Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms. RESEARCH DESIGN AND METHODSThis was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naïve adults (n 5 205) with type 2 diabetes and HbA 1c 7-10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80-130 mg/dL; adjustment ±21 units/week; n 5 51), B (80-130 mg/dL; ±28 units/week; n 5 51), or C (70-108 mg/dL; ±28 units/week; n 5 52), or once-daily insulin glargine U100 (IGlar U100) (80-130 mg/dL; ±4 units/day; n 5 51), all titrated weekly. Percentage of time in range (TIR) (70-180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring.

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<b>OBJECTIVE</b> <p>Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms.</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naïve adults (<i>n</i> = 205) with type 2 diabetes and HbA1c 7–10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (pre-breakfast self-measured blood glucose target, 80–130 mg/dL; adjustment ±21U/week; <i>n</i> = 51), B (80–130 mg/dL; ±28U/week; <i>n</i> = 51), C (70–108 mg/dL; ±28U/week; <i>n</i> = 52), or once-daily insulin glargine U100 (IGlar U100; 80–130 mg/dL; ±4U/day; <i>n</i> = 51), <a>all </a><a>titrated weekly. </a>Percentage time in range (TIR; 70–180 mg/dL) during weeks 15&16 was measured using continuous glucose monitoring.</p> <p><b>RESULTS</b></p> <p>TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15&16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference: 7.08%-points; 95% CI, 2.12%–12.04%; <i>P </i>= 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient/year for icodec titrations A, B, C, IGlar U100, respectively), with no episodes of severe hypoglycemia.</p> <p><b>CONCLUSION</b></p> <p>Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. <a></a><a></a><a>Icodec titration A (80–130 mg/dL; ±21U/week) displayed the best balance between glycemic control and risk of hypoglycemia.</a> </p>

Background DUAL I China, one of the DUAL trials, assessed efficacy/safety of insulin degludec/liraglutide (IDegLira) in Chinese adults with type 2 diabetes (T2D) not controlled by oral antidiabetic drugs (OADs). Methods This phase 3a, treat‐to‐target multicenter trial randomized participants (glycated hemoglobin [HbA1c] 53.0‐85.8 mmol/mol; previous metformin ± another OAD) 2:1:1 to IDegLira (n = 361), degludec (n = 179), or liraglutide (n = 180). Primary endpoint was change in HbA1c after 26 weeks. Secondary endpoints included: HbA1c < 53.0 mmol/mol attainment, weight change, treatment‐emergent hypoglycemia, end‐of‐treatment insulin dose, and safety. Results At 26 weeks, HbA1c had decreased by a mean 18.12 mmoL/moL (IDegLira), 12.37 mmoL/moL (degludec) (estimated treatment difference [ETD] −6.50 mmoL/moL; 95% confidence interval [CI] −7.96, −5.04; P < .0001), and 11.33 mmoL/moL (liraglutide) (ETD −6.87 mmoL/moL; 95% CI −8.33, −5.41; P < 0.0001), indicating noninferiority for IDegLira vs degludec and superiority vs liraglutide. HbA1c < 53.0 mmoL/moL attainment was 77.0% (IDegLira), 46.4% (degludec), and 48.3% (liraglutide). Mean weight change with IDegLira (0.1 kg) was superior to degludec (1.2 kg) (ETD −1.08 kg; 96% CI −1.55, −0.62; P < 0.0001). Severe or confirmed hypoglycemic event rates were 0.24 (IDegLira) and 0.17 (degludec) episodes/participant‐year (estimated rate ratio 1.46; 95% CI 0.71, 3.02; P = .3008, not significant). At the end of treatment, the IDegLira insulin dose was lower (24.5 U/d) vs degludec (30.3 U/d) (ETD −5.49 U; 95% CI −7.77, −3.21; P < 0.0001). No unexpected safety issues occurred. Conclusions IDegLira is efficacious and well tolerated in Chinese adults with T2D not controlled by OADs.

Aim To investigate the efficacy and safety of initiating insulin degludec/liraglutide (IDegLira) in patients with type 2 diabetes (T2D) who had discontinued pretrial sulphonylureas (SUs) or dipeptidyl peptidase‐4 inhibitors (DPP4is) versus patients not previously treated with these regimens. Materials and Methods In DUAL II, patients with T2D uncontrolled on basal insulin and metformin ± SU/glinides were randomized to insulin degludec or IDegLira (both capped at 50 U). In DUAL IX, patients were randomized to insulin glargine U100 (no maximum dose) or IDegLira, as add‐on to sodium‐glucose co‐transporter‐2 inhibitors ± oral antidiabetic drugs. In this post hoc analysis, patients were grouped according to pretrial use of SU (DUAL II) or DPP4i (DUAL IX). Results Regardless of pretrial SU/DPP4i use, IDegLira was favourable versus insulin comparators with respect to change in HbA1c and body weight. Lower hypoglycaemia rates and comparable end‐of‐trial daily insulin dose were achieved with IDegLira, regardless of pretrial regimen. There was no clinically relevant increase in mean self‐measured blood glucose in the early weeks after IDegLira initiation. There was no statistically significant interaction between the randomized treatments and previous SU/DPP4i use. Conclusions IDegLira was more favourable compared with degludec or glargine U100 in terms of change in HbA1c and body weight, regardless of antecedent treatment. Clinicians should be aware of a potential transient rise in self‐measured blood glucose when transitioning therapy in patients. This shows that SUs/DPP4is can be safely discontinued, without deterioration in glycaemic control when initiating IDegLira, allowing a simplified treatment regimen.

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<b>OBJECTIVE</b> <p>Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms.</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naïve adults (<i>n</i> = 205) with type 2 diabetes and HbA1c 7–10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (pre-breakfast self-measured blood glucose target, 80–130 mg/dL; adjustment ±21U/week; <i>n</i> = 51), B (80–130 mg/dL; ±28U/week; <i>n</i> = 51), C (70–108 mg/dL; ±28U/week; <i>n</i> = 52), or once-daily insulin glargine U100 (IGlar U100; 80–130 mg/dL; ±4U/day; <i>n</i> = 51), <a>all </a><a>titrated weekly. </a>Percentage time in range (TIR; 70–180 mg/dL) during weeks 15&16 was measured using continuous glucose monitoring.</p> <p><b>RESULTS</b></p> <p>TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15&16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference: 7.08%-points; 95% CI, 2.12%–12.04%; <i>P </i>= 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient/year for icodec titrations A, B, C, IGlar U100, respectively), with no episodes of severe hypoglycemia.</p> <p><b>CONCLUSION</b></p> <p>Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. <a></a><a></a><a>Icodec titration A (80–130 mg/dL; ±21U/week) displayed the best balance between glycemic control and risk of hypoglycemia.</a> </p>