How Do Antidiabetic Biguanides Dipeptidyl Peptidase-4 Inhibitors Work?

Antidiabetic biguanides/dipeptidyl peptidase-4 (DPP-4) inhibitors are combination medications used with a proper diet and exercise to control high blood sugar in people with type 2 diabetes mellitus (T2DM). T2DM is a long-term medical condition in which the body does not produce or use insulin normally and, therefore, cannot control the amount of sugar in the blood. Controlling high blood sugar helps in preventing kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems and may also reduce the risk of a heart attack or stroke. T2DM is a consequence of reduced sensitivity of muscle and fat to insulin, a hormone produced by the pancreas. The primary action of insulin is to control blood glucose levels by reducing the amount of glucose released by the liver into the blood and by enhancing the removal of glucose from the blood.

Biguanides/DDP-4 inhibitors are not used to treat insulin-dependent or type 1 diabetes (a condition in which the body does not produce insulin and therefore cannot control the amount of sugar in the blood) and diabetic ketoacidosis (increased ketones in the blood or urine).

Biguanides/DDP-4 inhibitors are administered orally (tablet and extended-release tablet) and are typically taken once or twice a day with meals.

Biguanides/DDP-4 inhibitors work in the following ways:

• Biguanides:
  • They work by increasing the amount of insulin produced by the body post meals when the blood sugar is expected to be high.
  • They activate an enzyme (AMPK) which increases the sensitivity to insulin (a natural substance that controls the amount of glucose in the blood produced by the pancreas), helping cells to respond more effectively to insulin and take in more glucose to use as energy and thus reduces the concentration of glucose in the bloodstream.
• DDP-4 inhibitors:
  • They block the action of DPP-4, an enzyme that destroys a group of gastrointestinal hormones called “incretins” (glucagon-like peptide-1 and gastric inhibitory peptide).
  • Incretins help to stimulate the production of insulin when it is needed (after eating) and reduce the production of glucagon by the liver when it is not needed (during digestion). 
  • They increase incretin levels which inhibits glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and thus decreases the blood glucose levels.
  • They increase the excretion of sugar by the kidneys and decrease the amount of sugar made by the liver and absorbed by the stomach and intestines.
  • In addition, they increase the sensitivity of the liver, muscle, fat, and other tissues to the effects of insulin thus increasing the sensitivity of tissues to insulin which causes more glucose to be removed from the blood and thereby reduces the level of glucose in the blood.

Antidiabetic biguanides/DDP-4 inhibitors are indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM.

Some of the common side effects include:

• Diarrhea
• Nausea
• Vomiting
• Loss of appetite
• Stomach upset
• Bloating
• Frequent urination
• Dry mouth
• Weakness
• Asthenia (abnormal physical weakness or lack of energy)
• Flatulence (gas)
• Myalgia (muscle pain)
• Heartburn (burning pain in the chest)
• Dyspepsia (a feeling of burning, pain, or discomfort in the digestive tract)
• Unpleasant metallic taste in the mouth
• Headache
• Stuffy nose
• Sore throat

Other rare side effects include:

• Hypoglycemia (low blood sugar level)
  • Sudden sweating
  • Fast heartbeat
  • Blurred vision
  • Tingling in hands/feet
• Upper respiratory tract infection
• Dizziness (feeling faint, weak, or unsteady)
• Lactic acidosis (increased lactic acid in the bloodstream, which is produced when oxygen levels become low in cells within the areas of the body where metabolism occurs)
• Low serum vitamin B 12
• Joint pains
• Pancreatitis (inflammation of the pancreas)
• Abdominal distention
• Dyslipidemia (blood lipid levels that are too high or low)
• Bullous pemphigoid (a rare skin condition that causes large, fluid-filled blisters)
• Nasopharyngitis (an inflammatory attack of the pharynx and nasal cavities)
• Signs of heart failure
  • Shortness of breath
  • Swelling in ankles/feet
  • Unusual tiredness
  • Sudden weight gain
• Signs of kidney problems 
  • Change in the amount of urine
  • Swelling in legs/feet
• Signs of urinary tract infection
  • Burning/painful/frequent/urgent urination
  • Pink/bloody urine

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of antidiabetic biguanides/DDP-4 inhibitors include:

• Alogliptin/metformin
• Janumet
• Janumet XR
• Jentadueto
• Jentadueto XR
• Kazano
• Kombiglyze XR
• Linagliptin/metformin
• Metformin/sitagliptin
• Saxagliptin/metformin