Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes.

INTRODUCTION: We compared the efficacy and safety of human regular insulin (HRI) versus rapid-acting insulin (RAI) in a type 2 diabetes population already using the V-Go insulin delivery device. RESEARCH DESIGN AND METHODS: This was a 14-week, multicenter, randomized, open-label, parallel-group, phase IV, non-inferiority study. Patients ≥21years of age, with inadequately controlled type 2 diabetes who were currently using the V-Go insulin delivery system with RAI, with glycated hemoglobin (HbA1c) ≥6.5% (≥48 mmol/L) to ≤12.5% (≤108 mmol/L) were randomized 1:1 to RAI continuation or switch to HRI. The primary outcome was estimated treatment difference (ETD) in HbA1c least-squares mean change from baseline at 14 weeks (prespecified non-inferiority hypothesis with 95% CI upper limit <0.4%). Primary analysis was by per protocol (PP); safety analysis was by intention to treat. RESULTS: We randomized 136 patients to continued RAI treatment (n=67) or HRI (n=69); 113 patients were included in the PP analysis (RAI, n=54; HRI, n=59). Mean change in HbA1c from baseline to study end was -0.60±1.1% (95% CI -0.90 to -0.29); -6.6±12.0 mmol/mol (95% CI -9.8 to -3.2) with HRI treatment and -0.38±1.3% (95% CI -0.70 to -0.05); -4.2±14.2 mmol/mol (95% CI -7.7 to -0.5) with RAI treatment, with ETD of -0.22% (95% CI -0.67 to 0.22); -2.4 mmol/mol (95% CI -7.3 to 2.4), p=0.007, confirming non-inferiority of HRI to RAI. No between-group differences in changes in total daily insulin doses, number of hypoglycemic values (≤70 mg/dL (≤39 mmol/L) or body weight were observed. No severe hypoglycemic events were reported. Direct pharmacy cost savings (-US$265.85; 95% CI -US$288.60 to -US$243.11; p<0.0001) were observed with HRI treatment. CONCLUSIONS: Individuals with type 2 diabetes requiring insulin can be treated with V-Go wearable insulin delivery device using HRI, safely and effectively, and potentially at a much lower cost compared with RAI, which can lead to improved access to insulin therapy for these individuals. TRIAL REGISTRATION NUMBER: NCT03495908.

EFFICACY AND SAFETY OF IGLARLIXI IN HISPANICS AND NON-HISPANIC WHITES WITH TYPE 2 DIABETES.

Objective: Type 2 diabetes (T2D) is more common in Hispanic than non-Hispanic white (NHW) populations worldwide, and ethnicity, among other factors, may affect response to therapy. The efficacy and safety of insulin glargine 100 units/mL (iGlar) and the fixed-ratio combination of iGlar and the glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi) was assessed in Hispanic and NHW patients with T2D from 25 countries. Methods: In this post hoc analysis, data from two 30-week randomized controlled trials comparing iGlar and iGlarLixi in patients with T2D uncontrolled on basal insulin ± oral antidiabetes drugs (OADs; LixiLan-L: NCT02058160) or uncontrolled on metformin ± OADs (LixiLan-O: NCT02058147) were evaluated. Results: Of the 1,512 patients included across trials, 301 were Hispanic and 1,211 NHW. Compared with iGlar, iGlarLixi resulted in greater reductions in glycated hemoglobin (A1C) and 2-hour postprandial glucose and a higher proportion of patients at target A1C <7.0% (<53 mmol/mol), regardless of ethnicity. Among NHWs from the LixiLan-L trial, documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL) rates were higher with iGlar compared with iGlarLixi (P = .06), whereas this trend was reversed among Hispanics (P = .07). Nevertheless, in both trials, a greater proportion of patients taking iGlarLixi than iGlar reached the composite efficacy endpoints of target A1C without hypoglycemia and target A1C without weight gain, regardless of ethnicity. Conclusion: These results indicate that iGlarLixi is a viable therapeutic option for both Hispanic and NHW patients with T2D, as it is efficacious without a significant increase in hypoglycemia, irrespective of ethnicity. Abbreviations: A1C = glycated hemoglobin; BMI = body mass index; FPG = fasting plasma glucose; FRC = fixed-ratio combination; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HDL-C = high-density-lipoprotein cholesterol; iGlar = insulin glargine; iGlarLixi = insulin glargine + lixisenatide; LDL-C = low-density-lipoprotein cholesterol; NHW = non-Hispanic white; OAD = oral antidiabetes drug; PPG = postprandial glucose; T2D = type 2 diabetes.

Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Basal insulins.

In healthy humans, the timing and amount of insulin release are exquisitely tied to the body's metabolic demands. Insulin is released at a relatively constant rate over 24 hours to meet the body's basal metabolic needs. In addition, insulin is released in short bursts in response to nutrient intake, as well as in response to changes in peripheral utilization, sensitivity, and endogenous production.To approximate this physiologic state, 2 general types of insulin formulations have been developed. Basal insulins are intended to address the body's basal metabolic needs over 24 hours, and prandial (or bolus) insulins to address the rapid rise in blood glucose in the postprandial state. The quest for a basal insulin with a constant physiologic effect over 24 hours has been challenging, in part because the subcutaneous route of administration remains the most practical, yet physiologically unnatural route for administering insulin.

CARDIOVASCULAR OUTCOME TRIALS OF THE INCRETIN-BASED THERAPIES: WHAT DO WE KNOW SO FAR?

OBJECTIVE: Diabetes is a well-established pro-inflammatory state with an increased risk for cardiovascular (CV) diseases. In recent years, the number of different classes of agents for the treatment of type 2 diabetes has increased substantially, and while glycemic control is the major focus of these medications, CV safety has become of interest. Two incretin-based therapies are currently available: glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: The literature was reviewed for information regarding the incretin-based therapies and their effects on the CV system. RESULTS: Independent of their glucose-lowering action, incretin-based therapies may have incretin-dependent mechanisms that positively affect blood pressure, weight, and other markers of CV disease risk, and, in the case of DPP-4 inhibition, nonincretin-dependent actions such as improving endothelial function. Several CV outcomes trials (CVOTs) with incretin-based therapies have recently completed with no excess CV risk observed, and positive effects have been reported in at least 1 trial of GLP-1 RAs, with more studies ongoing. Results for the risk for heart failure with DPP-4 inhibitor use are mixed, but no increase has been demonstrated with GLP-1 RAs. CONCLUSION: Future CVOTs will need to be redesigned to help address these questions in the context of the emerging scope of the underlying mechanisms of cardio-metabolic disease in populations with diabetes. ABBREVIATIONS: A1C = hemoglobin A1C ACS = acute coronary syndrome CHD = coronary heart disease CI = confidence interval CV = cardiovascular CVOT = Cardiovascular Outcome Trial DPP-4 = dipeptidyl peptidase 4 FDA = U.S. Food and Drug Administration GIP = glucose-dependent insulinotropic polypeptide GLP-1 = glucagon-like protein 1 GLP-1 RA = glucagon-like protein 1 receptor agonist HF = heart failure HR = hazard ratio LVEF = left ventricular ejection fraction MACE = major adverse cardiovascular events MI = myocardial infarction T2D = type 2 diabetes.

Type 1 diabetes treatment beyond insulin: role of GLP-1 analogs.

OBJECTIVE: To observe the efficacy and safety of glucagonlike peptide-1 (GLP-1) analogs in type 1 diabetes in a real-life medical practice setting. METHODS: We performed a retrospective chart review of patients with type 1 diabetes initiated on a GLP-1 analog and with at least one follow-up visit at more than 4 weeks. RESULTS: We identified 11 patients who were initiated on a GLP-1 analog and had a follow-up visit between 4 and 13 weeks (mean (SD) follow-up 10 ± 3 weeks; age 36.5 ± 16.4 years; duration of diabetes 17.3 ± 9.3 years; all on insulin pump therapy; all started on liraglutide). Seven of these patients had a second follow-up visit at approximately 20 weeks. By 10 weeks, there was a significant decrease in weight (4.2% of total body weight), total daily insulin dose (19.2%, of which 14.0% basal and 24.1% bolus), and mean (SD) insulin units/kg (0.57 [0.17] to 0.48 [0.17] units/kg). Hemoglobin A1c was significantly decreased (7.4 [0.7%] to 7.0 [0.7%], P = 0.02) without an increase in hypoglycemia. These effects were sustained at 20 weeks. Nausea was a common adverse effect and lead to drug discontinuation in 4 of 11 patients. CONCLUSIONS: Patients with long-standing type 1 diabetes can achieve weight loss and improved glycemic control on less insulin without an increase in hypoglycemia when liraglutide is added to insulin therapy.

New-onset diabetes after renal transplantation.

Transplantation medicine has grown to be an important element of medical practice, and with the development of modern immunosuppression agents and protocols, the occurrence of diabetes as renal transplantation is recognized as one of the metabolic consequences of therapy with these agents. New-onset diabetes after transplantation can be defined as diabetes mellitus developing in any patient without history of diabetes before transplantation, who has sustained hyperglycemia that meets the current diagnostic criteria by the American Diabetes Association or by the World Health Organization. New-onset diabetes after transplantation has been associated with the following risk factors: age, non-white ethnicity, hepatitis C infection, glucocorticoid therapy for rejection, and chronic immunosuppression with cyclosporine and tacrolimus. The observation that current immunosuppression using tacrolimus is one of the most important single risk factor for the development of new-onset diabetes after transplantation has been made. The pathophysiology of this condition resembles that of type 2 diabetes mellitus. There is conclusive evidence that pretransplantation end-stage renal disease is an insulin-resistant state, and after transplantation, glucocorticoids induce further peripheral insulin insensitivity. The "second hit" seems to be an acquired (yet reversible) insulin secretion defect caused by the calcineurin inhibitors cyclosporine but more pronounced with tacrolimus. Future directions include pretransplantation and posttransplantation testing using glucose measurements and other techniques to identify high-risk individuals and possibly develop treatment strategies aimed to modify insulin resistance as well as to preserve beta cell function.

Post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) is defined as sustained hyperglycemia developing in any patient without history of diabetes before transplantation, that meets the current diagnostic criteria by the American Diabetes Association or the World Health Organization. Several risk factors have been identified: age, nonwhite ethnicity, and glucocorticoid therapy for rejection and chronic immunosuppression with cyclosporine and especially tacrolimus. The pathophysiology of this condition resembles that of type 2 diabetes mellitus: pretransplantation end-stage liver/renal and heart disease are insulin-resistant states, and after transplantation, glucocorticoids induce further peripheral insulin insensitivity. The "second hit" appears to be an acquired (yet reversible) insulin secretion defect resulting from the calcineurin inhibitors cyclosporine and tacrolimus. An international panel of experts has recently published the proceeding of a Consensus Conference proposing strategies for the screening, prevention and management of PTDM. Future directions include pre- and post-transplantation glucose load testing for high-risk individuals and pharmacological agents to decrease insulin resistance and to preserve beta-cell function.

Use of an insulin pen by homeless patients with diabetes mellitus.

PURPOSE: To assess the impact of an insulin delivery system, the NovoPen, on diabetes treatment for the homeless. DATA SOURCES: Homeless patients (n = 23) with diabetes and using insulin were identified from a registry of patients with diabetes maintained at the Homeless Outreach Medical Services clinical sites. Baseline evaluations included glycosylated hemoglobin (HbA1c) measurements and a questionnaire about the patient's current treatment practices. Patients were instructed in the use of the NovoPen; HbA1c measurements and questionnaires were repeated after 3 and 6 months of participation. CONCLUSIONS: Reductions of HbA1c were observed at 3 and 6 months. The authors concluded that use of the pen improved patient compliance and thus glycemic control. IMPLICATIONS FOR PRACTICE: Patients had improved quality of life after using the pen to administer insulin. Nurse practitioners should recognize quality of life issues when treating patients with chronic diseases. Nurse practitioners who care for homeless diabetes patients can promote better care for this population by educating homeless shelter staff about diabetes and its management.