Journal of Diabetes & Clinical Practice
Open Access

Acarbose; Miglitol; HbA1c; Type 2 diabetes; Antidiabetic medications

Introduction

Type 2 diabetes mellitus is a chronic metabolic disorder affecting millions of people worldwide. It is characterized by insulin resistance and impaired glucose regulation, leading to elevated blood sugar levels. Proper management of type 2 diabetes is crucial to prevent complications and improve overall health. [1] One class of medications that plays a vital role in controlling blood glucose levels is alphaglucosidase inhibitors.

Mechanism of action

Alpha-glucosidase inhibitors, such as acarbose and miglitol, work by targeting the enzymes responsible for breaking down complex carbohydrates into simple sugars. These enzymes, known as alphaglucosidases, are found in the small intestine. By inhibiting their activity, these drugs slow down the digestion and absorption of carbohydrates, particularly starches and disaccharides [2].

When a person with type 2 diabetes takes an alpha-glucosidase inhibitor before a meal, it acts locally in the gastrointestinal tract to delay the conversion of complex carbohydrates into glucose. Consequently, the postprandial rise in blood glucose levels is attenuated, helping to maintain better glycemic control.

Clinical benefits

Postprandial glucose reduction: Alpha-glucosidase inhibitors effectively lower post-meal blood glucose spikes. [3] This is especially important as postprandial hyperglycemia has been associated with an increased risk of cardiovascular complications.

A1C reduction: Long-term use of alpha-glucosidase inhibitors has been shown to lead to modest reductions in HbA1c levels, a marker of average blood glucose over the past 2-3 months.

Weight-neutral: Unlike some other antidiabetic medications associated with weight gain, alpha-glucosidase inhibitors are weightneutral, making them a favorable choice for patients concerned about weight management.

Lower hypoglycemia risk: Alpha-glucosidase inhibitors do not significantly increase the risk of hypoglycemia when used as monotherapy. However, when combined with other diabetes medications like sulfonylureas or insulin, there may be a higher risk of low blood sugar [4].

Adverse effects

The most common side effects associated with alpha-glucosidase inhibitors are related to the gastrointestinal system. These may include flatulence, bloating, diarrhea, and abdominal discomfort. These side effects can be bothersome for some patients, but they often subside over time with continued use.

Precautions and considerations

Alpha-glucosidase inhibitors are not suitable for everyone. They may not be effective in individuals with severe kidney or liver disease. Moreover, patients with inflammatory bowel diseases or conditions that cause intestinal obstruction should avoid these medications. It is essential to take alpha-glucosidase inhibitors with the first bite of each main meal. Missing a dose or taking it after the meal may reduce its effectiveness.

Method

Drug discovery: Scientists and researchers identify potential compounds that could inhibit alpha-glucosidase enzymes. These compounds can be derived from natural sources, synthesized in the laboratory, or identified through high-throughput screening of chemical libraries [5].

Preclinical studies: In vitro studies and animal experiments are conducted to assess the effectiveness and safety of the potential alphaglucosidase inhibitors. Preclinical studies help researchers understand the mechanism of action, absorption, metabolism, and potential side effects of the drug candidates.

Clinical trials - phase i: If preclinical studies yield promising results, the drug candidate progresses to human clinical trials. Phase I trials involve a small group of healthy volunteers to assess the drug's safety, tolerability, and pharmacokinetics.

Clinical trials - phase ii: In Phase II trials, a larger group of patients with type 2 diabetes is enrolled. The primary goal is to evaluate the drug's effectiveness in reducing postprandial glucose levels and its impact on HbA1c. Safety and side effects are also closely monitored [6].

Clinical trials - phase iii: Phase III trials are larger and more comprehensive studies that involve thousands of patients across multiple locations. The objective is to further confirm the drug's efficacy, safety, and tolerability in a diverse population. These trials often compare the alpha-glucosidase inhibitor with a placebo or other standard diabetes medications.

Regulatory approval: Once the clinical trials demonstrate the drug's safety and efficacy, the pharmaceutical company submits a New Drug Application (NDA) to the regulatory authorities, such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The application includes all the data from preclinical and clinical studies.

Market access and post-marketing surveillance: After receiving regulatory approval, the alpha-glucosidase inhibitor becomes available for use in the market. Post-marketing surveillance helps monitor the drug's real-world effectiveness and any rare side effects that may not have been evident in clinical trials.

Prescription and use: Healthcare providers prescribe alphaglucosidase inhibitors to appropriate patients with type 2 diabetes as part of a comprehensive diabetes management plan. Patients are advised to take the medication with meals to achieve optimal glycemic control [7].

Ongoing research: Researchers continue to study alphaglucosidase inhibitors to explore potential new uses, combinations with other medications, and improvements in drug formulations to enhance their effectiveness and minimize side effects.

Result

Improved glycemic control: Alpha-glucosidase inhibitors help regulate blood glucose levels, particularly after meals, leading to better overall glycemic control. By reducing post-meal glucose spikes, they contribute to achieving target HbA1c levels, a critical marker of longterm blood sugar management.

Reduced risk of complications: Maintaining stable blood glucose levels is crucial for preventing diabetes-related complications such as cardiovascular disease, neuropathy, retinopathy, and nephropathy. By mitigating postprandial hyperglycemia, alpha-glucosidase inhibitors play a role in reducing the risk of these complications.

Weight-neutrality: Unlike some other antidiabetic medications associated with weight gain, alpha-glucosidase inhibitors do not promote weight gain. This feature makes them a preferred option for individuals concerned about weight management or those who are overweight or obese.

Adjunct to other diabetes medications: Alpha-glucosidase inhibitors can be used in combination with other oral antidiabetic agents or insulin therapy to achieve optimal glycemic control. [8] When used in combination, they can contribute to a comprehensive diabetes management plan tailored to individual patient needs. Favorable safety profile: Alpha-glucosidase inhibitors are generally well-tolerated. Although they may cause gastrointestinal side effects such as flatulence and diarrhea, these symptoms often subside over time and can be managed with dose adjustments.

Alpha-glucosidase inhibitors represent an important therapeutic option in the armamentarium against type 2 diabetes. They offer a complementary approach to managing blood glucose levels, especially in the postprandial period, and play a crucial role in reducing the risk of diabetes-related complications. However, their use should be guided by healthcare professionals, considering individual patient characteristics, medical history, and potential interactions with other medications. Continued research and clinical studies aim to further improve these drugs' effectiveness and safety to better serve the needs of patients with type 2 diabetes.

Discussion

Role in glycemic control: Alpha-glucosidase inhibitors effectively control blood glucose levels, especially after meals, by delaying the absorption of carbohydrates. [9] This postprandial glucose reduction is crucial in achieving target HbA1c levels and preventing long-term complications associated with diabetes. It complements the action of other antidiabetic medications like metformin and insulin.

Weight-neutral advantage: One notable benefit of alphaglucosidase inhibitors is their weight-neutral profile. This characteristic makes them particularly attractive for patients who are overweight or obese and may struggle with weight gain associated with some other diabetes medications.

Combination therapy: Alpha-glucosidase inhibitors are often used in combination with other oral antidiabetic agents or insulin. Combining medications with different mechanisms of action allows for a synergistic effect in glycemic control, providing flexibility in treatment options and individualizing patient care.

Gastrointestinal side effects: One limitation of alpha-glucosidase inhibitors is their association with gastrointestinal side effects, particularly in the initial stages of treatment. Flatulence, bloating, and diarrhea are common complaints, but they tend to improve with time as the body adjusts to the medication.

Individualized treatment approach: Like any medication, alphaglucosidase inhibitors may not be suitable for everyone. Their use should be carefully considered based on individual patient factors, such as age, kidney function, liver function, and gastrointestinal health. Close monitoring and regular follow-ups are essential to assess the drug's effectiveness and any adverse effects [10].

Real-world effectiveness: While clinical trials provide valuable insights into a drug's performance, real-world effectiveness may differ due to variations in patient adherence, lifestyle factors, and individual responses to treatment. Post-marketing surveillance helps identify any rare or long-term side effects that may not have been apparent during clinical trials.

Future research: Ongoing research aims to improve the efficacy and safety of alpha-glucosidase inhibitors. Potential areas of study include optimizing dosing regimens, investigating their use in combination with emerging diabetes therapies, and exploring new drug formulations with reduced gastrointestinal side effects. Alpha-glucosidase inhibitors play a crucial role in the management of type 2 diabetes by helping to regulate blood glucose levels, especially after meals. Their weight-neutral profile and combination therapy potential make them valuable options in the diverse landscape of diabetes treatment. While gastrointestinal side effects may pose challenges for some patients, their benefits in glycemic control and prevention of complications underscore their significance in diabetes care. With continued research and vigilant clinical use, alphaglucosidase inhibitors will likely continue to contribute to improved outcomes for individuals living with type 2 diabetes.

Conclusion

Alpha-glucosidase inhibitors are valuable tools in the management of type 2 diabetes. By slowing down carbohydrate absorption, they help regulate blood glucose levels and reduce the risk of postprandial hyperglycemia. However, like all medications, they have potential side effects and may not be suitable for everyone. Individuals with diabetes should work closely with their healthcare providers to determine the most appropriate treatment plan, which may include alpha-glucosidase inhibitors along with lifestyle modifications and other diabetes medications to achieve optimal glycemic control and improve overall health outcomes.

Acknowledgement

None

Conflict of Interest

None

1. Von-Seidlein L, Kim DR, Ali M, Lee HH, Wang X, et al. (2006) A multicentre study of Shigella diarrhoea in six Asian countries:  Disease burden, clinical manifestations, and microbiology. PLoS Med 3: e353.

Google Scholar, Crossref, Indexed at

2. Germani Y, Sansonetti PJ (2006) The genus Shigella. The prokaryotes In:  Proteobacteria:  Gamma Subclass Berlin:  Springer 6: 99-122.

Google Scholar

3. Aggarwal P, Uppal B, Ghosh R, Krishna Prakash S, Chakravarti A, et al. (2016) Multi drug resistance and extended spectrum beta lactamases in clinical isolates of Shigella:  a study from New Delhi, India. Travel Med Infect Dis 14: 407–413.

Google Scholar, Crossref, Indexed at

4. Taneja N, Mewara A (2016) Shigellosis:  epidemiology in India. Indian J Med Res 143: 565-576.

Google Scholar, Crossref, Indexed at

5. Farshad S, Sheikhi R, Japoni A, Basiri E, Alborzi A (2006) Characterizationof Shigella strains in Iran by plasmid profile analysis and PCR amplification of ipa genes. J Clin Microbiol 44: 2879–2883.

Google Scholar, Crossref, Indexed at

6. Jomezadeh N, Babamoradi S, Kalantar E, Javaherizadeh H (2014) Isolation and antibiotic susceptibility of Shigella species from stool samplesamong hospitalized children in Abadan, Iran. Gastroenterol Hepatol Bed Bench 7: 218.

Google Scholar, Indexed at

7. Sangeetha A, Parija SC, Mandal J, Krishnamurthy S (2014) Clinical and microbiological profiles of shigellosis in children. J Health Popul Nutr 32: 580.

Google Scholar, Indexed at

8. Ranjbar R, Dallal MMS, Talebi M, Pourshafie MR (2008) Increased isolation and characterization of Shigella sonnei obtained from hospitalized children in Tehran, Iran. J Health Popul Nutr 26: 426.

Google Scholar, Crossref, Indexed at

9. Zhang J, Jin H, Hu J, Yuan Z, Shi W, Yang X, et al. (2014) Antimicrobial resistance of Shigella spp. from humans in Shanghai, China, 2004–2011. Diagn Microbiol Infect Dis 78: 282–286.

Google Scholar, Crossref, Indexed at

10. Pourakbari B, Mamishi S, Mashoori N, Mahboobi N, Ashtiani MH, et al. (2010) Frequency and antimicrobial susceptibility of Shigella species isolated in children medical center hospital, Tehran, Iran, 2001–2006. Braz J Infect Dis 14: 153–157.

Google Scholar, Crossref, Indexed at