Hybrid Closed Loop Systems Improve Glycemic Control and Quality of Life in Historically Minoritized Youth with Diabetes.

Background: We assessed changes in glycemic control and person-reported outcome measures (PROMs) with t:slim X2 insulin pump with Control-IQ technology use among historically minoritized youth who are least likely to access hybrid closed loop (HCL) technology. Methods: This single-arm, prospective pilot study enrolled 15 publicly insured, insulin pump-naïve, non-Hispanic Black youth ages 6 to <21 years with type 1 diabetes and hemoglobin A1c (HbA1c) ≥10% in a 6-month study of HCL use. The primary outcome was absolute change in time in range (TIR) (70-180 mg/dL). Secondary outcomes included other continuous glucose monitor metrics, PROMs, and diabetic ketoacidosis (DKA) incidence. Results: For 13 youth (median 14.8 years, 53.3% female, HbA1c 11.7%) who completed the study, baseline TIR of 12.3% (6.3-27.1%) increased 23.7%-points (16.9, 30.5%; P < 0.001) or 5.7 h per day. Percent time >250 mg/dL decreased 33.9%-points (-44.8, -23.1%; P < 0.001) or 8.1 h per day from a baseline of 69.4% (51.6, 84.0%). Median time in HCL was 78.3% (59.7, 87.3%). Youth received 10.1 (9.2, 11.9) boluses per day, 71.7% (63.8, 79.3%) of which were HCL-initiated autoboluses. Diabetes-specific quality of life increased among parents (P < 0.001) and youth (P = 0.004), and diabetes distress decreased in both groups (P < 0.001, P = 0.005). Improvements in glycemia did not correlate with any baseline youth or parent PROMs. DKA was high at baseline (67 episodes/100-person years) and did not increase during the intervention (72 episodes/100-person years, P = 0.78). Conclusion: Improvements in glycemic control and quality of life exceeding pivotal trial findings without increased safety risks among historically minoritized youth emphasize the need for equitable access to HCL systems. ClinicalTrials.gov: clinicaltrials.gov ID (NCT04807374).

Challenges in achieving adequate glycemic control among children with type 1 diabetes mellitus in a resource-limited setting: A cross-sectional study from Sudan.

OBJECTIVE: To assess glycemic control and associated factors in children with type 1 diabetes mellitus (T1DM) attending the pediatric diabetes clinic in Wad-Madani City, Sudan. METHODS: This cross-sectional observational study was conducted at a referral center in Sudan. The study population consisted of children aged 1-18 years who had been diagnosed with T1DM for more than 1 year and were under regular follow-up in the clinic. Data on their glycemic control and sociodemographic and clinical characteristics were captured. RESULTS: Out of 211 enrolled patients, 120 (56.9 %) were females. The mean age was 11.7 years (SD = 4.0), with the mean age at diagnosis of 6.7 years (SD = 4.0). Only 6.2 % achieved adequate glycemic control. Adolescents had particularly poor control (97.8 %). The mean glycosylated hemoglobin (HBA1c) level was 10.4 % (90 mmol/mol). Inferior glycemic control was associated with advancing age, older age at diagnosis, belonging to single-parent households, less frequent self-monitoring of blood glucose (SMBG), and having a greater number of siblings or household members. A third of patients (33.8 %) had had one or more diabetes ketoacidosis (DKA) episodes in the previous year. There was a high prevalence of lipodystrophy (34.1 %) and arthropathy (25.1 %). CONCLUSIONS: An exceptionally low proportion of children with T1DM achieved adequate glycemic control, with adolescents particularly struggling. SMBG frequency and family dynamics emerged as potential factors, highlighting the urgent need for tailored interventions and improved diabetes education in resource-limited settings.

Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of empagliflozin versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Post-authorization safety study based on multinational cohorts.

AIM: To estimate risks of diabetic ketoacidosis (DKA), acute liver injury (ALI), acute kidney injury (AKI), chronic kidney disease (CKD), severe complications of urinary tract infection (UTI) and genital infection (GI) among patients with type 2 diabetes initiating empagliflozin versus those initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor. MATERIALS AND METHODS: In this large multinational, observational, new-user cohort study in UK, Danish and US healthcare data sources, patients initiated empagliflozin or a DPP-4 inhibitor between August 2014 and August 2019, were aged ≥18 years, and had ≥12 months' continuous health plan enrolment. Incidence rates by exposure and incidence rate ratios, adjusted for propensity-score deciles, were calculated. RESULTS: In total, 64 599 empagliflozin initiators and 203 315 DPP-4 inhibitor initiators were included. There was an increased risk [pooled adjusted incidence rate ratios (95% confidence interval)] of DKA [2.19 (1.74-2.76)] and decreased risks of ALI [0.77 (0.50-1.19) in patients without predisposing conditions of liver disease; 0.70 (0.56-0.88) in all patients] and AKI [0.54 (0.41-0.73)]. In the UK data, there was an increased risk of GI [males: 4.04 (3.46-4.71); females: 3.24 (2.81-3.74)] and decreased risks of CKD [0.53 (0.43-0.65)] and severe complications of UTI [0.51 (0.37-0.72)]. The results were generally consistent in subgroup and sensitivity analyses. CONCLUSIONS: Compared with DDP-4 inhibitor use, empagliflozin use was associated with increased risks of DKA and GI and decreased risks of ALI, AKI, CKD and severe complications of UTI. These associations are consistent with previous studies and known class effects of sodium-glucose cotransporter 2 inhibitors, including renoprotective effects and beneficial effects on alanine aminotransferase levels.

Outcomes measured in studies assessing health systems interventions for type 1 diabetes management: A scoping review.

AIMS: Describe the outcomes reported in research on health systems interventions for type 1 diabetes management in comparison to the outcomes proposed by a core outcome set (COS) for this condition, an essential list of outcomes that studies should measure. METHODS: Systematic search of studies published between 2010 and 2021 reporting health systems interventions directed to improve the management of type 1 diabetes using PubMed, EMBASE and CENTRAL. Information on the outcomes was extracted and classified according to a COS: self-management, level of clinical engagement, perceived control over diabetes, diabetes-related quality of life, diabetes burden, diabetes ketoacidosis, severe hypoglycemia, and glycated hemoglobin (HbA1C). RESULTS: 187 studies were included. Most of the studies included either children (n = 82/187) or adults (n = 82/187) living with type 1 diabetes. The most common outcome measured was HbA1C (n = 149/187), followed by self-management (n = 105/187). While the least measured ones were diabetes ketoacidosis (n = 15/187), and clinical engagement (n = 0/187). None of the studies measured all the outcomes recommended in the COS. Additionally, different tools were found to be used in measuring the same outcome. CONCLUSIONS: This study provides a description of what researchers are measuring when assessing health systems interventions to improve type 1 diabetes management. In contrast to a COS, it was found that there is a predominance of clinical-based outcomes over patient-reported outcome measures.

Fulminant type 1 diabetes: Focusing on triggering factors.

Fulminant type 1 diabetes (FT1D) is a novel type of type 1 diabetes that is caused by extremely rapid destruction of the pancreatic ß cells. Early diagnosis or prediction of FT1D is critical for the prevention or timely treatment of diabetes ketoacidosis, which can be life-threatening. Understanding its triggers or promoting factors plays an important role in the prevention and treatment of FT1D. In this review, we summarised the various triggering factors of FT1D, including susceptibility genes, immunological factors (cellular and humoural immunity), immune checkpoint inhibitor therapies, drug reactions with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome, pregnancy, viral infections, and vaccine inoculation. This review provides the basis for future research into the pathogenetic mechanisms that regulate FT1D development and progression to further improve the prognosis and clinical management of patients with FT1D.

Open-source Artificial Pancreas Systems Are Safe and Effective When Supported In-clinic: Outcomes in 248 Consecutive Type 1 Diabetes Clients.

OBJECTIVE: Our aim in this study was to determine the safety, glycemia, and quality of life (QoL) associated with in-clinic installation and management of supported open-source artificial pancreas systems (SOSAPS) in type 1 diabetes (T1D). METHODS: This investigation is a retrospective cohort study of consecutive SOSAPS users at a Canadian diabetes centre. SOSAPS were offered to all moderately tech-savvy T1D clients on sensor-augmented multiple daily injection or pump, able to pay for hardware, and willing to sign a consent and waiver document. SOSAPS were installed and maintained by clinic staff at no cost to clients. iPhone users were assigned to either Loop (n=108) or iPhone artificial pancreas systems (iAPS; n=114) and Android users to Android-type APS (n=24). Outcomes included severe hypoglycemia and diabetic ketoacidosis (DKA), time in range (TIR) 4.0 to 10.0 mmol/L, time below range (TBR) <4 mmol/L, glucose management indicator (GMI), mean sensor glucose (MSG), change in glycated hemoglobin (A1C), and QoL. RESULTS: Two hundred forty-eight subjects (131 males, 117 females), with a mean age of 36 years and diabetes duration of 21 years, experienced 3 episodes of severe hypoglycemia and no DKA over a follow-up of 17 months. TIR rose by 16%, from 64% to 80% (p<0.0001); TBR fell by 1.0%, from 3.5% to 2.5% (p=0.001); MSG fell from 9.0 to 8.1 mmol/L (p<0.001); GMI fell from 7.3% to 6.7% (p<0.001); and A1C fell from 7.2% to 6.7% (p<0.0001). QoL scores were healthy before and improved after SOSAPS. CONCLUSIONS: Clients with T1D using SOSAPS and supported with no-cost care to the client (software, technology, and physician/physician assistant) safely achieved improved TIR, GMI, A1C, and QoL.

The effect of sodium-glucose cotransporter 2 inhibitors as an adjunct to insulin in patients with type 1 diabetes assessed by continuous glucose monitoring: A systematic review and meta-analysis.

AIMS: Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken to analyze the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2Is), as an adjunct to insulin, on time in range (TIR) and glycemic variability in patients with type 1 diabetes, using continuous glucose monitoring (CGM). In addition, we examined which type of SGLT2I yielded a superior effect compared to others. METHODS: We conducted a comprehensive search of PubMed, EMBASE, the Cochrane Library, Web of Science, and clinical trial registry websites, retrieving all eligible randomized clinical trials (RCTs) published up until February 2023. We analyzed the mean TIR, mean amplitude of glucose excursions (MAGE), mean daily glucose (MDG), diabetic ketoacidosis (DKA), standard deviation (SD), total insulin dose, and severe hypoglycemia to evaluate the efficacy and safety of SGLT2Is. A random-effects model was also employed. RESULTS: This study encompassed 15 RCTs. The meta-analysis revealed that the use of SGLT2Is as an adjuvant therapy to insulin led to a significant increase in TIR (MD = 10.78, 95%CI = 9.33-12.23, I2 = 42 %, P < 0.00001) and a decrease in SD (MD = -0.38, 95%CI = -0.50 to -0.26, I2 = 0 %, P < 0.00001), MAGE (MD = -0.92, 95%CI = -1.17 to -0.67, I2 = 19 %, P < 0.00001), MDG(MD = -1.01, 95%CI = -1.32 to -0.70, I2 = 48 %, P < 0.00001), and total insulin dose (MD = -5.81, 95%CI = -7.81 to -3.82, I2 = 32 %, P < 0.00001). No significant increase was observed in the rate of severe hypoglycemia (RR = 1.04, 95 % CI = 0.76-1.43, P = 0.80). However, SGLT2I therapy was associated with increased DKA occurrence (RR = 2.79, 95 % CI = 1.42-5.48; P = 0.003, I2 = 16 %). In addition, the subgroup analyses based on the type of SGLT2Is revealed that dapagliflozin might exhibit greater efficacy compared to other SGLT2Is across most outcomes. CONCLUSIONS: SGLT2Is exhibited a positive effect on improving blood glucose level fluctuations. Subgroup analysis showed that dapagliflozin appeared to have more advantages. However, giving due consideration to preventing adverse effects, particularly DKA, is paramount. REGISTRATION: Prospero CRD42023408276.

Type 1 diabetes and low carbohydrate diets-Defining the degree of nutritional ketosis.

AIMS: Adopting a low- or very low-carbohydrate (LCD or VLCD) diet in type 1 diabetes mellitus (T1D) is a controversial intervention. The main fear is that these diets may increase the risk of diabetic ketoacidosis. However, there is little data about the ketoacidosis risk and the level of physiological nutritional ketosis in individuals following these diets. We aimed to define the level of ketosis in those with T1D following carbohydrate restricted diets in a real-world observational study. METHODS: Patients with T1D who had self-selected dietary carbohydrate restriction were enrolled from local clinics and were compared to those following an unrestricted regular carbohydrate control diet (RCCD). Participants completed a 3-day diary, documenting food intake, ketones, and blood/interstitial glucose concentrations. RESULTS: Participants were divided into three groups according to mean carbohydrate intake: VLCD (<50 g carbohydrates/day) n = 6, LCD (50-130 g carbohydrates/day) n = 6, and RCCD (>130 g carbohydrates/day) n = 3. Mean beta-hydroxybutyrate (BOHB) concentrations were 1.2 mmol/l (SD 0.14), 0.3 mmol/l (SD 0.12) and 0.1mmol/l (SD 0.05) in the VLCD, LCD and RCCD groups, respectively (p = 0.02). Post hoc Dunn test demonstrated this reached statistical significance between the VLCD and RCCD groups (p = 0.02). CONCLUSION: Carbohydrate restricted diets, in particular VLCDs, are associated with a higher BOHB level. However, the degree of ketosis seen is much lower than we expected, and significantly lower than the level typically associated with diabetic ketoacidosis. This may suggest the risk of ketoacidosis is lower than feared, although safety will need to be evaluated further in large scale randomised trials.

Safety of sodium-glucose cotransporter 2 inhibitors in elderly patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are particularly effective in preventing adverse outcomes of heart failure and chronic kidney disease, which are highly prevalent in the elderly. Here, we aimed to access the safety of SGLT2i in elderly patients with type 2 diabetes. MATERIALS AND METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) reporting safety outcomes of the elderly (≥65 years) patients with type 2 diabetes, randomized to an SGLT2i or placebo. We recorded the incidence of acute kidney injury, volume depletion, genital tract infections, urinary tract infections, bone fractures, amputations, diabetic ketoacidosis, hypoglycaemia and drug discontinuation, by group of treatment. RESULTS: Of the 130 RCTs screened, only six reported data on elderly patients. In total, 19 986 patients were included. The SGLT2i discontinuation rate was approximately 20%. The risk of acute kidney injury was significantly lower among SGLT2i users compared with placebo [risk ratio (RR) 0.73; 95% CI 0.62-0.87]. SGLT2i were associated with a six-fold increased risk of genital tract infections (RR 6.55; 95% CI 2.09-20.5). The rate of amputations was increased only among canagliflozin users (RR 1.94, 95% CI 1.25-3). The risk of fractures, urinary tract infection, volume depletion, hypoglycaemia and diabetic ketoacidosis was similar between SGLT2i and placebo. CONCLUSIONS: SGLT2is were well tolerated in the elderly. However, older patients are underrepresented in most RCTs and a call for action is need to favour clinical trials reporting safety outcomes stratified by age.

The silent diabetic decompensation epidemic during the SARS-CoV2 pandemic - The role of primary care in early diagnosis and prevention of severe diabetic decompensation.

AIM/HYPOTHESIS: Efficiency in controlling chronic diseases, especially in the primary care setting, is associated with reduced rates of hospitalizations. Poorly controlled diabetes is associated with severe diabetic decompensation, such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). It is hypothesized that, in addition to the SARS-CoV2 pandemic, there was a parallel increase in decompensation of previously controlled chronic diseases, such as diabetes. In this work, the impact of the SARS-CoV2 pandemic on hospitalizations for severe diabetic decompensation in a Portuguese hospital was assessed. METHODS: A retrospective study by hospital clinical file consultation was performed and a cohort of 177 patients admitted to a Portuguese hospital with a diagnosis of DKA or hyperosmolar hyperglycemic state HHS, excluding SARS-CoV2 infected patients, between 2019 and 2020 was analysed. RESULTS: In the population not infected by SARS-CoV2, statistically significant differences were found in the relative number of hospitalizations (5.59 vs 3.79 hospitalizations for DKA/HHS per 1000 patients not infected with SARS-CoV2, p = 0.0093) and lethality due to DKA/HHS (0941 vs 0337 deaths from DKA/HHS per 1000 patients not infected with SARS-CoV2, p = 0.0251). This increase in hospitalizations and lethality was accompanied by a statistically significant increase in newly type 2 diabetes diagnosis in DKA/HHS hospital admissions (p = 0.0156) and by a statistically significant increase in average age of patients (56.3 ± 22.4 vs 69.1 ± 17.6, p < 0.001). DISCUSSION AND CONCLUSIONS: These results show the empirical perspective that the consequences of the pandemic also had a considerable impact on the control of chronic diseases such as diabetes, with a higher percentage of hospitalizations due to severe decompensation, especially in the elderly population.

SGLT2i in Patients with Type 1 Diabetes: Benefits, Risks, and Preventive Strategies.

Sodium-glucose cotransporter inhibitors (SGLT2i) play an increasingly important role in type 2 diabetes mellitus (T2DM) due to their significant cardiovascular benefits and renal protection in addition to their hypoglycemic effects. In recent years, the application of SGLT2i in patients with type 1 diabetes mellitus (T1DM) has attracted more and more attention. Studies have shown that SGLT2i improves glycemic control, reduces total daily insulin dose, decrease body weight in patients with T1DM, without increasing the risk of severe hypoglycemia. SGLT2i also reduces urinary protein levels, prevents atherosclerosis, and offers cardiorenal benefits in patients with T1DM. But simultaneously, they significantly increased risk of diabetic ketoacidosis (DKA), which leads to increased hospitalization and mortality. Hence SGLT2i is recommended to T1DM who are motivated, adhere to self-glucose monitoring, well-trained in identifying DKA, and closely followed to ensure the efficacy and safety.

Impact of school-supervised ultra-long-acting basal insulin injections on ketosis in youth with T1D and elevated haemoglobin A1c: A pilot study.

BACKGROUND: In youth with type 1 diabetes (T1D), high haemoglobin A1c (HbA1c) levels are associated with an increased risk for diabetic ketoacidosis (DKA). AIMS: This study examined whether daily school-supervised basal insulin injections were feasible and if they reduced the risk of morning ketosis in children and adolescents with high HbA1c levels. We hypothesized that supervised glargine and degludec would reduce the risk of ketosis and that the prolonged action of degludec would protect from ketosis after consecutive days of unsupervised injections. MATERIALS & METHODS: After a 2-4-week run-in, youth (10-18 years, HbA1c ≥ 8.5%) managing T1D with injections were randomized to school-supervised administration of degludec or glargine for 4 months. School nurses observed daily blood ß-hydroxybutyrate (BHB) and glucose checks. During COVID closures, the research team supervised procedures remotely. RESULTS: Data from 28 youth (age 14.3 ± 2.3 years, HbA1c 11.4 ± 1.9%, 64% F) were analysed. School-supervised injections of both basal insulins for 1-4 days progressively lowered the percent of participants with elevated BHB. The percent of participants with elevated BHB (≥0.6 mmol/L) after 2 days of unsupervised basal insulin doses at home was greater in the glargine than degludec group but had a high p-value (17.2% vs. 9.0%, p = 0.3). HbA1c was unchanged in both groups. DISCUSSION: In youth with T1D at high risk for DKA, daily supervised long-acting insulin administration decreased the probability of elevated ketone levels on subsequent school days, regardless of basal insulin type. A larger sample size may have demonstrated that the longer action profile of degludec would offer additional protection from ketosis during days of not attending school. CONCLUSION: Engaging school-based caregivers in management of youth with T1D on injected insulin may decrease clinically significant ketosis and minimize acute complications of diabetes.

Peri-colonoscopy Implications of Sodium-Glucose Cotransporter-2 Inhibitor Therapy: A Mini-review of Available Evidence.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of oral glucose-lowering agents commonly used for the treatment of type 2 diabetes. With increased use, there has been an increase in the incidence of the rare but life-threatening complication of euglycemic diabetic ketoacidosis. A common but underappreciated precipitant is colonoscopy. In this work, we outline the pathophysiology of the interaction between colonoscopy and SGLT2i use, the evidence regarding SGLT2i use in the periprocedural setting and Australian Diabetes Society guidelines.

Reducing Diabetic Ketoacidosis Readmissions with a Hospital-School-Based Improvement Partnership.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes mellitus (T1D). Baseline data showed 139 of 182 DKA readmissions (76.4%) were due to missed basal insulin dosing. The team used quality improvement tools to implement a process change around basal insulin. The project utilized insulin degludec and school-based nurses when missed basal insulin was noted as a main driver for readmission. The DKA readmission rate averaged 5.25 per month from January 2017 to April 2019. The rate decreased to 3.64 per month during the intervention from May 2019 to March 2020, a 31% reduction over 11 months. This standardized approach for patients with T1D readmitted with DKA, using a school-based intervention and insulin degludec, reduced the number of DKA readmissions. This method is safe and effective for lowering DKA readmissions due to missed basal insulin in areas with reliable school nursing.

Management of Hyperosmolar Hyperglycaemic State (HHS) in Adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group.

Hyperosmolar Hyperglycaemic State (HHS) is a medical emergency associated with high mortality. It occurs less frequently than diabetic ketoacidosis (DKA), affects those with pre-existing/new type 2 diabetes mellitus and increasingly affecting children/younger adults. Mixed DKA/HHS may occur. The JBDS HHS care pathway consists of 3 themes (clinical assessment and monitoring, interventions, assessments and prevention of harm) and 5 phases of therapy (0-60 min, 1-6, 6-12, 12-24 and 24-72 h). Clinical features of HHS include marked hypovolaemia, osmolality ≥320 mOsm/kg using [(2×Na+ ) + glucose+urea], marked hyperglycaemia ≥30 mmol/L, without significant ketonaemia (≤3.0 mmol/L), without significant acidosis (pH >7.3) and bicarbonate ≥15 mmol/L. Aims of the therapy are to improve clinical status/replace fluid losses by 24 h, gradual decline in osmolality (3.0-8.0 mOsm/kg/h to minimise the risk of neurological complications), blood glucose 10-15 mmol/L in the first 24 h, prevent hypoglycaemia/hypokalaemia and prevent harm (VTE, osmotic demyelination, fluid overload, foot ulceration). Underlying precipitants must be identified and treated. Interventions include: (1) intravenous (IV) 0.9% sodium chloride to restore circulating volume (fluid losses 100-220 ml/kg, caution in elderly), (2) fixed rate intravenous insulin infusion (FRIII) should be commenced once osmolality stops falling with fluid replacement unless there is ketonaemia (FRIII should be commenced at the same time as IV fluids). (3) glucose infusion (5% or 10%) should be started once glucose <14 mmol/L and (4) potassium replacement according to potassium levels. HHS resolution criteria are: osmolality <300 mOsm/kg, hypovolaemia corrected (urine output ≥0.5 ml/kg/h), cognitive status returned to pre-morbid state and blood glucose <15 mmol/L.

Important Decrease in Hospitalizations for Acute Diabetes Events Following FreeStyle Libre System Initiation in People with Type 2 Diabetes on Basal Insulin Therapy in France.

Aims/Hypothesis: Initiation of insulin therapy in people with type 2 diabetes (T2DM) may be necessary to achieve glycemic targets but is associated with acute diabetes events (ADEs), including severe hypoglycemia (SH) or diabetic ketoacidosis (DKA). We assessed the impact of initiating FreeStyle Libre® system (FSL) on hospitalizations for ADEs in people with T2DM on basal insulin only regimen±noninsulin antidiabetic drugs. Materials and Methods: A retrospective study of the French national Système National des Données de Santé reimbursement claims database (≈66 million French people) identified people with T2DM on basal insulin therapy receiving a first reimbursement of FSL between August 1, 2017 and December 31, 2018. Claims data for the 12 months before, and up to 24 months after FSL initiation, were analyzed. Hospitalizations for ADEs were identified, using ICD-10 codes as main or related diagnosis, for: SH events; DKA events; comas; and hyperglycemia-related admissions. Results: A total of 5933 people with T2DM on basal insulin therapy initiated FSL during the selection period. Of the patients, 78.9% were on basal insulin and other hypoglycemic agents. Among the 5933 patients identified, 2.01% had at least one hospitalization for any ADE in the year before FSL initiation, compared to 0.75% (1 year) and 0.60% (2 years). Reductions in ADEs were driven by 75% fewer DKA admissions, with a 44% reduction in SH admissions. These patterns of reduced ADEs persisted after 2 years, with a further 43% reduction in DKA rates. Conclusions/Interpretation: This study emphasizes the value of the FSL system in reducing ADEs in people with T2DM in France not on intensive insulin therapy and initially treated with basal-only insulin therapy.

Re-examining the widespread policy of stopping sodium-glucose cotransporter-2 inhibitors during acute illness: A perspective based on the updated evidence.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are now seen as an integral part of therapy in type 2 diabetes to control not only blood glucose but to improve cardiovascular and kidney outcomes. Diabetic ketoacidosis (DKA) is an uncommon but serious complication of type 2 diabetes, which has a high case fatality rate. The absolute risk of DKA in large, prospective randomized clinical trials in people with type 2 diabetes using SGLT2 inhibitors has been low, although the relative risk is higher in those assigned to SGLT2 inhibitors compared with placebo. In those without diabetes but prescribed SGLT2 inhibitors for heart failure or chronic kidney disease, the risk of DKA is similar to placebo. Over the course of the COVID-19 pandemic, cases of DKA have also been reported in cases of COVID-19 hospitalizations. Consensus guidelines have recommended that SGLT2 inhibitors should be avoided in cases of serious illness and suggest they are not recommended for routine in-hospital use. However, recent data suggest potential beneficial effects of SGLT2 inhibitors in the setting of acute illness with COVID-19 with no increase in adverse events and low rates of DKA, which were non-severe. Given the low rates of DKA in cardiovascular outcome trials and in hospitalized patients with type 2 diabetes, the potential for SGLT2 inhibitors not being re-initiated following discharge and their cardiovascular and kidney benefits, we believe the practice of routine 'sick day' guidance should be re-examined based on current evidence with a call for further research in this area. Furthermore, high-quality trials of initiation of SGLT2 inhibitors in people admitted to hospital with cardiovascular disease or kidney disease, and trials of continuation of SGLT2 inhibitors in people, with careful monitoring of DKA should be conducted. These should be further supplemented with large observational studies.