PK/PD of clinical doses of Glargine 300 U/mL (Gla-300) and Gla-100 differ (Diabetes Care 2019;42:85), but any clinical relevance has been difficult to demonstrate.
Aim: to demonstrate that PK/PD differences of individual doses of Gla-300 vs. Gla-100 translate into clinical benefits in T1DM, as shown by interstitial glucose (IG) (CGM).
Methods: 18 persons with T1DM (age 40±12 yrs, diabetes duration 26±12 yrs, A1C 7.2±0.5 %, 55±6 mmol/mol) were randomized to Gla-300 or Gla-100 titrated for 3 months, followed by 2 month washout, and alternate treatment for 3 more months. Titrated mealtime rapid-acting insulin analogs were continued with both Gla-300 and Gla-100. Blinded CGM (iPro, Medtronic) was used during last 2 weeks of each 3-month treatment period.
Results: After 3 months, A1C was no different with Gla-300 vs. Gla-100 (both 6.9±0.5 %, 52±6 mmol/mol). CGM revealed lower 24 h IG (Figure); % time in range (70-180 mg/dl) was higher (82±8 vs. 72±10), whereas % time above range (>180 mg/dl, 16±7 vs. 24±8), % time below range (particularly from midnight to pre-breakfast) (<70 mg/dl, 2±3 vs. 4±4) and IG nocturnal variability (% CV 25±7 vs. 37±12) were lower with Gla-300 vs. Gla-100 (p<0.05). Dose was higher with Gla-300 (0.35±0.08 U/kg) vs. Gla-100 (0.28±0.07 U/kg).
Conclusions: Titrated Gla-300 improves glucose control, reduces variability and hypoglycemia risk vs. Gla-100, as predicted from PK/PD differences of individual doses.
L. Paola: None. P. Cioli: None. P. Candeloro: None. A. Marinelli Andreoli: None. G.B. Bolli: Consultant; Self; Sanofi. C.G. Fanelli: Advisory Panel; Self; Eli Lilly and Company, Sanofi. F. Porcellati: None.