Dataset Information

Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial.

ABSTRACT:

Objective

To assess whether low doses of empagliflozin as adjunct to hybrid closed-loop therapy improve glycemia compared with placebo in adults with type 1 diabetes (T1D) who are not able to achieve targets with the system alone.

Research design and methods

A double-blind crossover randomized controlled trial was performed in adults with suboptimally controlled T1D (HbA1c 7.0-10.5%) who were not able to achieve a target time in range (3.9-10.0 mmol/L) ≥70% after 14 days of hybrid closed-loop therapy. Three 14-day interventions were performed with placebo, 2.5 mg empagliflozin, or 5 mg empagliflozin as adjunct to the McGill artificial pancreas. Participants were assigned at a 1:1:1:1:1:1 ratio with blocked randomization. The primary outcome was time in range (3.9-10.0 mmol/L). Analysis was by intention to treat, and a P value <0.05 was regarded as significant.

Results

A total of 24 participants completed the study (50% male; age 33 ± 14 years; HbA1c 8.1 ± 0.5%). The time in range was 59.0 ± 9.0% for placebo, 71.6 ± 9.7% for 2.5 mg empagliflozin, and 70.2 ± 8.0% for 5 mg empagliflozin (P < 0.0001 between 2.5 mg empagliflozin and placebo and between 5 mg empagliflozin and placebo). Mean daily capillary ketone levels were not different between arms. There were no serious adverse events or cases of diabetic ketoacidosis or severe hypoglycemia in any intervention.

Conclusions

Empagliflozin at 2.5 and 5 mg increased time in range during hybrid closed-loop therapy by 11-13 percentage points compared with placebo in those who otherwise were unable to attain glycemic targets. Future studies are required to assess long-term efficacy and safety.

SUBMITTER: Pasqua MR

PROVIDER: S-EPMC9797647 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial.

Pasqua Melissa-Rosina MR Jafar Adnan A Kobayati Alessandra A Tsoukas Michael A MA Haidar Ahmad A

Diabetes care 20230101 1

<h4>Objective</h4>To assess whether low doses of empagliflozin as adjunct to hybrid closed-loop therapy improve glycemia compared with placebo in adults with type 1 diabetes (T1D) who are not able to achieve targets with the system alone.<h4>Research design and methods</h4>A double-blind crossover randomized controlled trial was performed in adults with suboptimally controlled T1D (HbA1c 7.0-10.5%) who were not able to achieve a target time in range (3.9-10.0 mmol/L) ≥70% after 14 days of hybrid ...[more]

PMID: 36331522

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Project description:OBJECTIVE:This study evaluated the feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions. RESEARCH DESIGN AND METHODS:In an open-label randomized crossover study, 12 suboptimally controlled adolescents on insulin pump therapy (mean ± SD age 14.6 ± 3.1 years; HbA1c 69 ± 8 mmol/mol [8.5 ± 0.7%]; duration of diabetes 7.8 ± 3.5 years) underwent two 21-day periods in which hybrid closed-loop insulin delivery was compared with sensor-augmented insulin pump therapy in random order. During the closed-loop intervention, a model predictive algorithm automatically directed insulin delivery between meals and overnight. Participants used a bolus calculator to administer prandial boluses. RESULTS:The proportion of time that sensor glucose was in the target range (3.9-10 mmol/L; primary end point) was increased during the closed-loop intervention compared with sensor-augmented insulin pump therapy by 18.8 ± 9.8 percentage points (mean ± SD; P < 0.001), the mean sensor glucose level was reduced by 1.8 ± 1.3 mmol/L (P = 0.001), and the time spent above target was reduced by 19.3 ± 11.3 percentage points (P < 0.001). The time spent with sensor glucose levels below 3.9 mmol/L was low and comparable between interventions (median difference 0.4 [interquartile range -2.2 to 1.3] percentage points; P = 0.33). Improved glucose control during closed-loop was associated with increased variability of basal insulin delivery (P < 0.001) and an increase in the total daily insulin dose (53.5 [39.5-72.1] vs. 51.5 [37.6-64.3] units/day; P = 0.006). Participants expressed positive attitudes and experience with the closed-loop system. CONCLUSIONS:Free-living home use of day-and-night closed-loop in suboptimally controlled adolescents with type 1 diabetes is safe, feasible, and improves glucose control without increasing the risk of hypoglycemia. Larger and longer studies are warranted.

Project description:BackgroundThe achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older.MethodsIn this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7·5-10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA1c. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9-10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual.FindingsFrom May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA1c was reduced from a screening value of 8·3% (SD 0·6) to 8·0% (SD 0·6) after the 4-week run-in, and to 7·4% (SD 0·6) after the 12-week intervention period. In the control group, the HbA1c values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA1c percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The time spent with glucose concentrations below 3·9 mmol/L (mean difference in change -0·83 percentage points, -1·40 to -0·16; p=0·0013) and above 10·0 mmol/L (mean difference in change -10·3 percentage points, -13·2 to -7·5; p<0·0001) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change -0·4%, 95% CI -1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI -0·005 to 0·067; p=0·09) and bodyweight did not differ (mean difference in change 0·68 kg, 95% CI -0·34 to 1·69; p=0·19). No severe hypoglycaemia occurred. One diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure. Two participants in each study group had significant hyperglycaemia, and there were 13 other adverse events in the closed-loop group and three in the control group.InterpretationHybrid closed-loop insulin delivery improves glucose control while reducing the risk of hypoglycaemia across a wide age range in patients with suboptimally controlled type 1 diabetes.FundingJDRF, NIHR, and Wellcome Trust.

Project description:ObjectiveTo compare the safety and efficacy of overnight closed loop delivery of insulin (artificial pancreas) with conventional insulin pump therapy in adults with type 1 diabetes.DesignTwo sequential, open label, randomised controlled crossover, single centre studies.SettingClinical research facility.Participants24 adults (10 men, 14 women) with type 1 diabetes, aged 18-65, who had used insulin pump therapy for at least three months: 12 were tested after consuming a medium sized meal and the other 12 after consuming a larger meal accompanied by alcohol.InterventionDuring overnight closed loop delivery, sensor measurements of glucose were fed into a computer algorithm, which advised on insulin pump infusion rates at 15 minute intervals. During control nights, conventional insulin pump settings were applied. One study compared closed loop delivery of insulin with conventional pump therapy after a medium sized evening meal (60 g of carbohydrates) at 1900, depicting the scenario of "eating in." The other study was carried out after a later large evening meal (100 g of carbohydrates) at 2030, accompanied by white wine (0.75 g/kg ethanol) and depicted the scenario of "eating out."Main outcome measuresThe primary outcome was the time plasma glucose levels were in target (3.91-8.0 mmol/L) during closed loop delivery and a comparable control period. Secondary outcomes included pooled data analysis and time plasma glucose levels were below target (≤ 3.9 mmol/L).ResultsFor the eating in scenario, overnight closed loop delivery of insulin increased the time plasma glucose levels were in target by a median 15% (interquartile range 3-35%), P = 0.002. For the eating out scenario, closed loop delivery increased the time plasma glucose levels were in target by a median 28% (2-39%), P = 0.01. Analysis of pooled data showed that the overall time plasma glucose was in target increased by a median 22% (3-37%) with closed loop delivery (P < 0.001). Closed loop delivery reduced overnight time spent hypoglycaemic (plasma glucose ≤ 3.9 mmol/L) by a median 3% (0-20%), P=0.04, and eliminated plasma glucose concentrations below 3.0 mmol/L after midnight.ConclusionThese two small crossover trials suggest that closed loop delivery of insulin may improve overnight control of glucose levels and reduce the risk of nocturnal hypoglycaemia in adults with type 1 diabetes. Trial registration ClinicalTrials.gov NCT00910767 and NCT00944619.

Project description:ObjectiveTo assess the efficacy and safety of a dual-hormone (DH [insulin and glucagon]) closed-loop system compared to a single-hormone (SH [insulin only]) closed-loop system in adolescents with type 1 diabetes.MethodsThis was a 26-hour, two-period, randomized, crossover, inpatient study involving 11 adolescents with type 1 diabetes (nine males [82%], mean ± SD age 14.8 ± 1.4 years, diabetes duration 5.7 ± 2.3 years). Except for the treatment configuration of the DiaCon Artificial Pancreas: DH or SH, experimental visits were identical consisting of: an overnight stay (10:00 pm until 7:30 am), several meals/snacks, and a 45-minute bout of moderate intensity continuous exercise. The primary endpoint was percentage of time spent with sensor glucose values below range (TBR [<3.9 mmol/L]) during closed-loop control over the 26-h period (5:00 pm, day 1 to 7:00 pm, day 2).ResultsOverall, there were no differences between DH and SH for the following glycemic outcomes (median [IQR]): TBR 1.6 [0.0, 2.4] vs. 1.28 [0.16, 3.19]%, p=1.00; time in range (TIR [3.9-10.0 mmol/L]) 68.4 [48.7, 76.8] vs. 75.7 [69.8, 87.1]%, p=0.08; and time above range (TAR [>10.0 mmol/L]) 28.1 [18.1, 49.8] vs. 23.3 [12.3, 27.2]%, p=0.10. Mean ( ± SD) glucose was higher during DH than SH (8.7 ( ± 3.2) vs. 8.1 ( ± 3.0) mmol/L, p<0.001) but coefficient of variation was similar (34.8 ( ± 6.8) vs. 37.3 ( ± 8.6)%, p=0.20). The average amount of rescue carbohydrates was similar between DH and SH (6.8 ( ± 12.3) vs. 9.5 ( ± 15.4) grams/participant/visit, p=0.78). Overnight, TIR was higher, TAR was lower during the SH visit compared to DH. During and after exercise (4:30 pm until 7 pm) the SH configuration produced higher TIR, but similar TAR and TBR compared to the DH configuration.ConclusionsDH and SH performed similarly in adolescents with type 1 diabetes during a 26-hour inpatient monitoring period involving several metabolic challenges including feeding and exercise. However, during the night and around exercise, the SH configuration outperformed DH.

Project description:Aims/hypothesisThe majority of hybrid closed-loop systems still require carbohydrate counting (CC) but the evidence for its justification remains limited. Here, we evaluated glucose control with simplified meal announcement (SMA) vs CC in youth and young adults with type 1 diabetes using the mylife CamAPS FX system.MethodsWe conducted a two-centre, randomised crossover, non-inferiority trial in two University Hospitals in Switzerland in 46 participants (aged 12-20 years) with type 1 diabetes using multiple daily injections (n=35), sensor-augmented pump (n=4) or hybrid closed-loop (n=7) therapy before enrolment. Participants underwent two 3 month periods with the mylife CamAPS FX system (YpsoPump, Dexcom G6) to compare SMA (individualised carbohydrate meal sizes) with CC, in a randomly assigned order using computer-generated sequences. The primary endpoint was the proportion of time glucose was in target range (3.9-10.0 mmol/l) with a non-inferiority margin of 5 percentage points. Secondary endpoints were other sensor glucose and insulin metrics, usability and safety endpoints.ResultsForty-three participants (18 women and girls) completed the trial. In the intention-to-treat analysis, time in range (mean±SD) was 69.9±12.4% with SMA and 70.7±13.0% with CC (estimated mean difference -0.6 percentage points [95% CI -2.4, 1.1], demonstrating non-inferiority). Time <3.9 mmol/l (median [IQR] 1.8 [1.2-2.2]% vs 1.9 [1.6-2.5]%) and >10.0 mmol/l (28.2±12.6% vs 27.2±13.4%) was similar between periods. Total daily insulin dose was higher with SMA (54.0±14.7 U vs 51.7±12.1 U, p=0.037). Three participants experienced serious adverse events, none of which were intervention-related.Conclusions/interpretationGlucose control using the CamAPS FX algorithm with SMA was non-inferior to its use with CC in youth and young adults with type 1 diabetes.Trial registrationClinicalTrials.gov NCT05481034.FundingThe study was supported by the Swiss Diabetes Foundation and by a YTCR grant from the Bangerter-Rhyner Foundation and the Swiss Academy of Medical Sciences. Dexcom and Ypsomed provided product support.

Dataset Information

Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial.

Objective

Research design and methods

Results

Conclusions

Publications

Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial.

Similar Datasets

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