Both acarbose and metformin are oral medications prescribed to manage blood sugar levels in individuals with type 2 diabetes mellitus (T2DM). T2DM is mainly the result of insulin resistance. These medications are often used alongside diet and exercise to improve glycemic control. While both drugs aim to lower blood sugar, they work through different mechanisms and have distinct profiles regarding side effects, contraindications, and potential benefits.
Mechanisms of Action
Acarbose
Acarbose is an alpha-glucosidase inhibitor. Acarbose inhibits digestion into monosaccharides and offsetting post-prandial glucose rise. It functions by slowing down the breakdown of carbohydrates into glucose in the small intestine, which helps reduce blood sugar spikes after meals. Specifically, it inhibits enzymes in the small intestine that digest carbohydrates.
Metformin
Metformin decreases glucose production in the liver, improves the body's sensitivity to insulin, and reduces the amount of sugar absorbed by the intestines. Metformin is often used as a first-line treatment due to its efficacy, safety profile, and additional benefits, such as weight stabilization and a low risk of hypoglycemia when used alone.
Approved Uses and Dosage
Acarbose
Acarbose is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. It is typically taken orally three times daily before meals. Acarbose comes in 25 mg, 50 mg, and 100 mg tablets. Off-label uses may include management of reactive hypoglycemia or use in polycystic ovary syndrome (PCOS) for insulin resistance, although these uses are less common.
Metformin
Metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with T2DM. It is typically taken orally once, twice, or three times daily. Metformin comes in 500 mg, 850 mg, and 1,000 mg tablets.
Read also: Understanding Acarbose
Side Effects
Acarbose
The most common side effects of acarbose are gastrointestinal, including abdominal pain, bloating, diarrhea, and flatulence.
Metformin
For metformin hydrochloride, the most common adverse reactions (>5%) are diarrhea, nausea/vomiting, flatulence, weakness, indigestion, abdominal discomfort, and headache.
Contraindications and Warnings
Acarbose
Acarbose is contraindicated in individuals with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction, or in patients predisposed to intestinal obstruction. It is also contraindicated in chronic intestinal diseases associated with marked disorders of digestion or absorption and conditions that may deteriorate due to increased gas formation in the intestine. Acarbose should not be administered to a nursing woman.
Metformin
Metformin is contraindicated in individuals with severe renal impairment (eGFR below 30 mL/min/1.73 m2) and hypersensitivity to metformin. It is also contraindicated in acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
Warnings and Precautions for Both
Acarbose:
- There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with acarbose.
- Acarbose can cause low blood sugar, especially when used with other diabetes medications.
- Elevated serum transaminase levels have been reported with acarbose use.
- Loss of control of blood sugar may occur.
- The safety of acarbose in pregnant women has not been established.
Metformin:
- Lactic Acidosis: Metformin carries a boxed warning regarding the risk of lactic acidosis, a rare but serious metabolic complication that can result in death. Risk factors include renal impairment, concomitant use of certain drugs, age >65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. If lactic acidosis is suspected, metformin should be discontinued, and prompt hemodialysis is recommended.
- Metformin may lower vitamin B12 levels.
- Low blood sugar can occur with concomitant use with insulin and insulin secretagogues.
- Females and males of reproductive potential should be aware of the potential for unintended pregnancy.
Drug Interactions
Acarbose
Drug interactions with acarbose can occur with drugs that tend to produce hyperglycemia, sulfonylureas, insulin, intestinal absorbents, and digoxin.
Read also: The Role of Acarbose in Weight Management
Metformin
Drug interactions with metformin can occur with carbonic anhydrase inhibitors and drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine). Alcohol can also interact with metformin, increasing the risk of lactic acidosis.
Comparative Studies and Efficacy
Several studies have compared the efficacy of acarbose and metformin in managing T2DM.
One study published in Lancet Diabetes Endocrinology compared acarbose and metformin as initial monotherapy in newly diagnosed T2DM patients in China. The 48-week randomized, open-label, non-inferiority trial found that acarbose was non-inferior to metformin in HbA1c reduction at both 24 and 48 weeks. At week 24, HbA1c reduction was -1.17% in the acarbose group and -1.19% in the metformin group. At week 48, the HbA1c reduction was -1.11% (acarbose) and -1.12% (metformin), with a difference of 0.01% (95% CI -0.12 to 0.14, p=0.8999).
Another study, published in Revista Prática, enrolled 108 drug-naïve patients with newly diagnosed T2DM with HbA1c between 7% and 10% and BMI greater than 24 kg/m2. Patients were randomized to acarbose (100 mg three times a day) or metformin (1.5 g/day) for 24 weeks. The study found that glucose control improved significantly in both groups. The percentage of patients achieving HbA1C <6.5% was comparable between the two groups. Body weight reduction from baseline to 24 weeks was 3.3 kg in the acarbose group and 2.7 kg in the metformin group, with similar changes in HbA1c and body weight in both groups. Interestingly, the early-phase insulin secretion index improved only in the acarbose group at 24 weeks, suggesting superior efficacy in improving islet α-cell function compared with metformin in overweight/obese patients with newly diagnosed T2DM.
Acarbose and Metformin in Type 1 Diabetes Mellitus (T1DM)
While both acarbose and metformin are primarily used in T2DM, some studies have explored their potential role as adjunct therapies in type 1 diabetes mellitus (T1DM). T1DM results from autoimmune-mediated beta cell destruction, leading to an absolute insulin deficiency. Insulin is the core treatment of T1DM, but insulin resistance may develop in some patients, stimulating interest in non-insulin pharmacological therapies.
Read also: Berberine and Metformin
One study compared the results of two placebo-controlled clinical trials conducted in two different time periods on 40 patients with T1DM. In the first section, metformin was given to the subjects, and after six months, metformin was replaced with acarbose in the therapeutic regimen. Placebo-controlled evaluation of selected factors showed a significant decrease in fasting blood sugar (FBS) and triglyceride (TG) levels in the metformin group during follow-up. The acarbose group showed a substantial influence on two-hour postprandial (2hpp) blood glucose and regular insulin intake decline. Moreover, comparison differences after the intervention between the two test groups showed that metformin had a superior impact on FBS and HbA1C decline in patients.
Considerations for Clinical Practice
Metformin is generally recommended as the first-line oral hypoglycemic drug for T2DM due to its proven efficacy, safety, and cost-effectiveness. However, acarbose may be a suitable alternative or adjunct therapy in specific situations, such as:
- Patients who experience significant gastrointestinal side effects with metformin.
- Patients in whom postprandial glucose control is a primary concern.
- Overweight/obese patients with newly diagnosed T2DM, where acarbose may offer superior efficacy in improving islet α-cell function.
It's important to note that the decision to use acarbose or metformin should be individualized based on the patient's specific clinical characteristics, preferences, and potential contraindications.