Skip to main content
Log in

Closed-Loop Artificial Pancreas Therapy for Type 1 Diabetes

  • Diabetes and Cardiovascular Disease (D Bruemmer, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Closed-loop insulin pump systems (artificial pancreas) represent the cutting edge of insulin delivery technology. There are only a few systems currently approved for use in the USA: the MiniMed 670G/770G (which share an algorithm), t:slim X2 Control IQ, and the Omnipod 5. We review these systems and look into the future of the technology.

Recent Findings

All of the approved closed-loop insulin pump systems have demonstrated in multicenter prospective trials improvements in time in range, hemoglobin A1c, and time spent in hypoglycemia. The newer systems have also improved time spent in automation. Comparisons between the systems with regard to glycemic control are difficult to make due to differences in clinical trial design, but there are notable differences in the user experience between systems.

Summary

The past few years have been a time of exponential development in the field of closed-loop insulin pump systems. However, more research is needed to provide full automation of these systems without any need for information from the user.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Boughton CK, Hovorka R. Automated Insulin Delivery in Adults. Endocrinol Metab Clin North Am. 2020;49(1):167–78. https://doi.org/10.1016/j.ecl.2019.10.007.

    Article  PubMed  Google Scholar 

  2. Clemens AH, Chang PH, Myers RW. The development of Biostator, a Glucose Controlled Insulin Infusion System (GCIIS). Horm Metab Res. 1977;Suppl 7:23–33.

  3. Leelarathna L, Choudhary P, Wilmot EG, Lumb A, Street T, Kar P, et al. Hybrid closed-loop therapy: Where are we in 2021? Diabetes Obes Metab. 2021;23(3):655–60. https://doi.org/10.1111/dom.14273.

    Article  CAS  PubMed  Google Scholar 

  4. Amadou C, Franc S, Benhamou PY, Lablanche S, Huneker E, Diabeloop Consortium, et al. Diabeloop DBLG1 Closed-Loop System Enables Patients With Type 1 Diabetes to Significantly Improve Their Glycemic Control in Real-Life Situations Without Serious Adverse Events: 6-Month Follow-up. Diabetes Care. 2021;44(3):844–846. https://doi.org/10.2337/dc20-1809.

  5. Saunders A, Messer LH, Forlenza GP. MiniMed 670G hybrid closed loop artificial pancreas system for the treatment of type 1 diabetes mellitus: overview of its safety and efficacy. Expert Rev Med Devices. 2019;16(10):845–53. https://doi.org/10.1080/17434440.2019.1670639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Medtronic [Internet]. Northridge(CA): c2022. MINIMED 670G SYSTEM DISCONTINUATION OF NEW SALES. [cited 2022 Apr 21]. Available from: https://www.medtronicdiabetes.com/products/minimed-670g-insulin-pump-system.

  7. Knebel T, Neumiller JJ. Medtronic MiniMed 670G Hybrid Closed-Loop System. Clin Diabetes. 2019;37(1):94–5. https://doi.org/10.2337/cd18-0067.

    Article  PubMed  PubMed Central  Google Scholar 

  8. •• Garg SK, Weinzimer SA, Tamborlane WV, Buckingham BA, Bode BW, Bailey TS, et al. Glucose Outcomes with the In-Home Use of a Hybrid Closed-Loop Insulin Delivery System in Adolescents and Adults with Type 1 Diabetes. Diabetes Technol Ther. 2017;19(3):155–63. https://doi.org/10.1089/dia.2016.0421. Pivotal trial for the MiniMed 670G system.

  9. Stone MP, Agrawal P, Chen X, Liu M, Shin J, Cordero TL, et al. Retrospective Analysis of 3-Month Real-World Glucose Data After the MiniMed 670G System Commercial Launch. Diabetes Technol Ther. 2018;20(10):689–92. https://doi.org/10.1089/dia.2018.0202.

    Article  CAS  PubMed  Google Scholar 

  10. •• Forlenza GP, Ekhlaspour L, DiMeglio LA, Fox LA, Rodriguez H, Shulman DI, et al. Glycemic outcomes of children 2–6 years of age with type 1 diabetes during the pediatric MiniMed™ 670G system trial. Pediatr Diabetes 2022;23(3):324–329. https://doi.org/10.1111/pedi.13312. Trial allowing for expanded age range for use of the MiniMed 770G system, down to 2 years of age.

  11. McVean J, Miller J. MiniMedTM780G Insulin pump system with smartphone connectivity for the treatment of type 1 diabetes: overview of its safety and efficacy. Expert Rev Med Devices. 2021;18(6):499–504. https://doi.org/10.1080/17434440.2021.1926984.

    Article  CAS  PubMed  Google Scholar 

  12. • Collyns OJ, Meier RA, Betts ZL, Chan DSH, Frampton C, Frewen CM, et al. Improved Glycemic Outcomes With Medtronic MiniMed Advanced Hybrid Closed-Loop Delivery: Results From a Randomized Crossover Trial Comparing Automated Insulin Delivery With Predictive Low Glucose Suspend in People With Type 1 Diabetes. Diabetes Care. 2021;44(4):969 975. https://doi.org/10.2337/dc20-2250. Dual-center randomized trial comparing the MiniMed 780G algorithm in a 670G pump to SAP with predictive low glucose management.

  13. Wheeler BJ, Collyns OJ, Meier RA, Betts ZL, Frampton C, Frewen CM, et al. Improved technology satisfaction and sleep quality with Medtronic MiniMed® Advanced Hybrid Closed-Loop delivery compared to predictive low glucose suspend in people with Type 1 Diabetes in a randomized crossover trial. Acta Diabetol 2022;59(1):31–37. https://doi.org/10.1007/s00592-021-01789-5.

  14. • Bergenstal RM, Nimri R, Beck RW, Criego A, Laffel L, Schatz D, et al. FLAIR Study Group. A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial. Lancet. 2021;397(10270):208–219. https://doi.org/10.1016/S0140-6736(20)32514-9. Multi-center randomized trial comparing MiniMed 780G to the 680G in adolescents and young adults.

  15. •• Carlson AL, Sherr JL, Shulman DI, Garg SK, Pop-Busui R, Bode BW, et al. Safety and Glycemic Outcomes During the MiniMed Advanced Hybrid Closed-Loop System Pivotal Trial in Adolescents and Adults with Type 1 Diabetes. Diabetes Technol Ther. 2022;24(3):178–189. https://doi.org/10.1089/dia.2021.0319. Pivotal trial for the MiniMed 780G.

  16. Berget C, Lange S, Messer L, Forlenza GP. A clinical review of the t:slim X2 insulin pump. Expert Opin Drug Deliv. 2020;17(12):1675–87. https://doi.org/10.1080/17425247.2020.1814734.

    Article  CAS  PubMed  Google Scholar 

  17. •• Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, et al. iDCL Trial Research Group. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019;381(18):1707–1717. https://doi.org/10.1056/NEJMoa1907863. Pivotal trial for the Control-IQ system.

  18. • Brown SA, Beck RW, Raghinaru D, Buckingham BA, Laffel LM, Wadwa RP, et al. iDCL Trial Research Group. Glycemic Outcomes of Use of CLC Versus PLGS in Type 1 Diabetes: A Randomized Controlled Trial. Diabetes Care. 2020;43(8):1822–1828. https://doi.org/10.2337/dc20-0124. Extension of the pivotal trial for the Control-IQ system where those randomized to Control-IQ were re-randomized to Basal-IQ vs Control-IQ.

  19. • Breton MD, Kanapka LG, Beck RW, Ekhlaspour L, Forlenza GP, Cengiz E, et al. iDCL Trial Research Group. A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes. N Engl J Med. 2022;383(9):836–845. https://doi.org/10.1056/NEJMoa2004736. Trial for the Control-IQ system in children aged 6–13 years old.

  20. Pinsker JE, Müller L, Constantin A, Leas S, Manning M, McElwee Malloy M, et al. Real-World Patient-Reported Outcomes and Glycemic Results with Initiation of Control-IQ Technology. Diabetes Technol Ther. 2021;23(2):120–7. https://doi.org/10.1089/dia.2020.0388.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Forlenza GP, Buckingham BA, Brown SA, Bode BW, Levy CJ, Criego AB, et al. First Outpatient Evaluation of a Tubeless Automated Insulin Delivery System with Customizable Glucose Targets in Children and Adults with Type 1 Diabetes. Diabetes Technol Ther. 2021;23(6):410–24. https://doi.org/10.1089/dia.2020.0546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. •• Brown SA, Forlenza GP, Bode BW, Pinsker JE, Levy CJ, Criego AB, et al. Omnipod 5 Research Group. Multicenter Trial of a Tubeless, On-Body Automated Insulin Delivery System With Customizable Glycemic Targets in Pediatric and Adult Participants With Type 1 Diabetes. Diabetes Care. 2021;44(7):1630–1640. https://doi.org/10.2337/dc21-0172. Pivotal trial for the Omnipod 5 system.

  23. Forlenza GP, Lal RA. Current Status and Emerging Options for Automated Insulin Delivery Systems. Diabetes Technol Ther. 2022. https://doi.org/10.1089/dia.2021.0514.

    Article  PubMed  Google Scholar 

  24. Tandem Diabetes Care. t:slim X2 Insulin Pump with Control-IQ Technology: User Guide. San Diego (CA): 2002 [cited 2022 Apr 2]. Available from: https://www.tandemdiabetes.com/docs/default-source/product-documents/t-slim-x2-insulin-pump/aw-1005628_d_user-guide-tslim-x2-control-iq-7-4-mgdl-artwork_web.pdf

  25. Insulet Corporation. Omnipod 5: User Guide. Acton (MA): 2022 [cited 2022 Mar 30]. Available from: https://www.omnipod.com/sites/default/files/Omnipod-5_User-guide.pdf.

  26. Weisman A, Bai JW, Cardinez M, Kramer CK, Perkins BA. Effect of artificial pancreas systems on glycaemic control in patients with type 1 diabetes: a systematic review and meta-analysis of outpatient randomised controlled trials. Lancet Diabetes Endocrinol. 2017;5(7):501–12. https://doi.org/10.1016/S2213-8587(17)30167-5.

    Article  CAS  PubMed  Google Scholar 

  27. Bekiari E, Kitsios K, Thabit H, Tauschmann M, Athanasiadou E, Karagiannis T, et al. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ. 2018;361: k1310. https://doi.org/10.1136/bmj.k1310.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Eckstein ML, Weilguni B, Tauschmann M, Zimmer RT, Aziz F, Sourij H, et al. Time in Range for Closed-Loop Systems versus Standard of Care during Physical Exercise in People with Type 1 Diabetes: A Systematic Review and Meta-Analysis. J Clin Med. 2021;10(11):2445. https://doi.org/10.3390/jcm10112445.

    Article  PubMed  PubMed Central  Google Scholar 

  29. • Bassi M, Teliti M, Lezzi M, Iosca A, Strati MF, Carmisciano L, et al. A Comparison of Two Hybrid Closed-Loop Systems in Italian Children and Adults With Type 1 Diabetes. Front Endocrinol (Lausanne). 2022;12:802419. https://doi.org/10.3389/fendo.2021.802419. PMID: 35116007; PMCID: PMC8805205. Head-to-head comparison of the glycemic control obtained by the MiniMed 780G and Control-IQ systems.

  30. Battelino T, Tehranchi R, Bailey T, Dovc K, Melgaard A, Yager Stone J, et al. Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: Results of a phase 3, randomized controlled trial. Pediatr Diabetes. 2021;22(5):734–41. https://doi.org/10.1111/pedi.13220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. • Pieber TR, Aronson R, Hövelmann U, Willard J, Plum-Mörschel L, Knudsen KM, et al. Dasiglucagon: A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia Results of Phase 3 Randomized Double-Blind Clinical Trial. Diabetes Care. 2021:dc202995. https://doi.org/10.2337/DC20-2995. Phase 3 trial on dasiglucagon, a stable glucagon that is stable for days at room temperature.

  32. Infante M, Baidal DA, Rickels MR, Fabbri A, Skyler JS, Alejandro R, et al. Dual-hormone artificial pancreas for management of type 1 diabetes: Recent progress and future directions. Artif Organs. 2021;45(9):968–86. https://doi.org/10.1111/aor.14023.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Boughton CK, Hovorka R. New closed-loop insulin systems. Diabetologia. 2021;64:1007–15. https://doi.org/10.1007/s00125-021-05391-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. • Haidar A, Legault L, Messier V, Mitre TM, Leroux C, Rabasa-Lhoret R. Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial Lancet Diabetes Endocrinol 2015;3(1):17–26. https://doi.org/10.1016/S2213-8587(14)70226-8. Comparison of a dual-hormone (insulin and glucagon) closed-loop system with a insulin-only closed-loop system and a conventional insulin pump.

  35. Haidar A, Messier V, Legault L, Ladouceur M, Rabasa-Lhoret R. Outpatient 60-hour day-and-night glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or sensor-augmented pump therapy in adults with type 1 diabetes: An open-label, randomised, crossover, controlled trial. Diabetes Obes Metab. 2017;19(5):713–20. https://doi.org/10.1111/dom.12880.

    Article  CAS  PubMed  Google Scholar 

  36. • Castellanos LE, Balliro CA, Sherwood JS, Jafri R, Hillard MA, Greaux E, et al. Performance of the Insulin-Only iLet Bionic Pancreas and the Bihormonal iLet Using Dasiglucagon in Adults With Type 1 Diabetes in a Home-Use Setting. Diabetes Care. 2021;44(6):e118–e120. https://doi.org/10.2337/dc20-1086. Glycemic outcomes of the iLet dual-hormone (insulin and glucagon) closed-loop system.

  37. • Haidar A, Tsoukas MA, Bernier-Twardy S, Yale JF, Rutkowski J, Bossy A, et al. A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial. Diabetes Care. 2020;43(3):597–606. https://doi.org/10.2337/dc19-1922. Comparison of a dual-hormone (insulin and pramlintide) closed-loop system with an insulin-only closed-loop system.

  38. El-Khatib FH, Balliro C, Hillard MA, Magyar KL, Ekhlaspour L, Sinha M, et al. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. 2017;389(10067):369–80. https://doi.org/10.1016/S0140-6736(16)32567-3.

    Article  CAS  PubMed  Google Scholar 

  39. Cameron F, Niemeyer G, Wilson DM, Bequette BW, Benassi KS, Clinton P, et al. Inpatient trial of an artificial pancreas based on multiple model probabilistic predictive control with repeated large unannounced meals. Diabetes Technol Ther. 2014;16(11):728–34. https://doi.org/10.1089/dia.2014.0093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Turksoy K, Bayrak ES, Quinn L, Littlejohn E, Cinar A. Multivariable adaptive closed-loop control of an artificial pancreas without meal and activity announcement. Diabetes Technol Ther. 2013;15(5):386–400. https://doi.org/10.1089/dia.2012.0283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Tirosh A, Shalit R, Hirsh ML, Cohen O, Kurtz N, Anirban R, et al. Unannounced meal Challenges using the Medtronic advanced Hybrid Closed Loop. Category: 12-D Clinical Therapeutics/New Technology—Insulin Delivery Systems ADA 80th Scientif Sess. 2020. Chicago.

  42. Battelino T, Danne T, Bergenstal RM, Amiel SA, 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 

  43. Warren M, Bode B, Cho JI, Liu R, Tobian J, Hardy T, et al. Improved postprandial glucose control with ultra rapid lispro versus lispro with continuous subcutaneous insulin infusion in type 1 diabetes: PRONTO-Pump-2. Diabetes Obes Metab. 2021;23(7):1552–61. https://doi.org/10.1111/dom.14368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bode B, Carlson A, Liu R, Hardy T, Bergenstal R, Boyd J, et al. Ultrarapid Lispro Demonstrates Similar Time in Target Range to Lispro with a Hybrid Closed-Loop System. Diabetes Technol Ther. 2021;23(12):828–36. https://doi.org/10.1089/dia.2021.0184.

    Article  CAS  PubMed  Google Scholar 

  45. Hsu L, Buckingham B, Basina M, Ekhlaspour L, von Eyben R, Wang J, et al. Fast-Acting Insulin Aspart Use with the MiniMedTM 670G System. Diabetes Technol Ther. 2021;23(1):1–7. https://doi.org/10.1089/dia.2020.0083.

    Article  CAS  PubMed  Google Scholar 

  46. Bally L, Thabit H, Hartnell S, Andereggen E, Ruan Y, Wilinska ME, et al. Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care. N Engl J Med. 2018;379(6):547–56. https://doi.org/10.1056/NEJMoa1805233.

    Article  CAS  PubMed  Google Scholar 

  47. Boughton CK, Bally L, Martignoni F, Hartnell S, Herzig D, Vogt A, et al. Fully closed-loop insulin delivery in inpatients receiving nutritional support: a two-centre, open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7(5):368–77. https://doi.org/10.1016/S2213-8587(19)30061-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Boughton CK, Tripyla A, Hartnell S, Daly A, Herzig D, Wilinska ME, et al. Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial. Nat Med. 2021;27(8):1471–6. https://doi.org/10.1038/s41591-021-01453-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Medtronic. MiniMed 770G: System User Guide. Northridge (CA): 2020 [cited 2022 Apr 3]. Available from: https://www.medtronicdiabetes.com/sites/default/files/library/download-library/user-guides/MiniMed_770G_System_User_Guide.pdf.

  50. Medtronic. MiniMed 780G:System User Guide. Northridge (CA): 2020 [cited 2022 Apr 3]. Available from: https://www.medtronic-diabetes.com.au/sites/default/files/minimed_780g_instructions_for_use.pdf.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Keren Zhou.

Ethics declarations

Conflict of Interest

Keren Zhou reports: Research Grant: NIDDK Grant through JAEB for work on the iLet. Diana Isaacs reports: Speaker: Dexcom, Medtronic; Consultant: Insulet; Research Grant: Dexcom.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

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

This article is part of the Topical Collection on Diabetes and Cardiovascular Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, K., Isaacs, D. Closed-Loop Artificial Pancreas Therapy for Type 1 Diabetes. Curr Cardiol Rep 24, 1159–1167 (2022). https://doi.org/10.1007/s11886-022-01733-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-022-01733-1

Keywords