Dataset Information

Once-Weekly Basal Insulin Fc Demonstrated Similar Glycemic Control to Once-Daily Insulin Degludec in Insulin-Naive Patients With Type 2 Diabetes: A Phase 2 Randomized Control Trial.

ABSTRACT:

Objective

Basal insulin Fc (BIF) (insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed the safety and efficacy of BIF versus degludec in insulin-naive patients with type 2 diabetes (T2D) previously treated with oral antihyperglycemic medications.

Research design and methods

During this randomized, parallel, open-label study, 278 insulin-naive patients with T2D were randomly assigned (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to fasting glucose of 80-100 mg/dL (4.4 to <5.6 mmol/L). The primary end point was HbA1c change from baseline to week 26 (noninferiority margin 0.4%). Secondary end points included fasting blood glucose (FBG), six-point glucose profiles, and rate of hypoglycemia.

Results

After 26 weeks of treatment, BIF demonstrated a noninferior HbA1c change from baseline versus degludec, with a treatment difference of 0.06% (90% CI -0.11, 0.24; P = 0.56). Both BIF and degludec treatment led to significant reductions in FBG from baseline. At week 26, the between-treatment difference for BIF versus degludec was 4.7 mg/dL (90% CI 0.1, 9.3; P = 0.09). The rate of level 2 hypoglycemia was low and not significantly different between treatment groups (BIF 0.22 events/patient/year, degludec 0.15 events/patient/year; P = 0.64); there was no severe hypoglycemia. The occurrence of treatment-emergent adverse events was also similar between BIF and degludec.

Conclusions

Once-weekly BIF achieved excellent glycemic control similar to degludec, with no concerning hypoglycemia or other safety findings.

SUBMITTER: Bue-Valleskey JM

PROVIDER: S-EPMC10154646 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Once-Weekly Basal Insulin Fc Demonstrated Similar Glycemic Control to Once-Daily Insulin Degludec in Insulin-Naive Patients With Type 2 Diabetes: A Phase 2 Randomized Control Trial.

Bue-Valleskey Juliana M JM Kazda Christof M CM Ma Chenchen C Chien Jenny J Zhang Qianyi Q Chigutsa Emmanuel E Landschulz William W Haupt Axel A Frias Juan P JP

Diabetes care 20230501 5

<h4>Objective</h4>Basal insulin Fc (BIF) (insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed the safety and efficacy of BIF versus degludec in insulin-naive patients with type 2 diabetes (T2D) previously treated with oral antihyperglycemic medications.<h4>Research design and methods</h4>During this randomized, parallel, open-label study ...[more]

PMID: 36944059

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Project description:ImportanceOnce-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes.ObjectiveTo evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes.Design, setting, and participantsRandomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol).InterventionsParticipants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294).Main outcomes and measuresThe primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes.ResultsAmong 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], -0.2 [95% CI, -0.3 to -0.1] percentage points), confirming noninferiority (P < .001) and superiority (P = .002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, -6 to 5] mg/dL; P = .90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, -0.19 to 1.10] kg; P = .17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P = .01).Conclusions and relevanceAmong people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups.Trial registrationClinicalTrials.gov Identifier: NCT04795531.

Project description: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) <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.

Project description:BackgroundType 2 diabetes mellitus is a progressive metabolic disease necessitating therapies with sustained efficacy and safety over time. Exenatide once weekly (ExQW), an extended-release formulation of the glucagon-like peptide-1 receptor agonist exenatide, has demonstrated improvements in glycemic and cardiometabolic measures from 30 weeks to 2 years of treatment. Here, the efficacy and safety of treatment with ExQW for 3 years are described.MethodsPatients were initially randomized to receive either ExQW (2 mg) or exenatide twice daily for 30 weeks. Following the initial 30 weeks, all patients were treated with ExQW in an open-label extension. Analyses of primary glycemic endpoints, beta-cell function, and cardiometabolic measures were assessed for patients who completed 3 years of ExQW treatment and for the intention-to-treat population. Safety and tolerability analyses were provided for the intention-to-treat population.ResultsSixty-six percent of the intention-to-treat population (n = 295) completed 3 years of treatment (n = 194). At 3 years, a significant reduction in hemoglobin A(1c) (least squares mean ± standard error) of -1.6% ± 0.08% was observed, with 55% and 33% of patients achieving hemoglobin A(1c) targets of <7% and ≤6.5%, respectively. Consistent with a sustained reduction in hemoglobin A(1c), improvements in beta-cell function were also observed. Body weight was significantly reduced by -2.3 ± 0.6 kg. Reductions in blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglycerides were also observed. Adverse events reported most frequently during both controlled and uncontrolled periods included diarrhea, nausea, and vomiting of mostly mild intensity. The incidence of these adverse events decreased over time. Incidence of minor hypoglycemia was low and no major hypoglycemia was observed.ConclusionExQW produced clinically meaningful improvements in glycemic control that were durable through 3 years of treatment. Significant improvements in cardiometabolic measurements were also observed. ExQW was well-tolerated during long-term treatment and no new adverse events were noted.Trial registrationClinicalTrials.gov NCT00308139.

Project description:BackgroundRandomized controlled trials have found that once-weekly insulin resulted in greater glycemic control compared to once-daily insulin in patients with type 2 diabetes. However, no direct comparisons have been made between different types of once-weekly insulin thus far. This systematic review and network meta-analysis aimed to evaluate the effect of the two most advanced once-weekly insulin analogues, namely insulin icodec and insulin Fc, in patients with type 2 diabetes.MethodsWe conducted a thorough search in the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. The search included articles published from the beginning to October 10, 2023, with no language limitations. Our aim was to conduct a systematic review of randomized controlled trials that investigated the effectiveness and safety of once-weekly insulin in individuals with type 2 diabetes. Our primary outcome was to evaluate excellent glycemic control, defined as patients achieving glycated hemoglobin levels below 7%.ResultsWe identified a total of 7 trials involving 2829 patients. The results showed that once-weekly insulin icodec is more effective than once-weekly insulin Fc (RR 1.59 [95% CI 1.08-2.38]), once-daily degludec (RR 1.43 [95% CI 1.14-1.83]), and once-daily glargine (RR 1.15 [95% CI 1.00-1.41]). Moreover, the incidence of severe hypoglycemia was lower with once-weekly insulin icodec compared to once-daily degludec (RR 0.00016 [95% CI 0 to 0.41]). However, no significant difference in the incidence of severe hypoglycemia was observed between once-weekly insulin icodec and once-daily glargine (RR 0.39 [95% CI 0.03 to 4.83]).ConclusionsIn patients with type 2 diabetes, once-weekly insulin icodec achieved superior glycemic control compared to once-weekly insulin Fc, with no significant difference in the occurrence of hypoglycemia. The ranking probability results have shown that one weekly icodec seems to be the preferred option in patients with type 2 diabetes.Trial registrationPROSPERO Identifier: CRD42023470894.

Project description:BackgroundThe once-weekly (QW) formulation of the glucagon-like peptide-1 receptor agonist exenatide has been demonstrated to improve A1C, fasting plasma glucose (FPG), body weight, serum lipid profiles, and blood pressure in patients with type 2 diabetes through 52 weeks of treatment. In this report, we describe the 2-year results of the open-label, open-ended extension to the DURATION-1 trial of exenatide QW for type 2 diabetes.MethodsA 2-stage protocol was used: patients received either exenatide QW (2 mg) or exenatide twice daily for 30 weeks (5 μg for the first 4 weeks and 10 μg thereafter), followed by 1.5 years of treatment with exenatide QW (2 mg), for a total of 2 years (104 weeks) of exenatide treatment. Of the 295 (intent-to-treat [ITT]) patients who entered the trial, 73% (n = 216) completed 2 years of treatment (completer population). Baseline characteristics (mean ± SE) for these patients were: A1C, 8.2 ± 0.1%; FPG, 168.4 ± 43.0 mg/dL; body weight, 101.1 ± 18.7 kg; and diabetes duration, 7 ± 5 years.ResultsIn the completer population, significant improvements (LS mean ± SE [95% CI]) were maintained after 2 years of treatment in A1C (-1.71 ± 0.08% [-1.86 to -1.55%]), FPG (-40.1 ± 2.9 mg/dL [-45.7 to -34.5 mg/dL]), and body weight (-2.61 ± 0.52 kg [-3.64 to -1.58 kg]) compared with baseline. The percentages of patients who achieved an A1C of <7.0% and ≤6.5% at 2 years were 60% and 39%, respectively. A significant reduction in systolic blood pressure (SBP; -3.0 ± 1.0 mmHg [-4.9 to -1.1 mmHg]) was maintained through 2 years of treatment. Serum lipid profiles were also significantly improved, including triglycerides (geometric LS mean change from baseline, -15 ± 2.7% [-21% to -10%]), total cholesterol (-8.6 ± 2.8 mg/dL [-14.0 to -3.1 mg/dL]), and low-density lipoproteins (-4.5 ± 2.2 mg/dL [-8.9 to -0.01 mg/dL]). Changes in A1C, body weight, FPG, SBP, and lipids in the ITT population were similar to those seen in the completer population. Nausea (predominantly mild in intensity) was the most common adverse event, although the frequency and intensity of nausea decreased over time. No severe hypoglycemia was observed.ConclusionsExenatide QW was well tolerated during the 2-year treatment period. This study demonstrated sustained glucose control and weight loss throughout 2 years of treatment with exenatide QW.Trial registrationClinicalTrials.gov NCT00308139.

Dataset Information

Once-Weekly Basal Insulin Fc Demonstrated Similar Glycemic Control to Once-Daily Insulin Degludec in Insulin-Naive Patients With Type 2 Diabetes: A Phase 2 Randomized Control Trial.

Objective

Research design and methods

Results

Conclusions

Publications

Once-Weekly Basal Insulin Fc Demonstrated Similar Glycemic Control to Once-Daily Insulin Degludec in Insulin-Naive Patients With Type 2 Diabetes: A Phase 2 Randomized Control Trial.

Similar Datasets

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