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Background Verinurad is a human uric acid (UA) transporter (URAT1) inhibitor known to decrease serum UA (sUA) levels and that may reduce albuminuria. In a Phase 2a study (NCT03118739), treatment with verinurad + febuxostat lowered urine albumin-to-creatinine ratio (UACR) at 12 weeks by 39% (90% confidence interval 4–62%) among patients with Type 2 diabetes mellitus, hyperuricaemia and albuminuria. The Phase 2b, randomized, placebo-controlled Study of verinurAd and alloPurinol in Patients with cHronic kIdney disease and hyperuRicaEmia (SAPPHIRE; NCT03990363) will examine the effect of verinurad + allopurinol on albuminuria and estimated glomerular filtration rate (eGFR) slope among patients with chronic kidney disease (CKD) and hyperuricaemia. Methods Adults (≥18 years of age) with CKD, eGFR ≥25 mL/min/1.73 m2, UACR 30–5000 mg/g and sUA ≥6.0 mg/dL will be enrolled. Approximately 725 patients will be randomized 1:1:1:1:1 to 12, 7.5 or 3 mg verinurad + allopurinol, allopurinol or placebo. An 8-week dose-titration period will precede a 12-month treatment period; verinurad dose will be increased to 24 mg at Month 9 in a subset of patients in the 3 mg verinurad + allopurinol arm. The primary efficacy endpoint the is change from baseline in UACR at 6 months. Secondary efficacy endpoints include changes in UACR, eGFR and sUA from baseline at 6 and 12 months. Conclusions This study will assess the combined clinical effect of verinurad + allopurinol on kidney function in patients with CKD, hyperuricaemia and albuminuria, and whether this combination confers renoprotection beyond standard-of-care.

Aims To evaluate the injection success and user perception of a shield‐triggered pen‐injector mechanism. Methods The trial (http://ClinicalTrials.gov NCT02627287) was an exploratory, two‐centre, one‐visit, open‐label, randomized controlled trial conducted in Germany in 150 injection‐experienced individuals with type 1 or type 2 diabetes. Participants self‐administered subcutaneous injections of a placebo solution using a prototype shield‐triggered pen‐injector, DV3316 (Novo Nordisk, Bagsvaerd, Denmark), and FlexPen (Novo Nordisk, Bagsvaerd, Denmark). Injection success was evaluated on a yes/no basis by the investigator. Participant confidence, leakage of fluid and pain were evaluated after each injection. Pain and device experience were assessed after completion of all injections with each pen‐injector. Overall preference was assessed after completion of all injections with both pen‐injectors. Results Injection success was high with both pen‐injectors (97.0%, DV3316 vs 99.7%, FlexPen). Participant confidence in dose delivery was similar for the two devices (88% of injections with DV3316 vs 81% with FlexPen were scored as “extremely confident”). The median injection pain score on a visual analogue scale (0‐100) was 3 with DV3316 vs 4 with FlexPen after each injection, and 4 with DV3316 vs 5 with FlexPen after all injections with each device. After all injections were completed, 55% of participants reported an overall preference for DV3316 vs 21% for FlexPen. Conclusion This study demonstrates that injection‐experienced individuals can achieve a high injection success rate with a shield‐triggered pen‐injector, with similar patient confidence and injection pain compared with FlexPen.

Aims Continuous subcutaneous insulin infusion (CSII) is increasingly used in patients with diabetes. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with a faster time-action profile. We evaluated the pharmacological characteristics of faster aspart versus IAsp> during CSII. Materials and methods: In this randomised, double-blind, crossover trial, 48 men and women aged 18–64 years with type 1 diabetes mellitus (T1DM) received faster aspart and IAsp as a 0.15 U/kg bolus dose using CSII on top of a basal rate (0.02 U/kg/h) in a glucose clamp setting (target 5.5 mmol/L). Results Following a CSII bolus dose, the pharmacokinetic/pharmacodynamic profiles for faster aspart were left-shifted compared with those for IAsp. For faster aspart versus IAsp, early glucose-lowering effect (AUCGIR,0-30min) was approximately two-fold higher (least square means: 24.9 versus 11.4 mg/kg; estimated ratio faster aspart/IAsp 2.18 [1.33;5.04], p = 0.002), onset of glucose-lowering effect (tEarly 50% GIRmax) occurred 11.1 minutes earlier (41.1 versus 52.3 minutes; 95% CI faster aspart - IAsp: [-15.4;-6.9], p

Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation, with faster absorption after s.c. injection. Twelve children (mean age 10.4 y), 13 adolescents (mean age 15.1 y) and 15 adults (mean age 20.2 y) received 0.2 U/kg single dose (mean: 8.3 U, 12.8 U, and 15.6 U, respectively) of faster aspart or IAsp before a meal test (68% carbohydrates; adjusted for body weight) in a randomized, double-blind, crossover design. Faster aspart vs. IAsp had significantly faster onset of appearance (LSmean, min: children, 5.2 vs. 9.8; adolescents, 5.3 vs. 11.0; adults, 5.5 vs. 12.3). Insulin exposure within 1 h was higher for faster aspart vs. IAsp (greatest diff. within 15 min; Table). Faster aspart had a greater glucose-lowering effect vs. IAsp (ΔPGav, significant in children; Table). PG1h treatment diff. (faster aspart-IAsp; estimates [95% CI], mmol/L): children, -1.87 [-3.71; -0.04]; adolescents, -0.64 [-2.26; 0.97]; adults, -1.10 [-2.64; 0.44]. Treatment effect did not differ significantly between age groups (PG1h, p = 0.56; ΔPGav, 0-1h, p = 0.15; ΔPGav, 0-2h, p = 0.32). There were no safety/tolerability issues. Faster onset and higher early insulin exposure with faster aspart vs. IAsp led to a larger glucose-lowering effect, though only significant for children, who are prone to rapidly fluctuating glucose levels and unplanned food intake.