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Aim: To study safety, efficacy and weight loss with ADO09, a co‐formulation of insulin A21G and pramlintide, in type 1 diabetes. Materials and Methods: A randomized, two‐arm ambulatory 16‐week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. Results: A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. Conclusions: These results extend previous observations on the efficacy and safety of this insulin/pramlintide co‐formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia. [ABSTRACT FROM AUTHOR]

Aim: Pramlintide improves postprandial glucose but requires additional injections. We investigated the pharmacokinetics/pharmacodynamics, efficacy and safety of ADO09, pramlintide/insulin A21G co‐formulation, in type 1 diabetes (T1D). Materials and Methods: This double‐blinded, randomized, two‐period cross‐over study compared prandial administration of ADO09 or insulin aspart over 24 days in T1D using either ≤40 U bolus insulin per day [low‐dose group (LD), n = 28] or 40‐75 U [high‐dose group (HD), n = 16]. Glycaemic responses through continuous glucose monitoring, and pharmacokinetics/pharmacodynamics profiles following mixed‐meal‐tolerance tests were evaluated at baseline and at the end of treatment. Results: Glucose increments from 0 to 4 h after mixed‐meal‐tolerance test (primary endpoint) were 39% (not statistically significantly) lower with ADO09 in the low‐dose group and 69% lower in the high‐dose group. Mean continuous glucose monitoring glucose during ambulatory treatment was lower with ADO09 than with aspart (LD: –8.2 ± 7.9 mg/dl, p =.0001; HD: –7.0 ± 10 mg/ml, p =.0127), and time‐in‐range (70–180 mg/dl) improved (LD: +4%, p =.0134; HD: +4%, p =.0432). Body weight declined significantly with ADO09 (LD: –0.8 kg; HD: –1.6 kg). Hypoglycaemic events were slightly more frequent with ADO09 versus aspart (LD: 142 vs. 115; HD: 96 vs. 79). Gastrointestinal events occurred more frequently with ADO09 but were generally transient, and no other safety signals were identified. Conclusions: In comparison with aspart, ADO09 was well tolerated and effective in T1D across a wide range of dosage, significantly improving the average blood glucose level and body weight during 24 days of ambulatory treatment. Meal test profiles confirmed improvement of glycaemic patterns and other responses with ADO09. [ABSTRACT FROM AUTHOR]

Aim: To compare the safety, pharmacokinetics and pharmacodynamics of ADO09 with insulin lispro (Lispro) and separate subcutaneous injections of human insulin and pramlintide (Ins&Pram) in 24 subjects with type 1 diabetes. Methods: At three dosing visits, participants received single doses of ADO09, Ins&Pram or Lispro immediately before eating a standardized mixed meal together with 1 g of acetaminophen, which was used as a surrogate marker to evaluate the kinetics of gastric emptying. Premeal blood glucose was adjusted to 126 mg/dL ± 10% by means of insulin and glucose infusions. The insulin dose was 7.5 U and the pramlintide dose was 45 μg. Blood glucose, glucagon and acetaminophen concentrations were assessed as pharmacodynamic endpoints; insulin and pramlintide concentrations were analysed as pharmacokinetic endpoints, and safety and tolerability were assessed. Results: Compared with Lispro, ADO09 reduced postprandial blood glucose (ppBG) excursions by more than 95% in the first hour postmeal (mean ± SD ∆AUC BG 0‐1 h: 1.4 ± 9.9 mg*h/dL vs. 43.5 ± 15.3 mg*h/dL; p <.0001). Maximum ppBG was significantly improved with ADO09 (∆BGmax 87.0 ± 35.5 mg/dL) versus both Lispro (109.2 ± 31.1 mg/dL; p =.0133) and Ins&Pram (109.4 ± 44.3 mg/dL; p =.0357). Gastric emptying with ADO09 was similar to Ins&Pram and significantly slower than with Lispro. All treatments were well tolerated and both adverse events and hypoglycaemic events were rare during the meal test procedure. Conclusion: ADO09 was well tolerated and markedly reduced ppBG compared with Lispro. ADO09 formulation was generally similar to the separate administration of insulin and pramlintide, except for a better BG level in the 4‐8 h interval postmeal. These positive results warrant further investigations with ADO09. [ABSTRACT FROM AUTHOR]

We investigated the pharmacodynamics (PD) and pharmacokinetics (PK) of BioChaperone insulin Lispro (BCLIS), faster insulin aspart (FIA) and insulin aspart (ASP) in patients with type 1 diabetes using an insulin pump. In this randomized, double‐blind, three‐way crossover glucose clamp study, 43 patients received a bolus dose of each insulin (0.15 U/kg) in addition to a basal rate (0.01 U/kg/h), delivered via an insulin pump. With BCLIS, the AUC‐GIR,0–60 minutes (primary endpoint) was improved compared to ASP (least square means ratio, 1.63; 95% CI, 1.44–1.88; P < 0.0001) and was similar compared to FIA (least square means ratio, 1.06; 95% CI, 0.94–1.18; P = 0.4609). BCLIS showed faster‐on PD (tearly0.5GIRmax) than ASP and faster‐off PD (tlate0.5GIRmax) than both FIA and ASP. BCLIS also demonstrated significantly higher early exposure (AUCins, 0–60 minutes) and lower late exposure (AUCins,120–600 minutes) than both other insulins. In patients with type 1 diabetes using an insulin pump, BCLIS better mimics prandial insulin secretion and action than ASP and shows a faster off‐PD than FIA. [ABSTRACT FROM AUTHOR]

Aim: To investigate the safety and efficacy of BioChaperone Lispo (BCLIS), an ultra‐rapid formulation of insulin lispro (LIS) in people with type 1 diabetes. Materials and Methods: In this randomized, double‐blind study, participants self‐administered individualized bolus doses of BCLIS or LIS during two 14‐day periods in a crossover fashion. Postprandial blood glucose (BG) was assessed after individualized solid mixed meal tests (MMTs) (50% carbohydrate, 29% fat, 21% protein), with additional randomization for the sequence of timing of insulin administration, immediately (t0), 15 minutes before (t − 15) and 15 minutes after (t + 15) meal start on days 1, 2 and 3, and with t0 administration on day 14. Pharmacokinetic (PK) variables were assessed for t0 MMTs. Participants also used individualized BCLIS or LIS doses immediately before meals during two 10‐day outpatient periods with an unchanged basal insulin regimen. Results: Overall, 35 participants completed both treatment periods. In MMTs with t0 administration, the higher early postprandial PK exposure of BCLIS led to significant reductions in 1‐ to 2‐hour postprandial BG excursions by 30% to 40% vs LIS and the accelerated absorption and action of BCLIS persisted over 14 days. There was no difference in glucose excursion over the full 360‐minute postprandial period. Postprandial BG control was similar between BCLIS injected at t + 15 and LIS injected at t0. BCLIS was shown to have safety and tolerability similar to LIS. No injection site reactions occurred with BCLIS. Conclusions: BCLIS was well tolerated and safe over 14 days of treatment and significantly improved postprandial BG vs LIS when administered at mealtime. [ABSTRACT FROM AUTHOR]