Alpha-glucosidase inhibitors (AGIs) are oral

anti-diabetic drug Drugs used in diabetes treat types of diabetes mellitus by decreasing blood sugar level, glucose levels in the blood. With the exception of Insulin (medication), insulin, most GLP-1 receptor agonists (liraglutide, exenatide, and others), and pra ...

s used for

diabetes mellitus type 2 Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

that work by preventing the digestion of carbohydrates (such as

starch Starch or amylum is a polymeric carbohydrate consisting of numerous glucose units joined by glycosidic bonds. This polysaccharide is produced by most green plants for energy storage. Worldwide, it is the most common carbohydrate in human diet ...

and

table sugar White sugar, also called table sugar, granulated sugar, or regular sugar, is a commonly used type of sugar, made either of beet sugar or cane sugar, which has undergone a refining process. It is nearly pure sucrose. Description The refining ...

). Naturally occurring AGIs are found in raw plants/herbs such as

cinnamon Cinnamon is a spice obtained from the inner bark of several tree species from the genus ''Cinnamomum''. Cinnamon is used mainly as an aromatic condiment and flavouring additive in a wide variety of cuisines, sweet and savoury dishes, biscuits, b ...

and

white mulberry White is the lightest color and is achromatic (having no chroma). It is the color of objects such as snow, chalk, and milk, and is the opposite of black. White objects fully (or almost fully) reflect and scatter all the visible wavelen ...

as well as some bacteria. Carbohydrates are normally converted into simple sugars (

monosaccharide Monosaccharides (from Greek '' monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built. Chemically, monosaccharides are polyhy ...

s) by alpha-glucosidase enzymes present on cells lining the intestine, enabling monosaccharides to be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of dietary carbohydrates on

blood sugar The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis. For a 70 kg (1 ...

Examples and differences

Examples of alpha-glucosidase inhibitors include: *

Acarbose Acarbose ( INN) is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay ( Bayer AG), in North America as Precose ( Bayer Pharmaceuticals), and in ...

– Precose or Glucobay *

Miglitol Miglitol is an oral alpha-glucosidase inhibitor used in the treatment of type 2 diabetes. It works by reversibly inhibiting alpha-glucosidase enzymes in the small intestine, which delays the digestion of complex carbohydrates and subsequently ...

– Glyset *

Voglibose Voglibose (International Nonproprietary Name, INN and United States Adopted Name, USAN, trade name Voglib, marketed by Mascot Health Series) is an alpha-glucosidase inhibitor used for lowering postprandial blood glucose levels in people with diab ...

Even though the drugs have a similar mechanism of action, there are subtle differences between acarbose and miglitol. Acarbose is an

oligosaccharide An oligosaccharide (; ) is a carbohydrate, saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including Cell–cell recognition, cell recognition and ce ...

, whereas miglitol resembles a

. Miglitol is fairly well absorbed into the bloodstream, as opposed to acarbose. Moreover, acarbose inhibits pancreatic alpha-amylase in addition to alpha-glucosidase, and is degraded by gut bacterial maltogenic alpha-amylase and

cyclomaltodextrinase The enzyme cyclomaltodextrinase () catalyzes the chemical reaction :cyclomaltodextrin + H2O \rightleftharpoons linear maltodextrin It belongs to the family of hydrolases, specifically those glycosidases that hydrolyse ''O''- and ''S''-glycosyl c ...

Natural alpha glucosidase inhibitors

There are a large number of natural products with alpha-glucosidase inhibitor action. In fact, the prototypic drug of this class (acarbose) is discovered from soil bacteria. For example, research has shown the culinary mushroom

Maitake ''Grifola frondosa'' (also known as hen-of-the-woods, in Japanese, ram's head or sheep's head) is a polypore mushroom that grows at the base of trees, particularly old growth oaks or maples. It is native to China, Europe, and North America. ...

(''Grifola frondosa'') has a

hypoglycemic Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

effect. The reason Maitake lowers blood sugar is because the mushroom naturally contains an alpha glucosidase inhibitor. All cinnamon species show acarbose-like activity. A single dose of raw cinnamon before a meal containing complex carbohydrates decreases the postprandial hyperglycemia (higher than 140 mg/dL; >7.8 mmol/L) in patients with type II diabetes. Another plant attracting a lot of attention is '' Salacia oblonga''.

Clinical use

Alpha-glucosidase inhibitors are used to establish greater

glycemic control Diabetes mellitus is a metabolic disease that is characterized by chronic elevated blood glucose levels (hyperglycemia). Therefore, the main goal of diabetes management is to keep blood glucose levels within normal limits or a target range as ...

over

hyperglycemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

, particularly with regard to

postprandial Prandial relates to a meal. Postprandial (from post prandium) means after eating a meal, while preprandial is before a meal. Usages of postprandial The term ''postprandial'' is used in multiple contexts. Gastronomic or social Refers to activiti ...

hyperglycemia. The intake of a single dose before a meal containing complex carbohydrates clearly suppresses the glucose spike and may decrease the postprandial hyperglycemia (higher than 140 mg/dL; >7.8 mmol/L) in patients with type II diabetes. This ability is observed in the native/raw state of the alpha-amylase inhibitor; therefore, its consumption inside a meal that undergo heating (baking, frying or cooking/boiling) is expected to blunt its property to decrease the activity of carbohydrate digesting enzymes. They may be used as monotherapy in conjunction with an appropriate

diabetic diet A diabetic diet is a Diet (nutrition), diet that is used by people with diabetes mellitus or high blood sugar to minimize symptoms and dangerous complications of long-term elevations in blood sugar (i.e.: cardiovascular disease, Diabetic nephrop ...

and exercise, or they may be used in conjunction with other anti-diabetic drugs. A Cochrane

systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...

assessed the effect of AGIs in people with impaired

glucose tolerance Prediabetes is a component of metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms, but people with prediabetes often have obesity ( ...

, impaired fasting blood glucose, elevated glycated hemoglobin A1c (HbA1c). It was found that Acarbose appeared to reduce incidence of diabetes mellitus type 2 when compared to placebo, however there was no conclusive evidence that acarbose compare to diet and exercise,

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, ...

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

, no intervention improved all-cause mortality, reducer or increased risk of cardiovascular mortality, serious or non-serious adverse events, non-fatal

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pr ...

, or non-fatal

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

. The same review found that there was no conclusive evidence that voglibose compared to diet and exercise or placebo reduced incidence of diabetes mellitus type 2, or any of the other measured outcomes. In patients with

diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone required ...

, alpha-glucosidase inhibitors use has not been officially approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

in the US but some data exists on the effectiveness in this population, showing potential benefits weighted against an increased risk of hypoglycemia.

Mechanism of action

Alpha-glucosidase inhibitors are

saccharide A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' m ...

s that act as

competitive inhibitor Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected b ...

s of enzymes needed to digest

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

s: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze

trisaccharide ''Trisaccharides'' are oligosaccharides composed of three monosaccharides with two glycosidic bonds connecting them. Similar to the disaccharides, each glycosidic bond can be formed between any hydroxyl group on the component monosaccharides. Even ...

s, and

disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar formed when two monosaccharides are joined by glycosidic linkage. Like monosaccharides, disaccharides are simple sugars soluble in water. Three common examples are sucrose, ...

s to

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases.

Pancreatic The pancreas (plural pancreases, or pancreata) is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

alpha-amylase hydrolyzes complex starches to

oligosaccharides An oligosaccharide (; ) is a saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition and cell adhesion. They are normally presen ...

in the lumen of the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In

diabetic Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long-term effect is a small reduction in hemoglobin _A1c level.

Dosing

Since alpha-glucosidase inhibitors are competitive inhibitors of digestive enzymes, they must be taken at the start of main meals to have maximal effect. Their effects on blood sugar levels following meals will depend on the amount of complex carbohydrates in the meal.

Formulation

The health benefits of a alpha-glucosidase-inhibiting herb powder were shown to be stronger when the powder is consumed orally dissolved in water as a beverage in comparison to its intake as ordinary hard gelatin capsules. The

package insert A package insert is a document included in the package of a medication that provides information about that drug and its use. For prescription medications, the insert is technical, providing information for medical professionals about how to pr ...

of acarbose tablet lists two ways to take it: chewing it down with the first bites of food, or swallowing it some time before eating. With the same brand of acarbose tablet, chewing food appears effective than swallowing in combating the blood sugar rise from drinking sucrose water.

Side effects and precautions

Since alpha-glucosidase inhibitors prevent the degradation of complex carbohydrates into glucose, the carbohydrates will remain in the intestine. In the colon, bacteria will digest the complex carbohydrates, thereby causing gastrointestinal side effects such as

flatulence Flatulence is the expulsion of gas from the Gastrointestinal tract, intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swal ...

and

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

. Since these effects are dose-related, it is generally advised to start with a low dose and gradually increase the dose to the desired amount.

Pneumatosis intestinalis Pneumatosis intestinalis (also called intestinal pneumatosis, pneumatosis cystoides intestinalis, pneumatosis coli, or intramural bowel gas) is pneumatosis of an intestine, that is, gas cysts in the bowel wall. As a radiological sign it is hig ...

is another reported side effect. If a patient using an alpha-glucosidase inhibitor suffers from an episode of

hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...

, the patient should eat something containing monosaccharides such as glucose tablets or a soft drink containing HFCS. Since the drug will prevent the digestion of polysaccharides (or non-monosaccharides), non-monosaccharide foods may not effectively reverse a hypoglycemic episode in a patient taking an alpha-glucosidase inhibitor.

References

{{Enzyme inhibition Alpha-glucosidase inhibitors