Continuous glucose monitors (CGMs) are valuable tools for improving glycemic control, yet their accuracy might be influenced by physical activity. This study sought to assess the accuracy of the ...three latest factory-calibrated CGM systems available in Europe at the time the study was conducted, both during aerobic exercise and in typical daily scenarios. The accuracy evaluation, based on metrics such as the median absolute relative difference (MARD) and point and rate error-grid analyses (PEGA and REGA), involved 13 adults with type 1 diabetes. Participants wore all sensors during a 1 h in-clinic exercise session followed by a subsequent 3-day home period, with blood glucose measurements serving as reference values in both contexts. During exercise, no statistically significant differences in MARD were observed (Dexcom G6: 12.6%, Guardian 4: 10.7%, and Freestyle Libre 2: 17.2%; p = 0.31), and similarly, no significant differences emerged in PEGA-zone-AB (100%, 100%, 96.8%; p = 0.37). Nevertheless, Freestyle Libre 2 showed comparatively diminished accuracy in estimating glucose trends during exercise (REGA-zone-AB: 100%, 93.0%, 73.3%; p = 0.0003). In the home environment, Freestyle Libre 2 exhibited a significantly higher MARD when compared to the other systems (10.2%, 11.9%, 16.7%, p = 0.02). Overall, Dexcom G6 and Guardian 4 demonstrated superior accuracy in both exercise and daily life scenarios compared to Freestyle Libre 2.
To 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.
...This 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).
Overall, 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.
DH 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.
IntroductionObesity increases the risk of comorbidities and diabetes-related complications and, consequently, efforts to prevent and reduce excess weight in people with type 1 diabetes are essential. ...The aim of this systematic review and network meta-analysis is to assess the effect of adjunctive glucose-lowering drugs on body weight and other important health outcomes in people with type 1 diabetes.Methods and analysisThis systematic review and network meta-analysis will include randomised controlled trials (RCTs) evaluating the use of adjunctive glucose-lowering drugs for treatment of people with type 1 diabetes. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform will be searched from inception to present. Key eligibility criteria include: RCT study design; adult participants with type 1 diabetes; treatment with a glucose-lowering drug for ≥24 weeks; and comparison of the intervention to placebo, usual care or another glucose-lowering drug. The primary outcome is change in body weight. Other major outcomes include change in HbA1c and total daily insulin dose and risk of hypoglycaemia and other adverse events. Dual study selection, data extraction and risk of bias assessment will be performed. Results from the meta-analysis will be presented as weighted mean differences for continuous outcomes and risk ratios for dichotomous outcomes. Sources of heterogeneity will be explored by subgroup and sensitivity analysis. A network meta-analysis for the primary outcome will be performed using an arm-based random-effects model based on the Bayesian framework while assessing for transitivity across studies and consistency between direct and indirect estimates. The overall quality of the evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach for each outcome.Ethics and disseminationNo ethical assessment is required. The results of this review will be disseminated through peer-reviewed publication and conference presentation.PROSPERO registration numberCRD42020158676
Introduction & objective: This post hoc analysis assessed the efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily (OD) basal insulin in insulin-naive (ONWARDS 1, 3, 5) and ...insulin-experienced (ONWARDS 2, 4) adults with T2D by kidney function subgroup. Methods: Treatment outcomes were analyzed by kidney function subgroup (eGFR ≥90; eGFR ≥60-<90; eGFR ≥30-<60; eGFR <30; all mL/min/1.73m2). Results: In ONWARDS 1, 3, and 5, there were no statistically significant treatment by kidney function subgroup interactions for change in A1C from baseline to planned end of treatment (EOT); however, in ONWARDS 2 and 4, there were significant subgroup interactions (Figure). No trend for heterogeneity was observed by kidney function subgroup for overall rates of clinically significant or severe hypoglycemia. Across kidney function subgroups, the proportion of participants achieving A1C <7% without clinically significant or severe hypoglycemic episodes at EOT was similar or higher for icodec vs comparators. Additionally, there were no statistically significant differences in average weekly insulin doses for icodec vs OD comparators by kidney function subgroup during the last 2 weeks of treatment in ONWARDS 1-5. Conclusion: Overall, the efficacy and safety for once-weekly icodec vs OD comparators was consistent, with no trend across kidney function subgroups. Disclosure P. Rossing: Other Relationship; AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Gilead Sciences, Inc., Novo Nordisk, Eli Lilly and Company, Novartis AG, Abbott Diagnostics. M. Benamar: Employee; Novo Nordisk A/S. A.Y.Y. Cheng: Advisory Panel; Abbott. Speaker's Bureau; Amgen Inc., AstraZeneca, Bausch Health. Advisory Panel; Bayer Inc. Speaker's Bureau; Abbott, Bayer Inc. Research Support; Applied Therapeutics Inc. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim, Dexcom, Inc. Advisory Panel; Dexcom, Inc., Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Eisai Inc. Speaker's Bureau; GlaxoSmithKline plc. Advisory Panel; HLS Therapeutics Inc. Speaker's Bureau; HLS Therapeutics Inc., Insulet Corporation. Advisory Panel; Insulet Corporation, Janssen Pharmaceuticals, Inc. Speaker's Bureau; Janssen Pharmaceuticals, Inc., Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Advisory Panel; Takeda Canada, AstraZeneca, Sanofi. Consultant; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc., Eisai Inc., Eli Lilly and Company, Insulet Corporation, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. C. Laugesen: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. P. Nielsen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. H.S. Bajaj: Research Support; Abbott, Amgen Inc., Anji Pharmaceuticals, Boehringer-Ingelheim, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc. Funding Novo Nordisk A/S
Objective: To compare the efficacy of low-dose s.c. dasiglucagon to oral carbohydrate consumption for prevention of insulin-induced hypoglycemia in people with type 1 diabetes. Methods: Twenty adults ...with type 1 diabetes using either multiple daily injection or insulin pump therapy completed a randomized, 3-arm cross-over study. On each study visit, an individualized s.c. insulin bolus was administered aiming for a plasma glucose concentration (PG) of 3.0 mmol/L. When reaching a PG of 4.5 mmol/L, either 80 µg dasiglucagon (D80), 120 µg dasiglucagon (D120) or 15 g carbohydrates from dextrose tablets (CHO) were administered. PG was measured frequently for the following 180 minutes. Results: Ten participants with CHO, 5 with D80 and 4 with D120 experienced a PG less than 3.9 mmol/L during the study (McNemar: CHO vs. D80, p=0.096; CHO vs. D120, p=0.034). The median time (95%CI) from intervention to first increase in PG of 1.1 mmol/L was 30 (25-50), 15 (15-20) and 15 (15-20) minutes for CHO, D80 and D120 (log-rank: CHO vs. D80, p=0.006; CHO vs. D120, p=0.003). No significant differences in visual analog scale-assessed expected adverse effects were observed between interventions. Conclusion: Low-dose dasiglucagon effectively prevented insulin-induced hypoglycemia with a faster glucose-elevating profile than dextrose tablets.
To compare the efficacy of low-dose subcutaneous dasiglucagon with oral glucose for prevention of insulin-induced hypoglycemia in people with type 1 diabetes.
Twenty adults with type 1 diabetes using ...multiple daily injection or insulin pump therapy completed a phase 2, randomized, three-arm crossover study. On each study visit, an individualized subcutaneous insulin bolus was administered aiming for a plasma glucose (PG) concentration of 3.0 mmol/L (54 mg/dL). When a PG concentration of 4.5 mmol/L (81 mg/dL) was reached, 15 g oral glucose (CHO) from dextrose tablets, 80 µg dasiglucagon (D80), or 120 µg dasiglucagon (D120) was administered. PG was measured frequently for the following 180 min.
Hypoglycemia (<3.9 mmol/L 70 mg/dL) occurred in 10 participants after CHO, in 5 after D80, and in 4 after D120 (CHO vs. D80, P = 0.096; CHO vs. D120, P = 0.034). Time spent in hypoglycemia (<3.9 mmol/L 70 mg/dL) was 14%, 7%, and 6% for CHO, D80, and D120, respectively (P = 0.273). The median time (95% CI) from intervention to first increase in PG of 1.1 mmol/L (20 mg/dL) was 30 (25-50), 15 (15-20), and 15 (15-20) minutes for CHO, D80, and D120, respectively (CHO vs. D80, P = 0.006; CHO vs. D120, P = 0.003). Episodes of nausea were numerically, but not significantly, higher after dasiglucagon administration. No significant differences in visual analog scale-assessed adverse effects were observed between interventions.
Low-dose dasiglucagon safely and effectively prevented insulin-induced hypoglycemia with a faster glucose-elevating profile than oral glucose.
Aims/hypothesis
Consumption of excess carbohydrates to manage hypoglycaemia can lead to rebound hyperglycaemia and promote weight gain. The objective of this trial was to evaluate the efficacy, ...safety and feasibility of pen-administered low-dose dasiglucagon for prevention and treatment of non-severe hypoglycaemia in people with type 1 diabetes during free-living conditions.
Methods
Twenty-four adults with insulin pump-treated type 1 diabetes (HbA
1c
≤70 mmol/mol 8.5%) completed a randomised, open-label, two-period crossover study with 2 week periods. During the usual care and dasiglucagon intervention (DASI) periods, participants managed impending and manifested episodes of hypoglycaemia with regular carbohydrate consumption or pen-administered low-dose (80 μg) s.c. dasiglucagon, respectively. Glycaemic control was evaluated using continuous glucose monitoring (Dexcom G6) and event registration of prevention and treatment episodes.
Results
Compared with usual care, the mean difference (95% CI) in the DASI period for time in (3.9–10.0 mmol/l) and below (<3.9 mmol/l) range was 2.4 %-points (−0.7, 5.5) and −0.5 %-points (−1.2, 0.2), respectively. In the DASI period, recovery rate (time from hypoglycaemia treatment to euglycaemia) was 44% (11, 87) faster while total daily carbohydrate intake was reduced by 11% (−18, −3). Dasiglucagon use was safe and well tolerated with mild nausea being the most frequent adverse effect. Among the participants, 96% (
p
<0.0001) were likely to include dasiglucagon in their future routine management of hypoglycaemia.
Conclusions/interpretation
Use of low-dose dasiglucagon to prevent and treat non-severe hypoglycaemia during free-living conditions was safe, fast and efficacious while significantly reducing the total daily carbohydrate intake and yielding high treatment satisfaction.
Trial registration
ClinicalTrials.gov
NCT04764968
Funding
The study was an investigator-initiated trial. Zealand Pharma supplied the investigational drug and device and provided financial support for the conduct of the trial.
Graphical abstract
Aim: To investigate whether the preceding rate of glucose fall affects the glucose response to subcutaneous (s.c.) low-dose glucagon administration.
Methods: Ten adults with insulin pump-treated type ...1 diabetes completed a randomized, single-blinded, 2-way cross-over study. Using hyperinsulinemic clamp technique, plasma glucose (PG) levels were initially stabilized at 8.0 mmol/l for ≥ 2 hrs. Thereafter, the glucose infusion rate was reduced to obtain either a rapid or a slow PG fall, while the insulin infusion was maintained at a fixed rate. When PG reached 3.9 mmol/l, insulin and glucose infusions were discontinued and a s.c. bolus of 150 µg glucagon was administered. PG levels were measured frequently for the following 120 min.
Results: The positive incremental area under the glucose curve (AUC) after administration of low-dose glucagon did not differ between the visits with a preceding rapid or slow glucose fall rate (mean ± s.e.m: 110 ± 25 vs. 73 ± 24 mmol/l x min, p = 0.21). Similarly, no significant difference in total AUC, peak PG, incremental peak PG, time-to-peak PG or PG at 120 min was observed.
Conclusions: Preceding glucose fall rate under fixed insulin level conditions did not affect the glucose response to low-dose s.c. glucagon administration.
Disclosure
C. Laugesen: None. S. Schmidt: Advisory Panel; Self; Medtronic. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. A. Ranjan: None.
Introduction & Objective: This post hoc analysis assessed the treatment effects of once-weekly insulin icodec (icodec) vs once-daily (OD) basal insulin comparators across different age groups in ...adults with T2D. Methods: Efficacy outcomes and hypoglycemia rates for icodec vs OD comparators across three age subgroups (<55, 55-64 and ≥65 years) were assessed, by trial, in insulin-naïve (ONWARDS 1, 3, 5) and insulin-treated (ONWARDS 2, 4) adults with T2D. Results: There were no statistically significant treatment by subgroup interactions for change in A1C from baseline to planned end of treatment (EOT) (Figure). A larger reduction in A1C with icodec was seen across age subgroups in ONWARDS 1-5, except for individuals ≥ 65 years in ONWARDS 4, where the opposite trend was seen. Overall, rates of clinically significant and severe hypoglycemic episodes were low in both treatment arms across age subgroups. In ONWARDS 1-5, the proportions of individuals achieving A1C <7% without clinically significant or severe hypoglycemic episodes at planned EOT were higher for icodec vs OD comparators irrespective of age, except for individuals < 55 and ≥ 65 years in ONWARDS 4; no statistically significant difference was seen in the treatment by subgroup interaction across different age subgroups. Conclusion: Overall, efficacy and hypoglycemia outcomes were consistent for icodec vs OD comparators irrespective of age. Disclosure A.G.D. Vianna: Board Member; Abbott, Lilly Diabetes, Novo Nordisk, Medtronic. Speaker's Bureau; AstraZeneca, Novo Nordisk. Research Support; Novo Nordisk, Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Research Support; Servier Laboratories. C. Desouza: Advisory Panel; Novo Nordisk, Bayer Inc., Madrigal Pharmaceuticals, Inc. Other Relationship; ADA/ACC Diabetes by Heart Program. Advisory Panel; Asahi Kasei. C. Laugesen: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. M. Fragão Marques: None. P. Nielsen: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. S.S. Shaikh: None. I. Lingvay: Consultant; Altimmune, Astra Zeneca, Bayer, Biomea, Boehringer-Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Mannkind, Mediflix, Merck, Metsera, Novo Nordisk, Pharmaventures, Pfizer, Sanofi. Research Support; NovoNordisk, Sanofi, Mylan, Boehringer-Ingelheim. Consultant; TERNS Pharma, The Comm Group, Valeritas, WebMD, and Zealand Pharma. Funding Novo Nordisk A/S
This post hoc analysis assessed continuous glucose monitoring (CGM)-based metrics and hypoglycemia duration with once-weekly insulin icodec versus once-daily basal insulin analogs in ...insulin-experienced individuals with long-standing type 2 diabetes from two 26-week phase 3a trials (ONWARDS 2 and ONWARDS 4).
Time in range (TIR) (3.9-10.0 mmol/L), time above range (TAR) (>10.0 mmol/L), and time below range (TBR) (<3.9 mmol/L and <3.0 mmol/L) were assessed during three CGM time periods (switch weeks 0-4, end of treatment weeks 22-26, and follow-up weeks 27-31) for icodec versus comparators (ONWARDS 2, insulin degludec basal regimen; ONWARDS 4, insulin glargine U100 basal-bolus regimen) using double-blind CGM data. CGM-derived hypoglycemic episode duration (<3.9 mmol/L) was assessed.
In both trials, there were no statistically significant differences in TIR, TAR, or TBR (<3.0 mmol/L) for icodec versus comparators across all time periods. In the end-of-treatment period, mean TIR was 63.1% (icodec) vs. 59.5% (degludec) in ONWARDS 2 and 66.9% (icodec) vs. 66.4% (glargine U100) in ONWARDS 4. Mean TBR <3.9 mmol/L and <3.0 mmol/L remained within recommended targets (<4% and <1%, respectively) across time periods and treatment arms. Hypoglycemic episode duration (<3.9 mmol/L) was comparable across time periods and treatment arms (median duration ≤40 min).
In insulin-experienced participants with long-standing type 2 diabetes, CGM-based TIR, TAR, and CGM-derived hypoglycemia duration (<3.9 mmol/L) were comparable for icodec and once-daily basal insulin analogs during all time periods. TBR remained within recommended targets.
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