Insulin Glargine U100 Research Articles

131-OR: ADA Presidents’ Select Abstract: Effect of Insulin Degludec vs. Insulin Glargine U100 on Occurrence of Nocturnal Hypoglycemia Assessed by Nocturnal Plasma Glucose Profiles in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia

Background and Aims: The risk of nocturnal hypoglycemia (NH) is a limiting factor for achieving good glycemic control in people with type 1 diabetes (T1D). Insulin degludec (IDeg) is proven to lower the risk of self-reported NH. As most episodes of NH are asymptomatic, we assessed differences in occurrence of NH by hourly plasma glucose (PG) measurements at treatments with IDeg or insulin glargine U100 (IGlar) in people with T1D suffering from recurrent nocturnal severe hypoglycemia. Materials and Methods: Pre-defined optional substudy of the HypoDeg trial, a 2-year investigator-initiated, randomized, cross-over trial where 149 participants with T1D were randomized to treatment with IDeg or IGlar. Fifty-one participants (mean (SD) age 58 (13) years, diabetes duration 28 (14) years and HbA1c 7.8 (1) %) were admitted for two nights for hourly blinded plasma glucose measurements for a minimum of one night (23:00h to 07:00h) during each 1-year treatment period. The primary endpoints were NH at level 1 (PG ≤ 3.9 mmol/L) and level 2 (PG < 3.0 mmol/L). Results: We collected data from 196 nights. A total of 57 nights (regardless of level) in 33 participants were hypoglycemic, including 20 nights with symptomatic hypoglycemia. The incidence of NH at level 1 was lower when treated with IDeg [17 events in 97 nights (18%)] as compared to IGlar [36 events in 99 nights (36%)], corresponding to a hazard ratio (HR) of 0.39 (95% CI: 0.22-0.71; p=0.002) during treatment with IDeg. At level 2, the incidence of NH was also lower during treatment with IDeg [8 events in 97 nights (8%)] as compared to IGlar [20 events in 99 nights (20%)], corresponding to an HR of 0.36 [95% CI: 0.16-0.80; p=0.013] during treatment with IDeg. Conclusion: In people with T1D and recurrent nocturnal severe hypoglycemia, treatment with IDeg as compared to IGlar results in a clinically significant lower rate of NH at both levels of hypoglycemia. Disclosure J. M. Brøsen: None. S. Lerche: None. K. Nørgaard: Advisory Panel; Self; Medtronic, Other Relationship; Self; Novo Nordisk Inc., Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic. H. D. Parving: None. L. Tarnow: None. B. Thorsteinsson: None. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S. R. Agesen: Employee; Self; Novo Nordisk. P. L. Kristensen: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. A. Alibegovic: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. H. U. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S. P. Gustenhoff: None. C. Hedetoft: None. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. C. B. Juhl: None. Funding Novo Nordisk

617-P: Association between Change in Time-in-Range and A1C in Basal Insulin-Treated People with Type 2 Diabetes

Background: The SWITCH PRO trial demonstrated increased time in range (TIR) with insulin degludec vs. insulin glargine U100 in basal insulin-treated type 2 diabetes (T2D). This post hoc analysis of SWITCH PRO evaluated correlation of change in TIR with change in A1C during the trial.Methods: Correlation between change in TIR (70-180 mg/dL) and change in A1C from baseline (BL) to end of Maintenance 1 in the full cohort or subgroups stratified by BL median A1C (<7.5% or ≥7.5%) was assessed using Spearman correlation coefficient (rs).Results: BL characteristics between subgroups were similar. A linear correlation between change in TIR and change in A1C was demonstrated (Figure) in the full (rs -0.400) and BL A1C ≥7.5% (rs -0.426) subgroups, but this was less apparent in the BL A1C <7.5% subgroup (rs -0.173) (interaction p = 0.07). Increase in TIR equated to the greatest decrease in A1C in the BL A1C ≥7.5% subgroup: a 5% increase in TIR corresponded to estimated decreases in A1C of -0.4%, -0.1% and -0.7% in full, BL A1C <7.5% and BL A1C ≥7.5% subgroups, respectively; and a 10% increase in TIR to estimated A1C decreases of -0.5%, -0.1% and -0.8%, respectively.Discussion: Change in TIR was associated with change in A1C in this basal insulin-treated population, with closer association at higher baseline A1C. Change in TIR may offer complementary insights to change in A1C in measuring response to therapy.View largeDownload slideView largeDownload slide DisclosureR. Goldenberg: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc., Sanofi, Speaker's Bureau; Self; Agora , Amgen Canada, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., CCRN, CHRC, CMS Canada, CSEM, Eli Lilly and Company, EOCI , HLS Therapeutics Inc., Inceptus, Janssen Pharmaceuticals, Inc., liV Medical Education Agency, Master Clinician Alliance , Medplan, Merck & Co., Inc., Mylan N. V., Novo Nordisk Canada Inc., Sanofi, Servier Laboratories, STA Communications Inc., TKTWG, Valeant . V. R. Aroda: Consultant; Self; Applied Therapeutics, Duke, Novo Nordisk, Pfizer Inc., Sanofi, Employee; Spouse/Partner; Janssen , Merck , Research Support; Self; Applied Therapeutics, Eli Lilly and Company, Fractyl , Medpace, Medpace, Novo Nordisk, Premier , Sanofi, Stock/Shareholder; Spouse/Partner; Janssen, Merck. L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi. A. Meller donatsky: Employee; Self; Novo Nordisk A/S. M. Frederiksen: Employee; Self; Novo Nordisk A/S. D. C. Klonoff: Consultant; Self; EOFlow, Fractyl Laboratories, Inc., LifeCare, Inc., Novo Nordisk, Roche Diagnostic USA, Samsung, Thirdwayv, Employee; Self; DIabetes Technology Society. E. Parvaresh rizi: Employee; Self; Novo Nordisk. R. M. Bergenstal: Advisory Panel; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk, Onduo LLC., Roche , Sanofi, United Healthcare , Consultant; Self; Abbott Diabetes, Ascensia , Dexcom, Inc., Eli Lilly and Company, Hygieia, Johnson & Johnson, Medtronic, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare, Other Relationship; Self; HealthPartners Institute, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Helmsley Charitable Trust, Hygieia, Johnson & Johnson, Medtronic, NIDDK, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare.FundingNovo Nordisk A/S

191-OR: Similar Hypoglycemia Duration with Once-Weekly Insulin Icodec vs. Insulin Glargine U100 in Insulin Naïve or Experienced Patients with T2D

Insulin icodec* (icodec) is a novel once-weekly basal insulin analog in development. This post hoc analysis explored hypoglycemia duration using double-blinded CGM (Dexcom G6®) data from 2 phase 2, randomized, open-label, treat-to-target 16-week trials. One trial compared 3 titration algorithms of icodec vs. insulin glargine U100 (IGlar U100) in 205 insulin-naïve patients with T2D (NCT03951805), the other assessed 154 basal insulin-treated patients with T2D switching from any daily basal insulin to icodec with or without a 100% loading dose vs. IGlar U100 (NCT03922750). In line with ATTD guidelines, a hypoglycemic episode was defined as a CGM period of interstitial glucose (IG) &amp;lt;70 mg/dL for at least 15 min, ending when IG ≥70 mg/dL for at least 15 min. In the titration trial, hypoglycemia duration was similar across all arms: median overall hypoglycemic episode duration (IQR) was 35.0 (20.0, 70.0) min for icodec titrations A (SMBG 80-130 mg/dL ±21 U/wk) and B (80-130 mg/dL ±28 U/wk) and for IGlar U100 (80-130 mg/dL ±4 U/day), and 39.0 (24.0, 70.0) min for icodec titration C (70-108 mg/dL ±28 U/wk). The distribution pattern of hypoglycemic episodes by duration was similar across all treatment arms. Results were similar for nocturnal hypoglycemic episodes. Similarly, in the switch trial, the duration of hypoglycemia was similar between arms, irrespective of loading dose use: median overall hypoglycemic episode duration (IQR) was 40.0 (20.0, 75.0) min for icodec with loading dose, 40.0 (25.0, 80.0) min for icodec without loading dose, and 35.0 (20.0, 60.0) min for IGlar U100.The distribution pattern of hypoglycemic episodes by duration was similar across treatment arms. Similar results were seen for the nocturnal period. In conclusion, CGM-derived hypoglycemic episode duration was similar with icodec vs. IGlar U100 in insulin-naïve and insulin-experienced patients with T2D, regardless of titration algorithm or initial loading dose use. *Proposed INN. Disclosure R. J. Silver: Advisory Panel; Self; Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. M. Asong: Employee; Self; Novo Nordisk A/S. K. Begtrup: None. M. M. Koefoed: Employee; Self; Novo Nordisk. S. R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Zealand Pharma A/S, Consultant; Self; Zealand Pharma A/S, Other Relationship; Self; Dexcom, Inc., Eli Lilly and Company, MannKind Corporation, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi.

606-P: Higher Derived Time-in-Range with IDegLira vs. Insulin Glargine U100 in Patients with T2D

Aims: To compare derived time in range (dTIR) with insulin degludec/liraglutide (IDegLira) and insulin glargine 100 units/mL (IGlar U100) in patients with type 2 diabetes (T2D). Methods: Data from DUAL V, a trial of patients with T2D uncontrolled on IGlar U100 randomized to switch to IDegLira or up-titration of IGlar U100 (+metformin; n=557), and DUAL VIII, a durability trial of insulin-naive patients with T2D randomized to either IDegLira or IGlar U100 (+ oral antidiabetic drugs; n=1012), were evaluated post hoc. Self-monitored blood glucose profiles (weeks 0, 12, and 26 [DUAL V] or weeks 0, 26, and 104 [DUAL VIII]) were used to derive the proportion of available readings within (dTIR: 70-180 mg/dL [3.9-10 mmol/L]), below (dTBR: 180 mg/dL [>10 mmol/L]) target range. Results: Estimated treatment differences (IDegLira− IGlar U100) for change from baseline to end of treatment (EOT) in dTIR were significantly greater with IDegLira vs. IGlar U100 (Figure). The proportion of patients achieving ≥70% dTIR at EOT with IDegLira and IGlar U100, respectively, was 62% and 60% in DUAL V, and 50% and 26% in DUAL VIII; the proportion achieving a ≥5% increase in dTIR from baseline to EOT was 63% in both groups in DUAL V, and 44% and 25%, respectively, in DUAL VIII. Conclusion: IDegLira was associated with significantly greater dTIR vs. IGlar U100 in insulin-experienced and insulin-naive patients with T2D. Disclosure A. Philis-tsimikas: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Consultant; Self; Sanofi-Aventis, Employee; Spouse/Partner; Ionis, Other Relationship; Self; Merck & Co., Inc., Research Support; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi-Aventis. V. R. Aroda: Consultant; Self; Applied Therapeutics, Duke, Novo Nordisk, Pfizer Inc., Sanofi, Employee; Spouse/Partner; Janssen , Merck , Research Support; Self; Applied Therapeutics, Eli Lilly and Company, Fractyl , Medpace, Medpace, Novo Nordisk, Premier , Sanofi, Stock/Shareholder; Spouse/Partner; Janssen, Merck. C. De block: Advisory Panel; Self; A. Menarini Diagnostics, Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim , Eli Lilly and Company, MSD, Novartis AG, Novo Nordisk, Roche Diagnostics, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker9s Bureau; Self; A. Menarini Diagnostics, Abbott Diagnostics, Boehringer Ingelheim , Eli Lilly and Company, Novo Nordisk, Sanofi. L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi. E. Hachmann-nielsen: Employee; Self; Novo Nordisk A/S. A. Liebl: Advisory Panel; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MSD, Novo Nordisk, Roche, Speaker9s Bureau; Self; AstraZeneca, Bayer, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Bristol Myers Squibb , Dexcom, Inc., Eli Lilly and Company, Medtronic, MSD, Novo Nordisk, OmniaMed, Roche, Sanofi. R. Sivarathinasami: Employee; Self; Novo Nordisk Service Centre India Private Ltd. J. M. D9cruz: Employee; Self; NovoNordisk GBS. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. Funding Novo Nordisk A/S

731-P: CGM-Based Measurements for Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 in Insulin-Treated Patients with T2D: A Post-hoc Analysis

Insulin icodec* (icodec) is a once-weekly basal insulin in clinical development. In a phase 2 treat-to-target trial (NCT03922750) in patients with T2D switching from daily insulin (N=154), icodec with an initial 100% loading dose (LD; doubling the first dose) showed greater time in range (TIR, 70-180 mg/dL) vs. insulin glargine U100 (IGlar U100) at weeks 15 and 16 (primary endpoint), as measured by double-blinded Dexcom G6® CGM. This post hoc analysis compared TIR, time above range (TAR, >180 mg/dL) and below range (TBR, 70% TIR and Disclosure H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. R. Beck bang: Employee; Self; Novo Nordisk A/S. A. Gowda: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. M. M. Koefoed: Employee; Self; Novo Nordisk. P. A. Senior: Other Relationship; Self; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Research Support; Self; Novo Nordisk. R. M. Bergenstal: Advisory Panel; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk, Onduo LLC., Roche , Sanofi, United Healthcare , Consultant; Self; Abbott Diabetes, Ascensia , Dexcom, Inc., Eli Lilly and Company, Hygieia, Johnson & Johnson, Medtronic, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare, Other Relationship; Self; HealthPartners Institute, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Helmsley Charitable Trust, Hygieia, Johnson & Johnson, Medtronic, NIDDK, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare.

733-P: A Randomized Controlled Trial Comparing Insulin Degludec U100 and Glargine U100 for the Inpatient Management of Medicine and Surgery Patients with Type 2 Diabetes: Degludec Hospital Trial

Limited data exist about the use of insulin degludec in the hospital. This prospective, open-label, randomized clinical trial compared the efficacy and safety of a basal-bolus regimen using degludec U100 or glargine U100 for the management of patients with T2D. A total of 181 general medicine and surgery patients (age: 56±11, diabetes duration: 13.0±9.2 years) with an admission BG: 140-400 mg/dL and treated with oral agents or insulin prior to admission were randomized to degludec (n=93) or glargine (n=88). Total daily insulin dose started at 0.4 U/kg/d for BG: 140-200 mg/dL or 0.5 U/kg/d for BG: 201-400 mg/dL half dose given as basal (degludec or glargine) once daily and half as prandial (aspart) before meals. Insulin was adjusted daily to a target BG before meals between 70-180 mg/dL. The primary outcome was a difference in mean daily BG during the hospital stay. For the entire cohort, the BG at randomization was 218.6±52 mg/dL and HbA1c: 9.79±2.0% [mean±SD]. There were no differences in mean daily BG (180.1±38 vs. 180.0±45 mg/dL, p=0.9), proportion of BG in target range of 70-180 mg/dL (54.5±29% vs. 55.3±28%, p=0.85), total daily insulin dose (56±24 vs. 59±36 units/day, p=0.92), basal insulin (29.6±13 vs. 30.4±18 units/day, p=0.85), length of stay (median (IQR): 6.7 (4.7-10.5) vs. 7.5 (4.7,11.6) days, p=0.61), hospital complications (23% vs. 23%, p=0.95), or treatment failures ([mean daily BG&amp;gt;240 mg/dL or &amp;gt;2 consecutive BG&amp;gt;240 mg/dL] 9.8% vs. 13%, p=0.62) between degludec and glargine. There were no differences in the proportion of patients with BG &amp;lt;70 mg/dL (17% vs. 19%, p=0.75) or &amp;lt;54 mg/dL (3.7% vs. 1.3%, p=0.62) between degludec and glargine, with no patients having a BG&amp;lt;40mg/dL. In summary, our study indicates that hospital treatment with degludec U100 or glargine U100 is equally effective and safe in improving glycemic control in general medicine and surgery patients with T2D. Disclosure R. J. Galindo: Consultant; Self; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi US, Valeritas, Inc., Research Support; Self; Dexcom, Inc., Novo Nordisk. S. Cardona: None. K. W. Zamudio: None. B. S. Albury: None. M. C. Perez-guzman: None. L. Peng: None. G. E. Umpierrez: Research Support; Self; AstraZeneca, Dexcom, Inc., Novo Nordisk. F. J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Research Support; Self; Dexcom, Inc., Merck &amp; Co., Inc. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. R. Z. Alicic: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. D. W. Lam: None. M. Fayfman: None. A. Migdal: None. M. A. Urrutia: None. G. Davis: None. Funding Novo Nordisk

732-P: CGM-Derived Parameters for Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 in Insulin-Naïve Patients with T2D

Insulin icodec* (icodec) is a once-weekly basal insulin in development. This post hoc analysis used data from the NCT03951805 trial to investigate CGM-derived time in, above, below range (TIR, TAR, TBR) and glycemic variability measured as coefficient of variation (CV%). Insulin-naive patients with T2D (N=205) received insulin glargine U100 (IGlar U100; pre-breakfast SMBG target 80-130 mg/dL, adjusted ±4U/day), icodec titration A (80-130 mg/dL, ±21U/week), B (80-130 mg/dL, ±28U/week; most relevant comparator to IGlar U100), or C (70-108 mg/dL, ±28U/week). Treatments were titrated weekly. TIR (70-180 mg/dL), TAR (>180 mg/dL), TBR ( 70% from weeks 7 and 8, TAR decreased to 70% TIR and TBR 70% TIR and TBR Disclosure I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. R. Beck bang: Employee; Self; Novo Nordisk A/S. M. M. Koefoed: Employee; Self; Novo Nordisk. J. K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Roche Diabetes Care, Speaker’s Bureau; Self; Abbott Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; decide Clinical Software GmbH. J. Pettus: Advisory Panel; Self; Novo Nordisk, Sanofi, Consultant; Self; Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, MannKind Corporation, Tandem Diabetes Care. L. Wagner: None. C. Mathieu: Advisory Panel; Self; Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma, Research Support; Self; Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics, Speaker’s Bureau; Self; Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis.

Clinical research of insulin glargine U300 basal-bolus therapy and insulin degludec/aspart co-formulation in type 2 diabetes mellitus: A real world experience.

Insulin degludec/aspart (IDegAsp) and insulin glargine U300 (IGlarU300) have recently emerged as popular new-generation insulin analogues. The aim of this real-life study was to investigate the patient profiles in which IGlarU300 and IDegAsp were preferred and the insulin combinations after which each of them were mostly used and also to analyse the effect of these two insulin analogues on blood glucose regulation and hypoglycaemia. The retrospective study included 174 patients that were switched from basal insulin, basal-bolus insulin, or premixed insulin to IGlarU300 or IDegAsp due to uncontrolled blood glucose levels or history of hypoglycaemia. Hypoglycaemia, body weight, body mass index (BMI), fasting plasma glucose (FPG) and HbA1c levels over 3-month periods were evaluated for each patient. There were 84 and 90 patients in the IGlarU300 and IDegAsp groups, respectively. Body weight was similar in both groups. Baseline FPG and HbA1c levels in the IGlarU300 and IDegAsp groups were 9.0%, 175.5mg/dL and 9.4%, 193.5mg/dL, respectively. A significant decrease was found in FPG and HbA1c levels in both groups (138.5, 7.8 vs 141.5, 8.2; P<.001 for all). Moreover, a significant weight gain was observed in both groups (P<.05 for both). The prevalence of hypoglycaemia in both groups decreased significantly and consistently between months 1 and 9 (P<.001). At month 12, although this decrease continued in the IGlarU300 group (P=.013), no significant decrease was observed in the IDegAsp group (P=.057). Both twice-daily IDegAsp±bolus insulin and IGlarU300 basal bolus insulin therapies are effective and safe treatment modalities.

Real-World Use of Insulin Glargine U100 and U300 in Insulin-Naïve Patients with Type 2 Diabetes Mellitus: DosInGlar Study.

IntroductionIn the EDITION clinical trial programme, patients with type 2 diabetes mellitus (T2DM) receiving insulin glargine (IGlar) U300 required 10–15% more insulin than those receiving IGlar U100. This study sought to determine whether this difference was apparent in real-world practice.MethodsIn this observational, retrospective cohort study, electronic medical records in the Big-Pac® database (Real Life Data) relating to adult insulin-naïve patients with T2DM who initiated IGlar U100 or U300 treatment in Spain in 2016–2017 and remained on treatment for 18 months were selected. IGlar U100- and U300-treated patients were matched 1:1 (propensity score matching). The primary analysis compared changes from baseline in mean daily IGlar dose (U and U/kg) at 6 (± 2), 12 (± 2) and 18 (± 2) months between cohorts (paired t tests). Changes in glycated haemoglobin (HbA1c) and weight were analysed descriptively.ResultsThe IGlar U100 and U300 cohorts included 556 matched pairs (46.9% female) with the following mean (standard deviation) values at baseline, respectively: age 63.6 (12.8) versus 63.7 (11.9) years; years since diagnosis 9.5 (1.4) versus 9.5 (1.3); HbA1c 8.8 (1.3) versus 8.7 (1.5) %; weight 84.6 (16.9) versus 84.7 (17.1) kg. Mean IGlar dose at baseline was 0.19 U/kg/day (both cohorts). Patients receiving IGlar U300 showed a greater increase from baseline in IGlar dose at 6, 12 and 18 months [mean dose (U/kg/day) 5.1%, 10.3% and 12.8% greater, respectively, in IGlar U300-treated patients]. Mean HbA1c was 8.1% in both cohorts at 18 months. Mean (SD) weight at 18 months with IGlar U100 and IGlar300 was 86.8 (17.0) kg and 85.0 (17.1) kg, respectively.ConclusionIn real-world practice, insulin dose was significantly higher in IGlar U300-treated than U100-treated patients at 6, 12 and 18 months, with similar reductions in HbA1c. At equal IGlar price/unit in Spain, the increased dose requirements of IGlar U300 would result in higher costs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01773-z.

Duration of type 2 diabetes does not appear to moderate hypoglycaemia rate with insulin degludec versus insulin glargine U100.

In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during the maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes. In this post hoc analysis, data from 7635 individuals from DEVOTE and 720 individuals from SWITCH 2 were analysed by subgroups of diabetes duration at baseline (<10, ≥10–<15, ≥15–<20 and ≥20 years) using prespecified models from both trials. There was a trend towards lower rates of hypoglycaemia with degludec versus glargine U100 across all diabetes duration subgroups in both trials, with the difference being statistically significant in some subgroups in DEVOTE and SWITCH 2. Overall, however, no significant interaction was observed between diabetes duration and treatment (DEVOTE interaction, P = .496; SWITCH 2 interaction, P = .144). Therefore, in this post hoc analysis of DEVOTE and SWITCH 2, diabetes duration did not appear to affect the reduction in rates of hypoglycaemia observed with degludec compared with glargine U100.

The differences between insulin glargine U300 and insulin degludec U100 in impact on the glycaemic variability, arterial stiffness and the lipid profiles in insulin na\xefve patients suffering from type two diabetes mellitus \u2013 outcomes from cross\u2010over open-label randomized trial

Background and aimsDiabetes mellitus type two is one of the major cardiovascular risk factors. Treatment of diabetes can reduce this risk, but the treatment options differ a lot in their risk-reducing capabilities. We compared the impact of insulin degludec (IDeg-100) and insulin glargine U300 (IGlar-300) on cardiovascular risk parameters - glycaemic variability (GV), arterial stiffness and lipid parameters - in insulin naive patients with DMT2.MethodsTo 23 individuals who previously had uncontrolled DMT2 on two or more oral antidiabetic drugs, IGlar-300 and IDeg-100 were applied for 12 weeks and then switched in a cross over design manner. Prior and after of each insulin phase, we analysed biochemical parameters,7-point SMBG profile over three days and arterial stiffness which was assessed indirectly by measuring the augmentation index (AIx) on the principles of applanation tonometry.ResultsThere were no significant differences between IGlar-300 and IDeg-100 regarding reduction of mean glucose values and coefficient of variation (CV). Both insulins insignificantly reduced AIx for standardised pulse of 75 beats/min and without differences between them. IGlar-300 and IDeg-100 reduced triglycerides and increased HDL with no significant difference between the two insulins. IGlar-300 increased the total cholesterol level and IDeg-100 decreased total cholesterol, but without statistically significant difference. IGlar-300 increased LDL level by 0.508 mmol/L and IDeg-100 decreased LDL by 0.217 mmol/L, with statistically significant difference (p = 0.0215).ConclusionsThis study did not show significant difference between IGlar-300 and IDeg-100 regarding glycaemic parameters and augmentation index using the same dose of 0.2 IU/kg for both insulins, but it has revealed possible differences in impact on lipid profile.Trial RegistrationClinicaltrials.gov, NCT04692415. Retrospectively registered on December 31th 2020.

Switching to Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Type 2 Diabetes Inadequately Controlled on Daily Basal Insulin: A Phase 2 Randomized Controlled Trial

OBJECTIVEInsulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine 100 units/mL (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and one or more oral glucose-lowering medications.RESEARCH DESIGN AND METHODSThis multicenter, open-label, treat-to-target phase 2 trial randomized (1:1:1) eligible basal insulin–treated (total daily dose 10–50 units) people with type 2 diabetes (HbA1c 7.0–10.0% [53.0–85.8 mmol/mol]) to icodec with an initial 100% loading dose (in which only the first dose was doubled [icodec LD]), icodec with no loading dose (icodec NLD), or IGlar U100 for 16 weeks. Primary end point was percent time in range (TIR; 3.9–10.0 mmol/L [70–180 mg/dL]) during weeks 15 and 16, measured using continuous glucose monitoring. Key secondary end points included HbA1c, adverse events (AEs), and hypoglycemia.RESULTSEstimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; n = 54), 66.0% (icodec NLD; n = 50), and 65.0% (IGlar U100; n = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points [95% CI 1.8–13.9]). Mean HbA1c reduced from 7.9% (62.8 mmol/mol) at baseline to 7.1% (54.4 mmol/mol icodec LD) and 7.4% (57.6 mmol/mol icodec NLD and IGlar U100); incidences and rates of AEs and hypoglycemic episodes were comparable.CONCLUSIONSSwitching from daily basal insulin to once-weekly icodec was well tolerated and provided effective glycemic control. Loading dose use when switching to once-weekly icodec significantly increased percent TIR during weeks 15 and 16 versus once-daily IGlar U100, without increasing hypoglycemia risk.

Effect of basal insulin therapy with glargine U300 versus basal bolus insulin therapy in hospitalized patients with type 2 diabetes. Real-world study from India

Background. Basal-bolus insulin therapy is the most widely accepted method of glycemic control in non-critically ill patients with T2DM. In this regimen glargine U100 is the most commonly used basal insulin. American Diabetes Association recommends either basal or basal bolus therapy for patients with type 2 diabetes mellitus admitted in general medical and surgical ward with ideal glycemic target ranging between 140–180 mg/dL by estimating four or 6 hourly capillary blood glucose per day. Insulin glargine U300 is a second generation long acting insulin analogue, which has a prolonged pharmacokinetic /pharmacodynamic profile compared to insulin glargine U100 resulting in glucose lowering activity exceeding 24 hours. Aim. To assess the efficacy and safety of basal insulin regimen (glargine U300) compared to a basal-bolus insulin regimen in patients with type 2 diabetes. Methods. A prospective single centred parallel group study comparing the efficacy and safety of basal insulin regimen with basal-bolus insulin regimen. A total of 60 patients with type 2 diabetes mellitus admitted in general medical and surgical ward for elective surgery and medical emergency were randomized to either of the two regimens. The baseline glycaemic parameters were assessed by capillary blood glucose testing thrice before meal and at bedtime with a target capillary blood glucose (CBG) between 140–180 mg/dL. All pa-tients were followed up for seven days. Results. The number of CBG readings within the target range were higher in basal insulin monotherapy (glargine U300) compared to basal-bolus regimen using (glargine U100 and regular human insulin) which was statistically significant. The incidence of hypoglycaemia was lower in the basal insulin regimen. Fewer units of insulin were required in the basal insulin regimen with lower glycaemic variability as compared to basal-bolus regimen. Conclusion. Glargine U 300 monotherapy as a basal insulin is non-inferior to basal- bolus therapy in non-critically ill hospitalised patients in glycaemic control, with fewer incidences of hypoglycaemia, less amount of insulin requirement to achieve target capillary blood glucose level and lower glycaemic variability.

Clinical research of insulin glargine U300 in type 1 diabetes mellitus patients with frequent hypoglycaemia: real-world experience.

IntroductionWe aimed to see whether insulin glargine U300 can provide better blood glucose control while reducing hypoglycaemia in a more homogeneous population compared to previous studies.Material and methodsThe retrospective study included type 1 diabetes mellitus (T1DM) patients with frequent hypoglycaemia. For evaluation of fasting blood glucose, haemoglobin glycated (HbA1c) and weight at 6 months and 12 months (final), observation windows of 120–240 days (4–8 months) and 240–480 days (9–16 months) after insulin glargine U300 initiation, respectively, were permitted. Mean follow-up time was 12 months. Hypoglycaemia was defined as blood glucose level < 70 mg/dl, either symptomatic or asymptomatic, measured in hospital or at home.ResultsForty-four patients were included in the study, and 35 patients completed the study – 20 (57.1%) females and 15 (42.9%) males, with a mean age of 24.1 ±6.6 years. Mean body mass index was 24.4 ±7.4 kg/m2. A significant decrease was not found between baseline and HbA1c values at 6 months (p = 0.199), but a significant decrease was found in the final period (between 9–16 months) (p = 0.025). Hypoglycaemic events occurred in all patients (100%) before using insulin glargine U300, while the incidence of hypoglycaemic events gradually decreased to 74.3%, 68.6%, and 68.6% between months 1–3, 3–6, and 6–9, respectively. Of the 26 patients who declared their level of satisfaction, 23 (88.5%) were satisfied, 2 (7.7%) indicated that there was no significant difference, and 1 (3.8%) patient was unsatisfied.ConclusionsOver 9–16 months of follow-up, insulin glargine U300 led to a significant reduction not only of HbA1c levels but also of the frequency of hypoglycaemia, and also yielded high satisfaction rates.

Advances in newer basal and bolus insulins: impact on type 1 diabetes.

Insulin administration is vitally important to maintain a good glycaemic control in people with type 1 diabetes mellitus (T1DM). The purpose of this review is to give a clinically relevant overview of the newer basal and bolus insulin analogues and to highlight their practicalities of use and advantages in specific categories of patients with T1DM. Second-generation rapid-acting insulin analogues (i.e. faster insulin aspart and ultrarapid-acting lispro) have shown to be safe, efficient and superior in controlling postprandial plasma glucose levels without an increase in hypoglycaemia. The newest basal insulin analogues, insulin glargine U300 and degludec, have proven to be efficient in reducing hypoglycaemic events due to a more stable action profile. The second-generation rapid-acting and basal insulin analogues approach better the desired physiological insulin pattern of the beta cell. Due to a faster absorption, it is possible to inject the prandial insulin analogues more closely or even after meals without compromising postprandial glucose control. Due to more stable release patterns, basal insulins now have more reliable and longer profiles, covering basal insulin demands in a superior way, leading to a better glycaemic control with less hypoglycaemia (especially nocturnal events) and an improved quality of life.

Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment

BackgroundIt is thought that a reduction in the frequency of basal insulin injections might facilitate treatment acceptance and adherence among patients with type 2 diabetes. Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment of diabetes.MethodsWe conducted a 26-week, randomized, double-blind, double-dummy, phase 2 trial to investigate the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (glycated hemoglobin level, 7.0 to 9.5%) while taking metformin with or without a dipeptidyl peptidase 4 inhibitor. The primary end point was the change in glycated hemoglobin level from baseline to week 26. Safety end points, including episodes of hypoglycemia and insulin-related adverse events, were also evaluated.ResultsA total of 247 participants were randomly assigned (1:1) to receive icodec or glargine. Baseline characteristics were similar in the two groups; the mean baseline glycated hemoglobin level was 8.09% in the icodec group and 7.96% in the glargine group. The estimated mean change from baseline in the glycated hemoglobin level was −1.33 percentage points in the icodec group and −1.15 percentage points in the glargine group, to estimated means of 6.69% and 6.87%, respectively, at week 26; the estimated between-group difference in the change from baseline was −0.18 percentage points (95% CI, –0.38 to 0.02, P=0.08). The observed rates of hypoglycemia with severity of level 2 (blood glucose level, <54 mg per deciliter) or level 3 (severe cognitive impairment) were low (icodec group, 0.53 events per patient-year; glargine group, 0.46 events per patient-year; estimated rate ratio, 1.09; 95% CI, 0.45 to 2.65). There was no between-group difference in insulin-related key adverse events, and rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and no serious events were deemed to be related to the trial medications.ConclusionsOnce-weekly treatment with insulin icodec had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes. (Funded by Novo Nordisk; NN1436-4383 ClinicalTrials.gov number, NCT03751657.)

(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.

(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.

Efficacy and Safety of Tofogliflozin and Ipragliflozin for Patients with Type-2 Diabetes: A Randomized Crossover Study by Flash Glucose Monitoring.

IntroductionSodium-glucose cotransporter 2 (SGLT2) inhibitors promote urinary glucose excretion. However, the differences in the effects of various SGLT2 inhibitors are unknown. We used flash glucose monitoring (FGM) to identify the differences between tofogliflozin and ipragliflozin in terms of efficacy in reducing glycemic variability and mitigate hypoglycemia risk.MethodsIn this crossover study, 24 patients with type-2 diabetes mellitus (T2DM) receiving insulin glargine U300 therapy were randomly allocated to tofogliflozin and ipragliflozin or ipragliflozin and tofogliflozin group. Glycemic variability and hypoglycemia were compared using to the 3-day FGM data per treatment period.ResultsGlucose level 2 h after each meal was significantly lower with tofogliflozin administration than with ipragliflozin administration. Time below the target glucose range after tofogliflozin administration was significantly lower than that after ipragliflozin administration (2.1% ± 4.4% vs. 8.7% ± 11.7%). The 24-h standard deviation of glucose level, mean amplitude of glycemic excursion, and mean percent time with nocturnal hypoglycemia after tofogliflozin administration were significantly lower than those after ipragliflozin administration.ConclusionsTofogliflozin was more effective and safer than ipragliflozin in reducing glycemic variability and mitigating hypoglycemia risk in patients with T2DM treated with insulin glargine U300.Trial RegistrationThis trial was registered at the University Hospital Medical Information Network Clinical Trial Registry (no. UMIN000037158).Electronic MaterialThe online version of this article (10.1007/s13300-020-00940-9) contains supplementary material, which is available to authorized users.

65 - Randomized Comparison of Initiating Insulin Glargine or Iglarlixi in South Asian Canadians With Type 2 Diabetes: VARIATION 2 SA Trial

To compare initiation of a fixed-ratio combination of glargine-lixisenatide (iGlarLixi) and insulin glargine U100 (iGlar), exclusively in South Asian origin Canadians.

Real-world cost-effectiveness of insulin degludec in type 1 and type 2 diabetes mellitus from a Swedish 1-year and long-term perspective

Background and aims The ReFLeCT study demonstrated that switching to insulin degludec from other basal insulins was associated with reductions in glycated hemoglobin and hypoglycemic events in type 1 (T1D) and type 2 diabetes (T2D), and reductions in insulin doses in T1D. The aim of the present analysis was to assess the short- and long-term cost-effectiveness of switching to insulin degludec in Sweden. Methods Short-term outcomes were evaluated over 1 year in a Microsoft Excel model, while long-term outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Cohort characteristics and treatment effects were sourced from the ReFLeCT study. Costs (in 2018 Swedish krona [SEK]) encompassed direct medical expenditure and indirect costs from loss of workplace productivity. In the long-term analyses, patients were assumed to receive insulin degludec or continue prior insulin therapy (primarily insulin glargine U100) for 5 years, before all patients intensified to once-daily degludec and mealtime aspart. Results Switching to insulin degludec was associated with improved quality-adjusted life expectancy of 0.04 and 0.02 quality-adjusted life years (QALYs) over 1 year, and 0.16 and 0.08 QALYs over patient lifetimes, in T1D and T2D. Combined costs in T1D and T2D were estimated to be SEK 1,249 lower and SEK 1,181 higher over the short-term, and SEK 157,258 and SEK 2,114 lower over the long-term. Benefits were due to lower insulin doses in T1D, reduced rates of hypoglycemia, and lower incidences of diabetes-related complications. Insulin degludec was associated with an incremental cost-effectiveness ratio of SEK 64,298 per QALY gained for T2D over 1 year and considered dominant for T1D and T2D in all other comparisons. Conclusions Insulin degludec was projected to be cost-effective or dominant versus other basal insulins for the treatment of T1D and T2D in Sweden.