Treatment Dosing Patterns and Clinical Outcomes for Patients with Type 2 Diabetes Starting or Switching to Treatment with Insulin Glargine (300 Units per Milliliter) in a Real-World Setting: A Retrospective Observational Study

Abstract

IntroductionUsage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 to assess whether the benefits observed in clinical trials translate into real-world settings.MethodsThis was a retrospective observational study using medical record data obtained by physician survey for patients starting treatment with insulin glargine at a strength of 100 units per milliliter (Gla-100) or Gla-300, or switching to treatment with Gla-300 from treatment with another basal insulin (BI). Differences in dosing and clinical outcomes before versus after treatment initiation or switching were examined by generalized linear mixed-effects models.ResultsAmong insulin-naive patients starting BI treatment, no difference in the final titrated dose was observed in patients starting Gla-300 treatment versus those starting Gla-100 treatment [least-squares (LS) mean 0.43 units per kilogram vs 0.44 units per kilogram; P = 0.77]. Both groups had significant hemoglobin A1c level reductions (LS mean 1.21 percentage points for Gla-300 and 1.12 percentage points for Gla-100 ; both P < 0.001). The relative risk of hypoglycemic events after Gla-300 treatment initiation was lower than that after Gla-100 treatment initiation [0.31, 95% confidence interval (CI) 0.12–0.81; P = 0.018] at similar daily doses. The daily dose of BI was significantly lower after switching to treatment with Gla-300 from treatment with another BI (0.73 units per kilogram before switch vs 0.58 units per kilogram after switch; P = 0.02). The mean hemoglobin A1c level was significantly lower after switching than before switching (adjusted difference − 0.95 percentage points, 95% CI − 1.13 to − 0.78 percentage points ; P < 0.0001). Hypoglycemic events per patient-year were significantly lower (relative risk 0.17, 95% CI 0.11–0.26; P < 0.0001).ConclusionsInsulin-naive patients starting Gla-300 treatment had fewer hypoglycemic events, a similar hemoglobin A1c level reduction, and no difference in insulin dose versus patients starting Gla-100 treatment. Patients switching to Gla-300 treatment from treatment with other BIs had significantly lower daily doses of BI, with fewer hypoglycemic events, without compromise of hemoglobin A1c level reduction. These findings suggest Gla-300 in a real-world setting provides benefits in terms of dosing, with improved hemoglobin A1c level and hypoglycemia rates.FundingSanofi US Inc. (Bridgewater, NJ, USA).

Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units/mL or 100 units/mL: Real‐world results from the DELIVER Naïve cohort study

“…With the removal of the requirement for a follow‐up HbA1c result, however, the sample size was approximately doubled and all but one of the differences in hypoglycaemia outcomes favouring Gla‐300 became statistically significant (Figure C,D). Similarly, in a retrospective observational study by Gupta et al, the risk of hypoglycaemia was statistically significantly lower among insulin‐naïve patients who initiated Gla‐300 versus Gla‐100 (relative risk 0.31; 95% confidence interval 0.12–0.81; P = 0.018), although there were similar reductions in HbA1c with Gla‐300 and Gla‐100. EDITION 3 reported on 48 different hypoglycaemia endpoints, based on incidence/event rates, nocturnal/any time, confirmed (≤3.9/<3.0 mmol/L [≤70/<54 mg/dL]) or severe, documented symptomatic (≤3.9/<3.0 mmol/L [≤70/<54 mg/dL]) and follow‐up time (0–6 months/0–8 weeks/9 weeks–6 months) .…”

“…21 For the various hypoglycaemia outcomes in the main analysis of the current DELIVER Naïve study ( Figure 4A,B 7 Of these, 13 were significantly in favour of Gla-300, 32 were numerically in favour of Gla-300, and three were numerically in favour of Gla-100. 7 It should be noted that the hypoglycaemia event rates in the three above-mentioned studies were very different, namely, 0.04 versus 0.08 events PPPY in the study by Gupta et al, 23 0.35 versus 0.49 events PPPY (main analysis) or 0.29 versus 0.39 events PPPY (sensitivity analysis) in DELIVER Naïve, and 2.33 versus 3.76 documented symptomatic hypoglycaemia ≤3.9 mmol/L (70 mg/dL) events PPPY in EDITION 3 7 for Gla-300 versus Gla-100, respectively. This is probably because of the very different data collection methods, potential differences between the patient populations, and differences in insulin titration.…”

“…This is probably because of the very different data collection methods, potential differences between the patient populations, and differences in insulin titration. In their observational study, Gupta et al asked physicians “Since being initiated on Gla‐300 or Gla‐100, has this patient reported experiencing any hypoglycaemic events?” and “How many hypo‐glycaemic events has this patient reported experiencing since being initiated on Gla‐300 or Gla‐100?”, which probably underestimated hypoglycaemia as it relied upon physician recall. Moreover, the physicians were not blinded to the therapy their patients were receiving.…”

Hypoglycaemia and treatment patterns among insulin‐treated patients with type 2 diabetes who switched to insulin glargine 300 units/mL versus other basal insulin in a real‐world setting

“…The substantially higher use of NPH insulin in the other switcher group is a possible explanation for this difference, as NPH insulin is associated with a higher rate of hypoglycaemia than Gla‐100 . It is notable that in a small retrospective study, concern regarding hypoglycaemia was one of the main reasons cited for switching to Gla‐300, a result somewhat in contrast to our own data …”

“…There is a growing body of real‐world evidence (RWE) for use of Gla‐300 in patients with T2D . Real‐world data arising from routine clinical care and healthcare service operations, when applied to research questions and analysed using rigorous scientific standards, become RWE and can help in the understanding of how the efficacy and safety data from randomized controlled trials translate in real‐world clinical practice settings and patient populations.…”