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1. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. (PubMed)

Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy.To assess the effects of insulin monotherapy compared (...) with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control.We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of articles. The date of the last search was November 2015 for all databases.Randomised controlled clinical trials of at least

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2016 Cochrane

2. Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. (PubMed)

Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. The use of short-acting insulin analogues (insulin lispro, insulin aspart, insulin glulisine) for adult, non-pregnant people with type 2 diabetes is still controversial, as reflected in many scientific debates.To assess the effects of short-acting insulin analogues compared to regular human insulin in adult, non-pregnant people with type 2 diabetes mellitus.For this update (...) we searched CENTRAL, MEDLINE, Embase, the WHO ICTRP Search Portal, and ClinicalTrials.gov to 31 October 2018. We placed no restrictions on the language of publication.We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues to regular human insulin in the treatment of people with type 2 diabetes, who were not pregnant.Two review authors independently extracted data and assessed the risk of bias. We assessed

2018 Cochrane

3. Insulin in a Pill: Barriers to Development of Oral Insulin

Insulin in a Pill: Barriers to Development of Oral Insulin Insulin in a Pill: Barriers to Development of Oral Insulin – Clinical Correlations Search Insulin in a Pill: Barriers to Development of Oral Insulin May 8, 2018 4 min read By Nicolas Gillingham Peer Reviewed Over 30 million Americans—9.4% of the population—live with diabetes, .[1] Insulin can be self-administered by subcutaneous injection, either classically via a syringe, an insulin pen, or using an insulin pump. However, patients (...) with diabetes report that these daily injections can feel particularly burdensome, not to mention stigmatizing, when compared to oral medications like metformin, .[2] What if our patients could take their insulin in a capsule alongside their morning metformin? Such a formulation would eliminate a significant barrier to medication adherence and would also better mimic the physiology of endogenous insulin. Endogenous and exogenous insulin take different paths to the liver, which affects how they influence

2018 Clinical Correlations

4. A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial

A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial A cluster randomised trial, cost-effectiveness analysis (...) and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial Heller S, White D, Lee E, Lawton J, Pollard D, Waugh N, Amiel S, Barnard K, Beckwith A, Brennan A, Campbell M, Cooper C, Dimairo M, Dixon S, Elliott J, Evans M, Green F, Hackney G, Hammond P, Hallowell N, Jaap A, Kennon B, Kirkham J, Lindsay R, Mansell P, Papaioannou D, Rankin D, Royle P, Smithson WH & Taylor C Record Status

2017 Health Technology Assessment (HTA) Database.

5. Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus. (PubMed)

Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus. Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates.To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes.We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non (...) -Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015).We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were

2016 Cochrane

6. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. (PubMed)

Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Diabetes results in a rise in blood glucose above normal physiological levels; if untreated this may cause damage to many systems including the cardiovascular and renal systems. Pregnancy increases resistance to insulin action; for those women who have pre-gestational diabetes, this results in an increasing insulin requirement. There are several methods of administering insulin (...) . Conventionally, insulin has been administered subcutaneously, formally referred to as intensive conventional treatment, but now more usually referred to as multiple daily injections (MDI). An alternative method of insulin administration is the continuous subcutaneous insulin infusion pump (CSII).To compare CSII with MDI of insulin for pregnant women with pre-existing and gestational diabetes.We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016) and reference lists

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2016 Cochrane

7. LEVEMIR (insulin detemir), long-acting human insulin analogue

LEVEMIR (insulin detemir), long-acting human insulin analogue Haute Autorité de Santé - LEVEMIR (insuline détémir), analogue de l’insuline humaine d’action lente Développer la qualité dans le champ sanitaire, social et médico-social Recherche Évaluation & Recommandation La HAS Accréditation & Certification Outils, Guides & Méthodes Agenda Avis sur les Médicaments LEVEMIR (insuline détémir), analogue de l’insuline humaine d’action lente Substance active (DCI) insuline détémir DIABETOLOGIE (...) - Nouvelle indication Nature de la demande Extension d'indication Avis de la CT du 21 septembre 2016 Pas d’avantage clinique démontré par rapport à TRESIBA dans la prise en charge du diabète de type 1 de l’enfant âgé de 1 an à 2 ans LEVEMIR a désormais l’AMM dans le diabète de type 1 chez l’enfant dès l’âge de 1 an. Les données cliniques d’efficacité disponibles chez l’enfant entre 1 et 2 ans, sont limitées à une étude de non infériorité versus insuline dégludec portant sur un effectif de 350 enfants

2017 Haute Autorite de sante

8. Fast-acting insulin aspart versus insulin aspart in the setting of insulin degludec-treated type 1 diabetes: Efficacy and safety from a randomized double-blind trial

Fast-acting insulin aspart versus insulin aspart in the setting of insulin degludec-treated type 1 diabetes: Efficacy and safety from a randomized double-blind trial To evaluate the efficacy and safety of mealtime or post-meal fast-acting insulin aspart (faster aspart) vs mealtime insulin aspart (IAsp), both in combination with insulin degludec, in participants with type 1 diabetes (T1D).This multicentre, treat-to-target trial (Clinical trial registry: NCT02500706, ClinicalTrials.gov (...) hypoglycaemia was seen 3 to 4 hours after meals with mealtime faster aspart.Mealtime and post-meal faster aspart in conjunction with insulin degludec provided effective glycaemic control compared with IAsp, with no increased safety risk. Mealtime faster aspart provided PPG control superior to that of IAsp.© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

2018 EvidenceUpdates

9. More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial

More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial To compare insulin glargine 300 units/mL (Gla-300) versus insulin degludec 100 units/mL (IDeg-100) in this first head-to-head randomized controlled trial.BRIGHT (NCT02738151) was a multicenter, open-label, active-controlled, two-arm, parallel-group, 24-week, noninferiority study in insulin-naive patients (...) mean difference -0.05% (95% CI -0.15 to 0.05) (-0.6 mmol/mol [-1.7 to 0.6])-demonstrating noninferiority of Gla-300 versus IDeg-100 (P < 0.0001). Hypoglycemia incidence and event rates over 24 weeks were comparable with both insulins, whereas during the active titration period (0-12 weeks) the incidence and rate of anytime (24-h) confirmed hypoglycemia (≤70 and <54 mg/dL) were lower with Gla-300. Both insulins were properly titrated and exhibited no specific safety concerns.Gla-300 and IDeg-100

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2018 EvidenceUpdates

10. Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial. (PubMed)

Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial. Insulin therapy is most effective if dosage titrations are done regularly and frequently, which is seldom practical for most clinicians, resulting in an insulin titration gap. The d-Nav Insulin Guidance System (Hygieia, Livonia, MI, USA) is a handheld device that is used to measure glucose, determine glucose patterns, and automatically determine (...) the appropriate next insulin dose. We aimed to determine whether the combination of the d-Nav device and health-care professional support is superior to health-care professional support alone.In this multicentre, randomised, controlled study, we recruited patients from three diabetes centres in the USA (in Detroit MI; Minneapolis, MN; and Des Moines IA). Patients were eligible if they were aged 21-70 years, diagnosed with type 2 diabetes with a glycated haemoglobin (HbA1c) concentration of 7·5% or higher (≥58

2019 Lancet

11. A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5)

A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5) To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) vs insulin aspart (IAsp) used in continuous subcutaneous insulin infusion (CSII) in participants with type 1 diabetes (T1D).This was a double-blind, treat-to-target, randomized, 16-week trial investigating CSII treatment with faster

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2019 EvidenceUpdates

12. Weight loss in patients with type 2 diabetes (T2D) mellitus receiving once-weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: An AWARD-4 post-hoc analysis across baseline body mass index subgroups. (PubMed)

Weight loss in patients with type 2 diabetes (T2D) mellitus receiving once-weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: An AWARD-4 post-hoc analysis across baseline body mass index subgroups. Insulin-treated patients with type 2 diabetes (T2D) and obesity are challenged in achieving body weight stability or reduction, in addition to glycaemic control. Post-hoc analyses of body weight and insulin dose data from the AWARD-4 trial involved comparison of treatment (...) with once-weekly dulaglutide 1.5 mg (N = 295) or 0.75 mg (N = 293) and treatment with daily insulin glargine (N = 296), each with prandial insulin lispro (± metformin).Changes in weight and in the proportion of patients without weight gain or with weight loss of at least 3%, 5% or 10% or composites of HbA1c less than 7% without weight gain and weight loss of at least 3% after 52 weeks were compared between the dulaglutide (either dose) groups and the insulin glargine group, overall and by baseline BMI

2019 obesity & metabolism

13. Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report. (PubMed)

Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report. Insulin injection, especially with insulin analogs, occasionally induces the production of insulin antibodies with high binding capacity and low affinity, similar to the insulin autoantibodies characteristic of insulin autoimmune syndrome (IAS). Production of these "IAS-like" insulin antibodies causes marked glycemic fluctuations (...) with postprandial hyperglycemia and fasting hypoglycemia.A 66-year-old man with a 27-year history of diabetes was admitted because of marked glycemic fluctuations. Human insulin treatment had been initiated at age 56, followed by multiple daily injections of insulin analogs 5 years later. After the initial year of insulin analog treatment, the patient began to experience frequent morning hypoglycemic attacks and day-time hyperglycemia. Marked hyperinsulinemia (4500 μU/mL) and high titers of insulin antibodies

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2019 BMC Endocrine Disorders

14. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. (PubMed)

Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. To confirm non-inferiority of insulin degludec/insulin aspart (IDegAsp) once-daily (OD) versus insulin glargine (IGlar) U100 OD + insulin aspart (IAsp) OD for HbA1c after 26 weeks, and compare efficacy and safety between groups at W26 + W38.A 38-week, randomised, open

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2019 Diabetes research and clinical practice

15. [The efficacy and safety of insulin degludec versus insulin glargine in insulin-naive subjects with type 2 diabetes: results of a Chinese cohort from a multinational randomized controlled trial]. (PubMed)

[The efficacy and safety of insulin degludec versus insulin glargine in insulin-naive subjects with type 2 diabetes: results of a Chinese cohort from a multinational randomized controlled trial]. Objective: To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM). Methods: This was a 26-week, randomized, open-label, parallel-group, treat-to-target trial in 560 Chinese subjects with T2DM (men/women (...) )]. No differences in other safety parameters were found between the two groups. Conclusions: IDeg was non-inferior to IGlar in terms of glycaemic control, and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia. IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment. Clinical trail registration: Clinicaltrials.gov, NCT01849289.

2019 Zhonghua nei ke za zhi

16. Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis)

Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis) In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (...) (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously

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2017 EvidenceUpdates

17. Insulin Bolus Administration in Insulin Pump Therapy: Effect of Bolus Delivery Speed on Insulin Absorption from Subcutaneous Tissue. (PubMed)

Insulin Bolus Administration in Insulin Pump Therapy: Effect of Bolus Delivery Speed on Insulin Absorption from Subcutaneous Tissue. This study assessed subcutaneous absorption kinetics of rapid-acting insulin administered as a bolus using bolus delivery speeds commonly employed in commercially available insulin pumps (i.e., 2 and 40 s for delivering 1 insulin unit).Twenty C-peptide-negative type 1 diabetic subjects were studied on two occasions, separated by at least 7 days, using (...) the euglycemic clamp procedure. After an overnight fast, subjects were given, in random order, a subcutaneous insulin bolus (15 U of insulin lispro, Eli Lilly) either for 30 s using an Animas IR2020 pump (fast bolus delivery) or for 10 min using a Medtronic Minimed Paradigm 512 pump (slow bolus delivery).Fast bolus delivery resulted in an earlier onset of insulin action as compared with slow bolus delivery (21.0 ± 2.5 vs. 34.3 ± 2.7 min; P < 0.002). Furthermore, time to reach maximum insulin effect was found

2019 Diabetes technology & therapeutics

18. Use of non-insulin diabetes medicines after insulin initiation: A retrospective cohort study. (PubMed)

Use of non-insulin diabetes medicines after insulin initiation: A retrospective cohort study. Clinical guidelines recommend that metformin be continued after insulin is initiated among patients with type 2 diabetes, yet little is known regarding how often metformin or other non-insulin diabetes medications are continued in this setting.We conducted a retrospective cohort study to characterize rates and use patterns of six classes of non-insulin diabetes medications: biguanides (metformin (...) ), sulfonylureas, thiazolidinediones (TZDs), glucagon-like peptide 1 receptor agonists (GLP1 receptor agonists), dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors), and sodium-glucose co-transporter inhibitors (SGLT2 inhibitors), among patients with type 2 diabetes initiating insulin. We used the 2010-2015 MarketScan Commercial Claims and Encounters data examining 72,971 patients with type 2 diabetes aged 18-65 years old who initiated insulin and had filled a prescription for a non-insulin diabetes medication

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2019 PLoS ONE

19. Effect of Bolus Insulin Administration Followed by a Continuous Insulin Infusion on Diabetic Ketoacidosis Management. (PubMed)

Effect of Bolus Insulin Administration Followed by a Continuous Insulin Infusion on Diabetic Ketoacidosis Management. Despite the high incidence of diabetic ketoacidosis (DKA) there is no consensus on the most appropriate way to manage insulin therapy. This study was conducted to evaluate the effect of an insulin bolus on the resolution of DKA. A retrospective chart review of patients admitted between 1 September 2014 and 30 June 2016 with a diagnosis of DKA was conducted. Patients were (...) assigned to the bolus or no bolus group based on provider preference. All patients were initiated on a 0.1 unit/kilogram (kg)/hour (h) intravenous (IV) regular insulin infusion, and patients in the bolus group were treated with a 0.1 unit/kg IV regular insulin bolus. Of the 145 admissions evaluated, 58 received a bolus and 87 did not. There was no difference in baseline demographics, except baseline blood glucose was higher in the bolus group (653 vs. 591 milligrams (mg)/deciliter (dL), p = 0.04

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2018 Pharmacy (Basel, Switzerland)

20. Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment (PubMed)

Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment Despite the consensus that neuro-inflammation and insulin resistance (IR) are two hallmarks of Alzheimer disease (AD), the molecular mechanisms responsible for the development of IR remain uncharacterized. MAPKs are signaling molecules that are implicated in the pathology of AD and have a role in IR development. Given that inflammatory mediators (...) are shown to interfere with insulin signaling pathway in different cell types, the present work aimed to investigate whether neuro-inflammation induced memory loss is associated with hippocampal IR and whether insulin treatment protects against this IR. Subsequently, possible roles of MAPKs in this situation were investigated. Male Wistar rats were cannulated, and LPS (15 µg, day 0), insulin (3 mU) or saline (vehicle) were administered intra-cerebroventricularly (ICV) (days 1-6). Spatial memory

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2018 EXCLI journal

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