Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial
Open accessAbstract
Background Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes.Methods CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA 1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971).Findings Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA 1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy.Interpretation In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements.Funding Diabetes Liga Research Fund and Medtronic.
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In that study, overnight pregnancy-specific TIR was higher in the AID group while using assistive techniques.
“The 24-h percentage of pregnancy-specific TIR was not different between groups, but the overnight percentage of pregnancy-specific TIR was higher in the AID group while using assistive techniques.”
From 7. Diabetes Technology: Standards of Care in Diabetes—2025 (2025) · cites this paper as [239]
In that study, time below range was lower over 24 h and overnight in the AID group.
“Time spent below range was lower over 24 h and overnight in the AID group as well.”
From 7. Diabetes Technology: Standards of Care in Diabetes—2025 (2025) · cites this paper as [239]
In another study of AID with lowest glucose target 100 mg/dL, 24-h pregnancy-specific TIR did not differ between AID and standard care.
“The 24-h percentage of pregnancy-specific TIR was not different between groups, but the overnight percentage of pregnancy-specific TIR was higher in the AID group while using assistive techniques.”
From 7. Diabetes Technology: Standards of Care in Diabetes—2025 (2025) · cites this paper as [239]
In that study, quality-of-life metrics improved in the AID group.
“Quality-of-life metrics were improved in the AID group in this study (239).”
From 7. Diabetes Technology: Standards of Care in Diabetes—2025 (2025) · cites this paper as [239]
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- Institute of Medicine, National Research Council. US Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight gain during pregnancy: reexamining the guidelines. Rasmussen KM, Yaktine AL, eds. Washington, DC: National Academies Press, 2009.
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- Authors
- Benhalima, K., Beunen, K., Van Wilder, N., Ballaux, D., Vanhaverbeke, G., Taes, Y., Aers, X.-P., Nobels, F., Marlier, J., Lee, D., Cuypers, J., Preumont, V., Siegelaar, S. E., Painter, R. C., Laenen, A., Gillard, P., & Mathieu, C.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- KU Leuven (BE)
- AZ Groeninge (BE)
- AZ Sint-Jan (BE)
- AZ Delta (BE)
- Onze Lieve Vrouwziekenhuis Hospital (BE)
- Ghent University Hospital (BE)
- Imelda Hospital (BE)
- AZ Turnhout (BE)
- Cliniques Universitaires Saint-Luc (BE)
- Amsterdam UMC Location University of Amsterdam (NL)
- Amsterdam University Medical Centers (NL)
- Corresponding author
- Benhalima, Katrien
- ORCID
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 12
- Issue
- 6
- Pages
- 390-403
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W4396520192
- Cited by
- 131
- References
- 34
- Citations by year
- 2026: 39 · 2025: 69 · 2024: 23
- FWCI
- 43.15
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Medtronic Inc
- Koning Boudewijn Stichting
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
- Keywords
- type 1 diabetes in pregnancy, MiniMed 780G, glycemic control, hypoglycemia, time in range, continuous glucose monitoring, insulin pump therapy, HbA1c, insulin dose reduction
- MeSH terms
- Glycemic Control, Adolescent, Adult, Blood Glucose, Diabetes Mellitus, Type 1, Female, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Pregnancy, Pregnancy in Diabetics, Blood Glucose Self-Monitoring, Young Adult
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