulin production and inhibiting glucose production. Medicines of this category imitate normal response of the body after a meal. There are two different types of medicines in this category: GLP-1 agonists and DPP4 inhibitors. GLP-1 agonists work like normal GLP-1, only for longer. They can also promote weight loss which is desirable in overweight/obese subjects. These drugs are injectable. Newer forms of longer release, injected once a week, are now available. DPP4 inhibitors slower the degradation of normal GLP-1 peptide by the enzyme DPP4, allowing it to work for longer. They can also promote weight loss. They are less potent than GLP-1 agonists.

Slowers of carbohydrate digestion (Alpha glucosidase inhibitors)

These drugs prevent ingested carbohydrates from splitting, making the absorption of sugar difficult and delayed, thus lowering blood sugar.

Glycosurics (SGLT2 inhibitors)

These drugs promote the clearance of glucose from the kidneys, by increasing its secretion in the urine. They are not available worldwide yet.

Insulin

All types of insulin are injectable. Insulin is categorized according to the time required for the onset of action (how fast it reaches the blood) and how long it works after injection:

• Rapid acting – acts in 15 minutes, action peaks at 1 hour, works for 2-4 hours.
• Short acting – acts in 30 minutes, action peaks at 2-3 hours, works for 3-6 hours.
• Intermediate acting – acts in 2-4 hours, action peaks at 4-12 hours, works for 12-18 hours.
• Long acting – acts after several hours, works for 24 hours.

Insulin can be administered either alone, or in combinations of different types of insulin depending on the patients’ habits, preferences and sugar metabolism. It can also be administered continuously through a pump.

• Medicines alone.
• Medicines + Insulin.
• Insulin alone.

All options are open depending on patient (body type, underlying disease, preferences) and glucose control.

Although generally well-tolerated, drugs can cause side effects.

Some side effects, such as hypoglycemia, can result from an excessive lowering of blood sugar (usually below 70 mg/dl), and therefore can be caused by any medication. However, not all the medications carry the same risk. This risk is higher with insulin and insulin secretagogues. Hypoglycemia can be very mild and non significant but if remains untreated can become life-threatening. Symptoms can differ from person to person. The most accurate way to diagnose hypoglycemia is to measure blood sugar, but people with diabetes must be trained to recognize promptly hypoglycemia symptoms.

Most common symptoms of hypoglycemia include:

• Shakiness, sweating, chills, pallor, fast heartbeat
• Hunger and nausea
• Nervousness, anxiety, irritability
• Anger, stubbornness, or sadness
• Fatigue, sleepiness
• Headache, lightheadedness, dizziness
• Blurred vision, numbness of the lips or tongue
• Confusion, lack of coordination, delirium
• Seizures
• Unconsciousness

When experiencing hypoglycemia symptoms, a patient must consume as soon as possible 15-20 gr of glucose or simple carbohydrates. If a patient is unconscious due to hypoglycaemia, then glucagon (a hormone that releases sugar from the liver into the blood) must be administered from a ready-to-use glucagon kit along with medical help seek. It is always better to treat hypoglycemia when suspected and blood sugar cannot be measured, because untreated hypoglycemia is an emergency, while untreated high blood sugar can give you some time.

Other side effects, which are drug category-specific, include the following:

• Gastrointestinal symptoms (nausea, vomiting, bloating, diarrhea): Metformin, incretin mimetics, alpha glucosidase inhibitors.
• Sodium retention, edema: Thiazolidinediones
• Weight gain: Insulin, insulin secretagogues.
• Metabolic acidosis: Exremely rare and under certain circumstances with metformin.

• Lower blood pressure.
• Lower cholesterol.
• Quit smoking.
• Check blood sugar.
• Check eyes annually.
• Check feet (self exam every day, routine physical examination).
• Check kidneys annually.