Aim: This trial assessed the outcomes on glucose control of the implantable Eversense real-time continuous glucose monitoring (CGM) system compared to self-monitoring of blood glucose or ...intermittently scanned CGM in patients with type 1 or type 2 diabetes (T1D or T2D).Patients and methods: This was a randomized (2:1), prospective, national, multicenter study. All participants, aged >18, on multiple daily insulin injections or insulin pump had a sensor inserted, activated only in the enabled group. Included patients had T1D or T2D with an HbA1c level >8% (cohort 1) or T1D with a time below range <70 mg/dL (TBR<70 ) >1.5 hour/day during the previous 28 days (cohort 2). The primary outcomes were the HbA1c change at D180 (cohort 1) or the change in TBR<54 during the period D90-D120 (cohort 2). A covariance model (ANCOVA) was used for endpoint analyses.Results: Overall, 149 patients were included in cohort 1 and 90 in cohort 2. In cohort 1, the adjusted mean 95%CI difference (enabled-control) in HbA1c at D180 was -0.1% -0.4; 0.1, p=0.341. No significant difference in time in range (TIR70-180 ) or time above range (TAR>180 ) was observed. In cohort 2, the mean adjusted difference in TBR<54 was -1.6% -3.1; -0.1, p=0.039 during D90-D120 and remained at -2.6%, -4.5; -0.6, p=0.011 during D150-D180 (pre-specified secondary outcome). There was no safety issue.Conclusion: This study shows that the Eversense CGM system can significantly decrease TBR<54 in patients with T1D prone to hypoglycemia.
Phase 3 trials have not compared oral semaglutide, a glucagon-like peptide 1 receptor agonist, with other classes of glucose-lowering therapy.
To compare efficacy and assess long-term adverse event ...profiles of once-daily oral semaglutide vs sitagliptin, 100 mg added on to metformin with or without sulfonylurea, in patients with type 2 diabetes.
Randomized, double-blind, double-dummy, parallel-group, phase 3a trial conducted at 206 sites in 14 countries over 78 weeks from February 2016 to March 2018. Of 2463 patients screened, 1864 adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea were randomized.
Patients were randomized to receive once-daily oral semaglutide, 3 mg (n = 466), 7 mg (n = 466), or 14 mg (n = 465), or sitagliptin, 100 mg (n = 467). Semaglutide was initiated at 3 mg/d and escalated every 4 weeks, first to 7 mg/d then to 14 mg/d, until the randomized dosage was achieved.
The primary end point was change in glycated hemoglobin (HbA1c), and the key secondary end point was change in body weight, both from baseline to week 26. Both were assessed at weeks 52 and 78 as additional secondary end points. End points were tested for noninferiority with respect to HbA1c (noninferiority margin, 0.3%) prior to testing for superiority of HbA1c and body weight.
Among 1864 patients randomized (mean age, 58 SD, 10 years; mean baseline HbA1c, 8.3% SD, 0.9%; mean body mass index, 32.5 SD, 6.4; n=879 47.2% women), 1758 (94.3%) completed the trial and 298 prematurely discontinued treatment (16.7% for semaglutide, 3 mg/d; 15.0% for semaglutide, 7 mg/d; 19.1% for semaglutide, 14 mg/d; and 13.1% for sitagliptin). Semaglutide, 7 and 14 mg/d, compared with sitagliptin, significantly reduced HbA1c (differences, -0.3% 95% CI, -0.4% to -0.1% and -0.5% 95% CI, -0.6% to -0.4%, respectively; P < .001 for both) and body weight (differences, -1.6 kg 95% CI, -2.0 to -1.1 kg and -2.5 kg 95% CI, -3.0 to -2.0 kg, respectively; P < .001 for both) from baseline to week 26. Noninferiority of semaglutide, 3 mg/d, with respect to HbA1c was not demonstrated. Week 78 reductions in both end points were statistically significantly greater with semaglutide, 14 mg/d, vs sitagliptin.
Among adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide, 7 mg/d and 14 mg/d, compared with sitagliptin, resulted in significantly greater reductions in HbA1c over 26 weeks, but there was no significant benefit with the 3-mg/d dosage. Further research is needed to assess effectiveness in a clinical setting.
ClinicalTrials.gov Identifier: NCT02607865.
To evaluate efficacy and safety of LixiLan (iGlarLixi), a novel titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide (Lixi), compared with both components, iGlar and Lixi, ...given separately in type 2 diabetes inadequately controlled on metformin with or without a second oral glucose-lowering drug.
After a 4-week run-in to optimize metformin and stop other oral antidiabetic drugs, participants (N = 1,170, mean diabetes duration ∼8.8 years, BMI ∼31.7 kg/m
) were randomly assigned to open-label once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum insulin dose of 60 units/day, or to once-daily Lixi (20 μg/day) while continuing with metformin. The primary outcome was HbA
change at 30 weeks.
Greater reductions in HbA
from baseline (8.1% 65 mmol/mol) were achieved with iGlarLixi compared with iGlar and Lixi (-1.6%, -1.3%, -0.9%, respectively), reaching mean final HbA
levels of 6.5% (48 mmol/mol) for iGlarLixi versus 6.8% (51 mmol/mol) and 7.3% (56 mmol/mol) for iGlar and Lixi, respectively (both P < 0.0001). More subjects reached target HbA
<7% with iGlarLixi (74%) versus iGlar (59%) or Lixi (33%) (P < 0.0001 for all). Mean body weight decreased with iGlarLixi (-0.3 kg) and Lixi (-2.3 kg) and increased with iGlar (+1.1 kg, difference 1.4 kg, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was similar with iGlarLixi and iGlar (1.4 and 1.2 events/patient-year) and lower with Lixi (0.3 events/patient-year). iGlarLixi improved postprandial glycemic control versus iGlar and demonstrated considerably fewer nausea (9.6%) and vomiting (3.2%) events than Lixi (24% and 6.4%, respectively).
iGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA
reductions, close to near normoglycemia without increases in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal adverse effects compared with Lixi.
Aim
To investigate the association between routine use of dipeptidyl peptidase‐4 (DPP‐4) inhibitors and the severity of coronavirus disease 2019 (COVID‐19) infection in patient with type 2 diabetes ...in a large multicentric study.
Materials and Methods
This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID‐19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP‐4 inhibitors users vs. non‐users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW).
Results
Five hundred and ninety‐six participants were under DPP‐4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non‐users of DPP‐4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW‐adjusted models showed no significant association between the use of DPP‐4 inhibitors and the primary outcome by Day 7 (OR 95% CI: 0.95 0.77–1.17) or Day 28 (OR 95% CI: 0.96 0.78–1.17). Similar neutral findings were found between use of DPP‐4 inhibitors and the risk of tracheal intubation and death.
Conclusions
These data support the safety of DPP‐4 inhibitors for diabetes management during the COVID‐19 pandemic and they should not be discontinued.
The efficacy and safety of IDegLira has been established in the DUAL clinical development program. This post-hoc analysis evaluated glycemic control in the subgroup of patients titrated to the ...maximum approved IDegLira dose of 50 units (U) (50 U insulin degludec + 1.8 mg liraglutide), from trials that evaluated IDegLira vs. other comparators (DUAL I-V and VII). In all DUAL trials, baseline A1C was similar between IDegLira and comparator arms. In DUAL I-V, regardless of end-of-trial (EOT) doses (50 or <50 U), more patients on IDegLira achieved the American Diabetes Association target of A1C <7% vs. monotherapy of basal insulin, glucagon-like peptide-1 receptor agonist or placebo comparators (Figure). In DUAL VII, compared with basal-bolus insulin therapy (insulin glargine 100 U/mL + insulin aspart ≤4 times daily mean total daily insulin dose of 84 U at EOT), the percentage of patients achieving an A1C <7% was greater for patients on <50 U of IDegLira and lower for patients at 50 U of IDegLira at EOT.
For patients at 50 U and <50 U of IDegLira, the mean change in A1C at EOT was numerically greater than or similar to comparators for all trials.
In conclusion, a high proportion of patients receiving the maximum approved dose of IDegLira are able to achieve good glycemic control.
Disclosure
L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Sanofi US, Novo Nordisk Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Other Relationship; Self; American Diabetes Association. S. Linjawi: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, Sanofi. Research Support; Self; Novo Nordisk A/S, Boehringer Ingelheim GmbH, AstraZeneca, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc.. Speaker's Bureau; Self; Novo Nordisk A/S, Eli Lilly and Company, Sanofi. P. Serusclat: Board Member; Self; Novo Nordisk A/S, Medtronic, Abbott. Research Support; Self; Novo Nordisk A/S, Eli Lilly and Company, Sanofi. T. Vilsbøll: Advisory Panel; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Consultant; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Speaker's Bureau; Self; Amgen Inc., Boehringer Ingelheim GmbH, Eli Lilly and Company, AstraZeneca, MSD K.K., Sanofi, Novo Nordisk A/S. Research Support; Self; Eli Lilly and Company, Novo Nordisk A/S. B.F. Agner: Employee; Self; Novo Nordisk A/S. T. Hansen: Employee; Self; Novo Nordisk A/S. L.A. Leiter: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier. Research Support; Self; Servier. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Amgen Inc., Esperion Therapeutics, Kowa Pharmaceuticals America, Inc., The Medicines Company. Advisory Panel; Self; Akcea Therapeutics, Novartis Pharmaceuticals Corporation.
Hyperglycemia exacerbates the progression of chronic kidney disease (CKD), but most glucose-lowering therapies do not address morbidities associated with CKD. Sodium/glucose cotransporter 2 (SGLT2) ...inhibitors offer potential benefits to patients with diabetes and CKD, but their effectiveness may be diminished with decreased kidney function. We aimed to evaluate the safety and effectiveness of bexagliflozin, a novel SGLT2 inhibitor, in patients with type 2 diabetes and CKD.
Phase 3, double-blind, placebo-controlled, multicenter, multinational, randomized trial.
54 sites across 4 countries. Patients with CKD stage 3a or 3b, type 2 diabetes mellitus, and hemoglobin A1c level of 7.0% to 10.5% and estimated glomerular filtration rate (eGFR) of 30 to 59mL/min/1.73m2 who were taking oral hypoglycemic agents for 8 weeks.
Bexagliflozin, 20mg, daily versus placebo for 24 weeks.
Primary outcome was change in percent hemoglobin A1c from baseline to week 24. Secondary end points included changes in body weight, systolic blood pressure, albuminuria, and hemoglobin A1c level stratified by CKD stage.
312 patients across 54 sites were analyzed. Bexagliflozin lowered hemoglobin A1c levels by 0.37% (95% CI, 0.20%-0.54%); P<0.001 compared to placebo. Patients with CKD stages 3a (eGFR, 45-<60mL/min/1.73m2) and 3b (eGFR, 30-<45mL/min/1.73m2) experienced reductions in hemoglobin A1c levels of 0.31% (P=0.007) and 0.43% (P=0.002), respectively. Bexagliflozin decreased body weight (1.61kg; P<0.001), systolic blood pressure (3.8mm Hg; P=0.02), fasting plasma glucose level (0.76mmol/L; P=0.003), and albuminuria (geometric mean ratio reduction of 20.1%; P=0.03). Urinary tract infection and genital mycotic infections were more common in the bexagliflozin group; otherwise, frequencies of adverse events were comparable between groups.
Not designed to evaluate the impact of treatment on long-term kidney disease and cardiovascular outcomes.
Bexagliflozin reduces hemoglobin A1c levels in patients with diabetes and stage 3a/3b CKD and appears to be well tolerated. Additional observed benefits included reductions in body weight, systolic blood pressure, and albuminuria.
Trial was sponsored by Theracos Sub, LLC.
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