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Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen

Open access
Adolfsson, Peter, Hartvig, Niels Væver, Kaas, Anne, Møller, Jonas Bech, Hellman, Jarl·2020·Diabetes Technology & Therapeutics
DOI 10.1089/dia.2019.0411PMC PMC7591375
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Abstract

Background: This observational study investigated whether the connected NovoPen ® 6 could influence insulin regimen management and glycemic control in people with type 1 diabetes (T1D) using a basal-bolus insulin regimen and continuous glucose monitoring in a real-world setting. Methods: Participants from 12 Swedish diabetes clinics downloaded pen data at each visit (final cohort: n = 94). Outcomes included time in range (TIR; sensor glucose 3.9–10.0 mmol/L), time in hyperglycemia (>10 mmol/L), and hypoglycemia (L1: 3.0– <3.9 mmol/L; L2: <3.0 mmol/L). Missed bolus dose (MBD) injections were meals without bolus injection within −15 and +60 min from the start of a meal. Outcomes were compared between the baseline and follow-up periods (≥5 health care professional visits). Data were analyzed from the first 14 days following each visit. For the TIR and total insulin dose analyses ( n = 94), a linear mixed model was used, and for the MBD analysis ( n = 81), a mixed Poisson model was used. Results: TIR significantly increased (+1.9 [0.8; 3.0] 95% CI h/day; P < 0.001) from baseline to follow-up period, with a corresponding reduction in time in hyperglycemia (−1.8 [−3.0; −0.6] 95% CI h/day; P = 0.003) and L2 hypoglycemia (−0.3 [−0.6; −0.1] 95% CI h/day; P = 0.005), and no change in time in L1 hypoglycemia. MBD injections decreased by 43% over the study ( P = 0.002). Change in MBD injections corresponded to a decrease from 25% to 14% based on the assumption that participants had three main meals per day. Conclusions: Our study highlights the potential benefit on glycemic control and dosing behavior when reliable insulin dose data from a connected pen contribute to insulin management in people with T1D.

AI snapshot

Written from the paper’s full text.

TL;DR

In a one-arm real-world study of adults with type 1 diabetes using CGM, introducing the connected NovoPen® 6 was associated with improved time in range and fewer missed bolus injections. The authors conclude connected pen data may support insulin regimen management, but the observational design cannot prove causality.

Key findings

  • Time in range increased by 1.9 h/day (95% CI 0.8; 3.0; P < 0.001), or 8.5% of the day (95% CI 3.7; 13.3; P < 0.001), from baseline to after ≥5 HCP visits.
  • Time in hyperglycemia decreased by 1.8 h/day (95% CI −3.0; −0.6; P = 0.003), and L2 hypoglycemia (<3.0 mmol/L) decreased by 0.3 h/day (95% CI −0.6; −0.1; P = 0.005); L1 hypoglycemia did not change significantly (P = 0.181).
  • Missed bolus dose injections decreased by 43% (estimated relative change −43.1%, 95% CI −60.5; −18.0; P = 0.002), from 0.74 to 0.42 daily MBD injections, corresponding to a decrease from 24.7% to 14.1% assuming three meals/day.
  • Bolus insulin dose increased by 28% (95% CI 9.4; 49.5; P = 0.002), while basal dose did not change significantly; coefficient of variation decreased by 3.8% (95% CI −6.1; −1.6; P = 0.001).

Methods

  • One-arm, prospective, observational proof-of-concept study across 12 Swedish diabetes clinics from May 2017 to April 2019; analyses used data from May 2017 to October 2018.
  • Final cohort: 94 adults with type 1 diabetes using CGM and the connected NovoPen® 6 (48 men, 46 women; mean age 40.1 years, range 18–83); MBD analysis included 81 participants with bolus pen data.
  • Outcomes compared baseline with follow-up after ≥5 HCP visits using the first 14 days after each visit and days with ≥70% CGM coverage; linear mixed models for TIR/total insulin dose and a mixed Poisson model for MBD injections, with meals detected by the GRID algorithm.

Limitations

  • The paper states this was a short, single-arm observational study, so it cannot conclude with certainty that connected pen use directly improved glycemic control; longer studies are needed to assess durability.
  • The paper states visit frequency and study duration varied by local practice, possibly causing selection bias, and many participant IDs (65%) were excluded during data cleaning; only 14 participants had TIR data at visit 5 or later, and 10 had MBD data at ≥5 visits.
  • Evident from the text: there was no control group, HbA1c was not recorded, most participants used isCGM with 15-min readings resampled from rtCGM, and the GRID algorithm was designed to detect meals containing at least 40 g carbohydrate, with undetected meals increasing significantly (25.4%, P = 0.003).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1089/dia.2019.0411

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 38 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Time in L2 hypoglycemia significantly reduced from baseline to follow-up period by 0.3 h/day (95% CI -0.6 to -0.1; P=0.005).

    “L2 hypoglycemia (−0.3 [−0.6; −0.1]95% CI h/day; P = 0.005)”
    Quote in the paperSubstantial claim
  • Findingown data

    There was a significant reduction in L2 hypoglycemia (<3.0 mmol/L) of −0.3 hours per day (95% CI −0.6 to −0.1) from baseline to after five HCP visits.

    “A significant reduction in L2 hypoglycemia (<3.0 mmol/L [<54 mg/dL]) of −0.3 [−0.6; −0.1]95% CI hours per day (P = 0.005)”
    Quote in the paperSubstantial claim
  • Findingown data

    MBD injections decreased by 43% over the study (P=0.002).

    “MBD injections decreased by 43% over the study (P = 0.002).”
    Quote in the paperSubstantial claim
  • Findingown data

    Average daily number of MBD injections significantly decreased by 43% (estimated relative change −43.1%, 95% CI −60.5 to −18.0) from baseline (0.74) to follow-up (0.42).

    “A significant decrease of 43% (estimated relative change: −43.1% [−60.5; −18.0]95% CI, P = 0.002; Table 2) in the average daily number of MBD injections was observed from baseline (0.74 [0.62; 0.88]95% CI) to the follow-up period (0.42 [0.30; 0.60]95% CI, P = 0.002; Table 2 and Fig. 5).”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no significant change in mean time spent in L1 hypoglycemia (3.0-<3.9 mmol/L) from baseline to after five HCP visits.

    “There was no significant change in mean time spent in L1 hypoglycemia (3.0– <3.9 mmol/L [54– <70 mg/dL]; P = 0.181; Table 1 and Fig. 4).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 16
  • Classified as probably not a substantial claim. 28
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    The change in MBD injections by visit showed a significant effect from visit 3, and was relatively consistent from this point onward.

    “The change in MBD injections by visit is included in Supplementary Figure S2, which shows that a significant effect was seen from visit 3, and that it was relatively consistent from this point onward.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The change in TIR was relatively stable from visit 4 onward.

    “The change in TIR was relatively stable from visit 4 onward, as shown in Supplementary Figure S1.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    TIR increased by 8.5% from baseline to after five HCP visits.

    “Based on these analyses, the 8.5% increase in TIR reported here would be expected to correspond to an improvement in HbA1c of ∼0.4–0.7% (4–7 mmol/mol).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    This amounts to five meals with a missed dose per week on average.

    “This amounts to five meals with a missed dose per week on average.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Participants have three main meals per day on average.

  • May combine two claims.

    Findingown data

    Missing bolus injections can be common for people with T1D; on average at least 25% of meals had a missed dose, assuming three meals per day.

    “The study data also confirmed that missing bolus injections can be common for people with T1D, where on average at least 25% of meals had a missed dose, assuming three meals per day.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Participants have three main meals per day on average.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The number of participants with data at visits 1, 2, 3, and 4 was 57, 30, 21, and 15, respectively.

    “The number of participants with data at visits 1, 2, 3, and 4 was 57, 30, 21, and 15, respectively.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A significance level of P < 0.05 was predefined for all statistical comparisons.

    “A significance level of P < 0.05 was predefined for all statistical comparisons.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Reductions in HbA1c have been reported with CGM use in people on MDI therapy and continuous subcutaneous insulin infusion therapy, with reduced time spent in hypoglycemia and improved hypoglycemia awareness.

    “Reductions in HbA1c have been reported with CGM use in people on multiple daily injection (MDI) therapy,19 and continuous subcutaneous insulin infusion therapy,20 with reduced time spent in hypoglycemia,20 and improved hypoglycemia awareness.21”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [19] Lind M, Polonsky W, Hirsch IB, et al.: Continuous glucose monitoring vs conventional therapy for glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections: the GOLD randomized clinical trial. JAMA 2017; 317: 379– 387 28118454 source

      Not checked in the free run.

    • cites [20] Battelino T, Conget I, Olsen B, et al.: The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial. Diabetologia 2012; 55: 3155– 3162 22965294 PMC3483098 source

      Not checked in the free run.

    • cites [21] Heinemann L, Freckmann G, Ehrmann D, et al.: Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial. Lancet 2018; 391: 1367– 1377 29459019 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    An approximate 5% increase in TIR is associated with clinically significant benefits, according to ATTD consensus recommendations.

    “The recent Advanced Technologies & Treatments for Diabetes Congress consensus recommendations suggest that an approximate 5% increase in TIR is associated with clinically significant benefits.27”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Battelino T, Danne T, Bergenstal RM, et al.: Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Diabetes Care 2019; 42: 1593– 1603 31177185 PMC6973648 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Participants were blinded to the injection data overview during the baseline period.

    “Participants were blinded to the injection data overview during the baseline period (baseline until visit 1; Fig. 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    There was no indication of a relationship between baseline parameters (age, glycemic control, or insulin dose) and study duration or visit frequency.

    “There was no indication of a relationship between baseline parameters (age, glycemic control, or insulin dose) and study duration or visit frequency.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Missed insulin injections impact HbA1c levels and lead to an increased risk of diabetes-related complications.

    “The impact of missed insulin injections on HbA1c levels is well established,7–12 leading to an increasing risk of diabetes-related complications.13,14”
    Quote in the paperSubstantial claim0 of 8 sources checked
    • cites [7] Randlov J, Poulsen JU: How much do forgotten insulin injections matter to hemoglobin a1c in people with diabetes? A simulation study. J Diabetes Sci Technol 2008; 2: 229– 235 19885347 PMC2771482 source

      Not checked in the free run.

    • cites [8] Munshi MN, Segal AR, Suhl E, et al.: Assessment of barriers to improve diabetes management in older adults: a randomized controlled study. Diabetes Care 2013; 36: 543– 549 23193208 PMC3579376 source

      Not checked in the free run.

    • cites [9] Hood KK, Peterson CM, Rohan JM, et al.: Association between adherence and glycemic control in pediatric type 1 diabetes: a meta-analysis. Pediatrics 2009; 124: e1171– e1179 19884476 source

      Not checked in the free run.

    • cites [10] Spaans E, van Hateren KJJ, Groenier KH, et al.: Mealtime insulin bolus adherence and glycemic control in adolescents on insulin pump therapy. Eur J Pediatr 2018; 177: 1831– 1836 30238153 source

      Not checked in the free run.

    • cites [11] Andrade CS, Ribeiro GS, Santos C, et al.: Factors associated with high levels of glycated haemoglobin in patients with type 1 diabetes: a multicentre study in Brazil. BMJ Open 2017; 7: e018094 PMC5736030 29247092 source

      Not checked in the free run.

    • cites [12] Olinder AL, Kernell A, Smide B: Missed bolus doses: devastating for metabolic control in CSII-treated adolescents with type 1 diabetes. Pediatr Diabetes 2009; 10: 142– 148 19175898 source

      Not checked in the free run.

    • cites [13] Nathan DM, Genuth S, Lachin J, et al.: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977– 986 8366922 source

      Not checked in the free run.

    • cites [14] Nathan DM, Cleary PA, Backlund JY, et al.: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353: 2643– 2653 16371630 PMC2637991 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All statistical models were verified based on residual plots.

    “All statistical models were verified based on residual plots (not shown).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CGM use helps people with T1D achieve target time in range and avoid hyper- and hypoglycemia.

    “The key benefits of CGM include real-time data monitoring for people with T1D and access for them and their HCPs to complete glucose datasets17; both of which help people to achieve their target time spent within the acceptable range (time in range [TIR]: 3.9–10.0 mmol/L [70–180 mg/dL]) and avoid hyper- and hypoglycemia.18”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] Slattery D, Choudhary P: Clinical use of continuous glucose monitoring in adults with type 1 diabetes. Diabetes Technol Ther 2017; 19(Suppl 2): S55– S61 28541131 PMC5444504 source

      Not checked in the free run.

    • cites [18] Bergenstal RM, Ahmann AJ, Bailey T, et al.: Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the Ambulatory Glucose Profile (AGP). Diabetes Technol Ther 2013; 15: 198– 211 23448694 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Robustness with respect to the choice of follow-up period was evaluated by estimating the change from baseline for each single visit (and for every visit for MBD).

    “Robustness with respect to the choice of follow-up period was evaluated by estimating the change from baseline for each single visit.”
    • Also stated in: § Statistical analyses · plain
      “Robustness with respect to the choice of follow-up period was evaluated by estimating the change from baseline for every visit.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Of the final cohort of 94 participants, 14 made ≥5 visits to a HCP.

    “Of the final cohort of 94 participants, 14 made ≥5 visits to a HCP (Supplementary Fig. S1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Improvements in glycemic control and glycemic variability were associated with an increased frequency of blood glucose testing and administration of bolus insulin.

    “A previous study has demonstrated that improvements in glycemic control and glycemic variability were associated with an increased frequency of blood glucose testing and administration of bolus insulin.30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Pfutzner A, Weissmann J, Mougiakakou S, et al.: Glycemic variability is associated with frequency of blood glucose testing and bolus: post hoc analysis results from the ProAct study. Diabetes Technol Ther 2015; 17: 392– 397 25734860 PMC4432784 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Even small improvements in TIR can yield corresponding improvements in HbA1c, and result in clinically significant benefits.

    “Therefore, even small improvements in TIR can yield corresponding improvements in HbA1c, and result in clinically significant benefits.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The number of participants achieving ≥5 visits was 10.

    “The number of participants achieving ≥5 visits was 10.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    The finding of only a small, nonsignificant, increase in basal dose may be due to relatively few participants in the study using connected pens for their basal insulin.

    “The finding of only a small, nonsignificant, increase in basal dose may be due to relatively few participants in the study using connected pens for their basal insulin.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Connected pens such as the NovoPen® 6 have the potential to improve glycemic control, decrease glucose variability and increase treatment concordance in people with T1D, addressing the large unmet need for optimal insulin treatment.

    “Nonetheless, our findings suggest that connected pens such as the NovoPen® 6 have the potential to improve glycemic control, decrease glucose variability and increase treatment concordance in people with T1D, addressing the large unmet need for optimal insulin treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Many people treated with insulin fail to reach their glycemic targets, which is known to increase the risk of microvascular and macrovascular complications, resulting in substantial morbidity and mortality.

    “Many people treated with insulin fail to reach their glycemic targets, which is known to increase the risk of microvascular and macrovascular complications, resulting in substantial morbidity and mortality.13,14,24”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [13] Nathan DM, Genuth S, Lachin J, et al.: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977– 986 8366922 source

      Not checked in the free run.

    • cites [14] Nathan DM, Cleary PA, Backlund JY, et al.: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353: 2643– 2653 16371630 PMC2637991 source

      Not checked in the free run.

    • cites [24] Bailey TS, Stone JY: A novel pen-based Bluetooth-enabled insulin delivery system with insulin dose tracking and advice. Expert Opin Drug Deliv 2017; 14: 697– 703 28359171 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Evaluating past dosing data together with HCPs may have helped participants to remember and administer their meal-time doses, or to improve the timing of the dose relative to the meal.

    “This suggests that evaluating past dosing data together with HCPs may have helped participants to remember and administer their meal-time doses, or to improve the timing of the dose relative to the meal.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Supporting people to engage with and optimize their insulin regimens is a key challenge for HCPs, with educational interventions having limited effects.

    “Supporting people to engage with and optimize their insulin regimens is a key challenge for HCPs, with educational interventions having limited effects.38”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Doggrell SA, Chan V: Adherence to insulin treatment in diabetes: can it be improved? J Diabetes 2015; 7: 315– 321 25195971 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    A connected pen may help people to reduce the number of missed bolus injections and to properly adjust doses, thus leading to better glycemic control.

    “Our findings indicate that a connected pen may help people to reduce the number of missed bolus injections and to properly adjust doses, thus leading to better glycemic control.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The time in study, number of HCP visits, and time between visits varied considerably between participants because visits were conducted according to local clinical practice.

    “Since visits were conducted according to local clinical practice, the time in study, number of HCP visits, and time between visits varied considerably between participants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    The study was a short single-arm study, so we cannot conclude with certainty that the use of a connected pen directly improved glycemic control, and other factors may have played a role.

    “As this was a short single-arm study, we cannot conclude with certainty that the use of a connected pen directly improved glycemic control, and other factors may have played a role.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    People with T1D may regard reducing glucose variability and improving TIR to be as important as achieving their target HbA1c value.

    “As measurements of HbA1c do not reflect glycemic variability and target HbA1c values may be achieved while still experiencing marked daily glycemic fluctuations, people with T1D may regard reducing glucose variability and improving TIR to be as important as achieving their target HbA1c value.36,37”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [36] Dandona P: Minimizing glycemic fluctuations in patients with type 2 diabetes: approaches and importance. Diabetes Technol Ther 2017; 19: 498– 506 28771387 PMC5647495 source

      Not checked in the free run.

    • cites [37] Runge AS, Kennedy L, Brown AS, et al.: Does time-in-range matter? Perspectives from people with diabetes on the success of current therapies and the drivers of improved outcomes. Clin Diabetes 2018; 36: 112– 119 29686449 PMC5898169 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A recent study observed that the rate of late or missed bolus injections was 27% in people using MDI therapy, and that missed bolus injections correlated with higher HbA1c levels.

    “A recent study observed that the rate of late or missed bolus injections was 27% in people using MDI therapy, and that missed bolus injections correlated with higher HbA1c levels.40”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Norlander LM, Anderson SA, Levy CJ, et al.: Late and missed meal boluses with multiple daily insulin injections. Diabetes 2018; 68(Suppl 1): A259

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fluctuations in blood glucose levels may contribute more to outcomes than constant high blood glucose concentrations.

    “Other studies have demonstrated that fluctuations in blood glucose levels may contribute more to outcomes than constant high blood glucose concentrations.31–35”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [31] Ceriello A, Esposito K, Piconi L, et al.: Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 2008; 57: 1349– 1354 18299315 source

      Not checked in the free run.

    • cites [32] Esposito K, Nappo F, Marfella R, et al.: Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002; 106: 2067– 2072 12379575 source

      Not checked in the free run.

    • cites [33] Hirakawa Y, Arima H, Zoungas S, et al.: Impact of visit-to-visit glycemic variability on the risks of macrovascular and microvascular events and all-cause mortality in type 2 diabetes: the ADVANCE trial. Diabetes Care 2014; 37: 2359– 2365 24812434 source

      Not checked in the free run.

    • cites [34] Ceriello A, Kilpatrick ES: Glycemic variability: both sides of the story. Diabetes Care 2013; 36(Suppl 2): S272– S275 23882058 PMC3920802 source

      Not checked in the free run.

    • cites [35] Sartore G, Chilelli NC, Burlina S, et al.: The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM). Acta Diabetol 2012; 49(Suppl 1): S153– S160 22466072 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    An engaging and open dialogue between HCPs and people with T1D is highly important for optimal disease management, as it promotes collaboration, communication, and people's participation in their own treatment decisions.

    “Previous studies have identified that an engaging and open dialogue between HCPs and people with T1D is highly important for optimal disease management, as it promotes collaboration, communication, and people's participation in their own treatment decisions.25,26”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [25] Heisler M, Bouknight RR, Hayward RA, et al.: The relative importance of physician communication, participatory decision making, and patient understanding in diabetes self-management. J Gen Intern Med 2002; 17: 243– 252 11972720 PMC1495033 source

      Not checked in the free run.

    • cites [26] Ritholz MD, Beverly EA, Brooks KM, et al.: Barriers and facilitators to self-care communication during medical appointments in the United States for adults with type 2 diabetes. Chronic Illn 2014; 10: 303– 313 24567195 PMC4157962 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    For the TIR analysis, only 14 participants had data from visit 5 onward, meaning that the estimated change is based on the data from these, while the remaining data are used to estimate the random variation between participants, visits, and days and thus contribute to degrees of freedom in the variance estimates.

    “For the TIR analysis, only 14 participants had data from visit 5 onward (Supplementary Fig. S1), meaning that the estimated change is based on the data from these, while the remaining data are used to estimate the random variation between participants, visits, and days and thus contribute to degrees of freedom in the variance estimates.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    The use of a linear mixed model with different levels of correlations was necessary because data were unbalanced; this allowed all data to be used, and including participant as a random effect ensured each participant had their own baseline level, and the estimated change from baseline to visit 5 can be interpreted as the mean change from this level.

    “Furthermore, as data were unbalanced, the use of a linear mixed model with different levels of correlations was necessary.42 This allowed all data to be used, and by including participant as a random effect, it ensured that each participant had their own baseline level, and the estimated change from baseline to visit 5 can be interpreted as the mean change from this level.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] Harrison XA, Donaldson L, Correa-Cano ME, et al.: A brief introduction to mixed effects modelling and multi-model inference in ecology. PeerJ 2018; 6: e4794 29844961 PMC5970551 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies have found significant correlations between HbA1c levels and the number of missing bolus injections.

    “Studies have found significant correlations between HbA1c levels and the number of missing bolus injections.7,39”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Randlov J, Poulsen JU: How much do forgotten insulin injections matter to hemoglobin a1c in people with diabetes? A simulation study. J Diabetes Sci Technol 2008; 2: 229– 235 19885347 PMC2771482 source

      Not checked in the free run.

    • cites [39] Burdick J, Chase HP, Slover RH, et al.: Missed insulin meal boluses and elevated hemoglobin A1c levels in children receiving insulin pump therapy. Pediatrics 2004; 113(Pt 1): e221– e224 14993580 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The visit frequency for most participants seemed to be higher than what would be expected in normal clinical practice.

    “In addition, the visit frequency for most participants seemed to be higher than what would be expected in normal clinical practice.41”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Kavanos P, Van den Aardweg S, Schurer W: Diabetes expenditure, burden of disease and management in 5 EU countries. www.lse.ac.uk/business-and-consultancy/consulting/assets/documents/diabetes-expenditure-burden-of-disease-and-management-in-5-eu-countries.pdf (accessed 12 2020)

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    There was limited access to background participant information within the dataset, such as diabetes status and comorbidities.

    “There was limited access to background participant information within the dataset, such as diabetes status and comorbidities.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Many participant IDs (65%) were excluded from the analyses during data cleaning.

    “Many participant IDs (65%) were excluded from the analyses during data cleaning.”
    Quote in the paperSubstantial claim
37 of 37

  • The authors state this as an assumption.

    Participants had three main meals per day.

    “based on the assumption that participants had three main meals per day.”

  • The authors state this as an assumption.

    Participants have three main meals per day on average.

    “Based on the assumption that participants have three main meals per day”
    “Assuming three meals per day on average.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Research from individuals using multiple daily injection therapy with continuous glucose monitoring and connected insulin pen or cap devices revealed that missed, mistimed, and mismatched insulin bolus doses are common and occur in both older and younger populations with T1D or T2D, and are associated with higher A1C.

    “Research from individuals using MDI therapy with CGM and connected insulin pen or cap devices revealed that missed, mistimed, and mismatched insulin bolus doses are common and occur in both older and younger populations with T1D or T2D, and are associated with higher A1C.13–18”

    From Shining the Spotlight on Multiple Daily Insulin Therapy: Real-World Evidence of the InPen Smart Insulin Pen (2024) · cites this paper as [13]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • In a prospective, observational trial of 94 participants with T1D, the use of a connected insulin pen with continuous glucose monitoring resulted in significant improvements in glycemia and a significant decrease in missed doses.

    “In a prospective, observational trial of 94 participants with T1D, the use of a connected insulin pen with CGM resulted in significant improvements in glycemia and a significant decrease in missed doses.13”

    From Shining the Spotlight on Multiple Daily Insulin Therapy: Real-World Evidence of the InPen Smart Insulin Pen (2024) · cites this paper as [13]

    The Methods describe a prospective, observational study, and the Results report significant improvements in glycemic measures among 94 adults with T1D using CGM. Missed bolus injections fell significantly, but that analysis included only 81 participants. The Discussion cautions that this single-arm study cannot establish that the connected pen directly caused the improvements, so “resulted in” overstates the finding. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Norlander LM, , Anderson SA, , Levy CJ, et al.: Late and missed meal boluses with multiple daily insulin injections. Diabetes, 2018; 68(Suppl 1):A259.

Cited by

Sorted by citations

Related

Authors
Adolfsson, P., Hartvig, N. V., Kaas, A., Møller, J. B., & Hellman, J.
Affiliations
  • Hallands sjukhus Kungsbacka (SE)
  • Novo Nordisk (Denmark) (DK)
  • Uppsala University (SE)
Corresponding author
Adolfsson, Peter
ORCID
Venue
Diabetes Technology & Therapeutics
Publisher
SAGE Publications
Published
2020-10
Volume
22
Issue
10
Pages
709-718
ISSN
  • 1520-9156 (ISSN-L)
  • 1557-8593
DOI
10.1089/dia.2019.0411
PMC
PMC7591375
OpenAlex
W3003592023
Semantic Scholar
6bdf45f719045b751c9c17e89a31142159c144b4
Cited by
139
References
41
Citations by year
2026: 21 · 2025: 29 · 2024: 20 · 2023: 23 · 2022: 21 · 2021: 17 · 2020: 8
FWCI
13.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Technology & Therapeutics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
Funders
Novo Nordisk
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 1 diabetes, smart insulin pens, connected insulin pens, time in range, multiple daily insulin injections, glycemic control, hypoglycemia, hyperglycemia, continuous glucose monitoring
MeSH terms
Blood Glucose, Diabetes Mellitus, Type 1, Humans, Hypoglycemic Agents, Injections, Subcutaneous, Insulin, Sweden, Blood Glucose Self-Monitoring

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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