- ACRONYMS AND DEFINITIONS
- A1C - Hemoglobin A1C
- ADA - American Diabetes Assoc
- CrCl - Creatinine clearance
- FDA - U.S. Food and Drug Administration
- GI - Gastrointestinal
- OGTT - Oral glucose tolerance test
- T2DM - Type two diabetes
- RCT - Randomized controlled trial
- DRUGS IN CLASS
- Alpha-glucosidase inhibitors
- Acarbose (Precose®)
- Miglitol (Glyset®)
- MECHANISM OF ACTION
- In order for carbohydrates to be absorbed into the bloodstream, they must first be metabolized in the small intestine
- Alpha-glucosidase and alpha-amylase are two enzymes that metabolize intestinal carbohydrates. Alpha-glucosidase is present in intestinal cells, and alpha-amylase is secreted into the intestine by the pancreas in response to food consumption.
- Acarbose blocks alpha-glucosidase and alpha-amylase while miglitol blocks alpha-glucosidase only. Blocking these enzymes inhibits carbohydrate metabolism and slows its absorption.
- FDA-APPROVED INDICATIONS
- Acarbose (Precose®) - adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- Miglitol (Glyset®) - adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- TYPE TWO DIABETES
Acarbose (Aca) monotherapy in placebo-controlled trials in type two diabetics | |||
---|---|---|---|
Aca 25 mg 3 times a day (N=110) |
Aca 50 mg 3 times a day (N=131) |
Aca 100 mg 3 times a day (N=244) |
|
HgA1C (%) (placebo-subtracted change) |
-0.44% | -0.77% | -0.74% |
Acarbose (Aca) added to metformin in a 6 month trial | ||
---|---|---|
Placebo + metformin | Aca 50 - 100 mg 3 times a day + metformin | |
HgA1C (%) (average change from baseline) |
+0.08% | -0.57% |
1 hour postprandial blood sugar (average change from baseline) |
+3.3 mg/dl | -31 mg/dl |
Miglitol (Mig) monotherapy for 14 weeks | |||
---|---|---|---|
Placebo |
Mig 50 mg 3 times a day | Mig 100 mg 3 times a day | |
HgA1C (%) (average change from baseline) |
+0.47% | -0.22% | -0.28% |
1 hour postprandial blood sugar (average change from baseline) |
+15 mg/dl | -52 mg/dl | -59 mg/dl |
- Body weight effects
- Alpha-glucosidase inhibitors do not appear to have a significant effect on body weight [3]
- Cholesterol effects
- Alpha-glucosidase inhibitors do not appear to have a significant effect on cholesterol [3]
- Clinical outcomes
- There have been no studies with alpha-glucosidase inhibitors that have evaluated significant clinical outcomes in diabetics
- ADA recommendations
- Summary
- Alpha-glucosidase inhibitors tend to lower hemoglobin A1C values by an average of 0.70 - 0.80% when compared to placebo. This effect is less than what is seen with other classes of diabetes medications. They are dosed three times a day, and their effects on clinical outcomes are not well-defined. For these reasons, they are not widely prescribed.
- T2DM PREVENTION
- Overview
- The STOP-NIDDM trial detailed below looked at the efficacy of acarbose in preventing type two diabetes among prediabetics
- The STOP-NIDDM trial enrolled 1429 prediabetics
Main inclusion criteria
- Age 40 - 70 years
- BMI 25 - 40
- OGTT of 140 - 200 mg/dl and FBS of 100 - 139 mg/dl
Baseline characteristics
- Average age 54 years
- Average weight - 191 lbs (87 kg)
- Average BMI - 31
- Average fasting glucose - 112 mg/dl
- Average 2-hour GTT - 167 mg/dl
Randomized treatment groups
- Group 1 (682 patients) - Acarbose with a target dose of 100 mg three times a day (mean dose achieved 194 mg/day)
- Group 2 (686 patients) - Placebo three times a day
- All patients were counseled on weight loss and encouraged to exercise
Primary outcome: Development of diabetes based on a 2-hour OGTT of > 200 mg/dl
Results
Duration: Average of 3.3 years | |||
Outcome | Acarbose | Placebo | Comparisons |
---|---|---|---|
Primary outcome (percent with diabetes) | 32% | 42% | HR 0.75, 95%CI [0.63 - 0.90], p=0.0015 |
Flatulence | 68% | 27% | N/A |
Diarrhea | 32% | 17% | N/A |
Abdominal pain | 17% | 12% | N/A |
Dropout rate | 31% | 19% | N/A |
|
Findings: Acarbose could be used, either as an alternative or in addition to changes in lifestyle, to delay development of type 2 diabetes in patients with impaired glucose tolerance
- ADA recommendations
- SIDE EFFECTS
- Gastrointestinal (GI) side effects
- Gastrointestinal side effects are by far the most common side effects seen with alpha-glucosidase inhibitors
- Alpha-glucosidase inhibitors block metabolism of carbohydrates in the small intestine which causes more carbohydrates to reach the large intestine where they are converted into gas by bacteria
GI side effect | Frequency (% of patients) |
---|---|
Flatulence | 40 - 70% |
Diarrhea | 30% |
Abdominal pain | 10 - 20% |
- Elevated liver enzymes (acarbose)
- In some studies, an increase in liver enzymes was observed in a small percentage of patients on acarbose
- The effect appears to be related to higher doses
- Severe cases of liver enzyme elevations were more common in patients who weighed less than 60 kg (132 pounds)
- Because of this, the dosing guidelines for acarbose restrict the maximum dose to 50 mg in patients who weigh 60 kg or less [1]
- Low blood sugar (hypoglycemia)
- When taken by themselves, alpha-glucosidase inhibitors do not cause low blood sugars
- When taken with other diabetes medications that can cause low blood sugars (ex. sulfonylureas, insulin, meglitinides), alpha-glucosidase inhibitors may increase the risk of low blood sugar [1,2]
- Patients who experience hypoglycemia on acarbose or miglitol should be treated with glucose tablets. See hypoglycemia treatment below.
- HYPOGLYCEMIA TREATMENT
- Because alpha-glucosidase inhibitors block the absorption of carbohydrates, they may interfere with the treatment of low blood sugar
- Sucrose (table sugar) metabolism is inhibited by alpha-glucosidase inhibitors, therefore consuming foods with sucrose may not raise blood sugars quickly
- Patients on alpha-glucosidase inhibitors should treat their low blood sugar with glucose (also called dextrose), not sucrose (table sugar)
- Glucose tablets are available in most pharmacies [1,2]
- Carbohydrates - review of the different types of carbohydrates
- CONTRAINDICATIONS
- Acarbose (Precose®)
- Cirrhosis
- Inflammatory bowel disease
- Colonic ulceration
- Partial intestinal obstruction
- Patients predisposed to intestinal obstruction
- Patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption and in patients who have conditions that may deteriorate as a result of increased gas formation in the intestine
- Miglitol (Glyset®)
- Inflammatory bowel disease, colonic ulceration, or partial intestinal obstruction, and in patients predisposed to intestinal obstruction
- Chronic intestinal diseases associated with marked disorders of digestion or absorption, or with conditions that may deteriorate as a result of increased gas formation in the intestine
- PRECAUTIONS
- Kidney disease
- Acarbose (Precose®)
- Acarbose blood levels are elevated in patients with kidney disease
- Acarbose should not be taken by patients with significant kidney disease [1]
- Miglitol (Glyset®)
- Miglitol blood levels are elevated in patients with kidney disease
- Patients with CrCl < 25 ml/min taking miglitol 25mg three times a day had a greater than two-fold increase in miglitol levels
- There is little information on the safety of miglitol in patients with significant kidney disease
- Miglitol should be avoided in patients with significant kidney disease [2]
- Liver disease
- Acarbose (Precose®)
- Acarbose should not be taken by patients with cirrhosis [1]
- Miglitol (Glyset®)
- No dosage adjustment is necessary in liver disease [2]
- Intestinal diseases
- Because alpha-glucosidase inhibitors increase the amount of gas produced in the bowel, they should not be taken by patients who have bowel diseases where this may cause problems
- Alpha-glucosidase inhibitors are contraindicated in the following conditions:
- Inflammatory bowel disease (Ulcerative colitis, Crohn's disease)
- Colonic ulcers
- Patients with bowel obstruction or those who are predisposed to bowel obstruction
- Intestinal disorders of absorption or digestion
- 1,5-Anhydroglucitol (1,5AG) monitoring
- 1,5-anhydroglucitol is a monosaccharide derived from food, and its plasma levels are sometimes used to assess blood sugar control
- Alpha-glucosidase inhibitors interfere with 1,5AG absorption, making it an unreliable measure of glucose control
- 1,5AG should not be used to monitor blood sugar control in patients taking alpha-glucosidase inhibitors
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Acarbose and Miglitol
- Diabetes medications - when taken with other diabetes medications (particularly sulfonylureas, insulins, and meglitinides), the risk of hypoglycemia is increased. Use caution when first combining.
- Digoxin - Acarbose and miglitol have both been shown to decrease blood levels of digoxin. It is unclear if this interaction is clinically significant.
- Miglitol (Glyset®)
- Glyburide (DiaBeta®) - miglitol has been shown to decrease blood levels of glyburide. It is unclear if this interaction is clinically significant.
- Ranitidine (Zantac®) - miglitol has been shown to decrease blood levels of ranitidine by 60%
- Propranolol (Inderal®) - miglitol has been shown to decrease blood levels of propranolol by 40%.
- Metabolism and clearance
- Acarbose is metabolized in the small intestine, primarily by bacteria
- Miglitol is not metabolized
- LONG-TERM SAFETY
- Acarbose was FDA approved in 1995
- Miglitol was FDA approved in 1996
- No long-term safety issues have arisen with either drug
- DOSING
- BIBLIOGRAPHY
- 1 - Acarbose PI
- 2 - Miglitol PI
- 3 - PMID 15846673
- 4 - PMID 12876091
- 5 - PMID 10372249
- 6 - PMID 18945920
- 7 - PMID 12086760
- 8 - PMID 17054235
- 9 - PMID 11375358