A 24-Week, Prospective, Randomized, Open-Label, Treat-To-Target Pilot Study of Obese Type 2 Diabetes Patients with Severe Insulin Resistance to Assess the Addition of Exenatide on the Efficacy of U-500 Regular Insulin Plus Metformin

Distiller, Larry A.; Nortje, Hendrik; Wellmann, Holger; Amod, Aslam; Lombard, Landman

doi:10.4158/ep14067.or

Cited by 14 publications

(18 citation statements)

References 13 publications

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“… 13 The two RCTs of U-500R also had algorithms using U-500R as insulin monotherapy. 15 16 This study is unique in being able to differentiate reduction in HbA1c postindex between those with U-500R use alone (group A; 0.78%) as compared with concomitant U-500R and U-100 therapy (group B; 0.60%) although groups A and B were not statistically different ( table 3 ). U-500R insulin monotherapy may also reduce the risk of dosing errors and confusion that might arise from concomitant use of non-dedicated U-100 insulin syringes or volumetric syringes for U-500R and U-100 insulins.…”

Section: Discussionmentioning

confidence: 94%

“…The overall HbA1c reduction of 0.68% in this cohort is statistically and clinically significant, but is less than that reported in the clinical case series (1.0–3.5% 4 6 7 18–20 ) and from the single RCT (1.0–1.7%). 15 However, this is not surprising since the prior clinical reports were conducted by investigators/institutions with particular clinical experience with use and titration of U-500R over time, thus likely representing more expert use than that captured by the Humedica EHR database for all U-500R use during the study period, within the prespecified study parameters. In addition, mean baseline HbA1c values for this study population were lower (9.1±1.7%) than in the reported case series (weighted mean HbA1c 10.0% 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…Severe hypoglycemia has occasionally been reported in clinical case series 11 19 21 24 with no reports in others 18 27–29 and no severe hypoglycemia in the recent U-500R RCT. 15 One case series (N=53) reported eight episodes of severe hypoglycemia occurring in six patients. 11 Severe hypoglycemia rate was reported as 0.1 episode per patient-year in one case series of U-500R by CSII (20; N=59).…”

Section: Discussionmentioning

confidence: 99%

“… 6 Only one small (N=28) randomized controlled trial (RCT) of U-500R has been published, which reported significant HbA1c reduction (from baseline 9.2% to 7.5% at 24-week end point, p=0.0001) with no reported episodes of severe hypoglycemia when combined with metformin. 15 A larger RCT (N=325) is currently in progress. 16…”

Section: Introductionmentioning

confidence: 99%

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Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study

Eby

Curtis

Gelwicks

et al. 2015

BMJ Open Diab Res Care

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AimDescribe the characteristics of patients initiating human regular U-500 insulin (U-500R) and their subsequent glycemic control in a real-world setting.MethodsUS Humedica electronic health record system data (July 2007–September 2011) were used to identify patients with diabetes aged ≥18 years with ≥1 records for U-500R prescriptions, 6 months of preindex data, 12 months following first use of U-500R, and at least one glycated hemoglobin (HbA1c) value in both preindex and postindex periods. Paired t tests were used to measure the change in HbA1c from preindex to postindex periods (last or most recent values) and hypoglycemia.ResultsAmong patients initiating U-500R (N=445), 96.9% had type 2 diabetes with mean age 57 years and mean body mass index 40.4 kg/m2. Postindex prescriptions were written for U-500R alone (47.0%, group A) and concomitant U-500R/U-100 insulins (53.0%, group B). Concomitant oral antihyperglycemic agents (AHAs) and non-insulin injectable AHAs were used by 43.4% and 14.6% of patients, respectively. Following initiation of U-500R, mean HbA1c improved 0.68% in all patients (p<0.0001 compared with baseline), but the decrease in HbA1c did not differ significantly between groups (A: 0.78%; B: 0.60%). Overall, hypoglycemic events, largely captured in the outpatient setting, increased in incidence from 6.7% to 11.9% (p≤0.0001) and from 0.23 to 0.39 events/patient/year, an increase of 0.16 (p=0.003), from preindex to postindex.ConclusionsThis real-world outcomes analysis demonstrates that U-500R initiation is associated with a clinically meaningful improvement in glycemic control over the subsequent 12-month period with modest increase in incidence and rate of hypoglycemia.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study

Eby

Curtis

Gelwicks

et al. 2015

BMJ Open Diab Res Care

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“…Over 12 weeks of follow-up study the authors reported a 1.4% drop in HbA1c from baseline along with a mean weight loss of 5.1 kg and a 28% decrease in insulin requirement. In another study by Distiller et al (9), exanetide was used with U500 insulin in 9 T2DM patients with suboptimal glycemic control. Interestingly, despite a 21% decrease in insulin requirement in the exanetide-treated patients, no significant decrease in HbA1c was noted in these patients.…”

Section: Discussionmentioning

confidence: 99%

Addition of Dulaglutide for a High-Dose Insulin Requiring Patient with Type 2 Diabetes Mellitus: A Remarkable Response

Kazim¹,

Trivedi²

2019

AACE Clinical Case Reports

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Objective: Despite the availability of several new classes of antidiabetic medications, a large proportion of patients with diabetes mellitus fail to achieve optimal glycemic control. Adding glucagon-like peptide-1 receptor agonists (GLP1 RAs) to basal insulin regimens has shown to improve glycemic control in type 2 diabetes mellitus (T2DM). Methods: We present a patient with T2DM who had marked improvement in glycemic control accompanied by weight loss and a decrease in insulin requirement after adding weekly dulaglutide to U500 regular insulin. Results: A 56-year-old man with T2DM, class III obesity (weight 314 pounds, body mass index 46.4 kg/m 2), and hyperlipidemia had uncontrolled glycemia with a hemoglobin A1c (HbA1c) of 9.7% (83 mmol/mol) despite using high-dose insulin therapy and metformin. Physical examination was unremarkable except for obesity. His HbA1c remained high despite increments in insulin dosage up to 400 units per day. A few months after adding dulaglutide to his regimen, the patient's HbA1c declined to 6.3% (45 mmol/mol) despite significant reduction in daily insulin dosage to 20 units (94% decrease), which was accompanied by a 20-pound weight loss. Conclusion: The patient had a dramatic decrease in HbA1c, weight, and insulin requirement after treatment with dulaglutide. In the literature we could only find 1 study where a GLP1 RA (liraglutide) was successfully used in 15 patients receiving U500 insulin (average dose 197 ± 72 units/day). However, their reductions in weight and HbA1c were markedly less than observed in our patient. GLP1 RAs should be considered in patients with T2DM who require high-dose insulin therapy. (AACE Clinical Case Rep. 2019;5:e142-e145) Abbreviations: AWARD-9 = study of dulaglutide (LY2189265) in participants with type II diabetes; DM = diabetes mellitus; GLP1 RA = glucagon-like peptide-1 receptor agonist; HbA1c = hemoglobin A1c; T2DM = type 2 diabetes mellitus

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A retrospective review of insulin requirements in patients using U-500 insulin hospitalized to a Veterans Affairs Hospital

Kedia

Desouza²,

Smith

et al. 2017

Journal of Diabetes and its Complications

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A 24-Week, Prospective, Randomized, Open-Label, Treat-To-Target Pilot Study of Obese Type 2 Diabetes Patients with Severe Insulin Resistance to Assess the Addition of Exenatide on the Efficacy of U-500 Regular Insulin Plus Metformin

Cited by 14 publications

References 13 publications

Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study

Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study

Addition of Dulaglutide for a High-Dose Insulin Requiring Patient with Type 2 Diabetes Mellitus: A Remarkable Response

A retrospective review of insulin requirements in patients using U-500 insulin hospitalized to a Veterans Affairs Hospital

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