Estimated Changes in Insulin Prices and Discounts After Entry of New Insulin Products, 2012-2019.

Importance: Despite the political salience of insulin prices, no study to date has quantified trends in insulin prices that account for manufacturer discounts (net prices). Objective: To describe trends in insulin list prices and net prices faced by payers from 2012 to 2019 and estimate changes in net prices after the 2015 to 2017 entry of new insulin products. Design, Setting, and Participants: This longitudinal study included an analysis of Medicare, Medicaid, and SSR Health drug pricing data from January 1, 2012, to December 31, 2019. Data analyses were performed from June 1, 2022, to October 31, 2022. Exposures: US sales of insulin products. Main Outcomes and Measures: Net prices faced by payers were estimated for insulin products as list prices minus manufacturer discounts negotiated in commercial and Medicare Part D markets (ie, commercial discounts). Trends in net prices were evaluated before and after the entry of new insulin products. Results: Net prices of long-acting insulin products increased at an annual rate of 23.6% from 2012 to 2014 but decreased at an annual rate of 8.3% after the introduction of insulin glargine (Toujeo and Basaglar) and degludec (Tresiba) in 2015. Net prices of short-acting insulin increased at an annual rate of 5.6% from 2012 to 2017 but then decreased from 2018 to 2019 after the introduction of insulin aspart (Fiasp) and lispro (Admelog). For human insulin products, which did not experience entry of new products, net prices increased at an annual rate of 9.2% from 2012 to 2019. From 2012 to 2019, commercial discounts increased from 22.7% to 64.8% for long-acting insulin products, from 37.9% to 66.1% for short-acting insulin products, and from 54.9% to 63.1% for human insulin products. Conclusions and Relevance: In this longitudinal study of US insulin products, results suggest that insulin prices substantially increased from 2012 to 2015, even after accounting for discounts. The introduction of new insulin products was followed by substantial discounting practices that lowered net prices faced by payers.

Associations between clinical and psychosocial factors and HbA1c in adult insulin pump users with type 1 diabetes.

AIMS: Many adults with type 1 diabetes do not achieve recommended glycemic goals despite intensive insulin therapy using insulin pumps. The aim of this study was to explore associations between clinical and psychosocial factors and HbA1c in insulin pump users to identify and prioritize areas for potential intervention. METHODS: A questionnaire-based survey covering clinical and psychosocial aspects of life with type 1 diabetes was distributed to all adult (≥ 18 years) insulin pump users in the Capital Region of Denmark. Responses were combined with data from medical records and national registries. Associations with HbA1c were modeled using regression-based machine learning. RESULTS: Of 1,591 invited individuals, 770 (48.4%) responded to the survey. Mean HbA1c among responders was 7.3% (56 mmol/mmol), and 35.6% had an HbA1c < 7.0% (53 mmol/mol). Six factors were significantly associated with HbA1c: diabetes duration (0.006% (0.1 mmol/mol) lower HbA1c per 1-year increase in diabetes duration); education (0.4% (4.3 mmol/mol) lower HbA1c with long higher education vs. primary school); insulin type (0.2% (2.2 mmol/mol) lower HbA1c with ultra-rapid-acting insulin vs. rapid-acting insulin); hypoglycemia awareness status (0.2% (2.2 mmol/mol) lower HbA1c with complete unawareness vs. full awareness); insulin device satisfaction (0.2% (2.7 mmol/mol) lower HbA1c per 1-point increase in Insulin Device Satisfaction Survey score); and diabetes distress (0.3% (3.1 mmol/mol) higher HbA1c per 1-point increase in Type 1 Diabetes Distress Scale score). CONCLUSIONS: This study identified several associations between clinical and psychosocial factors and HbA1c that may be considered when developing interventions targeted people with type 1 diabetes.

Prescription Pattern of Glucose-lowering Drugs in Patients with Controlled Type 2 Diabetes Mellitus Attending Dhaka Medical College Hospital.

The increasing number of patients with diabetes mellitus imposes an enormous burden on both the healthcare authorities and healthcare providers. The study's objective was to explore the prescription pattern of glucose-lowering drugs for patients with controlled type 2 Diabetes Mellitus (T2DM) attending a tertiary hospital in Bangladesh. This cross-sectional study was conducted at the Endocrinology Outpatient Department of Dhaka Medical College Hospital, Dhaka, Bangladesh, for one year (February 2017 to January 2018). A total of 120 patients aged >12 years with T2DM were included in the study. Prescription analysis and demographic data were collected and recorded in the pre-designed case record form. Among the 120 prescriptions, the number of drugs prescribed per encounter ranged from 1 to 4. Oral drugs were prescribed most frequently (n=88, 73.3%), followed by different preparations of insulin; both (oral and insulin) were prescribed in 13.3% (n=16) of cases. Single drugs were used in 76.7% (n=92) of patients, whereas combined fixed-dose formulation and both types of formulation (single drug and combined fixed dose) were used in 17.5% and 5.8%, respectively. Of all, Metformin was the single most common (67.5%; n=81) drug prescribed by the physicians, followed by Gliclazide (n=19, 15.84%), Glibenclamide (n=14, 11.67%), and short-acting insulin (n=14, 11.67%). Besides, the overall drug use pattern in prescription showed most frequently used drugs were Metformin + Sulphonylureas (21.7%), Metformin (19.2%), Metformin + DPP-4 inhibitors (14.2%), Insulins (13.3%), DPP-4 inhibitors (9.2%) and Metformin + Insulin (9.2%) with a small share of other drugs. Moreover, short-acting insulin was used more commonly (n=14, 11.67%) than other formulations of insulin: long-acting insulin (n=13, 10.83%), premixed insulin (n=12, 10%), intermediate-acting insulin (n=5, 4.16%) and ultra short-acting insulin (n=2, 1.67%).

Mass Casualty Incident Involving Rapid Acting Insulin.

We report on an unusual prehospital incident involving the inadvertent administration of short-acting insulin among a group of high school students. Sixteen students iatrogenically received 10 units of insulin lispro intradermally instead of tuberculin purified protein derivative (PPD), resulting in several students experiencing symptomatic hypoglycemia. A mass casualty incident was declared and the local poison center consulted. An incident command system, with the support of on-scene EMS physicians, was established to track, treat, and transport the involved patients.

Glucagon Prescribing and Costs Among U.S. Adults With Diabetes, 2011-2021.

OBJECTIVE: To characterize contemporary trends in glucagon fill rates and expenditures in a nationwide cohort of adults with diabetes overall and by key demographic and clinical characteristics. RESEARCH DESIGN AND METHODS: In this retrospective cohort study, we examined 1) glucagon fill rates per 1,000 person-years and 2) patient out-of-pocket and health plan costs per filled glucagon dose among adults with diabetes included in OptumLabs Data Warehouse between 1 January 2011 and 31 March 2021. RESULTS: The study population comprised 2,814,464 adults with diabetes with a mean age of 62.8 (SD 13.2) years. The overall glucagon fill rate decreased from 2.91 to 2.28 per 1,000 person-years (-22%) over the study period. In groups at high risk for severe hypoglycemia, glucagon fill rates increased from 22.46 to 36.76 per 1,000 person-years (64%) among patients with type 1 diabetes, 11.64 to 16.63 per 1,000 person-years (43%) among those treated with short-acting insulin, and 16.08 to 20.12 per 1,000 person-years (25%) among those with a history of severe hypoglycemia. White patients, women, individuals with high income, and commercially insured patients had higher glucagon fill rates compared with minority patients, males, individuals with low income, and Medicare Advantage patients, respectively. Total cost per dosing unit increased from $157.97 to $275.32 (74%) among commercial insurance beneficiaries and from $150.37 to $293.57 (95%) among Medicare Advantage beneficiaries. CONCLUSIONS: Glucagon fill rates are concerningly low and declined between 2011 and 2021 but increased in appropriate subgroups with type 1 diabetes, using short-acting insulin, or with a history of severe hypoglycemia. Fill rates were disproportionately low among minority patients and individuals with low income.

Costs and Outcomes Comparison of Diabetes Technology Usage Among People With Type 1 or 2 Diabetes Using Rapid-Acting Insulin.

BACKGROUND: Does initiation of a continuous glucose monitor (CGM) or insulin pump lower health care utilization and/or costs? METHODS: Distinct cohorts of people with type 1 diabetes (T1D) or type 2 diabetes (T2D) using a blood glucose monitor (BGM), CGM, pump, or CGM with pump were identified from a large claims database. Patients ≥40 years old with 12 months of continuous enrollment before and after the device start date qualified for the study. Outcomes included one-year medical utilization and costs (minus device) for events such as hospitalizations and office visits. Generalized linear models were fitted, controlling for numerous baseline covariates. The Holm method corrected for the multiplicity of hypotheses tested. RESULTS: Of the 8235 total patients, the BGM control group was the largest, had the lowest percentage of patients with T1D, and was significantly different from the device groups in most baseline categories. Formally, only two comparisons were statistically significant: Compared with BGM, the pump cohort had greater adjusted first-year total medical and office visit costs. Other secondary outcomes such as days hospitalized, emergency department visits and labs, favored pump. Most endpoints were favorable for CGM. Results for CGM with pump generally were intermediate between CGM and pump alone. CONCLUSIONS: During a one-year follow-up, unadjusted medical costs of both CGM and pump appear lower than BGM, but multivariable modeling yielded adjusted savings only for CGM use. Economic benefits might be observable sooner for CGMs than for pumps. Generalized linear models fitted to health care utilization event rates produced favorable results for both CGM and pump.

iGlarLixi versus basal plus Rapid-Acting insulin in adults with type 2 diabetes advancing from basal insulin therapy: The SoliSimplify Real-World study.

AIM: For people with suboptimally controlled type 2 diabetes (T2D) on basal insulin (BI), guidelines recommend several treatment advancement options. This study compared the clinical effectiveness of once-daily iGlarLixi versus a multiple-injection BI + rapid acting insulin (RAI) regimen in adults with T2D advancing from BI therapy in real-world clinical practice. MATERIALS AND METHODS: Electronic medical records from the Observational Medical Outcomes Partnership (OMOP) database were analysed retrospectively using propensity score matching to compare therapy advancement with iGlarLixi or BI + RAI in US adults ≥18 years with T2D on BI who had ≥1 valid glycated haemoglobin (HbA1c) value at baseline and at the 6-month follow-up. The primary objective was non-inferiority of iGlarLixi to BI + RAI in HbA1c change from baseline to 6 months (margin 0.3%). RESULTS: Propensity score matching generated cohorts with balanced baseline characteristics (N = 814 in each group). HbA1c reduction from baseline to 6 months with iGlarLixi was non-inferior to BI + RAI [mean difference (95% confidence interval): 0.1 (-0.1, 0.2)%; one-sided p = .0032]. At 6 months, weight gain was significantly lower with iGlarLixi than with BI + RAI [-0.8 (-1.3, -0.2) kg; two-sided p = .0069]. Achievement of HbA1c <7% without hypoglycaemia and weight gain were similar between groups [odds ratio (95% confidence interval): 1.15 (0.81, 1.63); p = .4280]. Hypoglycaemia was low in both groups, probably because of underreporting. CONCLUSIONS: In real-world clinical practice, glycaemic outcomes 6 months after treatment advancement from BI are similar for people with T2D using iGlarLixi versus BI + RAI, with iGlarLixi leading to less weight gain.

Predicting Blood Glucose Concentration after Short-Acting Insulin Injection Using Discontinuous Injection Records.

Diabetes is an increasingly common disease that poses an immense challenge to public health. Hyperglycemia is also a common complication in clinical patients in the intensive care unit, increasing the rate of infection and mortality. The accurate and real-time prediction of blood glucose concentrations after each short-acting insulin injection has great clinical significance and is the basis of all intelligent blood glucose control systems. Most previous prediction methods require long-term continuous blood glucose records from specific patients to train the prediction models, resulting in these methods not being used in clinical practice. In this study, we construct 13 deep neural networks with different architectures to atomically predict blood glucose concentrations after arbitrary independent insulin injections without requiring continuous historical records of any patient. Using our proposed models, the best root mean square error of the prediction results reaches 15.82 mg/dL, and 99.5% of the predictions are clinically acceptable, which is more accurate than previously proposed blood glucose prediction methods. Through the re-validation of the models, we demonstrate the clinical practicability and universal accuracy of our proposed prediction method.

Efficacy and safety of ultra-rapid insulin analogues in insulin pumps in patients with Type 1 Diabetes Mellitus: A systematic review and meta-analysis.

AIMS: To assess the efficacy and safety of ultra-rapid insulin analogues used with continuous subcutaneous insulin infusion systems (CSII) in adults with type 1 diabetes (T1DM). METHODS: We searched MEDLINE and Cochrane Library up to May 2022 for randomized controlled trials comparing ultra-rapid with rapid-acting insulin analogues (RAIAs) used with CSII. We performed random effects meta-analyses for % of 24-h time in range of 70-180 mg/dl (TIR), time in hypoglycaemia (<70 mg/dl) and hyperglycaemia (>180 mg/dl), 1- and 2-hour post-prandial glucose [PPG] increment after a meal test, HbA1c and average insulin dose at endpoint, unplanned infusion set changes and severe hypoglycaemia. RESULTS: Nine studies (1,156 participants) were included. Ultra-rapid insulins were superior to RAIAs on TIR (mean difference [MD] 1.1 %, 95 % CI 0.11-2.11), time spent in hypoglycaemia (MD -0.47 %, 95 % CI -0.63 to -30), and 1- and 2-hour PPG (MD -12.20 mg/dl, 95 % CI -19.85 to -4.54 and MD -17.61 mg/dl, 95 % CI -28.55 to -6.66, respectively). Ultra-rapid insulins increased odds of unplanned infusion set changes (odds ratio 1.60, 95 % CI 1.26-2.03). CONCLUSION: Ultra-rapid acting insulins provided better PPG control compared to RAIAs but their use might result in more infusion set changes.

Availability and affordability of essential medicines and diagnostic tests for diabetes mellitus in Africa.

OBJECTIVE: To investigate the current status of the availability and affordability of specific essential medicines and diagnostics for diabetes in Africa. METHODS: Systematic review and meta-analysis. Studies conducted in Africa that reported any information on the availability and affordability of short-acting, intermediate-acting, and premixed insulin, glibenclamide, metformin, blood glucose, glycated haemoglobin or HbA1c, and lipid profile tests were included. Random-effect model meta-analysis and descriptive statistics were performed to determine the pooled availability and affordability, respectively. RESULTS: A total of 21 studies were included. The pooled availability of each drug was as follows: short-acting insulin 33.5% (95% CI: 17.8%-49.2%, I2  = 95.02%), intermediate-acting insulin 23.1% (95% CI: 6.3%-39.9%, I2  = 91.6%), premixed insulin 49.4% (95% CI: 24.9%-73.9%, I2  = 90.57%), glibenclamide 55.9% (95% CI: 43.8%-68.0%, I2  = 96.7%), and metformin 47.0% (95% CI: 34.6%-59.4%, I2  = 97.54%). Regarding diagnostic tests, for glucometers the pooled availability was 49.5% (95% CI: 37.9%-61.1%, I2  = 97.43%), for HbA1c 24.6% (95% CI: 3.1%-46.1%, I2  = 91.64), and for lipid profile tests 35.7% (95% CI: 19.4%-51.9%, I2  = 83.77%). The median (IQR) affordability in days' wages was 7 (4.7-7.5) for short-acting insulin, 4.4 (3.9-4.9) for intermediate-acting insulin, 7.1 (5.8-16.7) for premixed insulin, 0.7 (0.7-0.7) for glibenclamide, and 2.1 (1.8-2.8) for metformin. CONCLUSION: The availability of the five essential medicines and three diagnostic tests for diabetes in Africa is suboptimal. The relatively high cost of insulin, HbA1c, and lipid profile tests is a significant barrier to optimal diabetes care. Pragmatic country-specific strategies are urgently needed to address these inequities in access and cost.

Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan.

BACKGROUND: The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy. METHODS: Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study. RESULTS: Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period. CONCLUSION: Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

Impact Of Prepregnancy Overweight And Obesity On Treatment Modality And Pregnancy Outcome In Women With Gestational Diabetes Mellitus.

Background: We aim to evaluate the impact of prepregnancy overweight on treatment modalities of Gestational Diabetes Mellitus (GDM). We assessed the association of increased pregravid Body Mass Index (BMI) with dosing of basal and rapid acting insulin as well as pregnancy outcome. Methods: We included 509 gestational diabetic women (normal weight: 200, overweight: 157, obese: 152), attending the pregnancy outpatient clinic at the Department of Obstetrics and Gynecology, Medical University of Vienna, in this retrospective study. We used a prospectively compiled database to assess patient characteristics, treatment approaches - particularly maximum doses of basal and rapid acting insulin or metformin - and pregnancy outcome. Results: Increased BMI was associated with the need of glucose lowering medication (odds ratio (OR): 1.08 for the increase of 1 kg/m² BMI, 95%CI 1.05-1.11, p<0.001). Mothers with pregestational obesity received the highest amount of insulin. Metformin was more often used in patients with obesity who also required higher daily doses. Maternal BMI was associated with increased risk of cesarean section (OR 1.04, 95%CI 1.01-1.07, p<0.001) and delivering large for gestational age offspring (OR 1.09, 95%CI 1.04-1.13, p<0.001). Birthweight percentiles were highest in patients with obesity who required glucose lowering therapy. Conclusions: Treatment modalities and outcome in GDM pregnancies are closely related to the extent of maternal BMI. Patients with obesity required glucose lowering medication more often and were at higher risk of adverse pregnancy outcomes. It is crucial to further explore the underlying pathophysiologic mechanisms to optimize clinical management and individual treatment approaches.

Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site.

OBJECTIVE: Ultra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the injection site dynamics of dye-labeled insulin lispro in the Humalog® and Lyumjev® formulations using the murine ear cutaneous model and correlated it with results from unlabeled insulin lispro in pig subcutaneous injection model. METHODS: We employed dual-wavelength optical-resolution photoacoustic microscopy to study the absorption and diffusion of the near-infrared dye-labeled insulin lispro in the Humalog and Lyumjev formulations in mouse ears. We mathematically modeled the experimental data to calculate the absorption rate constants and diffusion coefficients. We studied the pharmacokinetics of the unlabeled insulin lispro in both the Humalog and Lyumjev formulations as well as a formulation lacking both the zinc and phenolic preservative in pigs. The association state of insulin lispro in each of the formulations was characterized using SV-AUC and NMR spectroscopy. RESULTS: Through experiments using murine and swine models, we show that the hexamer dissociation rate of insulin lispro is not the absorption rate-limiting step. We demonstrated that the excipients in the Lyumjev formulation produce local tissue expansion and speed both insulin diffusion and microvascular absorption. We also show that the diffusion of insulin lispro at the injection site drives its initial absorption; however, the rate at which the insulin lispro crosses the blood vessels is its overall absorption rate-limiting step. CONCLUSIONS: This study provides insights into injection site dynamics of insulin lispro and the impact of formulation excipients. It also demonstrates photoacoustic microscopy as a promising tool for studying protein therapeutics. The results from this study address critical questions around the subcutaneous behavior of insulin lispro and the formulation excipients, which could be useful to make faster and better controlled insulin formulations in the future.

Assessment of insulin adherence in diabetic outpatients: An observational study.

OBJECTIVES: In the management of diabetic patients on insulin therapy, adherence to medication is a key element for avoiding chronic complications. The purpose of this study was to evaluate diabetic patients' ability to translate glycemic results into an appropriate insulin dose and thus, adherence to insulins. METHODS: This was an observational, retrospective, monocentric pilot study. Diabetic patients on insulin therapy being followed at the metabolic and endocrine diseases department were divided into two groups depending on their mode of glycemic control at home: capillary glycemia (Notebook group) or interstitial glycemia using the FreeStyle Libre® flash system (FSL group). Adherence was assessed based on the rate of compliance in adapting insulin doses to the prescribed protocols (depending on type of insulin, glycemic targets, and patients' characteristics) by a pharmacy resident and a senior diabetologist. Good adherence was defined as a minimum rate of 80% of conforming insulin injections for each patient. RESULTS: A total of 50 patients were included, 35 in the Notebook group and 15 in the FSL group. Two-thirds of patients were non-adherent to insulin. Dose adjustment errors mainly concerned rapid-acting insulin with 51.1% of non- conformities, 10.0% of which were due to underdosing in the Notebook group and 21.7% to overdosing in the FSL group. Hyperglycemia was predominant in both populations with a median time in range of 19.0% in the FSL group and well below recommendations (>70%). CONCLUSIONS: Despite the use of increasingly efficient, easy-to-use devices in diabetes monitoring, insulin non-adherence and glycemic imbalance are unresolved major issues. Diabetic patients require reinforced medical follow-up for optimal insulin management.

Application of Machine Learning to Assess Interindividual Variability in Rapid-Acting Insulin Responses After Subcutaneous Injection in People With Type 1 Diabetes.

OBJECTIVES: Circulating insulin concentrations mediate vascular-inflammatory and prothrombotic factors. However, it is unknown whether interindividual differences in circulating insulin levels are associated with different inflammatory and prothrombotic profiles in type 1 diabetes (T1D). We applied an unsupervised machine-learning approach to determine whether interindividual differences in rapid-acting insulin levels associate with parameters of vascular health in patients with T1D. METHODS: We re-analyzed baseline pretreatment meal-tolerance test data from 2 randomized controlled trials in which 32 patients consumed a mixed-macronutrient meal and self-administered a single dose of rapid-acting insulin individualized by carbohydrate counting. Postprandial serum insulin, tumour necrosis factor (TNF)-alpha, plasma fibrinogen, human tissue factor (HTF) activity and plasminogen activator inhibitor-1 (PAI-1) were measured. Two-step clustering categorized individuals based on shared clinical characteristics. For analyses, insulin pharmacokinetic summary statistics were normalized, allowing standardized intraindividual comparisons. RESULTS: Despite standardization of insulin dose, individuals exhibited marked interpersonal variability in peak insulin concentrations (48.63%), time to peak (64.95%) and insulin incremental area under the curve (60.34%). Two clusters were computed: cluster 1 (n=14), representing increased serum insulin concentrations; and cluster 2 (n=18), representing reduced serum insulin concentrations (cluster 1: 389.50±177.10 pmol/L/IU h-1; cluster 2: 164.29±41.91 pmol/L/IU h-1; p<0.001). Cluster 2 was characterized by increased levels of fibrinogen, PAI-1, TNF-alpha and HTF activity; higher glycated hemoglobin; increased body mass index; lower estimated glucose disposal rate (increased insulin resistance); older age; and longer diabetes duration (p<0.05 for all analyses). CONCLUSIONS: Reduced serum insulin concentrations are associated with insulin resistance and a prothrombotic milieu in individuals with T1D, and therefore may be a marker of adverse vascular outcome.

What is the value of faster acting prandial insulin? Focus on ultra rapid lispro.

Rapid-acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra-rapid-acting insulins, including ultra-rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head-to-head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

Adjustment of Anti-Hyperglycaemic Agents During Bowel Preparation for Colonoscopy in Patients with Diabetes.

OBJECTIVE: Due to the growing diabetes pandemic, the number of colonoscopies performed in patients with diabetes is steadily rising. However, recommendations on adjustments of anti-hyperglycaemic agents (AHG) during bowel preparation for colonoscopy are limited. METHODS: A total of nine articles were revealed on a PubMed search using the search terms "diabetes" and "colonoscopy", "sigmoidoscopy", "endoscopy", "endoscopic intervention", "endoscopic invasive diagnostics", "endoscopic surgery", or "diabetes care in the hospital" and manual screening of the references of the articles reporting on AHG adjustment during bowel preparation. RESULTS: Regular glucose measurements and the opportunity to contact the diabetes team were commonly advised. Recommendations also agreed that all oral AHG and short-acting insulin should be omitted when patients are on clear fluids. Recent studies suggest discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors even three days before the colonoscopy. In contrast, recommendations differed regarding adjustment of basal insulin depending on diabetes type and time point in relation to the intervention. CONCLUSIONS: While discontinuation of oral AHG and short-acting insulin during bowel preparation for colonoscopy is generally accepted, recommendations on the adaptation of basal insulin follow different approaches.

Sliding scale insulin use in a national cohort study of nursing home residents with type 2 diabetes.

BACKGROUND: Guidelines discourage sliding scale insulin (SSI) use after the first week of a nursing home (NH) admission. We sought to determine the prevalence of SSI and identify factors associated with stopping SSI or transitioning to another short-acting insulin regimen. METHODS: In an observational study from October 1, 2013, to June 30, 2017 of non-hospice Veterans Affairs NH residents with type 2 diabetes and an NH admission over 1 week, we compared the weekly prevalence of SSI versus two other short-acting insulin regimens - fixed dose insulin (FDI) or correction dose insulin (CDI, defined as variable SSI given alongside fixed doses of insulin) - from week 2 to week 12 of admission. Among those on SSI in week 2, we examined factors associated with stopping SSI or transitioning to other regimens by week 5. Factors included demographics (e.g., age, sex, race/ethnicity), frailty-related factors (e.g., comorbidities, cognitive impairment, functional impairment), and diabetes-related factors (e.g., HbA1c, long-acting insulin use, hyperglycemia, and hypoglycemia). RESULTS: In week 2, 21% of our cohort was on SSI, 8% was on FDI, and 7% was on CDI. SSI was the most common regimen in frail subgroups (e.g., 18% of our cohort with moderate-severe cognitive impairment was on SSI vs 5% on FDI and 4% on CDI). SSI prevalence decreased steadily from 21% to 16% at week 12 (p for linear trend <0.001), mostly through stopping SSI. Diabetes-related factors (e.g., hyperglycemia) were more strongly associated with continuing SSI or transitioning to a non-SSI short-acting insulin regimen than frailty-related factors. CONCLUSIONS: SSI is the most common method of administering short-acting insulin in NH residents. More research needs to be done to explore why sliding scale use persists weeks after NH admission and explore how we can replace this practice with safer, more effective, and less burdensome regimens.

An automated all-in-one system for carbohydrate tracking, glucose monitoring, and insulin delivery.

Glycemic control through titration of insulin dosing remains the mainstay of diabetes mellitus treatment. Insulin therapy is generally divided into dosing with long- and short-acting insulin, where long-acting insulin provides basal coverage and short-acting insulin supports glycemic excursions associated with eating. The dosing of short-acting insulin often involves several steps for the user including blood glucose measurement and integration of potential carbohydrate loads to inform safe and appropriate dosing. The significant burden placed on the user for blood glucose measurement and effective carbohydrate counting can manifest in substantial effects on adherence. Through the application of computer vision, we have developed a smartphone-based system that is able to detect the carbohydrate load of food by simply taking a single image of the food and converting that information into a required insulin dose by incorporating a blood glucose measurement. Moreover, we report the development of comprehensive all-in-one insulin delivery systems that streamline all operations that peripheral devices require for safe insulin administration, which in turn significantly reduces the complexity and time required for titration of insulin. The development of an autonomous system that supports maximum ease and accuracy of insulin dosing will transform our ability to more effectively support patients with diabetes.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.