Household food insecurity and associations with hemoglobin A1c and acute diabetes-related complications in youth and young adults with type 1 diabetes: The SEARCH for Diabetes in Youth study.

AIMS: To examine, among youth and young adults (YYA) with type 1 diabetes (T1D), the association of household food insecurity (HFI) with: 1) HbA1c and 2) episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia. METHODS: HFI was assessed using the U.S. Household Food Security Survey Module in SEARCH for Diabetes in Youth participants with T1D between 2016 and 2019. Linear and logistic regression models adjusted for age, diabetes duration, sex, race, ethnicity, clinic site, parent/participant education, household income, health insurance, and diabetes technology use. RESULTS: Of 1830 participants (mean age 20.8 ± 5.0 years, 70.0 % non-Hispanic White), HbA1c was collected for 1060 individuals (mean HbA1c 9.2 % ± 2.0 %). The prevalence of HFI was 16.4 %. In the past 12 months, 18.2 % and 9.9 % reported an episode of DKA or severe hypoglycemia, respectively. Compared to participants who were food secure, HFI was associated with a 0.33 % (95 % CI 0.003, 0.657) higher HbA1c level. Those with HFI had 1.58 (95 % CI 1.13, 2.21) times the adjusted odds of an episode of DKA and 1.53 (95 % CI 0.99, 2.37) times the adjusted odds of an episode of severe hypoglycemia as those without HFI. CONCLUSIONS: HFI is associated with higher HbA1c levels and increased odds of DKA in YYA with T1D.

Factors and economic burden of non-severe hypoglycemia among insulin-treated type 2 diabetes patients: a cross-sectional study.

OBJECTIVE: This cross-sectional survey was performed to assess the prevalence, factors, and economic burden of non-severe hypoglycemia among insulin-treated type 2 diabetes (T2D) patients in northern Thailand. METHODS: Between April 2021 and August 2022, 600 participants were evaluated via structured questionnaires containing sociodemographic and clinical characteristics, medications, and economic burden. Patients were divided into two groups (having and not having non-severe hypoglycemia). Variables with a p value <.05 in the univariate model were included in the multivariate model. RESULTS: The percentage of non-severe hypoglycemia was 50.3% (302/600). Of all participants, the average age was 61.4 ± 26.0 years, 55.7% were female, 53.5% used premix insulin, and the average duration of diabetes was 16.1 ± 10.0 years. Multivariate logistic regression analysis indicated that age (OR = .96; p <.001), duration of diabetes (OR = 1.04; p <.001), BMI (OR = .95; p = .002), thiazolidinedione (OR = 1.56; p = .012) and insulin regimens were associated with having non-severe hypoglycemia. Compared to basal insulin, basal bolus (OR = 6.93; p = .001), basal plus (OR = 3.58; p <.001), and premix insulin (OR = 1.83; p =.003) were associated with hypoglycemia. Greater numbers of sick leave were found in the hypoglycemia group (14 vs 4 patients, p = .029). CONCLUSIONS: These findings help to individuate those patients who are at higher risk of non-severe hypoglycemia in insulin-treated T2D patients. Compared to the non-hypoglycemia group, patients with hypoglycemia were younger, had longer diabetes duration, lower BMI, received thiazolidinedione and insulin regimens such as premix, basal plus, or basal bolus insulins, and more productivity loss.

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.

Real-World Analysis of Long-Acting and NPH-Containing Insulins on Glycemic Control.

Introduction Affordability of insulin products has become a concern in the past several years as the average price of various insulin products has increased. While awaiting legislation at the federal level that would address issues leading to high insulin costs, providers may have shifted prescribing practices to prescribe the lowest-priced insulin products to achieve patients' treatment goals. Objective To compare the prevalence of hypoglycemic events between patients receiving lower-cost neutral protamine Hagedorn (NPH)-containing human insulins and higher-cost long-acting insulin analogs in Medicare Part D enrollees within a management services organization, as well as assessing glycemic control and changes in body mass index. Methods This was a multicenter, retrospective study conducted at three primary care clinics. The co-primary outcomes were percent difference of documented mild and severe hypoglycemic events between individuals receiving NPH-containing human insulin and long-acting insulin. Results A total of 72 patients met inclusion criteria and were receiving NPH-containing human insulins or the long-acting insulin analogs, 15 and 57 patients, respectively. Severe hypoglycemic events occurred in 3.5% vs 0% of the long-acting insulin analog and NPH-containing human insulin group, respectively (P = 0.999). Mild hypoglycemic episodes were experienced by 31.6% versus 33.3% of long-acting insulin analog and NPH, respectively (P = 0.539). For secondary outcomes, no difference was observed in glycemic control outcomes across insulin groups. Conclusion Among Medicare Part D patients with type 2 diabetes mellitus, the use of NPH-containing human insulins was not associated with an increased risk of mild or severe hypoglycemia-related episodes or reduced glycemic control compared with long-acting insulin. Study findings suggest that lower-cost, NPH-containing human insulins may be an alternative to higher-cost, long-acting insulin analogs.

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.

Sulfonylureas as second line therapy for type 2 diabetes among veterans: Results from a National Longitudinal Cohort Study.

AIMS: To assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone. MATERIALS AND METHODS: This was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes. RESULTS: Switching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7-19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively). CONCLUSIONS: Switching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy.

Risk of Severe Hypoglycemia With Newer Second-line Glucose-lowering Medications in Older Adults With Type 2 Diabetes Stratified by Known Indicators of Hypoglycemia Risk.

BACKGROUND: Severe hypoglycemia is associated with adverse clinical outcomes. We evaluated the risk of severe hypoglycemia in older adults initiating newer glucose-lowering medications overall and across strata of known indicators of high hypoglycemia risk. METHODS: We conducted a comparative-effectiveness cohort study of older adults aged >65 years with type 2 diabetes initiating sodium-glucose cotransporter 2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) or SGLT2i versus glucagon-like peptide-1 receptor agonists (GLP-1RA) using Medicare claims (3/2013-12/2018) and Medicare-linked-electronic health records. We identified severe hypoglycemia requiring emergency or inpatient visits using validated algorithms. After 1:1 propensity score matching, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years. Analyses were stratified by baseline insulin, sulfonylurea, cardiovascular disease (CVD), chronic kidney disease (CKD), and frailty. RESULTS: Over a median follow-up of 7 (interquartile range: 4-16) months, SGLT2i was associated with a reduced risk of hypoglycemia versus DPP-4i (HR 0.75 [0.68, 0.83]; RD -3.21 [-4.29, -2.12]), and versus GLP-1RA (HR 0.90 [0.82, 0.98]; RD -1.33 [-2.44, -0.23]). RD for SGLT2i versus DPP-4i was larger in patients using baseline insulin than in those not, although HRs were similar. In patients using baseline sulfonylurea, the risk of hypoglycemia was lower in SGLT2i versus DPP-4i (HR 0.57 [0.49, 0.65], RD -6.80 [-8.43, -5.16]), while the association was near-null in those without baseline sulfonylurea. Results stratified by baseline CVD, CKD and frailty were similar to the overall cohort findings. Findings for the GLP-1RA comparison were similar. CONCLUSIONS: SGLT2i was associated with a lower hypoglycemia risk versus incretin-based medications, with larger associations in patients using baseline insulin or sulfonylurea.

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.

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.

Potential cost savings in the United States from a reduction in sensor-detected severe hypoglycemia among users of the InPen smart insulin pen system.

BACKGROUND: Severe hypoglycemia is a significant barrier to optimizing insulin therapy in both type 1 and type 2 diabetes and places a burden on the US health care system because of the high costs of hypoglycemia-related health care utilization. OBJECTIVE: To compare the frequency of sensor-detected severe hypoglycemic events (SHEs) among a population of continuous glucose monitoring (CGM) users on insulin therapy after initiation of the InPen smart insulin pen (SIP) system and to estimate the potential hypoglycemia-related medical cost savings across a population of SIP users. METHODS: SIP users of all ages with type 1 or type 2 diabetes were required to have at least 90 days of SIP use with a connected CGM device. The last 14 days of sensor glucose (SG) data within the 30-day period prior to the start of SIP use ("pre-SIP") and the last 14 days of SG data, along with the requirement of at least 1 bolus entry per day within the 61- to 90-day period after SIP start ("post-SIP"), were analyzed. Sensor-detected SHEs (defined as ≥10 minutes of consecutive SG readings at <54 mg/dL) were determined. Once factored, the expected medical intervention rates and associated costs were calculated. Intervention rates and costs were obtained from the literature. RESULTS: There were 1,681 SIP + CGM users from March 1, 2018, to April 30, 2021. The mean number of sensor-detected SHEs per week declined from 0.67 in the pre-SIP period to 0.58 in the post-SIP period (P = 0.008), which represented a 13% reduction. Assuming a range of 5%-25% of all sensor-detected SHEs resulted in a clinical event, the estimated cost reduction associated with reduced SHEs was $12-$59 and $110-$551 per SIP user per month and per year, respectively. For those aged at least 65 years, there were 166 SIP+CGM users and the reduction in the mean number of sensor-detected SHEs per week between the pre-SIP and post-SIP periods was 31%. CONCLUSIONS: Use of the SIP system with a connected CGM is associated with reduced sensor-detected severe hypoglycemia, which may result in significant cost savings. DISCLOSURES: Albert Chien, Glen Im, Kael Wherry, Janice MacLeod, and Robert A Vigersky are employees of Medtronic; Sneha Thanasekaran and Angela Gaetano were affiliated with Medtronic while doing this research. The submitted work did not involve study subject recruitment, enrollment, or participation in a trial and did not fall under human subject protection requirements (per the Department of Health and Human Services CFR Part 46) necessitating Internal Review Board approval or exemption.

SGLT-2 inhibitors and euglycemic diabetic ketoacidosis/diabetic ketoacidosis in FAERS: a pharmacovigilance assessment.

AIMS: To investigate the main feature and the association between euglycemic diabetic ketoacidosis (euDKA) /diabetic ketoacidosis (DKA) and sodium-dependent glucose transporters 2 inhibitors (SGLT-2i) from the FDA adverse event reporting system (FAERS). METHODS: Cases of SGLT-2i-associated with euDKA/DKA were extracted from the FAERS database and compared with the reports for other hypoglycemia agents (ATC10 class). Disproportionality analyses used the reporting odds ratio (ROR) and information components (IC). The lower limit of the IC 95% credibility interval for IC > 0 is considered a reported signal, with at least 3 cases. RESULTS: A total of 10,195 cases of euDKA (n = 1680) and DKA (n = 8515) associated with SGLT-2i were identified from the FAERS. The SGLT-2i was associated with higher reporting of euDKA and DKA compared to other hypoglycemia agents (ROR = 16.69 [95% CI 14.89-18.70], IC = 3.27 [95% CI 2.91-3.66] for euDKA; ROR = 16.44 [95% CI 15.72-17.20], IC = 3.19 [95% CI 3.05-3.34] for DKA). In available data, the median onset time of euDKA/DKA was 31 days, and canagliflozin had the longest onset time (96.5 days for euDKA and 75 days for DKA) compared with dapagliflozin and empagliflozin (p < 0.05). Male patients predominate in euDKA (51.9%), and female patients predominate in DKA (53.7%). Most patients discontinue the treatment (95.5% for euDKA, 93.9% for DKA), and approximately 49.0% (n = 3658) of patients had symptomatic remission after discontinuation of SGLT-2i, and 2.3% (n = 173) of patients had no remission. About 75.6% (n = 6126) of patients need hospitalization after euDKA/DKA. CONCLUSIONS: Post-marketing data showed that SGLT-2i was significantly associated with higher reporting of euDKA/DKA. Although euDKA/DKA is rare, clinicians should be aware of SGLT-2i-associated euDKA/DKA events.

A comprehensive risk assessment for nocturnal hypoglycemia in geriatric patients with type 2 diabetes: A single-center case-control study.

AIMS: To evaluate the overall association between clinically significant nocturnal hypoglycemia (CsNH) and risk factors in geriatric patients with type 2 diabetes. METHODS: Overall, 606 geriatric with type 2 diabetes were evaluated for CsNH using Freestyle Libre Pro® (Abbott Diabetes Care, Tokyo, Japan) during October 2018-February 2020. We defined CsNH as blood glucose level <54 mg/dL (3.0 mmol/L). We investigated clinical characteristics and efficacies of hypoglycemic agents and insulin and analyzed CsNH risk factors using univariate and multivariate logistic regression analyses. RESULTS: We enrolled 152 patients each for the CsNH and non-nocturnal hypoglycemia groups. Insulin use (OR = 3.77 [95 % CI: 1.92-7.67]; P = 0.0002), age (OR = 1.06 [95 % CI: 1.01-1.12]; P = 0.0492), estimated glomerular filtration rate (OR = 0.97 [95 % CI: 0.95-0.98]; P = 0.0492), and fasting blood glucose level (OR = 0.94 [95 % CI: 0.91-0.94]; P < 0.0001) were independent CsNH risk factors. The combined results demonstrated a higher predictability of CsNH than each of the individual risk factors. CONCLUSIONS: We identified risk factors that could help predict CsNH in geriatric patients with type 2 diabetes and demonstrated a comprehensive risk factor assessment.

Safety, efficacy, and cost-effectiveness of insulin degludec U100 versus insulin glargine U300 in adults with type 1 diabetes: a systematic review and indirect treatment comparison.

BACKGROUND: Clinical differences between degludec U100 (Deg-100) and glargine U300 (Gla-300) in type 1 diabetes (T1D) were unknown. AIM: To indirectly compare the safety, efficacy, and cost-effectiveness between Deg-100 and Gla-300 in T1D adults via systematic review. METHOD: Medline, the Cochrane Library, ClinicalTrials.gov, and Google Scholar were searched (October 2021). Randomized controlled trials comparing Deg-100 or Gla-300 vs. glargine U100 in T1D adults (follow-up ≥ 12 weeks) were selected and analyzed using a frequentist network meta-analysis. Cost-effectiveness analysis (CEA) was conducted over a 1-year time horizon from societal perspectives. RESULTS: Nine trials were included. Efficacy analysis suggested that Deg-100 was non-inferior to Gla-300 in reducing HbA1c (MD 0.03 [95% CI - 0.09 to 0.15]; P = 0.60), FPG (MD - 1.12 [- 2.19 to - 0.04]; P = 0.04), and pre-breakfast SMBG (MD - 0.71 [- 1.46 to 0.03]; P = 0.06). Safety analysis suggested that Deg-100 appeared to have lower rates of both severe (HR 0.44 [0.25-0.78]; P = 0.005) and nocturnal severe (HR 0.19 [0.08-0.44]; P < 0.001) hypoglycemia, with lower total (MD - 0.07 [- 0.13 to - 0.01]; P = 0.02) and basal (MD - 0.08 [- 0.12 to - 0.04]; P < 0.001) insulin doses compared with Gla-300. No significant differences were observed for other hypoglycemia outcomes, adverse events, serious adverse events, bolus insulin dose, and body weight. The CEA showed that Deg-100 appeared to be a dominant treatment in Japan (+ 0.0283 QALYs, ¥26,266 [$228] per patient) and the United States (+ 0.0267 QALYs, $986 per patient). CONCLUSION: Low-certainty indirect evidence suggested that Deg-100 appeared to have a favorable reduction in rates of severe hypoglycemia and more cost-effective compared with Gla-300 in T1D adults.

Real-world persistence, adherence, health care resource utilization, and costs in people with type 2 diabetes switching from a first-generation basal insulin to a second-generation (insulin glargine 300 U/mL) vs an alternative first-generation basal insulin.

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers' bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

Long-term cost-effectiveness of Dexcom G6 real-time continuous glucose monitoring system in people with type 1 diabetes in Australia.

INTRODUCTION: Real-time continuous glucose monitoring (rt-CGM) allows patients with diabetes to adjust insulin dosing, potentially improving glucose control. This study aimed to compare the long-term cost-effectiveness of the Dexcom G6 rt-CGM device versus self-monitoring of blood glucose (SMBG) and flash glucose monitoring (FGM) in Australia in people with type 1 diabetes (T1D). METHODS: Long-term costs and clinical outcomes were estimated using the CORE Diabetes Model. Clinical input data for the analysis of rt-CGM versus SMBG and FGM were sourced from the DIAMOND study and a network meta-analysis, respectively. Rt-CGM and FGM were associated with quality of life (QoL) benefits due to reduced fear of hypoglycaemia (FoH) and fingerstick testing. Analyses were performed over a lifetime time horizon from an Australian healthcare payer perspective, including direct costs from published data. Future costs and clinical outcomes were discounted at 5% per annum. RESULTS: Rt-CGM was associated with an increased quality-adjusted life expectancy of 1.199 quality-adjusted life years (QALYs), increased mean total lifetime costs of AUD 21,596 and an incremental cost-effectiveness ratio (ICER) of AUD 18,020 per QALY gained compared with SMBG. Compared with FGM, rt-CGM was associated with an increased quality-adjusted life expectancy of 0.569 QALYs, increased mean total lifetime costs of AUD 11,064 and an ICER of AUD 19,455 per QALY gained. Key drivers of outcomes included HbA1c benefits and QoL benefits associated with reduced FoH and fingerstick testing. CONCLUSIONS: Due to improved clinical outcomes and QoL gains rt-CGM is highly cost-effective compared with SMBG and FGM in people with T1D in Australia.

Assessment of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) Code Assignment Validity for Case Finding of Medication-related Hypoglycemia Acute Care Visits Among Medicare Beneficiaries.

OBJECTIVE: Administrative claims are commonly relied upon to identify hypoglycemia. We assessed validity of 14 International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code assignments to identify medication-related hypoglycemia leading to acute care encounters. RESEARCH DESIGN AND METHODS: A multisite, retrospective medical record review study was conducted in a sample of Medicare beneficiaries prescribed outpatient diabetes medications and who received hospital care between January 1, 2016 and September 30, 2017. Diagnosis codes were validated with structured medical record review using prespecified criteria (clinical presentation, blood glucose values, and treatments for hypoglycemia). Sensitivity, specificity, and positive and negative predictive value (PPV, NPV) were calculated and adjusted using sampling weights to correct for partial verification bias. RESULTS: Among 990 encounters (496 cases, 494 controls), hypoglycemia codes demonstrated moderate PPV (69.2%; 95% confidence interval: 65.0-73.0) and moderate sensitivity (83.9%; 95% confidence interval: 70.0-95.5). Codes performed better at identifying hypoglycemic events among emergency department/observation encounters compared with hospitalizations (PPV 92.9%, sensitivity 100.0% vs. PPV 53.7%, sensitivity 71.0%). Accuracy varied by diagnosis position, especially for hospitalizations, with PPV of 95.6% versus 46.5% with hypoglycemia in primary versus secondary positions. Use of adverse event/poisoning codes did not improve accuracy; reliance on these codes alone would have missed 97% of true hypoglycemic events. CONCLUSIONS: Accuracy of International Classification of Diseases, Tenth Revision codes in administrative claims to identify medication-related hypoglycemia varied substantially by encounter type and diagnosis position. Consideration should be given to the trade-off between PPV and sensitivity when selecting codes, encounter types, and diagnosis positions to identify hypoglycemia.

Association of Area-Level Socioeconomic Deprivation With Hypoglycemic and Hyperglycemic Crises in US Adults With Diabetes.

Importance: Social determinants of health play a role in diabetes management and outcomes, including potentially life-threatening complications of severe hypoglycemia and diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS). Although several person-level socioeconomic factors have been associated with these complications, the implications of area-level socioeconomic deprivation are unknown. Objective: To examine the association between area-level deprivation and the risks of experiencing emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises (ie, DKA or HHS). Design, Setting, and Participants: This cohort study used deidentified administrative claims data for privately insured individuals and Medicare Advantage beneficiaries across the US. The analysis included adults with diabetes who met the claims criteria for diabetes between January 1, 2016, and December 31, 2017. Data analyses were performed from November 17, 2020, to November 11, 2021. Exposures: Area deprivation index (ADI) was derived for each county for 2016 and 2017 using 17 county-level indicators from the American Community Survey. ADI values were applied to patients who were living in each county based on their index dates and were categorized according to county-level ADI quintile (with quintile 1 having the least deprivation and quintile 5 having the most deprivation). Main Outcomes and Measures: The numbers of emergency department visits or hospitalizations related to the primary diagnoses of hypoglycemia and DKA or HHS (ascertained using validated diagnosis codes in the first or primary position of emergency department or hospital claims) between 2016 and 2019 were calculated for each ADI quintile using negative binomial regression models and adjusted for patient age, sex, health plan type, comorbidities, glucose-lowering medication type, and percentage of White residents in the county. Results: The study population included 1 116 361 individuals (563 943 women [50.5%]), with a mean (SD) age of 64.9 (13.2) years. Of these patients, 343 726 (30.8%) resided in counties with the least deprivation (quintile 1) and 121 810 (10.9%) lived in counties with the most deprivation (quintile 5). Adjusted rates of severe hypoglycemia increased from 13.54 (95% CI, 12.91-14.17) per 1000 person-years in quintile 1 counties to 19.13 (95% CI, 17.62-20.63) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.41 (95% CI, 1.29-1.54; P < .001). Adjusted rates of DKA or HHS increased from 7.49 (95% CI, 6.96-8.02) per 1000 person-years in quintile 1 counties to 8.37 (95% CI, 7.50-9.23) per 1000 person-years in quintile 5 counties, corresponding to an incidence rate ratio of 1.12 (95% CI, 1.00-1.25; P = .049). Conclusions and Relevance: This study found that living in counties with a high area-level deprivation was associated with an increased risk of severe hypoglycemia and DKA or HHS. The concentration of these preventable events in areas of high deprivation signals the need for interventions that target the structural barriers to optimal diabetes management and health.

Angiotensin-Converting Enzyme Inhibitors Used Concomitantly with Insulin Secretagogues and the Risk of Serious Hypoglycemia.

Serious hypoglycemia is a major adverse event associated with insulin secretagogues. Previous studies have suggested a potential relationship between angiotensin-converting enzyme inhibitors (ACEIs) used with sulfonylureas and serious hypoglycemia, and widely used drug compendia warn of this potential drug-drug interaction. We investigated the association between serious hypoglycemia and concomitant use of ACEIs in patients receiving insulin secretagogues, using the self-controlled case series design and Medicaid claims data from 5 US states linked to Medicare claims from 1999-2011. The exposure of interest was active prescription for ACEIs during insulin secretagogue or metformin (negative control object drug) episodes. The outcome was hospital presentation for serious hypoglycemia, identified by discharge diagnosis codes in inpatient and emergency department claims (positive predictive value ~ 78-89%). We calculated confounder-adjusted rate ratios (RRs) and 95% confidence internals (CIs) of outcome occurrence during ACEI-exposed vs. ACEI-unexposed time using conditional Poisson regression. The RRs for ACEIs were not statistically elevated during observation time of glipizide (RR, 1.06; CI, 0.98-1.15), glyburide (RR, 1.05; CI, 0.96-1.15), repaglinide (RR, 1.15; CI, 0.94-1.41), or metformin (RR, 1.02; CI, 0.97-1.06); but was modestly elevated with glimepiride (RR, 1.23; CI, 1.11-1.37) and modestly reduced with nateglinide (RR, 0.73; CI, 0.56-0.96). The overall pattern of results do not suggest that ACEIs used with insulin secretagogues were associated with increased rates of serious hypoglycemia, with the possible exception of glimepiride.

Direct Medical Cost of Type 2 Diabetes Mellitus and Its Associated Complications in Indonesia.

OBJECTIVES: To estimate the direct medical cost of type 2 diabetes mellitus (T2DM) and its complications in the Indonesian population from a payer perspective using a prevalence-based approach. METHODS: The direct medical costs in 2016 were estimated using the database of Indonesia's National Health Insurance, known as Jaminan Kesehatan Nasional, which included diagnosis-related group costs and unbundled costs for patients accessing advanced care. The study population included people aged 30 years or older having a diagnosis of T2DM. T2DM and its related complications were identified using the International Classification of Diseases, 10th Revision, code. Hypoglycemia and all complications listed in the Diabetes Severity Complications Index were included. Descriptive analysis was conducted. Costs were converted to 2016 US dollar equivalent. RESULTS: Of the 18.9 million Jaminan Kesehatan Nasional members who accessed secondary and tertiary care, 812 204 (4%) were identified with T2DM, of which 57% had complications. The most common complication was cardiovascular diseases (24%). The total direct medical cost was US $576 million, with 56% spent on hospitalization, 38% on specialist visits, 4% on unbundled non-diabetes-related medication, and 2% on unbundled anti-hyperglycemic medications. Approximately 74% of the total costs was used for the management of people with complications. People with complications (US $930/person/year ± US $1480/person/year) incurred twice the cost of those without complications (US $421/person/year ± US $745/person/year). CONCLUSION: The direct medical cost for management of people with T2DM in Indonesia was high. Early diagnosis and optimal management of T2DM to prevent complications may reduce the costly sequelae and have a possibility of cost savings.

Deintensification of Treatment With Sulfonylurea and Insulin After Severe Hypoglycemia Among Older Adults With Diabetes.

Importance: Practice guidelines recommend deintensification of hypoglycemic agents among older adults with diabetes who are at high risk of hypoglycemia, yet real-world treatment deintensification practices are not well characterized. Objective: To examine the incidence of sulfonylurea and insulin deintensification after a hypoglycemia-associated emergency department (ED) visit or hospitalization among older adults with diabetes and to identify factors associated with deintensification of treatment. Design, Setting, and Participants: This retrospective cohort study included a random sample of 20% of nationwide fee-for-service US Medicare beneficiaries aged 65 years and older with concurrent Medicare parts A, B, and D coverage between January 1, 2007, and December 31, 2017. Individuals with diabetes who had at least 1 hypoglycemia-associated ED visit or hospitalization were included. Data were analyzed from August 1, 2020, to August 1, 2021. Exposures: Baseline medication for the treatment of diabetes (sulfonylurea, insulin, or both). Main Outcomes and Measures: Incidence of treatment deintensification (yes or no) in the 100 days after a severe hypoglycemic episode requiring an ED visit or hospitalization, with treatment deintensification defined as (1) a decrease in sulfonylurea dose, (2) a change from long-acting to short-acting sulfonylurea (glipizide), (3) discontinuation of sulfonylurea, or (4) discontinuation of insulin based on pharmacy dispensing claims. Results: Among 76 278 distinct Medicare beneficiaries who had a hypoglycemia-associated ED visit or hospitalization, the mean (SD) age was 76.6 (7.6) years. Of 106 293 total hypoglycemic episodes requiring hospital attention, 69 084 (65.0%) occurred among women, 26 056 (24.5%) among Black individuals; 4761 (4.5%) among Hispanic individuals; 69 704 (65.6%) among White individuals; and 5772 (5.4%) among individuals of other races and ethnicities (comprising Asian, North American Native, unknown race or ethnicity, and unspecified race or ethnicity). A total of 32 074 episodes (30.2%) occurred among those receiving sulfonylurea only, 60 350 (56.8%) occurred among those receiving insulin only, and 13 869 (13.0%) occurred among those receiving both sulfonylurea and insulin. Treatment deintensification rates were highest among individuals receiving both sulfonylurea and insulin therapies at the time of their hypoglycemic episode (6677 episodes [48.1%]), followed by individuals receiving sulfonylurea only (14 192 episodes [44.2%]) and insulin only (14 495 episodes [24.0%]). Treatment deintensification rates increased between 2007 and 2017 (sulfonylurea only: from 41.4% to 49.7%; P < .001 for trend; insulin only: from 21.3% to 25.9%; P < .001 for trend; sulfonylurea and insulin: from 45.9% to 49.6%; P = .005 for trend). Lower socioeconomic status (as indicated by the receipt of low-income subsidies) was associated with lower odds of deintensification, regardless of baseline hypoglycemic regimen (sulfonylurea only: adjusted odds ratio [AOR], 0.74 [95% CI, 0.70-0.78]; insulin only: AOR, 0.71 [95% CI, 0.68-0.75]; sulfonylurea and insulin: AOR, 0.72 [95% CI, 0.66-0.78]). A number of patient factors were associated with higher odds of treatment deintensification: higher frailty (eg, ≥40% probability of needing assistance with activities of daily living among those receiving sulfonylurea and insulin: AOR, 1.50; 95% CI, 1.32-1.71), chronic kidney disease (eg, sulfonylurea and insulin: AOR, 1.29; 95% CI, 1.19-1.40), a history of falls (eg, sulfonylurea and insulin: AOR, 1.20; 95% CI, 1.09-1.33), and depression (eg, sulfonylurea and insulin: AOR, 1.11; 95% CI, 1.02-1.20). Conclusions and Relevance: In this cohort study, deintensification of sulfonylurea and/or insulin therapy within 100 days after a hypoglycemia-associated ED visit or hospitalization occurred in fewer than 50% of older adults with diabetes; however, these deintensification rates may be increasing over time, and deintensification of insulin was likely underestimated because of challenges in capturing changes to insulin dosing using administrative claims data. These results suggest that greater efforts are needed to identify individuals at high risk of hypoglycemia to encourage appropriate treatment deintensification in accordance with current evidence.