Canagliflozin for the Treatment of Diabetic Kidney Disease and Implications for Clinical Practice: A Narrative Review

Type 2 diabetes mellitus (T2DM) affects millions of people worldwide, elevating their risk of developing a range of complications, including chronic kidney disease (CKD). People with T2DM and CKD (i.e., diabetic kidney disease, DKD) have an increased risk of progressing to end-stage kidney disease (ESKD), experiencing cardiovascular complications, and premature death. Despite this, DKD is primarily addressed through management of risk factors, and there are few pharmaceutical treatments capable of reversing or delaying disease progression. Canagliflozin is a sodium glucose co-transporter 2 inhibitor that was initially developed as a blood glucose-lowering agent for people with T2DM. Evidence from clinical trials of canagliflozin in people with T2DM, as well as evidence from cardiovascular outcomes trials in people with T2DM and high cardiovascular risk, provided preliminary evidence suggesting that it may also have beneficial renal effects. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was a dedicated renal outcomes trial of canagliflozin that assessed its renal effects in people with DKD. Overall, the CREDENCE trial demonstrated that canagliflozin improves renal outcomes and slows early disease progression in people with DKD. These data supported the approval of canagliflozin for the treatment DKD, the first new treatment in almost 20 years; therefore, it is important for clinicians to understand how to implement this treatment in their clinical practice

Cardiovascular risks in type 2 diabetes and the interpretation of cardiovascular outcome trials

Background: Patients with type 2 diabetes (T2D) are at increased cardiovascular (CV) risk compared to subjects without diabetes, with some data estimating that CV disease (CVD) risk is doubled in these individuals. Additionally, CVD remains the leading cause of death in patients with T2D, so it is paramount to determine the relationship between these two diseases. Purpose: Older diabetes treatments have limited CV safety data. In 2008, the US Food and Drug Administration published guidance for manufacturers on antihyperglycemic agents, requiring studies to ensure CV safety of new therapies. Since then, manufacturers of many newer agents have conducted and published results from CV outcomes trials (CVOTs), with more trials due to publish soon. This review discusses the relationship between CVD and T2D and explores findings from the latest CVOTs of glucose-lowering agents to guide nurse practitioners in their prescribing patterns for patients with T2D. Conclusion: Patients with T2D are at high risk of CVD, so CV risk should be carefully considered when managing these patients, and CV risks and benefits of antidiabetic drugs should be included in prescribing decisions

Hypoglycemia After Administration of Somatostatin Analog (SMS 201-995) in Metastatic Carcinoid

SMS 201-995 (Sandoz Pharmaceuticals. East Hanover NJ) is a synthetic peptide analog of native somatostatin that has been used to relieve .symptoms caused by neuroendocrine tumors. Reports have described an insulin suppressive effect of SMS 201-995 that results in elevations of blood glucose. We report a patient with a metastatic small bowel carcinoid and renal failure in whom mild symptomatic hypoglycemia occurred 30 to 60 minutes after SMS 201-995 administration. No increase in insulin or decreases in glucagon. Cortisol, or catecholamines were observed during these hypoglycemic episodes. Elevated levels of growth hormone fell gradually following SMS 201-995 administration and did not temporally correspond to the 30- to 60-minute nadir of blood glucose. However SMS 201-995 levels peaked during this 30- to 60-minute period. As clinical experience with this drug broadens, patients whose glucose control is dependent on counter-regulatory hormones should be monitored for the possibility of hypoglycemia

Experience with Biosynthetic Human Insulin in Diabetes

Thirty diabetic patients new to insulin were entered in an open label prospective study of biosynthetic human insulin (BHI). All patients experienced symptomatic control of diabetes attributable to dietary and BHI insulin therapy. Detailed six-month evaluation data were reviewed in 19 patients. A significant drop in fasting plasma glucose and glycosylated hemoglobin was noted at two months, and a further modest decrease occurred at six months. E. coli polypeptide antibodies were unchanged from baseline at six months, indicating that no bacterial protein contamination of BHI occurred. Percent binding of serum antibodies to human insulin measured in 19 patients at baseline and at six months showed a statistically significant increase in mean value without accompanying clinical symptoms. Clinical hypoglycemia did not differ from that seen in patients who received animal insulin. Biosynthetic human insulin appears comparable in clinical efficacy and safety to purified pork insulin. Ongoing studies will be required to determine whether BHI is less immunogenic than purified pork insulin

Real-world evidence supporting Tandem Control-IQ hybrid closed-loop success in the Medicare and Medicaid type 1 and type 2 diabetes populations

BACKGROUND: The Tandem Control-IQ (CIQ) system has demonstrated significant glycemic improvements in large randomized controlled and real-world trials. Use of this system is lower in people with type 1 diabetes (T1D) government-sponsored insurance and those with type 2 diabetes (T2D). This analysis aimed to evaluate the performance of CIQ in these groups. METHODS AND MATERIALS: A retrospective analysis of CIQ users was performed. Users age ≥6 years with a t:slim X2 Pump and >30 days of continuous glucose monitoring (CGM) data pre-CIQ and >30 days post-CIQ technology initiation were included. RESULTS: A total of 4243 Medicare and 1332 Medicaid CIQ users were analyzed among whom 5075 had T1D and 500 had T2D. After starting CIQ, the Medicare beneficiaries group saw significant improvement in time in target range 70–180 mg/dL (TIR; 64% vs. 74%; P < 0.0001), glucose management index (GMI; 7.3% vs. 7.0%; P < 0.0001), and the percentage of users meeting American Diabetes Association (ADA) CGM Glucometrics Guidelines (12.8% vs. 26.3%; P < 0.0001). The Medicaid group also saw significant improvement in TIR (46% vs. 60%; P < 0.0001), GMI (7.9% vs. 7.5%; P < 0.0001), and percentage meeting ADA guidelines (5.7% vs. 13.4%; P < 0.0001). Patients with T2D and either insurance saw significant glycemic improvements. CONCLUSIONS: The CIQ system was effective in the Medicare and Medicaid groups in improving glycemic control. The T2D subgroup also demonstrated improved glycemic control with CIQ use. Glucometrics achieved in this analysis are comparable with those seen in previous randomized controlled clinical trials with the CIQ system

Lost in translation: A disconnect between the science and Medicare coverage criteria for continuous subcutaneous insulin infusion

Numerous studies have demonstrated the clinical value and safety of insulin pump therapy in type 1 diabetes and type 2 diabetes populations. However, the eligibility criteria for insulin pump coverage required by the Centers for Medicare & Medicaid Services (CMS) discount conclusive evidence that supports insulin pump use in diabetes populations that are currently deemed ineligible. This article discusses the limitations and inconsistencies of the insulin pump eligibility criteria relative to current scientific evidence and proposes workable solutions to address this issue and improve the safety and care of all individuals with diabetes

Comparison of a Novel Insulin Bolus-Patch with Pen/Syringe Injection to Deliver Mealtime Insulin for Efficacy, Preference, and Quality of Life in Adults with Diabetes: A Randomized, Crossover, Multicenter Study

Objective: This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. Research Design and Methods: Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). Results: Using bolus-patch, MDBG (mean•SE) was equivalent to that using pen/syringe (8.61+/-0.28 vs. 9.02+/-0.26-mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18+/-0.18 vs. 3.63+/-0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2+/-1.7 vs. 40.3+/-1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). Conclusions: Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90477/1/dia-2E2011-2E0047.pd

Flash glucose monitoring in type 2 diabetes managed with basal insulin in the USA: a retrospective real-world chart review study and meta-analysis.

INTRODUCTION: Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. RESEARCH DESIGN AND METHODS: Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. RESULTS: Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p CONCLUSIONS: In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology

Design and Psychometrics for New Measures of Health-Related Quality of Life in Adults with Type 1 Diabetes: Type 1 Diabetes and Life (T1DAL)

AIMS: To use a three-phase process to develop and validate new self-report measures of diabetes-specific health-related quality of life (HRQOL) for adults with type 1 diabetes. We report on four versions of the Type 1 Diabetes and Life (T1DAL) measure for people age 18-25, 26-45, 46-60, and over 60 years. METHODS: We first conducted qualitative interviews to guide measure creation, then piloted the draft measures. We evaluated psychometric properties at six T1D Exchange Clinic Network sites via completion of T1DAL and validated measures of related constructs. Participants completed the T1DAL again in 4-6 weeks. We used psychometric data to reduce each measure to 23-27 items in length. Finally, we obtained participant feedback on the final measures. RESULTS: The T1DAL-Adult measures demonstrated good internal consistency (α=0.85-0.88) and test-retest reliability (r=0.77-0.87). Significant correlations with measures of general quality of life, generic and diabetes-specific HRQOL, diabetes burden, self-management, and glycemic control demonstrated validity. Factor analyses yielded 4-5 subscales per measure. Participants were satisfied with the final measures and reported they took 5-10 minutes to complete. CONCLUSIONS: The strong psychometric properties of the newly developed self-report T1DAL measures for adults with type 1 diabetes make them appropriate for use in clinical research and care