Estimated Sustainable Cost-Based Prices for Diabetes Medicines.

Importance: The burden of diabetes is growing worldwide. The costs associated with diabetes put substantial pressure on patients and health budgets, especially in low- and middle-income countries. The prices of diabetes medicines are a key determinant for access, yet little is known about the association between manufacturing costs and current market prices. Objectives: To estimate the cost of manufacturing insulins, sodium-glucose cotransporter 2 inhibitors (SGLT2Is), and glucagonlike peptide 1 agonists (GLP1As), derive sustainable cost-based prices (CBPs), and compare these with current market prices. Design, Setting, and Participants: In this economic evaluation, the cost of manufacturing insulins, SGLT2Is, and GLP1As was modeled. Active pharmaceutical ingredient cost per unit (weighted least-squares regression model using data from a commercial database of trade shipments, data from January 1, 2016, to March 31, 2023) was combined with costs of formulation and other operating expenses, plus a profit margin with an allowance for tax, to estimate CBPs. Cost-based prices were compared with current prices in 13 countries, collected in January 2023 from public databases. Countries were selected to provide representation of different income levels and geographic regions based on the availability of public databases. Main Outcomes and Measures: Estimated CBPs; lowest current market prices (2023 US dollars). Results: In this economic evaluation of manufacturing costs, estimated CBPs for treatment with insulin in a reusable pen device could be as low as $96 (human insulin) or $111 (insulin analogues) per year for a basal-bolus regimen, $61 per year using twice-daily injections of mixed human insulin, and $50 (human insulin) or $72 (insulin analogues) per year for a once-daily basal insulin injection (for type 2 diabetes), including the cost of injection devices and needles. Cost-based prices ranged from $1.30 to $3.45 per month for SGLT2Is (except canagliflozin: $25.00-$46.79) and from $0.75 to $72.49 per month for GLP1As. These CBPs were substantially lower than current prices in the 13 countries surveyed. Conclusions and Relevance: High prices limit access to newer diabetes medicines in many countries. The findings of this study suggest that robust generic and biosimilar competition could reduce prices to more affordable levels and enable expansion of diabetes treatment globally.

The Health Economics of Automated Insulin Delivery Systems and the Potential Use of Time in Range in Diabetes Modeling: A Narrative Review.

Intensive therapy with exogenous insulin is the treatment of choice for individuals living with type 1 diabetes (T1D) and some with type 2 diabetes, alongside regular glucose monitoring. The development of systems allowing (semi-)automated insulin delivery (AID), by connecting glucose sensors with insulin pumps and algorithms, has revolutionized insulin therapy. Indeed, AID systems have demonstrated a proven impact on overall glucose control, as indicated by effects on glycated hemoglobin (HbA1c), risk of severe hypoglycemia, and quality of life measures. An alternative endpoint for glucose control that has arisen from the use of sensor-based continuous glucose monitoring is the time in range (TIR) measure, which offers an indication of overall glucose control, while adding information on the quality of control with regard to blood glucose level stability. A review of literature on the health-economic value of AID systems was conducted, with a focus placed on the growing place of TIR as an endpoint in studies involving AID systems. Results showed that the majority of economic evaluations of AID systems focused on individuals with T1D and found AID systems to be cost-effective. Most studies incorporated HbA1c, rather than TIR, as a clinical endpoint to determine treatment effects on glucose control and subsequent quality-adjusted life year (QALY) gains. Likely reasons for the choice of HbA1c as the chosen endpoint is the use of this metric in most validated and established economic models, as well as the limited publicly available evidence on appropriate methodologies for TIR data incorporation within conventional economic evaluations. Future studies could include the novel TIR metric in health-economic evaluations as an additional measure of treatment effects and subsequent QALY gains, to facilitate a holistic representation of the impact of AID systems on glycemic control. This would provide decision makers with robust evidence to inform future recommendations for health care interventions.

Ambient Heat and Risk of Serious Hypoglycemia in Older Adults With Diabetes Using Insulin in the U.S. and Taiwan: A Cross-National Case-Crossover Study.

OBJECTIVE: To measure the association between ambient heat and hypoglycemia-related emergency department visit or hospitalization in insulin users. RESEARCH DESIGN AND METHODS: We identified cases of serious hypoglycemia among adults using insulin aged ≥65 in the U.S. (via Medicare Part A/B/D-eligible beneficiaries) and Taiwan (via National Health Insurance Database) from June to September, 2016-2019. We then estimated odds of hypoglycemia by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design. RESULTS: Among ∼2 million insulin users in the U.S. (32,461 hypoglycemia case subjects), odds ratios of hypoglycemia for HI >99th, 95-98th, 85-94th, and 75-84th percentiles compared with the 25-74th percentile were 1.38 (95% CI, 1.28-1.48), 1.14 (1.08-1.20), 1.12 (1.08-1.17), and 1.09 (1.04-1.13) respectively. Overall patterns of associations were similar for insulin users in the Taiwan sample (∼283,000 insulin users, 10,162 hypoglycemia case subjects). CONCLUSIONS: In two national samples of older insulin users, higher ambient temperature was associated with increased hypoglycemia risk.

Assessment of Meal Anticipation for Improving Fully Automated Insulin Delivery in Adults With Type 1 Diabetes.

OBJECTIVE: Meals are a consistent challenge to glycemic control in type 1 diabetes (T1D). Our objective was to assess the glycemic impact of meal anticipation within a fully automated insulin delivery (AID) system among adults with T1D. RESEARCH DESIGN AND METHODS: We report the results of a randomized crossover clinical trial comparing three modalities of AID systems: hybrid closed loop (HCL), full closed loop (FCL), and full closed loop with meal anticipation (FCL+). Modalities were tested during three supervised 24-h admissions, where breakfast, lunch, and dinner were consumed per participant's home schedule, at a fixed time, and with a 1.5-h delay, respectively. Primary outcome was the percent time in range 70-180 mg/dL (TIR) during the breakfast postprandial period for FCL+ versus FCL. RESULTS: Thirty-five adults with T1D (age 44.5 ± 15.4 years; HbA1c 6.7 ± 0.9%; n = 23 women and n = 12 men) were randomly assigned. TIR for the 5-h period after breakfast was 75 ± 23%, 58 ± 21%, and 63 ± 19% for HCL, FCL, and FCL+, respectively, with no significant difference between FCL+ and FCL. For the 2 h before dinner, time below range (TBR) was similar for FCL and FCL+. For the 5-h period after dinner, TIR was similar for FCL+ and FCL (71 ± 34% vs. 72 ± 29%; P = 1.0), whereas TBR was reduced in FCL+ (median 0% [0-0%] vs. 0% [0-0.8%]; P = 0.03). Overall, 24-h control for HCL, FCL, and FCL+ was 86 ± 10%, 77 ± 11%, and 77 ± 12%, respectively. CONCLUSIONS: Although postprandial control remained optimal with hybrid AID, both fully AID solutions offered overall TIR >70% with similar or lower exposure to hypoglycemia. Anticipation did not significantly improve postprandial control in AID systems but also did not increase hypoglycemic risk when meals were delayed.

Insulin Fills by Medicare Enrollees and Out-of-Pocket Caps Under the Inflation Reduction Act.

This study uses data from IQVIA's National Prescription Audit to assess the association of the Inflation Reduction Act's cap on cost sharing with insulin fills by Medicare beneficiaries.

Assessment of Commercial and Mandatory Discounts in the Gross-to-Net Bubble for the Top Insulin Products From 2012 to 2019.

Importance: Insulin list prices have grown substantially since 2010, but net prices have declined since 2015 because of manufacturer discounts, leading to an increasingly large difference between list and net prices of drugs often called the gross-to-net bubble. It remains unclear to what extent the gross-to-net bubble represents voluntary manufacturer discounts negotiated in commercial and Medicare Part D markets (hereafter called commercial discounts) vs mandatory discounts under the Medicare Part D coverage gap, Medicaid, and the 340B program. Objective: To decompose the overall gross-to-net bubble of leading insulin products into discount types. Design, Setting, and Participants: This economic evaluation obtained data from Medicare and Medicaid claims and spending dashboards, Medicare Part D Prescriber Public Use File, and SSR Health for the top 4 commonly used insulin products: Lantus, Levemir, Humalog, and Novolog. The gross-to-net bubble, which represents total discounts, was estimated for each insulin product and year (from 2012 to 2019). Analyses were conducted in June to December 2022. Main Outcomes and Measures: The gross-to-net bubble was decomposed into 4 discount types: (1) Medicare Part D coverage gap discounts, (2) Medicaid discounts, (3) 340B discounts, and (4) commercial discounts. Coverage gap discounts were estimated using Medicare Part D claims data. Medicaid and 340B discounts were estimated using a novel algorithm that accounted for best prices set by commercial discounts. Results: Total discounts for the 4 insulin products increased from $4.9 billion to $22.0 billion. Commercial discounts represented a majority of all discounts, increasing from 71.7% of the gross-to-net bubble in 2012 ($3.5 billion) to 74.3% ($16.4 billion) in 2019. Among mandatory discounts, coverage gap discounts remained relatively consistent as a proportion of discounts (5.4% in 2012 vs 5.3% in 2019). Medicaid rebates decreased as a proportion of total discounts, from 19.7% in 2012 to 10.6% in 2019. The 340B discounts increased as a proportion of total discounts from 3.3% in 2012 to 9.8% in 2019. Results for the contribution of discount types to the gross-to-net bubble were consistent across insulin products. Conclusions and Relevance: Results of a decomposition of the gross-to-net bubble for leading insulin products suggest that commercial discounts play a growing role in lowering net sales compared with mandatory discounts.

Incidence and costs of hypoglycemia in insulin-treated diabetes in Switzerland: A health-economic analysis.

AIMS: We assess the incidence and economic burden of severe and non-severe hypoglycemia in insulin-treated diabetes type 1 and 2 patients in Switzerland. METHODS: We developed a health economic model to assess the incidence of hypoglycemia, the subsequent medical costs, and the production losses in insulin-treated diabetes patients. The model distinguishes between severity of hypoglycemia, type of diabetes, and type of medical care. We used survey data, health statistics, and health care utilization data extracted from primary studies. RESULTS: The number of hypoglycemic events in 2017 was estimated at 1.3 million in type 1 diabetes patients and at 0.7 million in insulin-treated type 2 diabetes patients. The subsequent medical costs amount to 38 million Swiss Francs (CHF), 61 % of which occur in type 2 diabetes. Outpatient visits dominate costs in both types of diabetes. Total production losses due to hypoglycemia amount to CHF 11 million. Almost 80 % of medical costs and 39 % of production losses are due to non-severe hypoglycemia. CONCLUSIONS: Hypoglycemia leads to substantial socio-economic burden in Switzerland. Greater attention to non-severe hypoglycemic events and to severe hypoglycemia in type 2 diabetes could have a major impact on reducing this burden.

Use of insulin pumps and closed-loop systems among people living with diabetes: A narrative review of clinical and cost-effectiveness to enable access to technology and meet the needs of payers.

The use of continuous subcutaneous insulin infusion (CSII) via insulin pumps is today considered standard of care for type 1 diabetes (T1D). Closed-loop systems combining continuous glucose monitoring with automated algorithm-driven insulin delivery have been shown to be safe and efficacious in randomized controlled trials and real-life studies in both paediatric and adult participants with T1D. Implementation of hybrid closed-loop (HCL) systems has shown incremental effectiveness, with further reduction of hypoglycaemia and hyperglycaemia. Although less extensively studied in type 2 diabetes (T2D), insulin pumps have demonstrated their effectiveness in glucose control, along with a reduction in need for insulin and a neutral effect on weight. Recent studies have also shown promising results with the use of HCL systems in T2D. Cost-effectiveness studies in both T1D and T2D have shown that pump use is cost-effective in several countries, leading to improvements in quality-adjusted life-years. Insulin pumps are currently reimbursed for T1D in many European countries, but in only a few for individuals with T2D. HCL systems are to be evaluated in future trials performed in T2D to compare their incremental efficacy and cost-effectiveness in comparison with available intensification tools which include multiple daily insulin injections, metformin, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. There is a need for updated guidelines for the use of CSII and HCL in individuals living with T2D based on the emerging evidence, with identification of and recommendations for the people who would benefit the most, which would eventually form a basis for reimbursement and health policies.

Assessment of circulating insulin using liquid chromatography-mass spectrometry during insulin glargine treatment in type 2 diabetes: Implications for estimating insulin sensitivity and ß-cell function.

AIM: To determine the potential impact of the cross-reactivity of insulin glargine U-100 and its metabolites on insulin sensitivity and ß-cell measures in people with type 2 diabetes. MATERIALS AND METHODS: Using liquid chromatography-mass spectrometry (LC-MS), we measured concentrations of endogenous insulin, glargine and its two metabolites (M1 and M2) in fasting and oral glucose tolerance test-stimulated plasma from 19 participants and fasting specimens from another 97 participants 12 months after randomization to receive the insulin glargine. The last dose of glargine was administered before 10:00 PM the night before testing. Insulin was also measured on these specimens using an immunoassay. We used fasting specimens to calculate insulin sensitivity (Homeostatic Model Assessment 2 [HOMA2]-S%; QUICKI index; PREDIM index) and ß-cell function (HOMA2-B%). Using specimens following glucose ingestion, we calculated insulin sensitivity (Matsuda ISI[comp] index) and ß-cell response (insulinogenic index [IGI], and total incremental insulin response [iAUC] insulin/glucose). RESULTS: In plasma, glargine was metabolized to form the M1 and M2 metabolites that were quantifiable by LC-MS; however, the analogue and its metabolites cross-reacted by less than 100% in the insulin immunoassay. This incomplete cross-reactivity resulted in a systematic bias of fasting-based measures. By contrast, because M1 and M2 did not change following glucose ingestion, a bias was not observed for IGI and iAUC insulin/glucose. CONCLUSIONS: Despite glargine metabolites being detected in the insulin immunoassay, dynamic insulin responses can be used to assess ß-cell responsiveness. However, given the cross-reactivity of the glargine metabolites in the insulin immunoassay, fasting-based measures of insulin sensitivity and ß-cell function are biased.

Cost-Related Insulin Rationing in US Adults Younger Than 65 Years With Diabetes.

This study uses 2021 National Health Interview Survey data to examine the prevalence of insulin rationing among adults younger than 65 years in the US by demographic characteristics.

All 3 Major Insulin Manufacturers Are Cutting Their Prices-Here's What the News Means for Patients With Diabetes.

This Medical News article discusses recent announcements of price caps on some insulins.

Does Insulin Price Reduction Suggest a Path Forward for Lowering Drug Costs?

This Viewpoint investigates whether political pressure such as that used to decrease insulin pricing is a feasible method of lowering the cost of other drugs.

Gestão de riscos como melhoria para a aquisição e distribuição de insulinas pelo SUS / Risk management as an improvement for the acquisition and distribution of insulins by SUS

Objetivo: identificar a melhoria por meio da gestão de risco aplicada aos processos de aquisição e distribuição de insulinas humanas NPH. Método: O estudo foi realizado por etapas: em 1º momento foram realizadas reuniões (Brainstorming) e em 2º momento foi elaborado um formulário eletrônico em forma de questionário sendo mostrado os "eventos" de riscos com os pesos inerentes à probabilidade e ao impacto que geraram o risco inerente aos processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde. Resultados: Considerando os processos houve maior incidência de riscos médios. Não foi apontado risco muito baixo, não foi identificado risco extremo e foram apresentados apenas 02 (dois) riscos altos. Conclusão: A gestão de risco do referido estudo é uma ferramenta de melhoria para os processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde.(AU)

Objective: to identify improvement through risk management applied to the acquisition and distribution processes of NPH human insulins. Method: The study was carried out in stages: in the 1st moment, meetings were held (Brainstorming) and in the 2nd moment, an electronic form was elaborated in the form of a questionnaire, showing the risk "events" with the weights inherent to the probability and impact they generated the risk inherent in the acquisition and distribution processes of NPH and Regular human insulins by the Ministry of Health. Results: Considering the processes, there was a higher incidence of medium risks. No very low risk was indicated, no extreme risk was identified and only 02 (two) high risks were presented. Conclusion: The risk management of the aforementioned study is an improvement tool for the processes of acquisition and distribution of NPH and Regular human insulins by the Ministry of Health.(AU)

Initiation of Continuous Glucose Monitoring Is Linked to Improved Glycemic Control and Fewer Clinical Events in Type 1 and Type 2 Diabetes in the Veterans Health Administration.

OBJECTIVE: To determine the benefit of starting continuous glucose monitoring (CGM) in adult-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) with regard to longer-term glucose control and serious clinical events. RESEARCH DESIGN AND METHODS: A retrospective observational cohort study within the Veterans Affairs Health Care System was used to compare glucose control and hypoglycemia- or hyperglycemia-related admission to an emergency room or hospital and all-cause hospitalization between propensity score overlap weighted initiators of CGM and nonusers over 12 months. RESULTS: CGM users receiving insulin (n = 5,015 with T1D and n = 15,706 with T2D) and similar numbers of nonusers were identified from 1 January 2015 to 31 December 2020. Declines in HbA1c were significantly greater in CGM users with T1D (-0.26%; 95% CI -0.33, -0.19%) and T2D (-0.35%; 95% CI -0.40, -0.31%) than in nonusers at 12 months. Percentages of patients achieving HbA1c <8 and <9% after 12 months were greater in CGM users. In T1D, CGM initiation was associated with significantly reduced risk of hypoglycemia (hazard ratio [HR] 0.69; 95% CI 0.48, 0.98) and all-cause hospitalization (HR 0.75; 95% CI 0.63, 0.90). In patients with T2D, there was a reduction in risk of hyperglycemia in CGM users (HR 0.87; 95% CI 0.77, 0.99) and all-cause hospitalization (HR 0.89; 95% CI 0.83, 0.97). Several subgroups (based on baseline age, HbA1c, hypoglycemic risk, or follow-up CGM use) had even greater responses. CONCLUSIONS: In a large national cohort, initiation of CGM was associated with sustained improvement in HbA1c in patients with later-onset T1D and patients with T2D using insulin. This was accompanied by a clear pattern of reduced risk of admission to an emergency room or hospital for hypoglycemia or hyperglycemia and of all-cause hospitalization.

Assessing-and Extending-California's Insulin Manufacturing Initiative.

This Viewpoint reviews California's recently proposed CalRx initiative to manufacture biosimilar insulin, highlights challenges facing the initiative, and suggests ways in which, if successful, the initiative could serve as a model for state-managed development of drugs other than insulin, reduce drug prices, and provide other benefits.

Cost-Utility of an Online Education Platform and Diabetes Personal Health Record: Analysis Over Ten Years.

BACKGROUND AND AIMS: My Diabetes My Way (MDMW) is Scotland's interactive website and mobile app for people with diabetes and their caregivers. It contains multimedia resources for diabetes education and offers access to electronic personal health records. This study aims to assess the cost-utility of MDMW compared with routine diabetes care in people with type 2 diabetes who do not use insulin. MATERIALS AND METHODS: Analysis used the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model 2. Clinical parameters of MDMW users (n = 2576) were compared with a matched cohort of individuals receiving routine care alone (n = 11 628). Matching criteria: age, diabetes duration, sex, and socioeconomic status. Impact on life expectancy, quality-adjusted life years (QALYs), and costs of treatment and complications were simulated over ten years, including a 10% sensitivity analysis. RESULTS: MDMW cohort: 1670 (64.8%) men; average age 64.3 years; duration of diabetes 5.5 years. 906 (35.2%) women: average age 61.6 years; duration 4.7 years. The cumulative mean QALY (95% CI) gain: 0.054 (0.044-0.062) years. Mean difference in cost: -£118.72 (-£150.16 to -£54.16) over ten years. Increasing MDMW costs (10%): -£50.49 (-£82.24-£14.14). Decreasing MDMW costs (10%): -£186.95 (-£218.53 to -£122.51). CONCLUSIONS: MDMW is "dominant" over usual care (cost-saving and life improving) in supporting self-management in people with type 2 diabetes not treated with insulin. Wider use may result in significant cost savings through delay or reduction of long-term complications and improved QALYs in Scotland and other countries. MDMW may be among the most cost-effective interventions currently available to support diabetes.

Methods for Insulin Bolus Adjustment Based on the Continuous Glucose Monitoring Trend Arrows in Type 1 Diabetes: Performance and Safety Assessment in an In Silico Clinical Trial.

BACKGROUND: Providing real-time magnitude and direction of glucose rate-of-change (ROC) via trend arrows represents one of the major strengths of continuous glucose monitoring (CGM) sensors in managing type 1 diabetes (T1D). Several literature methods were proposed to adjust the standard formula (SF) used for insulin bolus calculation by accounting for glucose ROC, but each of them provides different suggestions, making it difficult to understand which should be applied in practice. This work aims at performing an extensive in-silico assessment of their performance and safety. METHODS: The methods of Buckingham (BU), Scheiner (SC), Pettus/Edelman (PE), Klonoff/Kerr (KL), Aleppo/Laffel (AL), Ziegler (ZI), and Bruttomesso (BR) were evaluated using the UVa/Padova T1D simulator, in single-meal scenarios, where ROC and glucose at mealtime varied between [-2,+2] mg/dL/min and [80,200] mg/dL, respectively. Efficacy of postprandial glucose control was quantitatively assessed by time in, above and below range (TIR, TAR, and TBR, respectively). RESULTS: For negative ROCs, all methods proved to increase TIR and decrease TAR and TBR vs SF, with KL, PE, and BR being the most effective. For positive ROCs, a general worsening of the performances is present, only BR improved the glycemic control when mealtime glucose was close to hypoglycemia, while SC resulted the safest in the other conditions. CONCLUSIONS: Insulin bolus adjustment methods are effective for negative ROCs, but they generally appear to overdose for positive ROCs, calling for safer strategies in such a scenario. These results can be useful in outlining guidelines to identify which adjustment to apply based on the mealtime condition.

Evaluating Factors Associated With Continuous Glucose Monitoring Utilization With the Type 1 Diabetes Exchange Registry.

BACKGROUND: The 2022 American Diabetes Association (ADA) Standards of Care recommends considering use of continuous glucose monitoring (CGM) for insulin-managed diabetes mellitus (DM), but equitable access remains challenging. This study evaluates socioeconomic and demographic metrics associated with CGM use. METHODS: RStudio 2021.09.1+372 was utilized to perform uni- and bivariable analysis, as well as binomial logistic regression modeling for categorical CGM use (yes/no) on the most recent cross-section from the Type 1 Diabetes Exchange (T1DX) Registry 2016-2018 cohort (n = 22 418). RESULTS: Compared with White Non-Hispanic participants, Black Non-Hispanic (OR = 0.45, CI = 0.36-0.57, P < 0.001) and American Indian/Alaskan Native individuals (OR = 0.33, CI = 0.14-0.70, P = 0.008) had lower odds of CGM use. Compared with private insurance, government insurance had reduced odds of CGM use (OR = 0.59, CI = 0.52-0.66, P < 0.001). Individuals earning $100,000 or more were twice as likely to use CGMs (OR = 2.06, CI = 1.75-2.45, P < 0.001) compared with those earning <$25,000 annually. Subgroup analysis based on income bracket demonstrated that government insured individuals earning <$25,000 annually were the least likely to use CGMs (OR = 0.44, CI = 0.32-0.61, P < 0.001), as compared with private insurance. CONCLUSIONS: T1DX Registry data demonstrate that CGM use follows the inverse care law, with health technology utilization inversely related to disease burden. Federal policies promoting CGM use in Medicare and Medicaid populations can facilitate the ADA's recommendation for patients with insulin-managed diabetes mellitus.