Automated Insulin Delivery Associated with Superior Glycemic Outcomes in Type 1 Diabetes: A Swedish National Registry Analysis
Fredrik Ståhl, PhD Fredrik.stahl@agnotech.se, Jarl Hellman, MD, and Charlotte Ekelund, MD, PhD
Abstract
Background:
Automated insulin delivery (AID) systems integrate continuous glucose monitoring (CGM) and insulin pumps with algorithms that adjust insulin delivery.
While randomized controlled trials (RCTs) demonstrate improvements in glycemic outcomes with AID, large-scale real-world data (RWD) analyses are needed to evaluate performance in routine care.
Methods:
This retrospective, registry-based cohort study included adults (≥18 years) with type 1 diabetes (T1D) in the Swedish National Diabetes Register (NDR) from 2014 to 2024.
Hemoglobin (Hb)A1c values were averaged per person-year and aggregated by clinic. Insulin delivery/glucose monitoring combinations included multiple daily injections (MDIs) with blood glucose meter (MDI-BG), MDI with CGM (MDI-CGM, reference), conventional continuous subcutaneous insulin infusion with blood glucose meter (CSII-BG), CSII with CGM (CSII-CGM), and AID systems (Tandem Control-IQ technology, Medtronic 670G, and Medtronic 780G).
Mixed-model regression assessed HbA1c outcomes, with treatment, year, age, diabetes duration, gender, body mass index, physical activity level, smoking habits, and clinic size as fixed effects; with random effects for clinics; and weighting by clinic sample size.
Results:
After adjusting for the covariates, Commpared with MDI-CGM: β = −4.0 mmol/mol (95% confidence interval [CI] −4.3 to −3.7, P < 0.001), with individual system effects, Tandem Control-IQ technology β = −4.8 mmol/mol (95% CI −5.2 to −4.5, P < 0.001), Medtronic 780G β = −3.1 (−3.5 to −2.7, P < 0.001), and Medtronic 670G β = −2.9 (95% CI −3.5 to −2.4, P < 0.001). CSII-CGM also outperformed MDI-CGM: β = −1.7 mmol/mol (95% CI −1.9 to −1.4, P < 0.001). Differences between the Tandem and Medtronic AID systems were significant (P < 0.001).
Conclusions:
In a nationwide RWD analysis, AID use was consistently associated with clinically and statistically significant HbA1c reductions in adults with T1D, with the greatest effect for Tandem Control-IQ technology.
These findings align with RCTs and international RWD, supporting AID as a preferred technology in routine diabetes care for T1D.
From the article
Introduction
Modern insulin therapy provides many different treatment modalities for type 1 diabetes (T1D) management in terms of glucose monitoring technology, means of insulin administration, and insulin analogs. Multiple daily insulin injection (MDI) remains the most common form of therapy worldwide but is often insufficient for maintaining acceptable glucose control. Insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) has proven to provide modest improvements in glycemic control when compared with MDI.1–3 Replacing conventional glucose monitoring (self-monitoring of blood glucose [SMBG]) with continuous glucose monitoring (CGM) in combination with either MDI (MDI-CGM) or CSII (with either an auxiliary CGM system or integrated with the pump, so-called sensor-augmented pump [SAP]) improves glycemic control,4,5 but it is unclear if insulin pumps retain their superiority.6 Despite improvements, the observed outcomes still fall short of bringing population-level HbA1c values within the internationally recognized therapeutic target of <53 mmol/mol.4,7
Automated insulin delivery (AID) systems, augmenting SAP systems with algorithm-driven insulin dosing to improve glycemic control, have emerged as the next technological step to push the treatment envelope. Several generations of AID systems have now been evaluated in randomized controlled trials (RCTs).8 The earlier systems incorporate features to down-regulate the basal delivery on existing (low glucose suspend [LGS]) or expected hypoglycemia (predicted LGS [PLGS]), whereas the modern systems can increase basal insulin during rising glucose and decrease or suspend insulin during falling glucose, with some also delivering automatic correction boluses. Commercially available AID systems include Medtronic MiniMed™ 670G and 780G, Tandem t:slim X2 and Tandem Mobi with Control-IQ technology, Omnipod 5, Medtrum TouchCare System Nano Pump, and CamAPS (in myLife YpsoPump, Dana Diabecare RS, and DANA-I pumps). Pivotal multicenter trials of CamAPS,9 Medtronic MiniMed 670G and 780G,10–12 Tandem Control-IQ technology,13 DBLG1,14 and Insulet Omnipod 5 systems15 consistently demonstrate superior glycemic outcomes compared with SAP or MDI with lower hemoglobin (Hb)A1c, higher time in range (TIR, 3.9–10.0 mmol/l), and reduced hypoglycemia (<3.9 mmol/l).
Beyond clinical trials, real-world data (RWD) are essential to evaluate system performance, safety, and sustainability over time. Several large-scale studies have demonstrated that glycemic benefits of AID persist in clinical practice settings. Examples include real-world evaluations of Tandem Control-IQ technology,16,17Medtronic MiniMed 780G,18,19 Diabeloop DBLG1,20 CamAPS FX,21 and Insulet Omnipod 5.22 Collectively, these studies report sustained improvements in HbA1c and increased TIR, without evidence of increased severe hypoglycemia or diabetic ketoacidosis, consistent with the results from RCTs.
These findings have been reinforced by registry data,23 systematic reviews,24–26 and meta-analyses,27,28 also covering additional AID systems, confirming that AID systems outperform conventional therapy across multiple outcome domains, with effect sizes consistent across age groups and trial settings.
Based upon these encouraging results, several consensus guidelines now recommend AID to be considered for all populations with T1D, as it increases the likelihood of reaching recommended glycemic targets.4,29,30The British National Institute for Health and Care Excellence recommends use for children and adolescents in gestational diabetes and for adults with HbA1c over 58 mmol/mol.31,32
Despite robust evidence supporting AID systems, several evidence gaps remain. Most RWD studies rely primarily on CGM-derived metrics such as TIR, with only a few reporting HbA1c, which remains the gold standard for assessing long-term risk and for health-economic modeling and allows for comparison to non-CGM-based therapies. Moreover, comparative analyses between treatment modalities or AID systems are scarce, and long-term follow-up beyond 1 year is uncommon. Addressing these gaps is essential to strengthen the evidence base for clinical guideline development and reimbursement decisions.
National registries provide a unique opportunity to evaluate the impact of different treatment modalities in a nationwide population. In Sweden, structured diabetes care is supported by the Swedish National Diabetes Register (NDR), covering >95% of individuals with T1D.33 CGM adoption became widespread in the mid-2010s, and AID uptake has accelerated since 2017. This study uses NDR data to evaluate the association between insulin delivery/glucose monitoring combinations and HbA1c in Swedish adults with T1D from 2014 to 2024, focusing on AID systems. We hypothesized that adults using AID would achieve significantly better HbA1c compared with those treated with MDI and CGM, consistent with the findings from clinical trials and real-world studies described above.
Discussion
In this nationwide, registry-based analysis of more than 600,000 annualized HbA1c measurements from adults with T1D in Sweden between 2014 and 2024, we found a clear hierarchy in terms of HbA1c reduction effect (Δ, mmol/mol) with ΔAID>ΔPLGS≥ΔCSII-CGM>ΔMDI-CGM≥ΔCSII-BG≥ΔMDI-BGa among the evaluated treatment modalities.
• CSII-BG versus MDI-BG
The difference in treatment effect between CSII-BG and MDI-BG was not significant (0.8 mmol/mol, P = 0.36). Specifically for the Swedish context, these findings contrast previous NDR analyses, which in the pre-AID era demonstrated a mean HbA1c difference of about 2 mmol/mol in favor of insulin pump therapy compared with MDI.38
• SMBG versus CGM-based therapies
No difference could be found between MDI-CGM and CSII-BG, but all CSII-CGM and AID systems outperformed both CSII-BG and MDI-BG, except Medtronic Unknown, which mainly consists of older Medtronic systems, and MDI-CGM proved better than MDI-BG. The positive effect of CGM has been demonstrated in several landmark studies.39–42
• CSII-CGM and AID
The CSII-CGM systems outperformed MDI-CGM (1.7 mmol/mol, P < 0.001). Previous studies have reported inconclusive results for this comparison.6 In the current material, the CSII-CGM group likely includes some AID systems (due to the uncertainty about AID functionality for the SAP Tandem and YpsoPump MyLife systems), but their small fraction of the total implies a negligible influence on the results.
The MyLife YpsoPump had a similar performance as the group (−2.2 mmol/mol, P < 0.001) compared with the reference. In a multicenter clinical trial, the AID functionality was found to reduce HbA1c from baseline by 4.0 mmol/mol more than the SAP control.9 It is unknown to what extent the AID capabilities have been used in our data, and the system is therefore categorized as a CSII-CGM pump, and direct comparison with the AID trial results should be done with caution.
The superiority of the AID systems found in this study aligns with evidence from both RCTs and large observational studies. Improvements in HbA1c in the magnitude of −5 to −6 mmol/mol for AID systems as a group compared with SAP were found in meta-analyses,27,43,44 well above the average −2.4 mmol/mol improvement seen here.
In the pivotal Control-IQ technology trial,13 adults experienced a mean HbA1c reduction of –3.6 mmol/mol over 6 months. Later real-world evidence studies have reported larger effects.17 Our results are situated somewhere in the middle (−4.9 mmol/mol vs. MDI-CGM).
For Medtronic 780G, multicenter studies show real-world HbA1c reductions of about –6 mmol/mol from baseline,45,46 larger than the –3.1 mmol/mol effect estimated in our dataset. In a study on poorly controlled subjects (baseline HbA1c: 100 mmol/mol), a reduction of 17 mmol/mol was attained.10 The earlier system, 670G, demonstrated smaller improvements (approximately –3 mmol/mol) compared with the newer system.44,47,48
A possible explanation for the smaller reduction in HbA1c observed in our dataset is the lower baseline HbA1c values (generally below 60 mmol/mol, considering that new users mainly come from CSII-CGM, Fig. 1) in this population compared with those in the literature, where initial HbA1c levels are often significantly higher (well above >60 mmol/mol).44 This is consistent with evidence from several studies indicating that effect sizes tend to increase with higher baseline HbA1c levels.46,48,49
Conclusions
This nationwide, registry-based analysis provides real-world evidence on glycemic outcomes associated with different insulin delivery and glucose monitoring technologies in Swedish adults with T1D over a 10-year period.
There has been a substantial improvement in average HbA1c at the national level, with an approximately 8 mmol/mol reduction between 2014 and 2024 paired with a dramatic increase in CGM usage from virtually zero to over 90% of the population.
Use of AID technology was consistently associated with lower HbA1c compared with both MDI-CGM and CSII-CGM, with the most treatment impact from Control-IQ technology. The AID group results corroborate previous results from RCTs and RWD studies that AID systems are associated with significantly better HbA1c outcomes than non-AID modalities, supporting the broader adoption of AID in routine care, and underscore the value of registry-based surveillance in monitoring long-term outcomes.
Further analyses are necessary to assess potential differences among subpopulations, evaluate the dynamics of glycemic improvement from onset onward to determine its stability, identify potential confounders and transition effects associated with switching treatment modalities, and delineate causal factors related to settings, algorithms, and training. Such investigations are essential to optimize interventions and enhance glycemic control within the diabetes community.
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