OBJECTIVE In participants with type 2 diabetes (T2D) and HbA1c >9.0–10.0%, guidelines recommend treatment with basal-bolus insulin. RESEARCH DESIGN AND METHODS This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0–15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups. RESULTS Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI −0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD −4.60, 95% CI −7.33, −1.87). CONCLUSIONS In participants with T2D and HbA1c ≥9.0–15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.

IDegLira-HIGH trial was a non-inferiority, prospective, randomized clinical trial, comparing the efficacy and safety of insulin degludec/liraglutide combination (IDegLira) and a regimen of multiple daily injections (MDI) with basal-bolus insulin (BB) in adults (>18-80 years of age) , with type 2 diabetes (T2D) , and very high HbA1c (>9%-15%) , previously treated with basal insulin or multiple oral agents. Primary endpoint was change in HbA1c from baseline to week 26. Secondary endpoints included incidence of hypoglycemia, changes on weight and glycemic variability (% coefficient of variation [%CV]) . Treatment with IDegLira and BB insulin resulted in similar improvement in glycemic control: 7.7±1.7% and 7.7±1.5%, (p=0.76) , with a reduction from baseline of -3.2±2.3% and -3.0±1.8%, (p=0.39) at 26-weeks. IDegLira resulted in lower rates of hypoglycemia <70 mg/dl (22% vs. 36%, p=0.05) , similar glycemic variability (CGM %CV 30.4±9.1% vs. 33.2±7.3%, p=0.08) , and greater weight loss (-3.7±4.1 kg vs. +8.4±5.4 kg, p<0.01) compared to BB. IDegLira was associated with higher rates of nausea (Table 1) . Conclusions: In patients with T2D and very high HbA1c (≥9%-15%) , a regimen of daily IDegLira injection is non-inferior to MDI with BB insulin on HbA1c reduction and was associated with weight loss and less hypoglycemia. Disclosure R.J.Galindo: Advisory Panel; Sanofi, WW International, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. B.Moazzami: None. M.F.Scioscia: None. P.Vellanki: n/a. G.M.Davis: Consultant; Medscape, Research Support; Insulet Corporation. F.J.Pasquel: Consultant; AI Health LLC, Boehringer Ingelheim International GmbH, Dexcom, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Merck & Co., Inc. M.Fayfman: None. A.L.Migdal: None. J.Saling: None. Funding Investigator-initiated study to Emory University (PI. Dr. Rodolfo J. Galindo) from Novo Nordisk.

Differing blood glucose (BG) targets are recommended by professional organizations in noncritical care settings. Previous Endocrine Society and ADA guidelines recommended a target BG of 70-140 and 140-180 mg/dl; however, the 2023 ADA Standards of Care recommends a target of 100-180 mg/dl. The lack of consensus is due to the lack of randomized clinical trials (RTC) to support a tight vs relaxed BG target. We performed a post-hoc analysis on 9 RCTs to assess hospital outcomes in non-critically ill insulin-treated subjects with T2D targeting BG 70-140 mg/dL vs. 140-180 mg/dL. Among 1446 patients, 640 were treated to a target of 70-140 mg/dl and 806 to a target of 140-180 mg/dL. Propensity score matching was used to reduce the bias including sex, HbA1c, and home insulin use, for a final count of 1,146 patients (573 subjects in each target group). Patients in the tight BG target group had lower mean BG (163.73±39.79 vs 170.15±39.94 mg/dL, p=0.004), less hyperglycemia (BG >180: 86% vs 92%, p=0.003; BG >240: 51% vs 62%, p<.001), similar rates of hypoglycemia (BG <70: 12% vs 15%, p=0.11; BG <54: 2.5% vs 4.0%, p=0.14). The intensive target resulted in a shorter length of stay (4.0 vs 6.0 days, p<.001) and lower composite of complication rate (acute kidney injury, infection, myocardial infarction, respiratory failure and stroke) (3.7% vs 6.8%, p=0.02) than the relaxed BG target, with similar mortality rates (0.9% vs 0.3%, p=0.36). There were no differences in glycemic variability (GV) between groups with greater GV in those experiencing hypoglycemia <70 mg/dL or hyperglycemia >200 mg/dL. Our results indicate that lower BG target of 70-140 mg/dl leads to lower mean daily BG, less severe hyperglycemia events, similar rates of hypoglycemia and glycemic variability, and lower length of stay and complication rates compared to a higher target of 140-180 mg/dl. RCTs are indicated to elucidate optimal glycemic targets in hospitalized patients with T2D. Disclosure J.Saling: None. A.L.Migdal: None. M.A.Urrutia: None. Z.Zabala: None. B.Moazzami: None. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. M.Fayfman: None. A.A.Rashied: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. Funding Jacob Family Funds

<p><u>Introduction</u>: In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin. </p> <p><u>Methods</u>: Randomized trial comparing the efficacy and safety of IDegLira and basal-bolus among participants with high HbA1c <u>></u>9.0-15.0%, previously treated with 2-3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n=73) or IDegLira (n=72). Primary endpoint was non-inferiority (0.4%) in HbA1c reduction between groups. </p> <p><u>Results</u>: Among 145 participants (HbA1c 10.8%±1.3), there was no statistically significant difference in HbA1c reduction (3.18%±2.29 vs. 3.00%±1.79, p=0.65, ETD 0.18%, 95%CI: -0.59, 0.94); between IDegLira and basal-bolus group. IDegLira resulted in significantly lower rates of hypoglycemia < 70 mg/dl (26% vs. 48%, p=0.008, ORs 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24±8.33 vs. 5.84±6.18 kg, p=0.001, ETD -4.60, 95% CI -7.33, -1.87).  </p> <p><u>Conclusions</u>: In participants with T2D and HbA1c <u>></u>9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, less weight gain, compared to basal-bolus regimen. </p>

<p><u>Introduction</u>: In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin. </p> <p><u>Methods</u>: Randomized trial comparing the efficacy and safety of IDegLira and basal-bolus among participants with high HbA1c <u>></u>9.0-15.0%, previously treated with 2-3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n=73) or IDegLira (n=72). Primary endpoint was non-inferiority (0.4%) in HbA1c reduction between groups. </p> <p><u>Results</u>: Among 145 participants (HbA1c 10.8%±1.3), there was no statistically significant difference in HbA1c reduction (3.18%±2.29 vs. 3.00%±1.79, p=0.65, ETD 0.18%, 95%CI: -0.59, 0.94); between IDegLira and basal-bolus group. IDegLira resulted in significantly lower rates of hypoglycemia < 70 mg/dl (26% vs. 48%, p=0.008, ORs 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24±8.33 vs. 5.84±6.18 kg, p=0.001, ETD -4.60, 95% CI -7.33, -1.87).  </p> <p><u>Conclusions</u>: In participants with T2D and HbA1c <u>></u>9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, less weight gain, compared to basal-bolus regimen. </p>