Rate Of Hypoglycemia Research Articles

Safety Event Outcomes and Glycemic Control with a Hybrid Closed-Loop System Used by Chinese Adolescents and Adults with Type 1 Diabetes Mellitus.

Background: While evidence supports glycemic control benefits for individuals with type 1 diabetes mellitus (T1DM) using hybrid closed-loop (HCL) systems, HCL automated insulin delivery therapy in China has not been assessed. This study evaluated safety events and effectiveness during HCL system use by Chinese adolescents and adults with T1DM. Methods: Sixty-two participants (n = 12 adolescents with a mean ± standard deviation [SD] of 15.5 ± 1.1 years and n = 50 adults [mean ± SD of 37.6 ± 11.1 years]) with T1DM and baseline A1C of 7.1% ± 1.0% underwent a run-in period (∼2 weeks) using open-loop Manual Mode (sensor-augmented pump) insulin delivery with the MiniMed™ 770G system with the Guardian™ Sensor (3) glucose sensor, followed by a study period (4 weeks) with HCL Auto Mode enabled. Analyses compared continuous glucose monitoring data and insulin delivered during the run-in versus study period (Wilcoxon signed-rank test or t-test). Safety events included rates of severe hypoglycemia and diabetic ketoacidosis (DKA). Results: Compared to baseline run-in, overall Auto Mode use increased time in range (TIR, 70-180 mg/dL) from 75.3% to 80.9% (P < 0.001) and reduced time below range (TBR, <70 mg/dL) from 4.7% to 2.2% (P < 0.001). Subgroup analysis demonstrated that participants (n = 29) with baseline A1C <7.0% had TBR that reduced from 5.6% to 2.0%, while participants (n = 21) with baseline A1C ≥7.5% had time above range (TAR, >180 mg/dL) that reduced from 31.6% to 20.8%. Auto Mode use also increased the percentage achieving combined recommendations for time at sensor glucose ranges (i.e., TIR of >70%, TBR of <4% and TAR of <25%) from 24.2% at baseline to 77.4% at study end. Total daily insulin dose reduced from 42.8 ± 19.8 to 40.7 ± 18.9 U (P = 0.013). There were no severe hypoglycemic, DKA, or serious adverse events. Conclusions: Chinese adolescents and adults, some of whom met target A1C at baseline, safely achieved significantly improved glycemia with 1 month of MiniMed 770G system use when compared to open-loop insulin delivery. ClinicalTrials.gov ID: NCT04663295.

A real-life comparison of hypoglycaemia symptomatology between insulin-treated type 2 diabetes participants with and without impaired awareness of hypoglycaemia.

We aim to compare and correlate Gold and Clarke questionnaire scores with hypoglycaemic symptomatic responses between insulin-treated type 2 diabetes participants with and without IAH in a real-life study. Insulin-treated type 2 diabetes participants attending an outpatient diabetes clinic in Singapore were asked to complete the Gold and Clarke questionnaires, record capillary blood glucose (CBG) and hypoglycaemic symptoms for 4 weeks. Data were collected from 153 participants (M:F = 98:55) with mean age 61.0 ± 9.4 years, duration of diabetes 19.5 ± 8.8 years and HbA1c 68 ± 17 mmol/mol (8.4 ± 1.5%). Gold and Clarke methods classified 19.6% and 26.8% of participants with IAH, respectively. Using CBG threshold of <3 mmol/L, significantly greater proportion of participants with intact awareness were experiencing autonomic symptoms than those with IAH with either method (Gold: 69% vs. 18%, p = 0.006; Clarke: 85% vs. 46%, p = 0.010). Significantly greater proportion of participants with IAH experienced no hypoglycaemia symptoms than those with intact awareness (Gold: 3.4% vs. 36%, p = 0.015; Clarke: 3.7% vs. 31%, p = 0.031). Participants with IAH had significantly higher rates of severe hypoglycaemia in the preceding year compared to those without (Gold: 17% vs. 3.3%; Clarke: 15% vs. 2.7%, p = 0.012). Gold and Clarke questionnaires are appropriate tools in ascertaining IAH status in insulin-treated type 2 diabetes participants. This is the first time whereby the hypoglycaemia symptomology has robustly validated the Gold and Clarke questionnaire in insulin-treated type 2 diabetes participants.

Antenatal corticosteroids in specific groups at risk of preterm birth: a systematic review

ObjectiveThis study aimed to synthesise available evidence on the efficacy of antenatal corticosteroid (ACS) therapy among women at risk of imminent preterm birth with pregestational/gestational diabetes, chorioamnionitis or fetal growth...

Comparison of Insulin Analogs and Human Insulins: A Narrative Review

Abstract Introduction Since insulin analogs have pharmacological properties that are similar to the normal physiological action of insulin, it has been suggested that they provide better glucose control and less rates of hypoglycemia compared to human insulins. Methods We performed a narrative, nonsystematic review of the literature including clinical trials, systematic reviews, meta-analyses, and professional guidelines related to the comparison of human insulins and insulin analogs in terms of glucose control, safety profile, and cost. Results Long-acting basal insulins result in mild improvement in glucose control and less rates of nocturnal hypoglycemic compared to neutral protamine Hagedorn insulin, mainly among patients with type 1 diabetes. Rapid-acting insulin analogs provide better glucose control and lower rates of hypoglycemia compared to regular insulin among patients with type 1 diabetes, whereas no advantage has been shown for insulin analogs among patients with type 2 diabetes for glucose control or hypoglycemia. Premixed insulin analogs provided no advantage in glucose control and inconsistent benefit in lowering the rates of hypoglycemia compared to human premixed insulins among patients with type 2 diabetes. The cost of insulin analogs is significantly higher than human insulins, and favorable cost-effectiveness has only been demonstrated for rapid-acting insulin analogs in type 1 diabetes. Conclusion Currently available evidence supports the use of rapid-acting insulin analogs and possibly long-acting basal insulin over human insulins for patients with type 1 diabetes. For patients with type 2 diabetes, the use of long-acting insulin analogs may be recommended for selected patients who are at an increased risk of significant hypoglycemia, while no clear benefits of meal insulin analogs over human insulins have been observed.

Neonatal outcomes and rationale for timing of birth in perinatal diabetes: a retrospective cohort study

The American College of Obstetricians and Gynecologists recommends delivery in the 39th week of pregnancy for patients with pregestational and medication-controlled gestational diabetes with consideration for earlier delivery among those with poor glucose control. We sought to evaluate the impact of birth before 39 weeks' gestation exclusively for diabetes-related indications on neonatal outcomes and clinician rationale for these recommendations. This was a retrospective cohort study of all singleton, nonanomalous pregnancies complicated by diabetes. Patients were identified through an obstetrical database containing information of 90,185 births from 2011 to 2021. Patients who delivered in a given week of gestation exclusively for diabetes-related indications were compared with ongoing pregnancies. Recommended births for other obstetrical indications were excluded from the diabetes-related indications cohorts. The primary outcome was neonatal intensive care unit admission. Secondary outcomes included neonatal intensive care unit length of stay, stillbirth, neonatal death, hypoglycemia, respiratory distress syndrome, and shoulder dystocia. For all births before 39 weeks' gestation, the electronic medical records were reviewed to confirm the rationale for the intervention for a diabetes-indicated condition. From the 90,185 recorded births that occurred in 2011 to 2021, 4750 patients with diabetes were identified. Of those, 30.5% (n=1449) had a recommended birth for a diabetes-related indications with 2.2% of those (n=32) occurring at 36 weeks' gestation, 7.9% (n=114) at 37 weeks' gestation, 9.7% (n=141) at 38 weeks' gestation, and 63.0% (n=913) at 39 weeks' gestation. Births that occurred at 36 and 37 weeks' gestation exclusively for diabetes-related indications had higher rates of neonatal intensive care unit admission than the respective ongoing pregnancies (62.5% vs 8.7%; P<.001 and 25.4% vs 7.2%; P<.001). There was no difference in neonatal intensive care unit admission for births at 38 or 39 weeks' gestation when compared with ongoing pregnancy. For neonates born at 36 and 37 weeks' gestation in comparison with ongoing pregnancies, the median neonatal intensive care unit length of stay was 11.0 vs 2.8 days, (P<.001) and 4.4 vs 2.6 days (P=.026), respectively. There were significantly increased rates of neonatal hypoglycemia and respiratory distress syndrome among births that occurred at 36, 37, and 38 weeks' gestation when compared with ongoing pregnancies. There were no differences in the rate of stillbirth in this cohort. Primary factors cited for early birth were poor glycemic control (71.4%), recommendation by a maternal-fetal medicine specialist (38.7%), and suspected fetal macrosomia (27.9%). Overall, 46.7%, 32.8%, and 20.6% of patients had 1, 2, or ≥3 indications, respectively, listed as rationale for early birth. Overall, few objective measures were used to recommend birth before 39 weeks' gestation owing to diabetes. In pregnancies complicated by diabetes, early birth exclusively for diabetes-related indications was associated with increased neonatal intensive care unit admission and length of stay and with neonatal morbidity. Little objective data are documented by clinicians to support their recommendations for early birth associated with diabetes. Additional clinical guidelines are needed to define suboptimal glucose control necessitating birth before 39 weeks' gestation.

Impact of an enteral nutrition holding guideline on daily nutrition goals in patients taking phenytoin.

Concomitant administration of enteral nutrition (EN) and phenytoin decreases phenytoin absorption. Concerns over impaired nutrition, however, may prevent EN from being held surrounding phenytoin administration. This study aimed to evaluate whether EN holding guidelines impacted nutrition goal achievement in patients taking phenytoin. Adult patients administered enteral phenytoin for acute or chronic seizures while receiving EN during a neurocritical care admission 6 months before and after EN holding guideline implementation were eligible. Patients without phenytoin concentrations or a clinical registered dietitian assessment were excluded. The primary outcome was the percentage of nutrition daily goals attained before and after implementation. Secondary end points included the incidence of hypoglycemia, differences in measured phenytoin concentrations, and rates of therapeutic (10-20 mcg/ml) and high-therapeutic (15-20 mcg/ml) concentration attainment. Concentrations were adjusted for hypoalbuminemia using the Winter-Tozer equation. Fifty-five patients representing 412 patient days and 1110 phenytoin administrations were included with 29 preimplementation and 26 postimplementation patients. Median percent attainment of daily EN goals was consistent preimplementation and postimplementation (86% vs 83%, P = 0.48). No significant change in rates of days with hypoglycemia was observed. Adjusted phenytoin concentrations were similar before and after implementation (14.1 vs 15.2 mcg/ml, P = 0.45), but the preimplementation cohort had a lower proportion of high-therapeutic concentrations (23% vs 36%, P = 0.018). Holding EN for phenytoin did not impact attainment of daily nutrition goals and was not associated with increased rates of hypoglycemia. This is the first study to evaluate the effect of EN holding on nutrition goals in patients receiving phenytoin.

Comparison of Perinatal Outcomes According to the Majority of Physicians: Obstetrics Versus Endocrinology

Purpose: To compare the perinatal outcomes among the majority of physicians who manage pregnancies complicated by gestational diabetes mellitus (GDM), particularly those who require insulin treatment.Methods: We conducted a retrospective study involving 206 singleton pregnant women diagnosed with GDM between January 2017 and September 2022. The study participants were divided into 2 groups according to the majority of physicians (obstetrics vs. endocrinology). We compared the maternal characteristics and perinatal outcomes between the 2 groups and performed a subgroup analysis of preterm birth cases.Results: During the study period, 206 pregnant women were diagnosed with GDM and 36.9% (76 of 206) required insulin treatment. Among the GDM A2 pregnancies, 26 patients visited or consulted endocrinologists, and 50 patients were managed by obstetricians. There were no significant differences in maternal characteristics and perinatal outcomes between the two groups. Eighteen infants were delivered before 37 weeks of gestation (12 in the obstetrician group and 6 in the endocrinologist group). In preterm-delivered patients, the birth weight was heavier in the endocrinology group (median [range], 2.66 [1.98–3.77] vs. 3.71 [2.48–4.17], p=0.025) despite similar gestational age at delivery (median [range], 35.5 [33.1–36.5] vs. 36.0 [34.2–36.6], p=0.511). However, there were no significant differences in perinatal outcomes, including the rate of neonatal hypoglycemia, oxygen treatment and the duration of neonatal intensive care unit admission.Conclusion: Our data show that GDM can be managed by obstetricians even in cases requiring insulin treatment.

Diabetes associated complicated disorders and its treatment a review article

Type 2 diabetes mellitus is increasingly prevalent in the worldwide and is associated with significant morbidity, mortality, and rising health care costs. Microvascular and, to a lesser extent, macrovascular complications are recognized to result from uncontrolled hyperglycemia. However, intensive therapy to achieve normal glucose levels is not without risk, as demonstrated by increased rates of hypoglycemia, weight gain, and all-cause mortality rates in the intensive treatment arm of the ACCORD trial. In addition, observational studies indicate that the presence of diabetes increases the risk of other comorbidities such as fracture and certain cancers, and treatment choice may affect risk. Thus, in an effort to maintain glucose control, the clinician encounters a complex interplay of primary disease management while simultaneously seeking to avoid complications associated with glucose lowering. The chronic nature of diabetes management, efficacy must be balanced against side effects to achieve a tolerable long-term regimen. The goal of this concept is to identify complications of non-insulin treatment of diabetes. The major classes of medication should be reviewed with special attention given to patient considerations, mechanism of action, effect on weight, and cardiovascular outcomes, and additional class-specific side effects including effects on bone. In addition, effects on β-cell function are rectified. It is possible to identify diabetes mellitus risk years or decades in advance on the basis of numerous personal, historic, and laboratory measures and user-friendly clinical decision-support tool to estimate absolute risk for individuals. The patient families, communities, and health organizations should encourage healthy eating and physical activity and should focus the most intensive diabetes mellitus prevention efforts on those at highest risk for progression to diabetes mellitus.

Compliance with the Golden Hour bundle in deliveries attended by a specialized neonatal transport team compared with staff at non-tertiary centres.

Preterm infants born at <32 weeks gestational age (GA) have increased morbidity if they are born outside tertiary centres (outborn). Stabilization and resuscitation after birth consistent with the neonatal Golden Hour practices (NGHP) are required to optimize outcomes. To evaluate physiological outcomes of hypothermia and hypoglycaemia, and compliance with NGHP by neonatal transport team (NTT) compared with referral hospital team (RHT) during the stabilization of infants born at <32 weeks GA. A retrospective case-control study of infants born at <32 weeks GA during 2016-2019 at non-tertiary perinatal centres where the NTT attended the delivery (cases) were matched to infants where the RHT team attended the delivery (controls). During the 4-year period, NTT team received 437 requests to attend deliveries at <32 weeks GA and attended 76 (17%) prior to delivery. These cases were matched 1:1 with controls composed of deliveries attended by the RHT. The rate of hypothermia was 15% versus 29% in the NTT and RHT groups, respectively (P = 0.01). The rate of hypoglycaemia (<2.2 mmol/L) was 5% versus 12% in the NTT and RHT groups, respectively (P = 0.64). For compliance with the NGHP, use of fluid boluses was 8% versus 33%, use of thermoregulation practices, that is, plastic bag, was 76% versus 21%, and establishment of intravenous access was 20 min versus 47 min, in the NTT and RHT groups, respectively. High-risk preterm deliveries attended by the NTT compared with the RHT had increased compliance and earlier implementation of the NGHP elements, associated with improved physiological stability and lower hypothermia rates. Outreach education for RHT should ensure that these key elements are included during the training in the stabilization of high-risk preterm deliveries.

Severe hypoglycemia and falls in older adults with diabetes: The Diabetes & Aging Study

ObjectiveTo estimate rates of severe hypoglycemia and falls among older adults with diabetes and evaluate their association. Research Design and MethodsSurvey in an age-stratified, random sample adults with diabetes age 65–100 years; respondents were asked about severe hypoglycemia (requiring assistance) and falls in the past 12 months. Prevalence ratios (adjusted for age, sex, race/ethnicity) estimated the increased risk of falls associated with severe hypoglycemia. ResultsAmong 2,158 survey respondents, 79 (3.7%) reported severe hypoglycemia, of whom 68 (86.1%) had no ED visit or hospitalization for hypoglycemia. Falls were reported by 847 (39.2%), of whom 745 (88.0%) had no fall documented in outpatient or inpatient records. Severe hypoglycemia was associated with a 70% greater prevalence of falls (adjusted prevalence ratio = 1.7 (95% CI, 1.3–2.2)). ConclusionWhile clinical documentation of events likely reflects severity or care-seeking behavior, severe hypoglycemia and falls are common, under-reported life-threatening events.

Glucagon prescribing and prevention of hospitalization for hypoglycemia in a large health system

AimsTo examine glucagon prescribing trends among patients at high risk of severe hypoglycemia and assess if a glucagon prescription is associated with lower rates of severe hypoglycemia requiring hospital care. MethodsRetrospective analysis of electronic health records from a large integrated healthcare system between May 2019 and August 2021. We included adults (≥18 years) with type 1 diabetes or with type 2 diabetes treated with short-acting insulin and/or recent history of hypoglycemia-related emergency department visit or hospitalization. We calculated rates of glucagon prescribing overall and by patient characteristics. We then matched 1:1 those who were and were not prescribed glucagon and assessed subsequent hypoglycemia-related hospitalization. ResultsOf 9,200 high risk adults, 2063 (22.4%) were prescribed glucagon. Among patients more likely to be prescribed glucagon were those younger, female, White, living in urban areas, with prior severe hypoglycemia, and with a recent endocrinology specialist visit. In the matched cohort (N = 1707 per arm), 62 prescribed glucagon and 33 not prescribed glucagon were hospitalized for hypoglycemia (adjusted incidence rate ratio 1.71, 95% CI 1.10–2.66; P = 0.018). ConclusionGlucagon prescribing was infrequent with significant racial and rural disparities. Patients with glucagon prescriptions did not have lower rates of hospitalization for hypoglycemia.

A comparison of 2 doses of antenatal dexamethasone for the prevention of respiratory distress syndrome: an open-label, noninferiority, pragmatic randomized trial

Antenatal corticosteroids have been used for the prevention of respiratory complications, intraventricular hemorrhage, necrotizing enterocolitis, and other adverse neonatal outcomes for over 50 years, with limited evidence about their optimal doses. Higher steroid doses or frequencies of antenatal corticosteroids in preterm newborns pose adverse effects such as prolonged adrenal suppression, negative effects on fetal programming and metabolism, and increased risks of neurodevelopmental and neuropsychological impairments. Conversely, lower doses of antenatal corticosteroids may be an effective alternative to induce fetal lung maturation with less risk to the fetus. Late preterm births represent the largest population of all preterm neonates, with a respiratory distress syndrome risk of 8.83%. Therefore, determining the optimal antenatal corticosteroid dosage is of particular importance for this population. This study aimed to compare the efficacy of 5-mg and 6-mg dexamethasone in preventing neonatal respiratory distress syndrome in women with preterm births at 320 to 366 weeks of gestation. This was an open-label, randomized, controlled, noninferiority trial. Singleton pregnant women (n=370) at 320 to 366 weeks of gestation with spontaneous preterm labor or preterm premature rupture of membranes were enrolled. They were randomly assigned (1:1) to a 5-mg or 6-mg dexamethasone group. Dexamethasone was administered intramuscularly every 12 hours for 4 doses or until delivery. The primary outcome was the reduction in neonatal respiratory distress syndrome cases, whereas the secondary outcomes were any adverse maternal or neonatal events. Between December 2020 and April 2022, 370 eligible women, anticipating deliveries within the gestational range of 32 0/7 to 36 6/7 weeks, willingly participated in the study. They were evenly split, with 185 women assigned to the 5-mg group and 185 to the 6-mg group. The study revealed that the demographic profiles of the participants in the 2 groups were remarkably similar, with no statistically significant disparities (P>.05). It is noteworthy that most of these women gave birth after 34 weeks of gestation. Despite a substantial proportion not completing the full course of steroid treatment, the 5-mg dose exhibited noninferiority compared with the 6-mg dose of dexamethasone, as indicated by a modest proportional difference of 0.5% (95% confidence interval,-2.8 to 43.9). Neonatal respiratory distress syndrome occurred in a relatively low percentage of newborns in both groups, affecting 2.2% in the 5-mg group and 1.6% in the 6-mg group. Notably, the risk difference of 0.6% fell comfortably within the predefined noninferiority threshold of 10%. Our study suggests that a 5-mg dexamethasone dose is noninferior to a standard 6-mg dose in preventing neonatal respiratory distress syndrome in preterm births.

Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes

Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes. To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes. Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol). Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294). The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes. Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], -0.2 [95% CI, -0.3 to -0.1] percentage points), confirming noninferiority (P < .001) and superiority (P = .002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, -6 to 5] mg/dL; P = .90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, -0.19 to 1.10] kg; P = .17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P = .01). Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups. ClinicalTrials.gov Identifier: NCT04795531.

179-OR: Improved A1C and TIR with Once-Weekly Insulin Icodec vs. Insulin Glargine U100 in Insulin-Naïve T2D—ONWARDS 1

Long-term efficacy and safety of once-weekly insulin icodec (icodec) vs insulin glargine U100 (IGlar), both with non-insulin glucose-lowering agents, including SGLT2i and GLP‑1 RA, were assessed in this randomized, open-label, treat-to-target phase 3a trial (52-week + 26-week extension) in insulin-naïve adults with T2D (NCT04460885). Participants (n=984) were randomized 1:1 to icodec or IGlar. Prespecified primary analysis at week 52 showed A1C reduction from a baseline (BL) of 8.5% to 6.9% with icodec vs 8.4% to 7.1% with IGlar (estimated treatment difference [ETD]: −0.19%-points [95% CI: −0.36, −0.03]), confirming non‑inferiority (p&amp;lt;0.0001) and superiority (p=0.0210) of icodec. Time spent in target glycemic range (TIR, from week 48-52) was significantly improved to 72% (icodec) vs 67% (IGlar), confirming superiority; ETD 4.27%-points (95% CI: 1.92; 6.62, p=0.0004). There were no significant differences in mean weekly insulin dose (week 50-52), or in body weight change from BL. Level 2 or 3 hypoglycemia rates (BL to week 52) were low in both groups, with numerically higher rates with icodec. A higher proportion achieved A1C &amp;lt;7% without level 2 or 3 hypoglycemia with icodec vs IGlar (52.6% vs 42.6%, p=0.0028). In totality, glycemic control (A1C, TIR, A1C &amp;lt;7% without hypoglycemia) was significantly improved by once-weekly icodec vs daily glargine U100 with low rates of hypoglycemia in both arms. Disclosure J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. S.C.Bain: Advisory Panel; Novo Nordisk, Sanofi, Lilly, Boehringer Ingelheim Inc., AstraZeneca. A.Gowda: Employee; Novo Nordisk A/S. H.Horio: Employee; Novo Nordisk. E.Jodar: Other Relationship; Amgen Inc., AstraZeneca, Eli Lilly and Company, FAES, Novo Nordisk, UCB, Inc., Speaker's Bureau; Merck &amp; Co., Inc., Asofarma, ZP Pharmaceuticals. L.Lang lehrskov: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp &amp; Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. R.Trevisan: Advisory Panel; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Other Relationship; Boehringer Ingelheim Inc., Sanofi. O.Mosenzon: Advisory Panel; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Bayer Inc., Employee; BOL Pharma, Research Support; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Sanofi. Funding Novo Nordisk A/S

Hypoglycemia in children and young adults with cystic fibrosis during oral glucose tolerance testing vs. continuous glucose monitoring.

Hypoglycemia is common in people with cystic fibrosis (pwCF) during oral glucose tolerance tests (OGTTs) and in the free-living setting, yet its pathophysiology remains unclear. To evaluate hypoglycemia in children and young adults with CF by OGTT and continuous glucose monitoring (CGM). A 3-h OGTT was performed in children and young adults with CF and healthy controls (HC). Individuals were classified as experiencing hypoglycemia on OGTT (glucose <70 mg/dL) or not. Insulin, C-peptide, glucose, glucagon, and incretins were measured. CGM was performed for 7 days in the free-living setting. Measures of insulin sensitivity, beta cell function accounting for insulin sensitivity, and insulin clearance were calculated. A total of 57 participants (40 CF and 17 HC) underwent assessment. Rates of hypoglycemia by OGTT were similar in pwCF (53%, 21/40) compared to HC (35%, 6/17), p = 0.23. PwCF compared to HC had higher A1c; on OGTT higher and later glucose peaks, later insulin peaks; and on CGM more glucose variability. CF Hypo+ versus CF Hypo- had higher lung function, higher insulin sensitivity, higher beta cell function accounting for insulin sensitivity, and decreased CGM variability. When comparing CF Hypo+ to HC Hypo+, although rates of hypoglycemia are similar, pwCF had blunted glucagon responses to hypoglycemia. OGTT hypoglycemia was not associated with CGM hypoglycemia in any group. Youth with CF have increased insulin sensitivity and impaired glucagon response to hypoglycemia on OGTT. Hypoglycemia on OGTT did not associate with free-living hypoglycemia.

178-OR: Better Glycemic Control with Once-Weekly Insulin Icodec vs. Once-Daily Insulin Degludec in Insulin-Naïve Type 2 Diabetes (ONWARDS 3)

Efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin degludec (degludec) in insulin-naïve adults with T2D were examined in ONWARDS 3 (NCT04795531), a 26-week, randomized, double blind, double dummy, treat-to-target, phase 3a trial. Participants (n=588) were randomized 1:1 to icodec or degludec. Key outcomes are shown in the table. The primary endpoint was A1C change from baseline (BL) to week 26. Estimated mean A1C change was greater with icodec (−1.57%; BL: 8.55%) vs degludec (−1.36%; BL: 8.48%); estimated treatment difference −0.21%-points (95% CI −0.34, −0.08), confirming non-inferiority (p&amp;lt;0.0001) and superiority (p=0.0016). Level 2 or 3 hypoglycemia rates were numerically but not statistically significantly higher with icodec vs degludec in the on-treatment period. Odds of achieving A1C &amp;lt;7% without level 2 or 3 hypoglycemia were statistically significantly higher with icodec vs degludec. There were no significant differences in weekly insulin dose from week 24 to 26 or body weight change from BL to week 26 between arms. No unexpected safety findings were observed. Overall, once-weekly icodec demonstrated superior A1C reduction vs once-daily degludec with low level 2 or 3 hypoglycemia rates in both arms. Icodec may facilitate insulin treatment acceptance and adherence by reducing basal insulin injections from ≥365 to 52 per year. Disclosure I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp &amp; Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. M.Asong: Employee; Novo Nordisk. C.Desouza: Advisory Panel; Novo Nordisk A/S, Bayer Inc., Consultant; Asahi Kasei Corporation, Research Support; Eli Lilly and Company. P.Gourdy: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Sanofi, Bayer Inc., Merck Sharp &amp; Dohme Corp., Novartis, Intercept Pharmaceuticals, Inc., Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Sanofi, Abbott, AstraZeneca, Boehringer-Ingelheim. S.Kar: None. A.G.Vianna: Advisory Panel; AstraZeneca, Board Member; Abbott Diabetes, Novo Nordisk, Medtronic, Research Support; Novo Nordisk, Anji Pharmaceuticals, Lilly, Speaker's Bureau; AstraZeneca, Novo Nordisk, Medtronic. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. S.M.Vinther: Employee; Novo Nordisk. Y.Mu: Speaker's Bureau; Abbott Diabetes, Boehringer Ingelheim Inc., Novo Nordisk (China), Sanifit. Funding Novo Nordisk A/S

1794-PUB: Potential for Improving CGM Systems? Anticipated Benefits from Increasing the Glucose Prediction of Current CGM Algorithms

Current CGM algorithms allow a glucose prediction up to 30 minutes. To elaborate on the potential to improve current CGM systems, we investigated if a possible increase in this prediction window to up to 2 hours would be perceived as a significant benefit. People with type 1 and type 2 diabetes currently using a CGM system were invited to participate. Participants were presented with a scenario depicting the potential of a hypothetical CGM algorithm to predict the course of glucose for up to 2 hours. They were instructed to imagine how such a long-term prediction would affect their diabetes management. They were asked to complete the T1-Diabetes Distress Scale (T1-DDS) and the Hypoglycemia Fear Survey (HFS-II) and rate each item regarding the perceived potential change from using such a long-term prediction (scale: -2 strong deterioration, -1 deterioration, 0 no change, 1 improvement, 2 strong improvement). 206 people participated (29.1% type 2 diabetes). Participants expected moderate improvements in hypoglycemia and management distress (Box plots shown in Figure 1 for T1-DDS). Similar improvements in HFS-II scores (0.57±0,49) were seen with no differences between diabetes types. Increasing the glucose prediction to up to 2 hours would be seen as a potential improvement regarding reductions in hypoglycemia distress and fear of hypoglycemia by both people with type 1 and type 2 diabetes. Disclosure D.Ehrmann: Advisory Panel; Roche Diabetes Care, mySugr, Dexcom, Inc., Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc. T.Glatzer: Employee; Roche Diabetes Care, Berlin-Chemie AG. L.Priesterroth: Speaker's Bureau; Ypsomed AG. B.Olesen: Advisory Panel; AstraZeneca, Evivamed, Berlin-Chemie AG, Speaker's Bureau; Medtronic, Medtrixx. B.Kulzer: Advisory Panel; Berlin-Chemie AG, Abbott Diabetes, Bayer Inc., Dexcom, Inc., Novo Nordisk, Insulet Corporation, embecta, Research Support; Sanofi, Roche Diabetes Care. N.Hermanns: Advisory Panel; Insulet Corporation, Research Support; Sanofi-Aventis Deutschland GmbH, Roche Diagnostics, Becton, Dickinson and Company, Speaker's Bureau; Dexcom, Inc., Berlin-Chemie AG. Funding Roche Diabetes Care

Safety and efficacy of non-insulin therapy in non-critically ill hospitalized patients with type 2 diabetes mellitus

IntroductionClinical guidelines recommend insulin as the mainstay of therapy for hospitalized patients with diabetes mellitus. The aim of the current study is to evaluate safety and efficacy of non-insulin anti-hyperglycemic therapy in hospitalized patients. Materials and methodsSystematic review and meta-analysis of randomized controlled trials (RCTs) examining treatment of hospitalized patients with type 2 diabetes with insulin vs non-insulin therapy. We searched PubMed and the Cochrane Library for RCTs published from inception to November 30, 2022. Primary outcomes were 30-day mortality and hypoglycemic events during hospitalization. This meta-analysis includes two parts, the first is a comparison between insulin and non-insulin therapy and the second is a comparison between insulin only and a combination of insulin+non-insulin therapy. ResultsA total of 14 randomized control studies and 1570 patients were included. There was a lower incidence of 30-day mortality in the insulin+non-insulin group compared with the insulin group without statistical significance, RR 0.64 (95%CI 0.30–1.35). Hypoglycemic events were significantly lower with the non-insulin therapies compared to insulin therapy, RR 0.23 (95%CI 0.09–0.55). Mean daily glucose levels were significantly lower in the insulin+non-insulin group compared to the insulin group by 10.83 mg/dL (95%CI -14.78-(-6.87)). ConclusionsNon-insulin either with or without insulin, results in lower rates of hypoglycemia. Non-insulin+insulin is more effective than insulin alone in reducing blood glucose levels. Non-insulin-based therapy is safe and effective for control of hyperglycemia. Insulin combined with non-insulin drugs seems to be the preferred treatment option for the majority of hospitalized patients with type 2 DM in the non-critical care setting.

251-OR: The Impact of Identifying Sleep with a Fitbit on Calculated Rates of Nocturnal Hypoglycemia—The Hypo-Metrics Study

Consensus defines nocturnal hypoglycemia as occurring between 00:00 and 06:00 hrs. However, this may introduce bias, as for many, these hours only partially match real sleeping hours. Therefore, we compared rates of hypoglycemia while asleep (defined by Fitbit Charge 4) to rates of conventionally-defined nocturnal hypoglycemia. Hypo-METRICS study participants wore a Fitbit charge 4 and blinded FreeStyle Libre glucose monitor for up to 70 days. Every hypoglycemia episode (≤70mg/dL or ≤54mg/dL for ≥15 min) was classified as ‘asleep’ or ‘awake’ based on Fitbit sleep intervals and ‘nocturnal’ (00:00-06:00 hrs) or ‘day-time’. We compared weekly sensor-detected hypoglycemia (SDH) rates whilst asleep to nocturnal SDH rates using a paired sample Wilcoxon test. We included 542 participants (269 with type 1 diabetes, median (IQR) age 56 (44-66) years, HbA1c 7.3%(6.7-7.9), with 69 (65-70) nights with sleep data/participant). Sleep duration was 6.1 (5.2-6.8) hours. Median weekly rates of SDH while asleep were higher than rates of nocturnal SDH both ≤70mg/dL (1.3 (0.6-2.5) vs 0.9 (0.4-1.8), p&amp;lt;0.001) and ≤54mg/dL (0.4 (0.2-0.9) vs 0.3 (0.1-0.7), p&amp;lt;0.001). Stratifying by type of diabetes did not change the direction or magnitude of the differences in SDH rates. Using clock time to estimate nocturnal hypoglycemia underestimates hypoglycemia whilst asleep by up to a third. Using activity trackers such as Fitbit to identify sleep offers a novel way to estimate hypoglycemia whilst asleep to better reflect lived experience of nocturnal hypoglycemia. Disclosure G.Martine-edith: Other Relationship; Novo Nordisk A/S. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. E.Renard: Consultant; Abbott Diabetes, Dexcom, Inc., AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Roche Diabetes Care. S.R.Heller: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Other Relationship; Eli Lilly and Company, Research Support; Dexcom, Inc., Speaker's Bureau; Novo Nordisk, Medtronic. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. Hypo-resolve consortium: n/a. P.Divilly: None. N.Zaremba: None. U.Soeholm: Employee; Novo Nordisk A/S. A.Kingsnorth: None. Z.Mahmoudi: Employee; Novo Nordisk. M.Gomes: Employee; Novo Nordisk A/S. B.E.De galan: Research Support; Novo Nordisk. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi, Vertex Pharmaceuticals Incorporated. Funding Innovative Medicines Initiative 2 Joint Undertaking (777460)

446-P: Antihyperglycemic Medication Initiation after Cardiovascular Hospitalization in Older Adults with Diabetes Increases Hypoglycemia without Improving Survival

Background: The short-term safety and long-term cardiovascular benefits of initiating new antihyperglycemic medications at hospital discharge are unclear, especially for elderly patients with acute cardiovascular disease. This study aimed to determine if initiation of a new diabetes medication is associated with differences in outcomes in this patient population. Methods: This was a population-based cohort study of individuals ≥65 years with diabetes on antihyperglycemic medication who were discharged from a hospitalization for heart failure, acute myocardial infarction, or stroke in Ontario, Canada from April 2011 to March 2019. We categorized individuals based on initiation of a new diabetes medication (initiators) within 30 days of discharge. Primary outcome was a composite of death or cardiovascular hospitalization. Secondary outcome was rate of hypoglycemia. We performed a Cox-regression on a propensity matched cohort. Results: A total of 54,117 individuals were included, with 5,129 (9.5%) initiators and 48,988 (90.5%) non-initiators. Median age was 78 years (IQR 71-84) and 56.7% were male. Matched pair analysis included 4,844 pairs of initiators and non-initiators with standardized differences of ≤0.05 for all baseline variables. Median follow-up was near 2.2 years in both groups. There were no significant differences in the hazard of the composite of death/cardiovascular hospitalization (HR 0.97, 95% CI 0.92-1.02, p=0.18) or the hazard of death (HR 0.98, 95% CI 0.93-1.04, p=0.56). There was a higher risk of hypoglycemia among initiators (113 [2.3%] vs 76 [1.6%]) within one year of follow-up (HR: 1.49, 95% CI 1.12-1.98, p=0.007). Conclusion: Starting a new antihyperglycemic medication in patients with diabetes who are discharged after hospitalization for a cardiovascular event is associated with an increased risk of hypoglycemia but does not reduce mortality or cardiovascular events. Disclosure A.Farahvash: None. A.Sivaswamy: None. H.Abdel-qadir: Other Relationship; AstraZeneca, JAZZ Pharmaceuticals. I.C.Lega: None.