Skip to main content

Advertisement

SpringerLink
Log in

The efficacy of switching basal–bolus insulin therapy to basal insulin-supported oral therapy with a glinide and an α-glucosidase inhibitor in patients with type 2 diabetes depends on insulin secretory capacity, but not on blood glucose profiles and insulin dosages prior to the switching

  • Original Article
  • Published:
Diabetology International Aims and scope Submit manuscript

Abstract

Aims

We aimed to identify patients who would benefit from basal insulin-supported oral therapy (BOT) with a glinide and an α-glucosidase inhibitor (a fixed-dose combination tablet of mitiglinide 10 mg and voglibose 0.2 mg) in Japanese type 2 diabetic patients.

Methods

Patients who were hospitalized to improve hyperglycemia received basal–bolus insulin therapy. After the reduction of glucose toxicity, a 75 g oral glucose tolerance test and a glucagon test were performed. Thereafter, the basal–bolus insulin therapy was switched to BOT with mitiglinide, followed by further addition of voglibose. Interstitial glucose levels were continuously monitored throughout the study period. Diurnal glucose profile was recorded and analyzed. Patients were divided into two groups according to whether their percentage of time in range (TIR, 70–180 mg/dL) under BOT with mitiglinide/voglibose was higher than 70% or not, and the differences in clinical characteristics between the groups were analyzed.

Results

Twenty patients were enrolled, and 19 of them completed the study. BOT with mitiglinide/voglibose achieved ≥ 70% of TIR in thirteen patients. The area under the curve of serum C-peptide levels during the oral glucose tolerance test was significantly higher in the patients with ≥ 70% of TIR. The daily insulin dosages and blood glucose profiles were comparable between the two groups.

Conclusions

The efficacy of BOT with mitiglinide/voglibose depended on residual insulin secretory abilities. This therapy would be a useful therapeutic option for patients with type 2 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The data sets used and/or analysed in this study are available from the corresponding author on reasonable request.

References

  1. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan B, et al. IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109109. https://doi.org/10.1016/j.diabres.2021.109119.

    Article  Google Scholar 

  2. Takeshita Y, Takamura T, Kita Y, Takazakura A, Kato K, Isobe Y, et al. Sitagliptin versus mitiglinide switched from mealtime dosing of a rapid-acting insulin analog in patients with type 2 diabetes: a randomized, parallel-group study. BMJ Open Diabetes Res Care. 2015. https://doi.org/10.1136/bmjdrc-2015-000122.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tsukube S, Ikeda Y, Kadowaki T, Odawara M. Improved treatment satisfaction and self-reported health status after introduction of basal-supported oral therapy using insulin glargine in patients with type 2 diabetes: sub-analysis of ALOHA2 study. Diabetes Ther. 2015. https://doi.org/10.1007/s13300-015-0111-5.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Li H. Revisiting the strategies for the pharmacological management of type 2 diabetes—from glycemic control, organ protection, safety to weight reduction. J Diabetes Investig. 2022;13(1):3–5. https://doi.org/10.1111/jdi.13726.

    Article  PubMed  CAS  Google Scholar 

  5. Danne T, Bluhmki T, Seufert J, Kaltheuner M, Rathmann W, Beyersmann J, et al. Treatment intensification using long-acting insulin -predictors of future basal insulin supported oral therapy in the DIVE registry. BMC Endocr Disord. 2015;15:54. https://doi.org/10.1186/s12902-015-0051-0.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Xu W, Qiu L, Luo S, Li M, Weng J, Guo X, et al. Status of basal-supported oral therapy in Chinese type 2 diabetic patients with inadequate glycemic control on oral anti-diabetic drugs. Diabetes Metab Res Rev. 2015;31(8):796–802. https://doi.org/10.1002/dmrr.2709.

    Article  PubMed  CAS  Google Scholar 

  7. Rathmann W, Czech M, Franek E, Kostev K. Regional differences in insulin therapy regimens in five European countries. Int J Clin Pharmacol Ther. 2017;55(5):403–8. https://doi.org/10.5414/CP202906.

    Article  PubMed  Google Scholar 

  8. ElSayed N, Aleppo G, Aroda V, Bannuru R, Brown F, Bruemmer D, et al. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S140–57. https://doi.org/10.2337/dc23-S009.

    Article  PubMed  CAS  Google Scholar 

  9. Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Häring H, Joost H, et al. Medical antihyperglycaemic treatment of type 2 diabetes mellitus: update of the evidence-based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes. 2009;117(9):522–57. https://doi.org/10.1055/s-0029-1239559.

    Article  PubMed  CAS  Google Scholar 

  10. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72. https://doi.org/10.1056/NEJMoa0802987.

    Article  PubMed  CAS  Google Scholar 

  11. United Kingdom Prospective Diabetes Study Group. United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med. 1998;128(3):165–75. https://doi.org/10.7326/0003-4819-128-3-199802010-00001.

    Article  Google Scholar 

  12. Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Diabetes Control and Complications Trial Research Group, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977–86. https://doi.org/10.1056/nejm199309303291401.

    Article  PubMed  CAS  Google Scholar 

  13. Katsuno T, Watanabe N, Nagai E, Okazaki K, Yokoyama A, Hamaguchi T, et al. Comparison of efficacy of concomitant administration of mitiglinide with voglibose and double dose of mitiglinide in patients with type 2 diabetes mellitus. J Diabetes Investig. 2011;2(3):204–9. https://doi.org/10.1111/j.2040-1124.2010.00082.x.

    Article  PubMed  CAS  Google Scholar 

  14. Ono Y, Kameda H, Cho K. Mitiglinide/voglibose fixed-dose combination improves postprandial glycemic excursions in Japanese patients with type 2 diabetes mellitus. Expert Opin Pharmacother. 2013;14(4):361–70. https://doi.org/10.1517/14656566.2013.770839.

    Article  PubMed  CAS  Google Scholar 

  15. Fujimoto K, Shibayama Y, Yamaguchi E, Honjo S, Hamasaki A, Hamamoto Y. Glucose excursions and hypoglycemia in patients with type 2 diabetes treated with mitiglinide/voglibose versus glimepiride: a randomized cross-over trial. J Diabetes. 2018;10(8):675–82. https://doi.org/10.1111/1753-0407.12658.

    Article  PubMed  CAS  Google Scholar 

  16. Ihana-Sugiyama N, Yamamoto-Honda R, Sugiyama T, Tsujimoto T, Kakei M, Noda M. Cross-over study comparing postprandial glycemic increase after addition of a fixed-dose mitiglinide/voglibose combination or a dipeptidyl peptidase-4 inhibitor to basal insulin therapy in patients with type 2 diabetes mellitus. Med Sci Monit Basic Res. 2017;23:36–44. https://doi.org/10.12659/msmbr.902218.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Murakami M, Bouchi R, Ohara N, Fukuda T, Minami I, Hashimoto K, et al. Beneficial effect of combination therapy with mitiglinide and voglibose on fasting and postprandial endothelial dysfunction in patients with type2 diabetes: a pilot study. Integr Obesity Diabetes. 2017;3:1.

    Article  Google Scholar 

  18. Ihana N, Tsujimoto T, Yamamoto-Honda R, Kishimoto M, Kajio H, Noto H, et al. Improvement of both fasting and postprandial glycemic control by the two-step addition of miglitol and mitiglinide to basal insulin therapy: a pilot study. Diabetol Metab Syndr. 2014;6:48. https://doi.org/10.1186/1758-5996-6-48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Battelino T, Danne T, Bergenstal R, Amiel S, Beck R, Biester T, et al. Clinical targets for continuous glucose monitoring data interpretation: recommendations from the International Consensus on Time in Range. Diabetes Care. 2019;42(8):1593–603. https://doi.org/10.2337/dci19-0028.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Service F, Molnar G, Rosevear J, Ackerman E, Gatewood L, Taylor W. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes. 1970;19(9):644–55. https://doi.org/10.2337/diab.19.9.644.

    Article  PubMed  Google Scholar 

  21. Wallace T, Levy J, Matthews D. Use and abuse of HOMA modeling. Diabetes Care. 2004;27(6):1487–95. https://doi.org/10.2337/diacare.27.6.1487.

    Article  PubMed  Google Scholar 

  22. Vos R, van Avendonk M, Jansen H, Goudswaard A, van den Donk M, Gorter K, et al. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. Cochrane Database Syst Rev. 2016;9(9):CD006992. https://doi.org/10.1002/14651858.CD006992.pub2.

    Article  PubMed  Google Scholar 

  23. Chang C, Hsieh C, Huang J, Huang I. Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus. Acta Diabetol. 2012;49(Suppl 1):S171–7. https://doi.org/10.1007/s00592-012-0398-x.

    Article  PubMed  CAS  Google Scholar 

  24. Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003;52(11):2795–804. https://doi.org/10.2337/diabetes.52.11.2795.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang X, Xu X, Jiao X, Wu J, Zhou S, Lv X. The effects of glucose fluctuation on the severity of coronary artery disease in type 2 diabetes mellitus. J Diabetes Res. 2013;2013:576916. https://doi.org/10.1155/2013/576916.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mazze R, Strock E, Borgman S, Wesley D, Stout P, Racchini J. Evaluating the accuracy, reliability, and clinical applicability of continuous glucose monitoring (CGM): Is CGM ready for real time? Diabetes Technol Ther. 2009;11(1):11–8. https://doi.org/10.1089/dia.2008.0041.

    Article  PubMed  CAS  Google Scholar 

  27. Mu P, Liu D, Lin Y, Liu D, Zhang F, Zhang Y, et al. The postprandial-to-fasting serum c-peptide ratio is a predictor of response to basal insulin-supported oral antidiabetic drug(s) therapy: a retrospective analysis. Diabetes Ther. 2018;9(3):963–71. https://doi.org/10.1007/s13300-018-0404-6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. DECODE Study Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161(3):397–405. https://doi.org/10.1001/archinte.161.3.397.

    Article  Google Scholar 

  29. Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care. 1999;22(6):920–4. https://doi.org/10.2337/diacare.22.6.920.

    Article  PubMed  CAS  Google Scholar 

  30. Chittari M, McTernan P, Bawazeer N, Constantinides K, Ciotola M, O’Hare J, et al. Impact of acute hyperglycaemia on endothelial function and retinal vascular reactivity in patients with Type 2 diabetes. Diabet Med. 2011;28(4):450–4. https://doi.org/10.1111/j.1464-5491.2010.03223.x.

    Article  PubMed  CAS  Google Scholar 

  31. Gapstur S, Gann P, Lowe W, Liu K, Colangelo L, Dyer A. Abnormal glucose metabolism and pancreatic cancer mortality. JAMA. 2000;283(19):2552–8. https://doi.org/10.1001/jama.283.19.2552.

    Article  PubMed  CAS  Google Scholar 

  32. Abbatecola A, Rizzo M, Barbieri M, Grella R, Arciello A, Laieta M, et al. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology. 2006;67(2):235–40. https://doi.org/10.1212/01.wnl.0000224760.22802.e8.

    Article  PubMed  CAS  Google Scholar 

  33. International Diabetes Federation Guideline Development Group. Guideline for management of postmeal glucose in diabetes. Diabetes Res Clin Pract. 2014;103(2):256–68. https://doi.org/10.1016/j.diabres.2012.08.002.

    Article  Google Scholar 

  34. Sunaga Y, Gonoi T, Shibasaki T, Ichikawa K, Kusama H, Yano H, et al. The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide. Eur J Pharmacol. 2001;431(1):119–25. https://doi.org/10.1016/s0014-2999(01)01412-1.

    Article  PubMed  CAS  Google Scholar 

  35. Assaloni R, Da Ros R, Quagliaro L, Piconi L, Maier A, Zuodar G, et al. Effects of S21403 (mitiglinide) on postprandial generation of oxidative stress and inflammation in type 2 diabetic patients. Diabetologia. 2005;48(9):1919–24. https://doi.org/10.1007/s00125-005-1849-5.

    Article  PubMed  CAS  Google Scholar 

  36. Kitasato L, Tojo T, Hatakeyama Y, Kameda R, Hashikata T, Yamaoka-Tojo M. Postprandial hyperglycemia and endothelial function in type 2 diabetes: focus on mitiglinide. Cardiovasc Diabetol. 2012;11:79. https://doi.org/10.1186/1475-2840-11-79.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Bonds D, Miller M, Bergenstal R, Buse J, Byington R, Cutler J, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ. 2010;340:b4909. https://doi.org/10.1136/bmj.b4909.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zoungas S, Patel A, Chalmers J, de Galan B, Li Q, Billot L, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010. https://doi.org/10.1056/NEJMoa1003795.

    Article  PubMed  Google Scholar 

  39. Chow E, Bernjak A, Williams S, Fawdry R, Hibbert S, Freeman J, et al. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk. Diabetes. 2014;63(5):1738–2347. https://doi.org/10.2337/db13-0468.

    Article  PubMed  CAS  Google Scholar 

  40. Funakoshi S, Fujimoto S, Hamasaki A, Fujiwara H, Fujita Y, Ikeda K, et al. Utility of indices using C-peptide levels for indication of insulin therapy to achieve good glycemic control in Japanese patients with type 2 diabetes. J Diabetes Investig. 2011;2(4):297–303. https://doi.org/10.1111/j.2040-1124.2010.00096.x.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to many people for their guidance and support in conducting this study and preparing this manuscript, including the following medical staff in Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine: Yusuke Hayashi, Risa Shimauchi, Yukiko Funahashi, Yuki Uchihara, and Nobuhiro Hirai.

Funding

This study was conducted with funding from Kissei Pharmaceutical Co. Ltd.

Author information

Authors and Affiliations

  1. Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan

    Toshihito Ando, Masaki Kondo, Yuriko Asada-Yamada, Miyuka Kawai, Emi Asano-Hayami, Tomohide Hayami, Mikio Motegi, Yohei Ejima, Eriko Nagao, Rina Kasagi, Hiromi Nakai-Shimoda, Saeko Asano, Makoto Kato, Yuichiro Yamada, Emiri Yura-Miura, Takahiro Ishikawa, Yukako Sugiura-Roth, Chika Kojima, Ena Naito, Tatsuhito Himeno, Shin Tsunekawa, Yoshiro Kato, Jiro Nakamura & Hideki Kamiya

Authors
  1. Toshihito Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masaki Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuriko Asada-Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miyuka Kawai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emi Asano-Hayami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomohide Hayami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mikio Motegi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yohei Ejima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eriko Nagao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rina Kasagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hiromi Nakai-Shimoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Saeko Asano
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Makoto Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yuichiro Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Emiri Yura-Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Takahiro Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Yukako Sugiura-Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Chika Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Ena Naito
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Tatsuhito Himeno
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Shin Tsunekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Yoshiro Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Jiro Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Hideki Kamiya
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: HK, JN; methodology: TH, ST, YK; formal analysis and investigation: TA, MK, YA-Y, MK, EA-H, TH, MM, YE, EN, RK, HN-S, SA, MK, YY, EY-M, TI, YS-R, CK, EN; writing—original draft preparation: TA, MK, TH; writing—review and editing: HK, JN; supervision: HK, JN.

Corresponding author

Correspondence to Hideki Kamiya.

Ethics declarations

Conflict of interest

Hideki Kamiya: lecture fees: Novo Nordisk Pharma, Sanofi, Sumitomo Pharma, Nippon Boehringer Ingelheim, Eli Lilly Japan, Daiichi Sankyo, Ono Pharmaceutical, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma, Kowa, Novartis Pharma, MSD, Sanwa Kagaku Kenkyusho, Otsuka Pharmaceutical, Ltd., Terumo, Taisho Pharmaceutical. Research funding: Ono Pharmaceutical, Eli Lilly Japan, Kissei Pharmaceutical. Subsidies or donations: Ono Pharmaceutical, Taisho Pharmaceutical, Sumitomo Pharma, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Japan Tobacco, Novo Nordisk Pharma. Endowed departments by commercial entities: Ono Pharmaceutical, Abbott Japan, Sanwa Kagaku Kenkyusho, Kowa, Terumo. Jiro Nakamura: lecture fees: Novo Nordisk Pharma, Sanofi, Daiichi Sankyo, Ono Pharmaceutical, Novartis Pharma, MSD, Taisho Pharmaceutical, Takeda Pharmaceutical, Terumo. Research funding: Eli Lilly Japan, Ono Pharmaceutical, Kissei Pharmaceutical. Subsidies or donations: MSD, Ono Pharmaceutical, Sumitomo Pharma, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Japan Tobacco, Novo Nordisk Pharma, Taisho Pharmaceutical. Endowed departments by commercial entities: Ono Pharmaceutical, Abbott Japan, Sanwa Kagaku Kenkyusho, Kowa, Terumo. The other authors declare no conflict of interest.

Ethical approval

All the procedures followed were in accordance with the ethical standards of the Ethics Committee of the Aichi Medical University (Approval No. 15-035, approval data: 09/04/2015) and with the Helsinki Declaration of 1964 and later versions.

Informed consent

Informed consent or substitute for it was obtained from all the patients for being included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ando, T., Kondo, M., Asada-Yamada, Y. et al. The efficacy of switching basal–bolus insulin therapy to basal insulin-supported oral therapy with a glinide and an α-glucosidase inhibitor in patients with type 2 diabetes depends on insulin secretory capacity, but not on blood glucose profiles and insulin dosages prior to the switching. Diabetol Int 15, 99–108 (2024). https://doi.org/10.1007/s13340-023-00651-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13340-023-00651-z

Keywords

Search

Navigation