Glargine U100 Research Articles

Basal insulin analogues in type 1 diabetes – does one size fit all? Lessons from the HypoDeg trial based on single-patient outcomes

AimsIn the HypoDeg trial, a randomised crossover trial in people with type 1 diabetes prone to nocturnal severe hypoglycaemia, treatment with insulin degludec (IDeg) resulted in significantly reduced rates of nocturnal symptomatic hypoglycaemia and all-day severe hypoglycaemia compared to insulin glargine U100 (IGlar). We analysed HypoDeg data at a single-patient level to assess the proportion of participants to whom the overall result applied. MethodsPost hoc analysis using single-patient data (n=133) on nocturnal symptomatic hypoglycaemia, all-day severe hypoglycaemia and HbA1c. The outcome was classified as superior with IDeg, superior with IGlar, or similar between treatments for the three outcomes. We also assessed a composite endpoint based on these outcomes to evaluate the overall superior treatment for each participant. ResultsA higher percentage (38%) had IDeg as superior treatment compared to IGlar (15%) for nocturnal symptomatic hypoglycaemia (p < 0.001). There was no difference between the treatments for all-day severe hypoglycaemia or HbA1c. A higher percentage (44%) had a composite endpoint favouring IDeg compared to IGlar (16%) (p < 0.001). ConclusionsThe superiority of IDeg was confirmed in many of the participants. However, a minority had IGlar as superior treatment, underscoring the need for individualised basal insulin therapy in clinical practice.

Icodec: A Novel Once-Weekly Basal Insulin for Diabetes Management.

To evaluate the efficacy, safety, and clinical implications of insulin icodec, a novel once-weekly basal insulin for the treatment of type 1 diabetes (T1D) and type 2 diabetes (T2D), with an emphasis on its advantages and challenges in comparison with existing daily basal insulins. A literature search was performed using PubMed, Google Scholar, Embase, and ClinicalTrials.gov up to August 26, 2024, using the search terms icodec and ONWARDS trial. Studies involving patients living with T1D or T2D on once-weekly insulin icodec compared with once-daily insulins glargine U100, glargine U300, and degludec were considered for this review. Relevant English-language studies and those conducted in humans were considered. Insulin icodec offers reduced dosing frequency and potentially superior glycemic management with a safety profile comparable to existing basal insulins. Insulin icodec once-weekly dosing could significantly improve convenience and efficacy over daily basal insulins, representing a significant innovation in insulin therapy. Insulin icodec emerges as a promising option for diabetes management, potentially improving treatment adherence and quality of life.

7363 Comparing the Effectiveness of Various Insulin in Insulin Naive Type 2 Diabetes Mellitus Patients: A Study from Central India

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. N. Kumari: None. A. Gwal: None. Introduction: Insulin is the cornerstone of treatment of type 2 diabetes mellitus (T2DM) and is the most efficacious treatment option. The evaluation of efficacy and safety of insulin therapy in real world setting is desirable as numerous options are currently available. This study aimed to compare the efficacy and safety of four different insulins in patients with T2DM. Methods: We conducted a retrospective observational study at our tertiary care hospital using medical records of patients with glycated hemoglobin (HbA1c) &amp;gt;8.5% who were not controlled on oral antidiabetic (OAD) medication and received add-on insulin treatment (Glargine U300, Lispro Biphasic 25/75, Glargine U100, IdegAsp). Glycemic control and incidence of hypoglycemia were analyzed from baseline to 6 months. Results: 101 patients were included. Mean age 56.4 years. 61.4% men. Mean duration of T2DM 13.3 years. 23 (22.8%), 27 (26.7%), 27 (26.7%), and 24 (23.8%) patients received Glargine U300, Lispro Biphasic 25/75, Glargine U-100, IdegAsp insulin respectively. At baseline, the mean (SD) HbA1c were 11.93% (1.85), 10.61% (1.55), 10.65% (1.59), and 10.58% (1.89) in patients receiving Glargine U300, Lispro Biphasic 25/75, Glargine U100, and IdegAsp, respectively. HbA1c, fasting plasma glucose (FPG) &amp; post-prandial plasma glucose (PPG) improved significantly from baseline to 6 months across all four treatment groups (p&amp;lt;0.001). Glargine U300 showed a significantly greater mean reduction in HbA1c by 4.57% compared to Lispro Biphasic 25/75 (3.39%; p=0.032), Glargine U100 (2.88%; p=0.004), and IdegAsp (2.38%; p&amp;lt;0.001). The mean reduction in FPG, PPG, total cholesterol and triglycerides were comparable across all four treatment groups. The mean insulin doses (SD) were 15.48 (5.65) U, 23.83 (9.49) U, 20.44 (8.76) U, and 34.17 (14.57) U at baseline and 18.89 (5.39) U, 35.52 (10.37) U, 26.07 (8.92) U, and 43.58 (15.76) at 6 months, respectively. The doses of all insulins were titrated to fasting, post-meal, or pre-dinner SMBG readings as appropriate. There were no significant changes observed in the mean body weight and insulin dose in all four subgroups. The incidence of hypoglycemia (&amp;lt;70 mg/dL and &amp;lt;54 mg/dL) was numerically lower in Glargine U300 (3 and 1) group, than in Lispro Biphasic 25/75 (8 and 5), Glargine U100 (3 and 2), and IdegAsp (7 and 3) groups. As expected, biphasic insulin had a higher numerical incidence of hypoglycemia. Conclusion: All insulins demonstrated significant improvements in glycemic parameters over the study period. However, Glargine U300 demonstrated a significantly higher reduction in HbA1c with minimal hypoglycemia events compared to other insulins and can be considered in OAD uncontrolled patients. Our results should be interpreted with caution as the study was retrospective and had a small sample size. Presentation: 6/3/2024

6905 The Necessity For New Criteria To Evaluate Overbasalization In East Asian Patients With Type 2 Diabetes Using Basal Insulin

Abstract Disclosure: H. Jang: None. Background: Overbasalization, which refers to adjusting the dose of basal insulin beyond an appropriate dose, should be avoided when using basal insulin in patients with type 2 diabetes. It is recommended to evaluate overbasalization when the basal insulin dose exceeds 0.5 units/kg/day or when post-meal glucose levels are &amp;gt; 180 mg/dL. However, this is an expert opinion, and specific criteria for East Asians have not been presented. Methods: Patients with type 2 diabetes using basal insulin (insulin glargine U-100, insulin glargine U-300, insulin degludec, NPH) at Seoul National University Bundang hospital from December 2020 to November 2023, with fasting plasma glucose (FPG) levels between 80 mg/dL and 130 mg/dL, were retrospectively analyzed. Patients with CKD ≤ grade 3b (estimated glomerular filtration rate &amp;lt; 45 mL/min/1.73m2), those taking medications such as steroids that may affect blood glucose levels, and patients undergoing cancer treatment were excluded. Results: A total of 548 patients were analyzed. The mean age of the subjects was 64.7 ± 12.4 years, with 299 (54.6%) being male, and the mean body mass index was 25.1 ± 6.6 kg/m2. The mean duration of diabetes was 18.1 ± 9.6 years. The mean HbA1c level was 7.7 ± 1.1%, while the mean fasting plasma glucose and median fasting C-peptide levels were 105.4 ± 13.9 mg/dL and 1.4 [0.8, 2.1] ng/mL, respectively. Insulin degludec being the most commonly administered (279 [50.9%]). The mean 2-hr postprandial glucose was 206.3 ± 64.8 mg/dL, with 350 (63.9%) having 2-hr postprandial glucose &amp;gt; 180 mg/dL. The administered insulin dose was 0.35 ± 0.17 units/kg/day, and 101 (18.4%) had an insulin dose &amp;gt; 0.5 units/kg/day. Conclusion: In East Asian patients with type 2 diabetes receiving basal insulin, although high 2-hr postprandial glucose levels suggest the possibility of overbasalization, the administered dosage of basal insulin was relatively low. Considering the lower insulin secretion capacity in East Asians, it is thought that new, specific criteria for overbasalization in East Asians are necessary. Presentation: 6/3/2024

Continuous glucose monitoring-based metrics and the duration of hypoglycaemia events with once-weekly insulin icodec versus once-daily insulin glargine U100 in insulin-naive type 2 diabetes: an exploratory analysis of ONWARDS 1

Continuous glucose monitoring (CGM) can provide a comprehensive assessment of glycaemic control. This exploratory analysis of the ONWARDS 1 trial assessed CGM-based metrics and CGM-derived hypoglycaemia duration in insulin-naive individuals with type 2 diabetes treated with subcutaneous once-weekly insulin icodec (icodec) versus once-daily insulin glargine U100 (glargine U100). ONWARDS 1 was a 78-week (52-week main treatment phase and a 26-week treatment extension phase plus a 5-week follow-up), randomised, open-label, treat-to-target, phase 3a trial done at 143 sites (outpatient clinics and hospital departments) across 12 countries. Adults (aged ≥18 years) with type 2 diabetes (HbA1c: 7·0-11·0%) who had not previously received insulin were randomly assigned (1:1) via an interactive web-response system to once-weekly icodec or once-daily glargine U100. Double-masked CGM data were collected during treatment initiation (weeks 0-4), midtrial (weeks 22-26), end of main phase (weeks 48-52), end of extension phase (weeks 74-78), and follow-up (weeks 78-83). Secondary and exploratory outcomes were CGM-based metrics, including the mean percentages of time in glycaemic range (TIR; sensor glucose 3·9-10·0 mmol/L [70-180 mg/dL]), time in tight range (TITR; 3·9-7·8 mmol/L [70-140 mg/dL]), time above range (TAR; >10·0 mmol/L [>180 mg/dL]), and time below range (TBR; <3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]), and CGM-derived hypoglycaemic episode durations (episodes defined by sensor glucose <3·9 mmol/L [<70 mg/dL for ≥15 consecutive minutes]). Analyses were done in the full analysis set (all randomly assigned participants). The ONWARDS 1 trial is registered with ClinicalTrials.gov, NCT04460885, and is complete. Participants were enrolled and randomly assigned in ONWARDS 1 between Nov 25, 2020, and Dec 1, 2022 (n=492 in each treatment group). During treatment initiation, we observed no statistically significant differences in the mean percentages of TIR, TITR, TAR, and TBR with icodec versus glargine U100. During the midtrial, end of main phase, and end of extension phase periods, the mean percentages of TIR and TITR were statistically significantly greater and the mean percentages of TAR statistically significantly lower with icodec versus glargine U100. The mean percentages of TIR met the internationally recommended CGM target (>70%) with icodec but not with glargine U100 during the three periods. TBR (<3·9 mmol/L [<70 mg/dL] and <3·0 mmol/L [<54 mg/dL]) was low and below recommended targets (<4% and <1%, respectively) across all study periods in both treatment groups, with no statistically significant differences between treatment groups for the lower threshold (<3·0 mmol/L [<54 mg/dL]). During the follow-up period, mean percentages of TIR, TITR, TAR, and TBR did not statistically significantly differ with icodec versus glargine U100. The duration of overall hypoglycaemic episodes was similar between treatment groups throughout the trial (median duration ≤35 min). These CGM data support the long-term efficacy and safety of icodec versus glargine U100 during treatment and indicated no increase in the duration of individual hypoglycaemic episodes with icodec versus glargine U100 in insulin-naive individuals with type 2 diabetes. Novo Nordisk.

Improved treatment satisfaction with once-weekly insulin icodec compared with once-daily basal insulin in individuals with type 2 diabetes: An analysis of patient-reported outcomes and participant interviews from ONWARDS 2 and 5 and a physician survey from ONWARDS 1

AimsThe ONWARDS phase 3a clinical trials evaluated once-weekly insulin icodec (icodec) versus once-daily basal insulin in type 2 diabetes. This analysis investigated the treatment-related experiences of participants from ONWARDS 5 and 2, and physicians from ONWARDS 1. MethodsPatient-reported outcomes were only collected during ONWARDS 5 (icodec with a dosing guide app vs. once-daily basal analogues) and 2 (icodec vs. once-daily insulin degludec). ONWARDS 1 (icodec vs. once-daily insulin glargine U100) physicians’ treatment preferences and satisfaction were obtained via an online survey. ResultsIn ONWARDS 5 and 2, there was a statistically significantly greater increase in total treatment satisfaction from baseline to end of treatment for icodec/icodec with app versus once-daily comparators, mostly driven by participants’ willingness to continue and recommend treatment. In ONWARDS 2, 93.7 % of icodec users preferred once-weekly over once-daily basal insulin, mainly owing to less frequent injections and ease of use. ONWARDS 1 physicians reported greater satisfaction with once-weekly than with once-daily basal insulin and were more likely to recommend once-weekly injections. ConclusionsThese results demonstrate improved treatment satisfaction with, and strong preferences for, once-weekly versus once-daily basal insulin. Treatment convenience and willingness to continue and recommend once-weekly basal insulin treatment were highlighted.Clinical trial registrations: ONWARDS 1: NCT04460885; ONWARDS 2: NCT04770532; ONWARDS 5: NCT04760626

Efficacy and safety of once-weekly insulin icodec versus once-daily basal insulin in Japanese individuals with type 2 diabetes: A subgroup analysis of the ONWARDS 1, 2 and 4 trials.

To explore the efficacy and safety of once-weekly insulin icodec (icodec) in Japanese adults (≥20 years old) with type 2 diabetes from the global ONWARDS 1, 2 and 4 trials. Insulin-naive (ONWARDS 1) and insulin-experienced (ONWARDS 2 and 4) individuals were randomized to icodec or a once-daily insulin comparator: insulin glargine U100 [ONWARDS 1 (basal insulin only) and 4 (basal-bolus regimen)] or insulin degludec [ONWARDS 2 (basal insulin only)]. The primary outcome was change in glycated haemoglobin from baseline to end of treatment (EOT) (ONWARDS 1: Week 52; ONWARDS 2 and 4: Week 26). Here, we present the Japanese subgroup results. Similar reductions in glycated haemoglobin from baseline to EOT were observed in each trial for icodec and comparators. The proportion of time in range (blood glucose 3.9-10.0 mmol/L) at EOT was also comparable across treatment groups (time in range: 58%-68%), as was time spent with blood glucose below 3.0 mmol/L (<1.0%). Combined clinically significant (blood glucose <3.0 mmol/L) or severe (requiring external assistance for recovery) hypoglycaemia rates were low, with no severe events (ONWARDS 1 and 2) or a single severe event (ONWARDS 4; icodec group) reported. These results generally aligned with findings from the respective global populations. No new safety issues were identified. Icodec improved glycaemic control to a similar degree as once-daily basal insulin comparators while maintaining low levels of clinically significant or severe hypoglycaemia. The findings support icodec use in Japanese individuals with different levels of type 2 diabetes progression.

Once-Weekly Insulin Icodec in Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (ONWARDS Clinical Program).

One hundred years have passed since the discovery of insulin, which is one of the most relevant events of the 20th century. This period resulted in extraordinary progress in the development of novel molecules to improve glucose control, simplify the insulin regimen, and ameliorate the quality of life. In late March 2024, the first once-weekly basal analog Icodec was approved for diabetes mellitus, generating high expectations. Our aim was to systematically review and meta-analyze the efficacy and safety of Icodec compared to once-daily insulin analogs in type 1 (T1D) and type 2 diabetes (T2D). PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for randomized clinical trials (RCTs). Studies were included for the synthesis according to the following prespecified inclusion criteria: uncontrolled T1D or T2D, age ≥ 18 years, insulin Icodec vs. active comparators (Degludec U100, Glargine U100, Glargine U300, and Detemir), phase 3, multicenter, double-blind or open-label RCTs, and a study duration ≥ 24 weeks. The systematic review included 4347 patients with T1D and T2D inadequately controlled (2172 randomized to Icodec vs. 2175 randomized to once-daily basal analogs). Icodec, compared to once-daily basal analogs, slightly reduced the levels of glycated hemoglobin (HbA1c) with an estimated treatment difference (ETD) of -0.14% [95%CI -0.25; -0.03], p = 0.01, and I2 68%. Patients randomized to Icodec compared to those on once-daily basal analogs had a greater probability to achieve HbA1c < 7% without clinically relevant or severe hypoglycemic events in 12 weeks from randomization with an estimated risk ratio (ERR) of 1.17, [95%CI 1.01, 1.36], p = 0.03, and I2 66%. We did not find a difference in fasting glucose levels, time in range, and time above range between Icodec and comparators. Icodec, compared to once-daily basal analogs, resulted in a slight but statistically significant weight gain of 0.62 kg [95%CI 0.25; 0.99], p = 0.001, and I2 25%. The frequency of hypoglycemic events (ERR 1.16 [95%CI 0.95; 1.41]), adverse events (ERR 1.04 [95%CI 1.00; 1.08]), injection-site reactions (ERR 1.08 [95%CI 0.62; 1.90]), and the discontinuation of treatments were similar between the two groups. Icodec was found to work better when used in a basal-only than basal-bolus regimen with an ETD in HbA1c of -0.22%, a probability of achieving glucose control of +33%, a probability of achieving glucose control without clinically relevant or severe hypoglycemia of +28%, more time spent in target (+4.55%) and less time spent in hyperglycemia (-5.14%). The risk of clinically relevant or severe hypoglycemic events was significantly higher when background glinides and sulfonylureas were added to basal analogs (ERR 1.42 [95%CI 1.05; 1.93]). Insulin Icodec is substantially non-inferior to once-daily insulin analogs in T2D, either insulin-naïve or insulin-treated. However, Icodec works slightly better than competitors when used in a basal-only rather than basal-bolus regimen. Weight gain and hypoglycemic risk are substantially low but not negligible. Patients' education, adequate lifestyle and pharmacological interventions, and appropriate therapy adjustments are essential to minimize risks. This systematic review is registered as PROSPERO CRD42024568680.

A comparative evaluation of bioequivalence of Gan & Lee glargine U300 and Toujeo® in Chinese healthy male participants.

To assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants. A single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax). GL Glargine U300 demonstrated comparable PK parameters (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of M1) and PD responses [AUCGIR.0-24h, GIRmax, AUCGIR.0-12h, and AUCGIR.12-24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events. The PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®. https://www.chinadrugtrials.org.cn/, identifier CTR20212419.

Insulin icodec: A novel once-weekly treatment for diabetes.

To summarize the results of clinical studies of insulin icodec, an investigational insulin analog designed for once-weekly administration, in adults with type 1 and type 2 diabetes. Thirteen published articles describing clinical studies of insulin icodec were identified in PubMed, and data pertinent to key study outcomes were selected for inclusion in this review. In insulin-naïve and insulin-treated individuals, icodec demonstrated efficacy in glycaemic control superior or noninferior to that of insulins glargine U100, glargine U300 and degludec. Icodec exhibited a safety profile comparable to marketed insulins, with the exception of hypoglycaemic event rates. As a once-weekly alternative to daily basal insulin, icodec is expected to improve patient adherence and satisfaction, reducing the required number of injections per year from 365 to 52 and providing a dosing option potentially attractive to a wide range of insulin users. However, clinical data suggest a notable risk of hypoglycaemia with weekly icodec administration, especially in individuals with type 1 diabetes.

Nocturnal Glucose Profile According to Timing of Dinner Rapid Insulin and Basal and Rapid Insulin Type: An Insulclock® Connected Insulin Cap-Based Real-World Study.

A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): -45-15 min (n = 136; 17.5%, 175.9 ± 271.0); -15-0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D.

Once-weekly insulin icodec compared with daily basal insulin analogues in type 2 diabetes: Participant-level meta-analysis of the ONWARDS 1-5 trials.

To perform a participant-level post hoc meta-analysis of Phase 3a trials in type 2 diabetes (T2D) to characterize the hypoglycaemia safety and glycaemic efficacy of once-weekly insulin icodec (icodec). All ONWARDS 1-5 randomized participants were pooled as overall T2D, insulin-naive, an insulin-experienced subgroups, and by once-daily trial comparator (degludec or glargine U100). The main outcomes included incidence and rates of clinically significant and severe hypoglycaemia. Additional endpoints included change in glycated haemoglobin (HbA1c) from baseline and HbA1c target achievement without clinically significant or severe hypoglycaemia. The meta-analysis comprised 3765 participants (1882 icodec vs. 1883 comparators). In the overall T2D pool, clinically significant hypoglycaemia incidence was similar in the icodec group versus the comparator group (17.9% vs. 16.2%, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.94, 1.38); however, rates were low but significantly higher in the icodec group (1.15 vs. 1.00 episodes/participant-year of exposure, estimated rate ratio 1.51 [95% CI 1.24, 1.85]). Fewer severe hypoglycaemic episodes occurred with icodec than with comparators (8 vs. 18). A greater reduction in HbA1c occurred with icodec versus comparators, irrespective of subgroup (estimated treatment difference range [-0.10 to -0.29%]; all p < 0.05). Across subgroups, except for the insulin-experienced subgroup, the odds of achieving HbA1c <53 mmol/mol (7.0%) without clinically significant or severe hypoglycaemia were greater with icodec than with comparators (OR range 1.30-1.55; all p < 0.05). Icodec was associated with a similar incidence but higher rates of clinically significant hypoglycaemia (equating to one additional hypoglycaemic episode every 6 years) and fewer severe hypoglycaemic episodes versus comparators. Our findings also confirmed the greater efficacy of icodec that was demonstrated in the ONWARDS trial programme.

Once-weekly insulin efsitora alfa: Design and rationale for the QWINT phase 3 clinical development programme.

Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This review describes the study design and rationale of the efsitora phase 3 Once Weekly (QW) Insulin Therapy (QWINT) clinical development programme, including the five trials, QWINT-1 through QWINT-5. The five trials included insulin-naïve adults (QWINT-1 and -2) with type 2 diabetes (T2D), adults with T2D previously treated with basal insulin (QWINT-3 and -4), and QWINT-5 in adults with type 1 diabetes. All five trials were designed as multicentre, randomized, controlled, open-label, treat-to-target studies to investigate the efficacy and safety of efsitora versus active once-daily basal insulin comparators (insulin glargine U100 or insulin degludec U100). The primary objective of each trial is to compare the change in HbA1c from baseline to week 26 or 52 between efsitora and the active comparator. The key secondary objectives include change in fasting glucose, insulin dose and continuous glucose monitoring variables, and patient-reported outcome questionnaires. The QWINT development programme includes a racially and geographically diverse population to provide important information regarding the efficacy and safety of efsitora and its clinical management of people with diabetes.

Evaluating the efficacy and safety of weekly Insulin Icodec vs. Daily Insulin Glargine in type 2 Diabetes Mellitus: a systematic review and meta-analysis.

Various insulin therapies for Diabetes Mellitus offer different benefits while having potential risks. We aim to compare Insulin Icodec, a novel Insulin analogue with the ease of once-weekly administration, to the once-daily Insulin Glargine U100 regarding glycemic control and safety profile. We performed a systematic literature search of electronic databases for peer-reviewed articles from inception until September 1 2023. A total of 2215 type 2 diabetic patients were included, of which 1209 received Insulin Icodec and1048 recieved Insulin Glargine U100. In terms of glycemic control, Insulin Icodec showed a significantly longer time in the target glucose range (MD: 0.304, CI: 0.069, P = 0.000) and a more significant reduction in HbA1c (MD: -0.154, CI: 0.003, P = 0.005) compared to Insulin Glargine U100. Fasting Plasma Glucose did not differ significantly. Insulin Icodec led to a more significant increase in body weight (MD: 0.161kg, P = 0.029), while Insulin Glargine required a higher insulin dose (MD: 1.920IU, P = 0.000). Regarding safety, the two groups had no significant differences in hypoglycemic events or adverse outcomes. Once-weekly Insulin Icodec demonstrates superior glycemic control with a reduced HbA1c compared to Once-Daily Insulin Glargine U100 while maintaining similar safety profiles. The online version contains supplementary material available at 10.1007/s40200-024-01431-5.

Effects of Switching from Degludec to Glargine U300 in Patients with Insulin-Dependent Type 1 Diabetes: A Retrospective Study.

Background and Objectives: Degludec (Deg) and glargine U300 (Gla-300) are insulin analogs with longer and smoother pharmacodynamic action than glargine U100 (Gla-100), a long-acting insulin that has been widely used for many years in type 1 and type 2 diabetes. Both improve glycemic variability (GV) and the frequency of hypoglycemia, unlike Gla-100. However, it is unclear which insulin analog affects GV and hypoglycemia better in patients with insulin-dependent type 1 diabetes. We evaluated the effects of switching from Deg to Gla-300 on the day-to-day GV and the frequency of hypoglycemia in patients with insulin-dependent type 1 diabetes treated with Deg-containing basal-bolus insulin therapy (BBT). Materials and Methods: We conducted a retrospective study on 24 patients with insulin-dependent type 1 diabetes whose treatment was switched from Deg-containing BBT to Gla-300-containing BBT. We evaluated the day-to-day GV measured as the standard deviation of fasting blood glucose levels (SD-FBG) calculated by the self-monitoring of blood glucose records, the frequency of hypoglycemia (total, severe, and nocturnal), and blood glucose levels measured as fasting plasma glucose (FPG) levels and hemoglobin A1c (HbA1c). Results: The characteristics of the patients included in the analysis with high SD-FBG had frequent hypoglycemic events, despite the use of Deg-containing BBT. For this population, SD-FBG and the frequency of nocturnal hypoglycemia decreased after the switch from Deg to Gla-300. Despite the decrease in the frequency of nocturnal hypoglycemia, the FPG and HbA1c did not worsen by the switch. The change in the SD-FBG had a negative correlation with the SD-FBG at baseline and a positive correlation with serum albumin levels. Conclusions: Switching from Deg to Gla-300 improved the SD-FBG and decreased the frequency of nocturnal hypoglycemia in insulin-dependent type 1 diabetes treated with Deg-containing BBT, especially in cases with low serum albumin levels and a high GV.

Single Center Evaluation of Long-Term Results of Glargin U-300 in Insulin Naive Patients In a Real-World Setting

Objective: Insulin therapy stands as one of the most effective and well-established therapeutic options for managing glycemic control in Diabetes Mellitus (DM). Glargine 300 U/mL (Gla-300) represents a new long-acting insulin analog, which has demonstrated a decrease in the risk of hypoglycemia and a reduction in the total number of injections due to prolonged insulin absorption. In this study, we investigated the long-term effects of Gla-300 on Fasting Plasma Glucose (FPG) and HbA1c levels, as well as the incidence of hypoglycemia in insulin-naive patients admitted to the Internal Medicine outpatient clinic, over a period of 0, 3, 6, 12, and 24 months.. Material and Methods: Between January 2018 and June 2022, insulin-naive patients diagnosed with Type 2 Diabetes Mellitus (T2DM) who initiated treatment with Gla-300 and sought care at the Internal Medicine outpatient clinic were subjected to retrospective analysis. Results: The study included 49 insulin-naive patients. A statistically significant decrease was observed in Fasting Plasma Glucose (FPG) (p = 0.03) and HbA1c (p = 0.02) levels during the 24-month follow-up period of Glargine U-300. Additionally, a significant reduction in both FPG (p &lt; 0.01) and HbA1c (p &lt; 0.01) values was achieved at the time of diagnosis and at 3 months. Hypoglycemia was reported in only 1 patient (2%) during our study, indicating a very low hypoglycemia rate. Conclusion: Diabetes mellitus (DM) poses a significant public health challenge, resulting in economic burden and diminished quality of life. Developed to address these challenges, Gla-300 serves as a long-acting basal insulin that effectively reduces the risk of hypoglycemia while offering targeted glycemic control, as evidenced by our study findings. In Turkey, there is a pressing need for multicenter, prospective real-world studies that incorporate parameters such as insulin dosage and weight monitoring.

Efficacy and Safety of Insulin Icodec Versus Glargine U100: A Meta-Analysis of Randomized Controlled Trials: Erratum.

Efficacy and Safety of Insulin Icodec Versus Glargine U100: A Meta-Analysis of Randomized Controlled Trials: Erratum.

Safety and Efficacy of Switching SAR341402 Insulin Aspart and Originator Insulin Aspart vs Continuous Use of Originator Insulin Aspart in Adults With Type 1 Diabetes: The GEMELLI X Trial.

SAR341402 insulin aspart (SAR-Asp) is a rapid-acting insulin analog developed as an interchangeable biosimilar to the marketed insulin aspart reference product (NovoLog; NN-Asp). GEMELLI X was a randomized controlled trial to assess outcomes with a biosimilar in line with the US Food and Drug Administration requirements for designation as an interchangeable biosimilar. This report assessed whether multiple switches between SAR-Asp and NN-Asp lead to equivalent safety and efficacy compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D) treated with multiple daily injections, using once-daily insulin glargine U100 (Lantus) as the basal insulin. This open-label randomized (1:1), parallel-group, phase 3 trial compared four × four weeks of alternating use of individually titrated SAR-Asp and NN-Asp (NN-Asp for first four weeks, SAR-Asp in last four weeks; switching group) vs 16 weeks of continuous use of NN-Asp (nonswitching group). End points included pharmacokinetics, immunogenicity, adverse events, hypoglycemia, insulin dose, and change in efficacy parameters. Of the 210 patients randomized, 200 (95.5%) completed the trial. Patients assigned to switching group (n = 104) and nonswitching group (n = 106) showed similar safety and tolerability, including anti-insulin aspart antibody responses, adverse events, and hypoglycemia. At week 16, there was no relevant difference between switching vs nonswitching groups in the change from baseline in glycated hemoglobin (least square [LS] mean difference = 0.05% [95% confidence interval [CI] = -0.13, 0.22]; 0.50 mmol/mol [-1.40, 2.39]), fasting plasma glucose (LS mean difference = 0.23 mmol/L [95% CI = -1.08, 1.53]; 4.12 mg/dL [-19.38, 27.62]), and changes in insulin dosages. Alternating doses of SAR-Asp and NN-Asp compared with continuous use of NN-Asp showed similar safety, immunogenicity, and clinical efficacy in adults with T1D. This study supports interchangeability between SAR-Asp and NN-Asp in T1D management.

Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years' duration, HbA1c 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up. Across treatments, diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (-0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (-0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms. Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults with early T2DM.

Real-World Study on Effectiveness of Insulin Glargine U300 After Oral Antidiabetic Drug Failure in Patients with Type 2 Diabetes in the Gulf Region.

The effectiveness and safety of long-acting insulin glargine U300 (Gla-300), in patients with type2 diabetes mellitus (T2DM) requiring insulin, has not been reported in the Gulf region. Insulin-naïve patients with T2DM, uncontrolled on OADs, and prescribed Gla-300 were followed up in a 12-month prospective observational study. Gla-300 was titrated to glycemic targets. The primary endpoint (achieving glycemic targets) was evaluated at month 6 of treatment. The need for treatment intensification, safety, and patient-reported outcomes (PRO) were also reported. The study included 412 patients (61.7% men; age 52.2 ± 11.1years and T2DM duration 10.7 ± 6.8years). Almost 50% were on more than 3 OADs, mostly biguanides, sulfonylureas, and dipeptidyl-peptidase-4 inhibitors. Baseline HbA1c level was 9.2% ± 1.1% and targets were set at 6.9% ± 0.4%. Baseline fasting plasma glucose was 11.5 ± 3.8mmol/l. Fifty-seven patients (13.8%) achieved glycemic targets at month 6, hindered by baseline HbA1c ≥ 10%, frequent co-morbidities, older age, suburban/rural residence, and full-time employment. Levels of HbA1c dropped progressively by 0.96% ± 0.07% (month 3), 1.29% ± 0.08% (month 6), and 1.76% ± 0.06% (month 12). Gla-300 dose was 17.0 ± 9.0IU/day at baseline, 24.6 ± 9.6 IU/day at month 3, 28.5 ± 9.9IU/day at month 6, and 30.7 ± 10.7IU/day at month 12. Three patients experienced non-severe hypoglycemia and a slight decrease in body weight and PROs improved. In the Gulf, Gla-300 in patients with T2DM uncontrolled on OADs improved glycemic control, with low rates of hypoglycemia and improved PROs. Gla-300 dose up-titration from baseline to month 6 did not, however, result in a vast proportion of patients achieving their pre-determined HbA1c targets. ClinicalTrials.gov identifier: NCT03703869.