Table 5.

Smart insulin pens.

Study, year	Device studied/device compared	Type of insulin/company (number of users)	Participants	Study design	Results
Adolfsson et al., 2020 (133)	NovoPen® 6	Basal and/or bolus insulin: deguldec (n = 21), detemir (n = 1), aspart (n = 79), human insulin (n = 1), faster-acting insulin (n = 1)	94 participants (48 men and 46 women; aged 18–83 years, mean 40.1 years) with T1DM	Multicenter, prospective, observational, proof-of-concept study, Participants were using continuous glucose monitoring (CGM) and administered bolus and/or basal insulin with NovoPen® 6. During each healthcare professional (HCP) visit, pen and CGM data were downloaded. The analysis 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 done (MBD) injections were meals without bolus injection within -15 and +60 min from the start of a meal. These outcomes were compared between the baseline (until visit 1) and follow-up periods (at least 5 HCP visits).	TIR increased (+1.9, 95% CI: 0.8–3.0 h/day, p < 0.001) from baseline to follow-up period with a reduction in time in hyperglycemia (-1.8; 95% CI:- 3.0–(-0.6) h/day, p = 0.003) and L2 hypoglycemia (-0.3; 95% CI: -0.6–(-0.1) h/day; p = 0.005) but with no change in time in L1 hypoglycemia. MBD injections decreased by 43% over the study (p = 0.002).
Jendle et al., 2021 (134)	NovoPen® 6	Basal and/or bolus insulin: deguldec (n = 21), detemir (n = 1), aspart (n = 79), human insulin (n = 1), faster-acting insulin (n = 1)	94 participants (48 men and 46 women; aged 18–83 years, mean 40.1 years) with T1DM	Multicenter prospective, observational, proof-of-concept study, continuation of Swedish study (Adolfsson et al., 2020 (80)) Clinical outcomes and healthcare costs (in 2018 Swedish krona, SEK) were projected to estimate cost-effectiveness of smart insulin pen use over patients’ lifetime.	Smart insulin pen use was associated with improvement of mean discounted life expectancy (+0.90 years) and quality-adjusted life expectancy (+1.15 quality-adjusted life-years). Moreover, using smart injectors was a source of cost savings (direct SEK 124,270; indirect SEK 373,725) in comparison to standard care. The abovementioned profits were a result of projected lower frequency and delayed onset of diabetes complications versus standard care.
Vigersky et al., 2021 (142)	InPen™	Bolus insulin	529 individuals with non-optimal glycemic control (423 ones with glucose management indicator (GMI) >8.0% and 106 ones with GMI >9.5%)	Observational study CGM data were collected and compared before and up to 90 days after initiating InPen™ use. The outcomes were evaluated including means sensor glucose (SG), GMI, TIR, time above range (TAR), and time below range (TBR).	Patients with suboptimal metabolic control (GMI >8.0%) presented increased TIR (+2.3%, 0.6 h/day), reduced GMI (0.1%), SG (-4.3 mg/dl), and TAR (-2.4%) with no change in TBR, in comparison to pre-InPen™ use. Participants with poorest glycemic control at baseline (GMI >9.5) had TIR improvement by +5.0% (1.2 h/day), GMI by -0.4%, SG by -14.9 mg/dl, and TAR by 5.1% (1.2 h/day) with no change in TBR. From the first month to 90-days, post-InPen™ use bolus frequency decreased (from 3.7 to 3.6/day and 3.3 to 3.2/day, respectively) and total rapid-acting daily dose of insulin increased (from 26.29 to 27.19 U/day and 27.57 to 29.24 U/day, respectively). All mentioned results were significant (p < 0.05).

T1DM, type 1 diabetes mellitus; CGM, continuous glucose monitoring; HCP, healthcare professional; TIR, time in range (70–180 mg/dl; 3.9–10.0 mmol/l); GMI, glucose management indicator; SG, sensor glucose; TAR, time above range (>180 mg/dl; >10.0 mmol/l); TBR, time below range (<70 mg/dl; <3.9 mmol/l); U, units of insulin.