Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials

BackgroundUltra-rapid-acting insulin (URAI) improves glycemic control by reducing variability; however, optimal strategies for its use, especially within hybrid closed-loop (HCL) insulin delivery systems, remain unclear. This meta-analysis assesses the efficacy and safety of combining URAI with HCL...

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Main Authors: Mohamed Saad Rakab, Rahma Mogahed Rateb, Basel Hatem Elsalakawi, Bashar M. Al Zoubi, Abubakar Nazir, Mutaz Moath Abu-Laila, Abdelrahman Sherif Ghanem, Alaa Maamoun, Mohab Mattar, Basma Ataallah, Brian T. Layden, Abeer M. Mahmoud
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1600157/full
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author Mohamed Saad Rakab
Rahma Mogahed Rateb
Basel Hatem Elsalakawi
Bashar M. Al Zoubi
Abubakar Nazir
Mutaz Moath Abu-Laila
Abdelrahman Sherif Ghanem
Alaa Maamoun
Mohab Mattar
Basma Ataallah
Brian T. Layden
Brian T. Layden
Abeer M. Mahmoud
Abeer M. Mahmoud
author_facet Mohamed Saad Rakab
Rahma Mogahed Rateb
Basel Hatem Elsalakawi
Bashar M. Al Zoubi
Abubakar Nazir
Mutaz Moath Abu-Laila
Abdelrahman Sherif Ghanem
Alaa Maamoun
Mohab Mattar
Basma Ataallah
Brian T. Layden
Brian T. Layden
Abeer M. Mahmoud
Abeer M. Mahmoud
author_sort Mohamed Saad Rakab
collection DOAJ
description BackgroundUltra-rapid-acting insulin (URAI) improves glycemic control by reducing variability; however, optimal strategies for its use, especially within hybrid closed-loop (HCL) insulin delivery systems, remain unclear. This meta-analysis assesses the efficacy and safety of combining URAI with HCL systems in maintaining the euglycemic range and reducing glycemic excursions.MethodsWe systematically searched PubMed, Scopus, Cochrane Library, Web of Science, and related article citations for relevant studies. Outcomes assessed included time in range (TIR), time below range (TBR), and time above range (TAR) during overall 24-hour periods, daytime, nighttime, postprandial, and post-exercise periods, as well as adverse events. Dichotomous outcomes were summarized using risk ratios (RR), and continuous outcomes were pooled using mean differences (MD) presented with 95% confidence intervals (CI).ResultsURAI showed a modest, statistically non-significant improvement in TIR (70–180 mg/dL) compared to standard insulin (MD 0.87%, 95% CI [-0.21 to 1.85], P = 0.12). Importantly, glycemic variability significantly improved with URAI, as demonstrated by reductions in the coefficient of variation (CV) (MD -0.78%, 95% CI [-1.44 to -0.12], P = 0.02). The combination of URAI with HCL systems significantly reduced hypoglycemia (TBR <70 mg/dL: MD -0.32%, 95% CI [-0.56 to -0.13], P = 0.002). However, overall reductions in TAR >250 mg/dL and TAR >180 mg/dL were statistically non-significant.ConclusionThe integration of URAI with HCL demonstrates encouraging improvements in glycemic outcomes, notably reduced glucose variability and nighttime hypoglycemia risk. However, further research with larger sample sizes is essential to confirm these benefits and establish broader clinical recommendations.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024594375, identifier CRD42024594375.
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spelling doaj-art-fa704e32ba0e4eb39ccf6e9963c5c3da2025-08-20T02:03:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-06-011610.3389/fendo.2025.16001571600157Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trialsMohamed Saad Rakab0Rahma Mogahed Rateb1Basel Hatem Elsalakawi2Bashar M. Al Zoubi3Abubakar Nazir4Mutaz Moath Abu-Laila5Abdelrahman Sherif Ghanem6Alaa Maamoun7Mohab Mattar8Basma Ataallah9Brian T. Layden10Brian T. Layden11Abeer M. Mahmoud12Abeer M. Mahmoud13Faculty of Medicine, Mansoura University, Mansoura, EgyptFaculty of Medicine, Assiut University, Assiut, EgyptFaculty of Medicine, Mansoura University, Mansoura, EgyptFaculty of Medicine, Hashemite University, Zarqa, JordanCollege of Medicine, King Edward Medical University, Lahore, PakistanFaculty of Medicine, Yarmouk University, Irbid, JordanFaculty of Medicine, Mansoura University, Mansoura, EgyptFaculty of Medicine, Mansoura University, Mansoura, EgyptFaculty of Medicine, Zagazig University, Zagazig, EgyptDepartment of Medicine, Houston Methodist/Willowbrook Hospital, Houston, TX, United StatesDepartment of Medicine, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, United StatesDepartment of Medicine, Division of Endocrinology, Diabetes, and Metabolism, College of Medicine, University of Illinois Chicago, Chicago, IL, United States0Department of Kinesiology and Nutrition, College of Applied Health Sciences, University of Illinois Chicago, Chicago, IL, United StatesBackgroundUltra-rapid-acting insulin (URAI) improves glycemic control by reducing variability; however, optimal strategies for its use, especially within hybrid closed-loop (HCL) insulin delivery systems, remain unclear. This meta-analysis assesses the efficacy and safety of combining URAI with HCL systems in maintaining the euglycemic range and reducing glycemic excursions.MethodsWe systematically searched PubMed, Scopus, Cochrane Library, Web of Science, and related article citations for relevant studies. Outcomes assessed included time in range (TIR), time below range (TBR), and time above range (TAR) during overall 24-hour periods, daytime, nighttime, postprandial, and post-exercise periods, as well as adverse events. Dichotomous outcomes were summarized using risk ratios (RR), and continuous outcomes were pooled using mean differences (MD) presented with 95% confidence intervals (CI).ResultsURAI showed a modest, statistically non-significant improvement in TIR (70–180 mg/dL) compared to standard insulin (MD 0.87%, 95% CI [-0.21 to 1.85], P = 0.12). Importantly, glycemic variability significantly improved with URAI, as demonstrated by reductions in the coefficient of variation (CV) (MD -0.78%, 95% CI [-1.44 to -0.12], P = 0.02). The combination of URAI with HCL systems significantly reduced hypoglycemia (TBR <70 mg/dL: MD -0.32%, 95% CI [-0.56 to -0.13], P = 0.002). However, overall reductions in TAR >250 mg/dL and TAR >180 mg/dL were statistically non-significant.ConclusionThe integration of URAI with HCL demonstrates encouraging improvements in glycemic outcomes, notably reduced glucose variability and nighttime hypoglycemia risk. However, further research with larger sample sizes is essential to confirm these benefits and establish broader clinical recommendations.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024594375, identifier CRD42024594375.https://www.frontiersin.org/articles/10.3389/fendo.2025.1600157/fullclosed-loop systemsultra fast acting insulin analogstype 1 diabetesglucose variabilitymeta-analysis
spellingShingle Mohamed Saad Rakab
Rahma Mogahed Rateb
Basel Hatem Elsalakawi
Bashar M. Al Zoubi
Abubakar Nazir
Mutaz Moath Abu-Laila
Abdelrahman Sherif Ghanem
Alaa Maamoun
Mohab Mattar
Basma Ataallah
Brian T. Layden
Brian T. Layden
Abeer M. Mahmoud
Abeer M. Mahmoud
Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials
Frontiers in Endocrinology
closed-loop systems
ultra fast acting insulin analogs
type 1 diabetes
glucose variability
meta-analysis
title Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials
title_full Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials
title_fullStr Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials
title_full_unstemmed Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials
title_short Ultra-rapid lispro or fast-acting aspart compared to standard insulin lispro and aspart using closed-loop insulin therapy: a systematic review and meta-analysis of randomized control trials
title_sort ultra rapid lispro or fast acting aspart compared to standard insulin lispro and aspart using closed loop insulin therapy a systematic review and meta analysis of randomized control trials
topic closed-loop systems
ultra fast acting insulin analogs
type 1 diabetes
glucose variability
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1600157/full
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