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Clinical Diabetes & Therapeutics
Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
Hae Kyung Yang, Seung-Hwan Lee, Juyoung Shin, Yoon-Hee Choi, Yu-Bae Ahn, Byung-Wan Lee, Eun Jung Rhee, Kyung Wan Min, Kun-Ho Yoon
Diabetes Metab J. 2019;43(3):287-301.   Published online December 20, 2018
DOI: https://doi.org/10.4093/dmj.2018.0054
  • 5,897 View
  • 105 Download
  • 14 Web of Science
  • 14 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.

Methods

A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita, n=65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb, n=66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment, n=34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.

Results

The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (P<0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%, P=0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%, P=0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L, P=0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups.

Conclusion

In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.

Citations

Citations to this article as recorded by  
  • The effect of acarbose on inflammatory cytokines and adipokines in adults: a systematic review and meta-analysis of randomized clinical trials
    Ali Mohammadian, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Niloufar Rasaei, Hossein Bahari, Samira Rastgoo, Reza Bagheri, Farideh Shiraseb, Omid Asbaghi
    Inflammopharmacology.2024; 32(1): 355.     CrossRef
  • An Update on Dipeptidyl Peptidase-IV Inhibiting Peptides
    Sachithanantham Annapoorani Sivaraman, Varatharajan Sabareesh
    Current Protein & Peptide Science.2024; 25(4): 267.     CrossRef
  • Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling
    Sameh S. Elhady, Noha M. Alshobaki, Mahmoud A. Elfaky, Abdulrahman E. Koshak, Majed Alharbi, Reda F. A. Abdelhameed, Khaled M. Darwish
    Metabolites.2023; 13(8): 942.     CrossRef
  • Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract
    Choong Whan Lee, Byoung Hoon You, Sreymom Yim, Seung Yon Han, Hee-Sung Chae, Mingoo Bae, Seo-Yeon Kim, Jeong-Eun Yu, Jieun Jung, Piseth Nhoek, Hojun Kim, Han Seok Choi, Young-Won Chin, Hyun Woo Kim, Young Hee Choi
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • A Comprehensive Review on Weight Loss Associated with Anti-Diabetic Medications
    Fatma Haddad, Ghadeer Dokmak, Maryam Bader, Rafik Karaman
    Life.2023; 13(4): 1012.     CrossRef
  • The effects of acarbose treatment on cardiovascular risk factors in impaired glucose tolerance and diabetic patients: a systematic review and dose–response meta-analysis of randomized clinical trials
    Mohammad Zamani, Mahlagha Nikbaf-Shandiz, Yasaman Aali, Niloufar Rasaei, Mahtab Zarei, Farideh Shiraseb, Omid Asbaghi
    Frontiers in Nutrition.2023;[Epub]     CrossRef
  • The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials
    Mohsen Yousefi, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Samira Rastgoo, Reza Bagher, Alireza Khadem, Farideh Shiraseb, Omid Asbaghi
    BMC Pharmacology and Toxicology.2023;[Epub]     CrossRef
  • A systematic review, meta-analysis, dose-response, and meta-regression of the effects of acarbose intake on glycemic markers in adults
    Sina Raissi Dehkordi, Naseh Pahlavani, Mahlagha Nikbaf-Shandiz, Reza Bagheri, Niloufar Rasaei, Melika Darzi, Samira Rastgoo, Hossein Bahari, Farideh Shiraseb, Omid Asbaghi
    Journal of Diabetes & Metabolic Disorders.2023;[Epub]     CrossRef
  • Inhibitory activity of xanthoangelol isolated from Ashitaba (Angelica keiskei Koidzumi) towards α-glucosidase and dipeptidyl peptidase-IV: in silico and in vitro studies
    Diah Lia Aulifa, I Ketut Adnyana, Sukrasno Sukrasno, Jutti Levita
    Heliyon.2022; 8(5): e09501.     CrossRef
  • Design, synthesis, and in silico studies of benzimidazole bearing phenoxyacetamide derivatives as α-glucosidase and α-amylase inhibitors
    Nahal Shayegan, Aida Iraji, Nasim Bakhshi, Ali Moazzam, Mohammad Ali Faramarzi, Somayeh Mojtabavi, Seyyed Mehrdad Mostafavi Pour, Maliheh Barazandeh Tehrani, Bagher Larijani, Zahra Rezaei, Pardis Yousefi, Mehdi Khoshneviszadeh, Mohammad Mahdavi
    Journal of Molecular Structure.2022; 1268: 133650.     CrossRef
  • American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan—2022 Update
    Lawrence Blonde, Guillermo E. Umpierrez, S. Sethu Reddy, Janet B. McGill, Sarah L. Berga, Michael Bush, Suchitra Chandrasekaran, Ralph A. DeFronzo, Daniel Einhorn, Rodolfo J. Galindo, Thomas W. Gardner, Rajesh Garg, W. Timothy Garvey, Irl B. Hirsch, Danie
    Endocrine Practice.2022; 28(10): 923.     CrossRef
  • Combination of Bawang Dayak Extract and Acarbose against Male White Rat Glucose Levels
    Aditya Maulana Perdana Putra, Ratih Pratiwi Sari, Siska Musiam
    Borneo Journal of Pharmacy.2021; 4(2): 84.     CrossRef
  • Natural α-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitors: A Source of Scaffold Molecules for Synthesis of New Multitarget Antidiabetic Drugs
    Massimo Genovese, Ilaria Nesi, Anna Caselli, Paolo Paoli
    Molecules.2021; 26(16): 4818.     CrossRef
  • Impact of Simulated Gastrointestinal Conditions on Antiglycoxidant and α-Glucosidase Inhibition Capacities of Cyanidin-3-O-Glucoside
    Didier Fraisse, Alexis Bred, Catherine Felgines, François Senejoux
    Antioxidants.2021; 10(11): 1670.     CrossRef
Clinical Care/Education
Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment
Yeoree Yang, Jeong-Ah Shin, Hae Kyung Yang, Seung-Hwan Lee, Seung-Hyun Ko, Yu-Bae Ahn, Kun-Ho Yoon, Jae-Hyoung Cho
Diabetes Metab J. 2016;40(6):454-462.   Published online October 11, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.6.454
  • 4,244 View
  • 44 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   
Background

There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin.

Methods

In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT.

Results

Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group.

Conclusion

Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Citations

Citations to this article as recorded by  
  • Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries
    Gregory R. Fulcher, Shahid Akhtar, Saleh J. Al-Jaser, Johan Medina, Mafauzy Mohamed, Nemencio A. Nicodemus, Anne Helene Olsen, Kiran P. Singh, Adri Kok
    Advances in Therapy.2022; 39(8): 3735.     CrossRef
  • Use of Insulin Glargine 100 U/mL for the Treatment of Type 2 Diabetes Mellitus in East Asians: A Review
    Takahisa Hirose, Ching-Chu Chen, Kyu Jeung Ahn, Jacek Kiljański
    Diabetes Therapy.2019; 10(3): 805.     CrossRef
  • Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    Diabetes & Metabolism Journal.2017; 41(5): 367.     CrossRef
  • Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017
    Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
    The Korean Journal of Internal Medicine.2017; 32(6): 967.     CrossRef
Effects of 6-Month Sitagliptin Treatment on Insulin and Glucagon Responses in Korean Patients with Type 2 Diabetes Mellitus
Hae Kyung Yang, Borami Kang, Seung-Hwan Lee, Hun-Sung Kim, Kun-Ho Yoon, Bong-Yun Cha, Jae-Hyoung Cho
Diabetes Metab J. 2015;39(4):335-341.   Published online July 17, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.4.335
  • 3,689 View
  • 35 Download
  • 4 Web of Science
  • 3 Crossref
AbstractAbstract PDFPubReader   
Background

This study aimed to evaluate the effect of sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, on insulin secretion and glucagon suppression in Korean subjects with type 2 diabetes mellitus.

Methods

Twenty-four subjects underwent a 75-g oral glucose tolerance test (OGTT) before and after 6 months of sitagliptin treatment. Sitagliptin, insulin, and sulfonylurea were withdrawn for 3 days before OGTT to eliminate any acute effects on β-cell insulin or α-cell glucagon secretion. Venous samples were drawn five times during each OGTT to measure plasma glucose, insulin, and glucagon. Indices on insulin secretion and resistance were calculated.

Results

Early phase insulin secretion, measured by the insulinogenic index significantly increased after 6 months of sitagliptin treatment, especially in the higher baseline body mass index group and higher baseline glycosylated hemoglobin (HbA1c) group. There were no significant differences in the insulin resistance indices before and after sitagliptin treatment. Although no significant differences were observed in the absolute levels of glucagon and the glucagon-to-insulin ratio, there was a significant reduction in the percentile change of glucagon-to-insulin ratio at 30- and 120-minute during the OGTT.

Conclusion

Although the HbA1c level did not decrease significantly after 6 months of sitagliptin treatment, an increase in insulin secretion and reduction in early phase postprandial plasma glucagon-to-insulin ratio excursion was confirmed in Korean subjects with type 2 diabetes.

Citations

Citations to this article as recorded by  
  • A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes
    Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
    Medicine.2016; 95(44): e5155.     CrossRef
  • Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial
    Mingyuan Tian, Zerong Liang, Rui Liu, Ke Li, Xinrong Tan, Yong Luo, Mengliu Yang, Harvest F Gu, Hua Liu, Ling Li, Gangyi Yang
    European Journal of Endocrinology.2016; 174(2): 147.     CrossRef
  • Effects of Sitagliptin on Insulin and Glucagon Levels in Type 2 Diabetes Mellitus
    Ji Hyun Kim
    Diabetes & Metabolism Journal.2015; 39(4): 304.     CrossRef
The Insulin Resistance but Not the Insulin Secretion Parameters Have Changed in the Korean Population during the Last Decade
Hae Kyung Yang, Jin Hee Lee, In-Young Choi, Hyuk Sang Kwon, Jeong Ah Shin, Seung Hee Jeong, Seung-Hwan Lee, Jae Hyoung Cho, Ho Young Son, Kun Ho Yoon
Diabetes Metab J. 2015;39(2):117-125.   Published online April 20, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.117
  • 4,561 View
  • 46 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   
Background

This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s.

Methods

Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea.

Results

A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s.

Conclusion

After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.

Citations

Citations to this article as recorded by  
  • Longitudinal Changes in Insulin Resistance, Beta-Cell Function and Glucose Regulation Status in Prediabetes
    Chul-Hee Kim, Hong-Kyu Kim, Eun-Hee Kim, Sung-Jin Bae, Jaewon Choe, Joong-Yeol Park
    The American Journal of the Medical Sciences.2018; 355(1): 54.     CrossRef
  • Association of serum 25-hydroxyvitamin D and diabetes-related factors in Korean adults without diabetes: The Fifth Korea National Health and Nutrition Examination Survey 2010–2012
    Hyunah Kim, Hyunyong Lee, Hyeon Woo Yim, Hun-Sung Kim
    Primary Care Diabetes.2018; 12(1): 59.     CrossRef
  • Long‐term effects on glycaemic control and β‐cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial
    Suk Chon, Sang Youl Rhee, Kyu Jeung Ahn, Sei Hyun Baik, Yongsoo Park, Moon Suk Nam, Kwan Woo Lee, Soon Jib Yoo, Gwanpyo Koh, Dae Ho Lee, Young Seol Kim, Jeong‐Taek Woo
    Diabetes, Obesity and Metabolism.2018; 20(5): 1121.     CrossRef
  • Four Plasma Glucose and Insulin Responses to a 75 g OGTT in Healthy Young Japanese Women
    Kei Takahashi, Hidetaka Nakamura, Hiroshi Sato, Hideto Matsuda, Kazuo Takada, Tomiko Tsuji
    Journal of Diabetes Research.2018; 2018: 1.     CrossRef
  • Comparison of insulin intensification strategies with insulin lispro low mixture twice daily versus basal insulin glargine and prandial insulin lispro once daily in East Asian and Caucasian patients with type 2 diabetes mellitus
    In‐Kyung Jeong, Choon Hee Chung, Zhiguang Zhou, Jeong Hee Han, Ran Duan, Diana M. Edralin, Angel Rodriguez
    Journal of Diabetes.2017; 9(4): 396.     CrossRef
  • Insulin Secretory Capacity and Insulin Resistance in Korean Type 2 Diabetes Mellitus Patients
    Jong-Dai Kim, Won-Young Lee
    Endocrinology and Metabolism.2016; 31(3): 354.     CrossRef
  • Antisenescence activity of G9a inhibitor BIX01294 on human bone marrow mesenchymal stromal cells
    Min-Ji AHN, Sin-Gu JEONG, Goang-Won CHO
    TURKISH JOURNAL OF BIOLOGY.2016; 40: 443.     CrossRef
  • Urinary N-acetyl-β-D-glucosaminidase, an early marker of diabetic kidney disease, might reflect glucose excursion in patients with type 2 diabetes
    So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Eun Seok Kang, Bong-Soo Cha, Jeong-Ho Kim, Byung-Wan Lee
    Medicine.2016; 95(27): e4114.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal