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The New England Journal of Medicine Sep 2022The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain.
METHODS
In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, measured quarterly, of 7.0% or higher that was subsequently confirmed, and the secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%.
RESULTS
A total of 5047 participants (19.8% Black and 18.6% Hispanic or Latinx) who had received metformin for type 2 diabetes were followed for a mean of 5.0 years. The cumulative incidence of a glycated hemoglobin level of 7.0% or higher (the primary metabolic outcome) differed significantly among the four groups (P<0.001 for a global test of differences across groups); the rates with glargine (26.5 per 100 participant-years) and liraglutide (26.1) were similar and lower than those with glimepiride (30.4) and sitagliptin (38.1). The differences among the groups with respect to a glycated hemoglobin level greater than 7.5% (the secondary outcome) paralleled those of the primary outcome. There were no material differences with respect to the primary outcome across prespecified subgroups defined according to sex, age, or race or ethnic group; however, among participants with higher baseline glycated hemoglobin levels there appeared to be an even greater benefit with glargine, liraglutide, and glimepiride than with sitagliptin. Severe hypoglycemia was rare but significantly more frequent with glimepiride (in 2.2% of the participants) than with glargine (1.3%), liraglutide (1.0%), or sitagliptin (0.7%). Participants who received liraglutide reported more frequent gastrointestinal side effects and lost more weight than those in the other treatment groups.
CONCLUSIONS
All four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, more effective in achieving and maintaining target glycated hemoglobin levels. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).
Topics: Blood Glucose; Comparative Effectiveness Research; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Liraglutide; Metformin; Sitagliptin Phosphate; Sulfonylurea Compounds; Treatment Outcome
PubMed: 36129996
DOI: 10.1056/NEJMoa2200433 -
JAMA Nov 2023Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described.
OBJECTIVE
To assess the efficacy and safety of tirzepatide vs insulin lispro as an adjunctive therapy to insulin glargine.
DESIGN, SETTING, AND PARTICIPANTS
This open-label, phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020, to November 1, 2022) in 1428 adults with type 2 diabetes taking basal insulin.
INTERVENTIONS
Participants were randomized (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).
MAIN OUTCOMES AND MEASURES
Outcomes included noninferiority of tirzepatide (pooled cohort) vs insulin lispro, both in addition to insulin glargine, in HbA1c change from baseline at week 52 (noninferiority margin, 0.3%). Key secondary end points included change in body weight and percentage of participants achieving hemoglobin A1c (HbA1c) target of less than 7.0%.
RESULTS
Among 1428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was -2.1% vs -1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, -0.98% [95% CI, -1.17% to -0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was -9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, -12.2 kg [95% CI, -13.4 to -10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro.
CONCLUSIONS AND RELEVANCE
In people with inadequately controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared with prandial insulin as an additional treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04537923.
Topics: Female; Humans; Male; Middle Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Treatment Outcome; Internationality; Aged
PubMed: 37786396
DOI: 10.1001/jama.2023.20294 -
Journal of Microbiology and... Oct 2016Glargine insulin is a long-acting insulin analog that helps blood glucose maintenance in patients with diabetes. We constructed the pPT-GI vector to express prepeptide...
Glargine insulin is a long-acting insulin analog that helps blood glucose maintenance in patients with diabetes. We constructed the pPT-GI vector to express prepeptide glargine insulin when transformed into JM109. The transformed cells were cultured by fed-batch fermentation. The final dry cell mass was 18 g/l. The prepeptide glargine insulin was 38.52% of the total protein. It was expressed as an inclusion body and then refolded to recover the biological activity. To convert the prepeptide into glargine insulin, citraconylation and trypsin cleavage were performed. Using citraconylation, the yield of enzymatic conversion for glargine insulin increased by 3.2-fold compared with that without citraconylation. After the enzyme reaction, active glargine insulin was purified by two types of chromatography (ion-exchange chromatography and reverse-phase chromatography). We obtained recombinant human glargine insulin at 98.11% purity and verified that it is equal to the standard of human glargine insulin, based on High-performance liquid chromatography analysis and Matrix-assisted laser desorption/ionization Time-of-Flight Mass Spectrometry. We thus established a production process for high-purity recombinant human glargine insulin and a method to block Arg (B31)-insulin formation. This established process for recombinant human glargine insulin may be a model process for the production of other human insulin analogs.
Topics: Cloning, Molecular; Escherichia coli; Fermentation; Humans; Insulin; Insulin Glargine; Protein Refolding; Recombinant Proteins
PubMed: 27363479
DOI: 10.4014/jmb.1602.02053 -
Journal of Veterinary Emergency and... Jul 2021To determine whether basal-bolus administration of glargine insulin is a safe and effective alternative treatment compared to the standard continuous rate infusion (CRI)...
OBJECTIVES
To determine whether basal-bolus administration of glargine insulin is a safe and effective alternative treatment compared to the standard continuous rate infusion (CRI) protocol.
DESIGN
Prospective randomized clinical trial.
SETTING
University teaching hospital.
ANIMALS
Twenty cats diagnosed with diabetic ketoacidosis (DKA).
INTERVENTIONS
The cats were block-randomized to either a CRI protocol using regular insulin (CRI-group; n = 10) or a basal-bolus SC and IM glargine protocol (glargine-group, n = 10). Baseline blood gases, electrolytes, glucose, and β-hydroxybutyrate (β-OHB) concentrations were measured at the time of admission and later at predefined intervals until reaching the primary endpoint of the study, defined as a β-hydroxybutyrate concentration < 2.55 mmol/L.
MEASUREMENTS AND MAIN RESULTS
The main outcome measure was time (h) to resolution of ketonemia. Secondary outcome measures were time until first improvement of hyperglycemia and ketonemia, decrease of glucose to ≤13.9 mmol/L (250 mg/dL), resolution of acidosis, consumption of first meal, and discharge from hospital. Additionally, occurrence of treatment-associated adverse events and death were compared. Seventeen cats (85%) survived to discharge, with no difference in survival between groups (P = 1.0). Median times to β-OHB < 2.55 mmol/L were 42 (CRI-group) and 30 (glargine-group) hours, respectively (P = 0.114). Median times to first improvement of hyperglycemia (glargine-group: 2 h; CRI-group: 6 h; P = 0.018) and until discharge from hospital (glargine-group: 140 h; CRI-group: 174 h; P = 0.033) were significantly shorter in the glargine-group. No significant differences were observed in any other parameter under investigation (P > 0.05).
CONCLUSIONS
Basal-bolus administration of glargine insulin appears to be an effective and safe alternative to the current standard CRI-protocol for the management of DKA in cats. The positive outcomes and simplicity make it a viable option for the treatment of feline DKA.
Topics: Animals; Blood Glucose; Cat Diseases; Cats; Clinical Trials, Veterinary as Topic; Diabetic Ketoacidosis; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Prospective Studies
PubMed: 33945208
DOI: 10.1111/vec.13062 -
The New England Journal of Medicine Aug 2017Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec.
METHODS
We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-to-target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-to-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome.
RESULTS
Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P<0.001 for noninferiority). At 24 months, the mean glycated hemoglobin level was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg per deciliter, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 187 patients (4.9%) in the degludec group and in 252 (6.6%) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). Rates of adverse events did not differ between the two groups.
CONCLUSIONS
Among patients with type 2 diabetes at high risk for cardiovascular events, degludec was noninferior to glargine with respect to the incidence of major cardiovascular events. (Funded by Novo Nordisk and others; DEVOTE ClinicalTrials.gov number, NCT01959529 .).
Topics: Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin Glargine; Insulin, Long-Acting; Kaplan-Meier Estimate; Male; Middle Aged
PubMed: 28605603
DOI: 10.1056/NEJMoa1615692 -
Hepatology (Baltimore, Md.) Jun 2019To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and... (Comparative Study)
Comparative Study Randomized Controlled Trial
Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.
To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.
Topics: Adult; Aged; Blood Glucose; Body Weight; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Insulin Glargine; Linear Models; Lipid Metabolism; Liraglutide; Male; Metformin; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Prognosis; Prospective Studies; Sitagliptin Phosphate; Treatment Outcome
PubMed: 30341767
DOI: 10.1002/hep.30320 -
Diabetes Care Jul 2021Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Insulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms.
RESEARCH DESIGN AND METHODS
This was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naive adults ( = 205) with type 2 diabetes and HbA 7-10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80-130 mg/dL; adjustment ±21 units/week; = 51), B (80-130 mg/dL; ±28 units/week; = 51), or C (70-108 mg/dL; ±28 units/week; = 52), or once-daily insulin glargine 100 units/mL (IGlar U100) (80-130 mg/dL; ±4 units/day; = 51), all titrated weekly. Percentage of time in range (TIR) (70-180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring.
RESULTS
TIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15 and 16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference 7.08%-points; 95% CI 2.12 to 12.04; = 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient-year of exposure for icodec titrations A, B, and C and IGlar U100, respectively), with no episodes of severe hypoglycemia.
CONCLUSIONS
Once-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. The results for icodec titration A (80-130 mg/dL; ±21 units/week) displayed the best balance between glycemic control and risk of hypoglycemia.
Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting
PubMed: 33875484
DOI: 10.2337/dc20-2878 -
Diabetes Care Aug 2023Tirzepatide reduces HbA1c and body weight, and creatinine-based estimated glomerular filtration rate (eGFR) decline. Unlike creatine-derived eGFR (eGFR-creatinine),...
OBJECTIVE
Tirzepatide reduces HbA1c and body weight, and creatinine-based estimated glomerular filtration rate (eGFR) decline. Unlike creatine-derived eGFR (eGFR-creatinine), cystatin C-derived eGFR (eGFR-cystatin C) is unaffected by muscle mass changes. We assessed effects of tirzepatide on eGFR-creatinine and eGFR-cystatin C.
RESEARCH DESIGN AND METHODS
Our primary outcome was eGFR change from baseline at 52 weeks with pooled tirzepatide (5, 10, and 15 mg) and titrated insulin glargine in adults with type 2 diabetes and high cardiovascular risk (SURPASS-4).
RESULTS
Least squares mean (SE) eGFR-creatinine (mL/min/1.73 m2) changes from baseline with tirzepatide and insulin glargine were -2.5 (0.38) and -3.9 (0.38) (between-group difference, 1.4 [95% CI 0.3-2.4]) and -3.5 (0.37) and -5.3 (0.37) (between-group difference, 1.8 [95% CI 0.8-2.8]) for eGFR-cystatin C. Baseline, 1-year, and 1-year change from baseline values significantly correlated between eGFR-cystatin C and eGFR-creatinine. Measures of eGFR changes did not correlate with body weight changes.
CONCLUSIONS
Tirzepatide slows the eGFR decline rate, supporting a kidney-protective effect.
Topics: Adult; Humans; Insulin Glargine; Diabetes Mellitus, Type 2; Cystatin C; Creatinine; Glomerular Filtration Rate; Kidney; Body Weight
PubMed: 37267479
DOI: 10.2337/dc23-0261 -
Diabetologia Aug 2023This study compared the frequency of hypoglycaemia, time to hypoglycaemia and recovery from hypoglycaemia after double or triple doses of once-weekly insulin icodec vs... (Randomized Controlled Trial)
Randomized Controlled Trial
Hypoglycaemia frequency and physiological response after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100 in type 2 diabetes: a randomised crossover trial.
AIMS/HYPOTHESIS
This study compared the frequency of hypoglycaemia, time to hypoglycaemia and recovery from hypoglycaemia after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100. Furthermore, the symptomatic and counterregulatory responses to hypoglycaemia were compared between icodec and glargine U100 treatment.
METHODS
In a randomised, single-centre (Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria), open-label, two-period crossover trial, individuals with type 2 diabetes (age 18-72 years, BMI 18.5-37.9 kg/m, HbA ≤75 mmol/mol [≤9.0%]) treated with basal insulin with or without oral glucose-lowering drugs received once-weekly icodec (for 6 weeks) and once-daily glargine U100 (for 11 days). Total weekly doses were equimolar based on individual titration of daily glargine U100 during the run-in period (target fasting plasma glucose [PG]: 4.4-7.2 mmol/l). Randomisation was carried out by assigning a randomisation number to each participant in ascending order, which encoded to one of two treatment sequences via a randomisation list prepared prior to the start of the trial. At steady state, double and triple doses of icodec and glargine U100 were administered followed by hypoglycaemia induction: first, euglycaemia was maintained at 5.5 mmol/l by variable i.v. infusion of glucose; glucose infusion was then terminated, allowing PG to decrease to no less than 2.5 mmol/l (target PG). The PG was maintained for 15 min. Euglycaemia was restored by constant i.v. glucose (5.5 mg kg min). Hypoglycaemic symptoms score (HSS), counterregulatory hormones, vital signs and cognitive function were assessed at predefined PG levels towards the PG.
RESULTS
Hypoglycaemia induction was initiated in 43 and 42 participants after double dose of icodec and glargine U100, respectively, and in 38 and 40 participants after triple doses, respectively. Clinically significant hypoglycaemia, defined as PG <3.0 mmol/l, occurred in comparable proportions of individuals treated with icodec vs glargine U100 after double (17 [39.5%] vs 15 [35.7%]; p=0.63) and triple (20 [52.6%] vs 28 [70.0%]; p=0.14) doses. No statistically significant treatment differences were observed in the time to decline from PG values of 5.5 mmol/l to 3.0 mmol/l (2.9-4.5 h after double dose and 2.2-2.4 h after triple dose of the insulin products). The proportion of participants with PG ≤2.5 mmol/l was comparable between treatments after double dose (2 [4.7%] for icodec vs 3 [7.1%] for glargine U100; p=0.63) but higher for glargine U100 after triple dose (1 [2.6%] vs 10 [25.0%]; p=0.03). Recovery from hypoglycaemia by constant i.v. glucose infusion took <30 min for all treatments. Analyses of the physiological response to hypoglycaemia only included data from participants with PG <3.0 mmol/l and/or the presence of hypoglycaemic symptoms; in total 20 (46.5%) and 19 (45.2%) individuals were included after a double dose of icodec and glargine U100, respectively, and 20 (52.6%) and 29 (72.5%) individuals were included after a triple dose of icodec and glargine U100, respectively. All counterregulatory hormones (glucagon, adrenaline [epinephrine], noradrenaline [norepinephrine], cortisol and growth hormone) increased during hypoglycaemia induction with both insulin products at both doses. Following triple doses, the hormone response was greater with icodec vs glargine U100 for adrenaline at PG (treatment ratio 2.54 [95% CI 1.69, 3.82]; p<0.001), and cortisol at PG (treatment ratio 1.64 [95% CI 1.13, 2.38]; p=0.01) and PG (treatment ratio 1.80 [95% CI 1.09, 2.97]; p=0.02). There were no statistically significant treatment differences in the HSS, vital signs and cognitive function.
CONCLUSIONS/INTERPRETATION
Double or triple doses of once-weekly icodec lead to a similar risk of hypoglycaemia compared with double or triple doses of once-daily glargine U100. During hypoglycaemia, comparable symptomatic and moderately greater endocrine responses are elicited by icodec vs glargine U100.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03945656.
FUNDING
This study was funded by Novo Nordisk A/S.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Insulin Glargine; Diabetes Mellitus, Type 2; Cross-Over Studies; Hydrocortisone; Hypoglycemia; Hypoglycemic Agents; Insulin; Glucose; Epinephrine; Blood Glucose
PubMed: 37308751
DOI: 10.1007/s00125-023-05921-8 -
Diabetes Care Jul 2021Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
OBJECTIVE
Insulin 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 METHODS
This 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 (HbA 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 HbA, adverse events (AEs), and hypoglycemia.
RESULTS
Estimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; = 54), 66.0% (icodec NLD; = 50), and 65.0% (IGlar U100; = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points [95% CI 1.8-13.9]). Mean HbA 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.
CONCLUSIONS
Switching 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.
Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting
PubMed: 33875485
DOI: 10.2337/dc20-2877