Diabetes Therapy最新文献

Introduction: A post hoc analysis from a 90-day proof-of-concept study demonstrated increased efficacy and no new safety concerns for an ultra-rapid-acting inhaled insulin, Technosphere^® Insulin (TI), when a higher modified conversion dose was compared to the conversion dose in the current US prescribing insert (approx. 2 × vs approx. 1.3 × TI per rapid-acting insulin analogue [RAA] unit [U] across the 1-24 U range). This post hoc analysis evaluates the safety and efficacy of the modified conversion dose in the postprandial period.

Methods: Participants with type 1 diabetes (T1D) were randomly assigned to administer TI using the modified dosing (TI group) or continue using their automated insulin delivery (AID) system (AID controls) in this in-clinic standardized meal challenge. Postprandial glucose was measured via capillary self-monitored blood glucose over 2 h post-meal to evaluate mean peak glucose and mean peak glucose excursion.

Results: The TI group (n = 21) demonstrated faster and lower mean peak glucose and mean peak glucose excursion vs AID controls (n = 5). Mean peak glucose and glucose excursion were reached 30 min earlier with TI. One TI + AID participant (modified dose) experienced one level 1 hypoglycemia event in the 2-h postprandial period and recovered in-clinic. No serious adverse events were reported.

Conclusions: TI group demonstrated a more favorable glycemic response in the 2-h postprandial period vs AID control. Data from this and previous studies suggest this higher modified conversion TI dose from subcutaneous RAA may help further reduce postprandial hyperglycemia in T1D.

Trial registration: ClinicalTrials.gov NCT05243628.

Introduction: The rising prevalence of diabetes has driven extensive research into effective management strategies, emphasizing the importance of integrating self-management routines into daily life. This study presents real-world observations on the impact of the mySugr^® app, used in conjunction with the Accu-Chek^® Instant blood glucose monitoring device, on glycemic control and patient satisfaction in India.

Methods: This retrospective, observational, non-interventional study was conducted at 29 sites in India, involving people with diabetes (PwD) who used the mySugr^® app in conjunction with the Accu-Chek^® Instant glucose meter for at least 3 months. Data from electronic health records and paper-based records were analyzed. The primary objective was to evaluate changes in glycated hemoglobin (HbA1c) levels over 3 months. Additionally, the study assessed the frequency of hypoglycemic and hyperglycemic events, changes in HbA1c based on monitoring frequency, and the use of insulin and non-insulin therapies. Patient satisfaction with the mySugr^® app was also assessed.

Results: A total of 111 PwD were included and had an average age of 53.2 years. The mean HbA1c level significantly decreased from 8.8% to 7.5% (p < 0.0001) in PwD using the mySugr^® app in conjunction with the Accu-Chek^® Instant glucose meter for at least 3 months. Frequent monitoring (≥ 6 times per week) resulted in a greater HbA1c reduction (1.5%-points) compared to less frequent monitoring (1.0%-point). Insulin-treated PwD showed a larger HbA1c reduction (1.6%-points) compared to those not on insulin (0.8%-points). PwD reported an average of 1.9 hypoglycemic and 20.0 hyperglycemic events.

Conclusion: The mySugr^® app, used in conjunction with the Accu-Chek^® Instant glucose meter, demonstrated improved glycemic control. Future research should focus on larger, diverse samples and long-term evaluations to confirm these findings and explore the cost-effectiveness of integrating such applications into routine diabetes care.

Introduction: This study aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of the ketohexokinase inhibitor LY3522348 in healthy participants.

Methods: This first-in-human phase 1 study evaluated LY3522348, a highly selective, oral dual inhibitor of human ketohexokinase (KHK) isoforms C and A. The study was conducted in two parts: a single-ascending dose (SAD) study and a multiple-ascending dose (MAD) study, including a drug-drug interaction analysis with midazolam. Participants in the SAD study received single oral doses of LY3522348 ranging from 5 to 380 mg, while participants in the MAD study received once-daily doses of 50 mg, 120 mg, and 290 mg for 14 days.

Results: A total of 65 healthy participants were included; of these 40 were in the SAD study (placebo = 10; LY3522348: 5 mg = 6; 15 mg = 6; 50 mg = 6; 150 mg = 6; 380 mg = 6) and 25 in the MAD study (placebo = 6; LY3522348: 50 mg = 6; 120 mg = 6; 290 mg = 7). LY3522348 was well tolerated, with the majority of the reported adverse events being mild. PK analysis showed an approximately dose-proportional increase in LY3522348 exposure, and the half-life ranged from 23.7 to 33.8 h. PD analysis indicated a dose-dependent increase in plasma fructose concentrations following the administration of a fructose beverage, supporting the inhibition of fructose metabolism by LY3522348.

Conclusions: LY3522348 demonstrated a favorable safety profile and well-behaved pharmacokinetics following once-daily oral dosing, and effective inhibition of fructose metabolism. The study was registered on ClinicalTrials.gov (NCT04559568).

Introduction: This study evaluated healthcare resource utilization (HCRU) and costs in the USA for people with type 2 diabetes (T2D) who discontinued the injectable glucagon-like peptide 1 receptor agonist (GLP-1 RA) once-daily liraglutide for T2D (with no other glucose-lowering agent added) or switched from liraglutide to the GLP-1 RA once-weekly semaglutide for T2D.

Methods: In this observational cohort study, we utilized claims data (Merative MarketScan [Merative, Ann Arbor, MI, USA] Commercial and Medicare Database; January 1, 2017-March 31, 2021) to compare HCRU and costs between individuals who discontinued liraglutide ("discontinuers") and those who switched from liraglutide to semaglutide ("switchers"). Patients were indexed between January 1, 2018 and March 31, 2020. Outcomes were compared between discontinuers and switchers over the 360-day post-index period using stabilized inverse probability of treatment weighting.

Results: Characteristics of the two cohorts were balanced after weighting. Switchers had significantly lower HCRU in inpatient and emergency department (ED) settings compared with discontinuers. Mean [standard deviation] total medical costs were significantly lower for switchers ($8513 [$18,931]) than for discontinuers ($13,585 [$52,011], p < 0.001), driven by reduced inpatient costs (2.6 times lower) and ED costs (1.6 times lower).

Conclusion: This analysis demonstrates that the cohort of people switching from liraglutide to semaglutide was associated with significantly lower HCRU and costs when compared with people discontinuing liraglutide only. These findings imply that switching to semaglutide could be a good option for people with T2D for whom liraglutide is no longer optimal.

Aims: Overprescribing is common in older adults with diabetes, potentially leading to hospitalisation and reduced quality of life. Additionally, diabetes care in older adults is often complicated by multiple interacting conditions and cognitive impairment, resulting in challenging self-management. Although evidence suggests that de-intensification of medications is safe in older adults, there are no data evaluating glucose ranges during this process.

Methods: eDMED is a 12-week feasibility study including 49 adults, aged ≥ 65 years with type 2 diabetes and residing in care homes. All eligible participants will receive medication de-intensification and continuous glucose monitoring (CGM). Primary healthcare professionals (HCPs) will undergo structured training on a de-intensification algorithm and CGM, while care home staff will receive tailored education on diabetes management and CGM application to ensure safe and effective implementation.

Planned outcomes: The primary outcome is the percentage of participants achieving a composite of > 50% time in range and < 1% time below range at 12 weeks, measured via CGM. Secondary outcomes include trends in time above and below range (quantified by level of hyper- or hypoglycaemia), change in quality of life (EQ-5D-5L), percentage of data captured to indicate adherence to the CGM and the acceptability of the intervention to participants, their consultees and carers (Theoretical Framework of Acceptability questionnaire).

Trial registration: International Clinical Trials Registry Platform (ID: ISRCTN 69024008).

Introduction: The oral formulation of the glucagon-like peptide-1 receptor agonist semaglutide has dosing requirements that could impact adherence. We compared perceptions of physicians and individuals with type 2 diabetes (T2D) in Japan, before and after initiating oral semaglutide, with respect to adherence to dosing requirements.

Methods: In this observational study, online questionnaires were completed by treating physicians and adults with T2D who had received either oral semaglutide or other oral antidiabetic medications for ≥ 6 months. Physicians reported the expected adherence of their patients to oral semaglutide and expected patient difficulties around the dosing requirements prior to (baseline) and after (time of survey) initiating oral semaglutide. Patient-reported adherence and difficulties experienced with the dosing requirements were assessed after oral semaglutide was initiated.

Results: Overall, 330 physicians and 412 individuals with T2D responded. There was a statistically significant difference (P < 0.001) between baseline and time of survey in the distribution of physicians who expected that ≥ 80% or < 80% of their patients would adhere to oral semaglutide, with 17.2% of physicians expecting ≥ 80% of their patients to be adherent before treatment initiation versus 44.6% reporting ≥ 80% of their patients to be adherent after treatment initiation. There was also a statistically significant difference (P < 0.001) in the distribution of expected versus reported adherence among individuals who received oral semaglutide. After semaglutide initiation, 95.2% of patients reported missing ≤ 1 dose/week. Before prescribing oral semaglutide, 186 (56.4%) physicians were resistant to it, due to the dosing requirements. After prescribing oral semaglutide, 146 (44.2%) reported their resistance had decreased, whereas only 28 (8.5%) reported increased resistance.

Conclusions: We identified an improvement in physician perceptions of oral semaglutide adherence due to dosing requirements following semaglutide initiation. Our findings suggest that individuals with T2D in Japan are capable of adhering to the dosing requirements of oral semaglutide.

Type 2 diabetes mellitus (T2DM) is a global health crisis, with cardiovascular disease (CVD) accounting for 75% of mortality in this population. Despite advances in managing traditional risk factors, such as low-density lipoprotein cholesterol (LDL) cholesterol reduction (IMPROVE-IT, FOURIER), antithrombotic therapies (PEGASUS, COMPASS), and triglyceride-lowering agents (REDUCE-IT), a substantial residual cardiovascular risk persists, driven in part by chronic low-grade systemic inflammation. Chronic low-grade inflammation is a central driver of cardiovascular-kidney-metabolic (CKM) syndrome in T2DM, perpetuating residual cardiovascular risk despite optimal management of traditional risk factors. This narrative review synthesizes evidence on how inflammation accelerates coronary heart disease (CHD), heart failure (HF), stroke, diabetic kidney disease (DKD), and peripheral artery disease (PAD). We evaluate the anti-inflammatory mechanisms of current therapies such as statins, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, as well as emerging agents like colchicine and interleukin (IL)-1β/IL-6 inhibitors, emphasizing their differential efficacy across CKM traits. By integrating pathophysiological insights with clinical trial data, we propose biomarker-guided strategies to target inflammation as a modifiable risk factor, offering a roadmap to bridge the gap in diabetes-related cardiovascular care.

Introduction: The clinical benefits of insulin glargine 300 U/ml (Gla-300) have been confirmed in randomized clinical trials (EDITION and BRIGHT) and real-world studies (ATOS, Toujeo-1, and ORION) in different regions of the world. However, safety data for the Indian population are lacking. The current post-marketing surveillance study evaluated the safety and efficacy of Gla-300 in people with type 2 diabetes (T2D) from India.

Methods: SAFEGUARD was a multicenter, phase 4, single-arm, open-label, 24-week study conducted at 15 centers across India between August 10, 2021 and December 26, 2022. The study included insulin-naïve participants (aged ≥ 18 years) with T2D uncontrolled (HbA1c ≥ 7.5% and ≤ 10%) on oral anti-hyperglycemic drugs. The primary endpoint was the percentage of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and hypoglycemic episodes.

Results: Of the 220 participants included, 218 (36.8% female) were eligible for efficacy analysis. The mean ± standard deviation age was 54.0 ± 9.6 years, the baseline HbA1c was 8.8 ± 0.9%, and the duration of T2D was 9.3 ± 7.0 years. Among the 220 participants who took at least one dose of Gla-300, 24.5% (n = 54) reported 64 TEAEs, which included one (0.5%) SAE. The most reported event was infections (10.9%). In total, 29.5% of participants (n = 65) reported a level 1 hypoglycemic event, and 27.7% of participants (n = 18) reported the main symptom of sweating. Glycemic control improved with reductions in mean HbA1c levels (- 1.14 ± 1.2%), fasting plasma glucose (- 37.0 ± 59.3 mg/dl), and fasting self-monitored blood glucose (- 52.0 ± 44.1 mg/dl) from baseline to week 24.

Conclusions: Gla-300 was well tolerated with improved glycemic control and a low hypoglycemia risk in insulin-naïve people with T2D living in India.

Trial registration: Clinical Trials Registry-India (CTRI number): CTRI/2021/07/035244. WHO identifier number: U1111-1255-5143. NCT number: NCT04980027.

Introduction: This study aims to evaluate the impact of using FreeStyle Libre continuous glucose monitoring (FSL-CGM) on maternal glucose control and obstetric and neonatal outcomes among women with gestational diabetes mellitus (GDM).

Methods: A total of 3062 women with GDM in gestational weeks 24-28 were enrolled in this study and divided into FSL-CGM and self-monitoring of blood glucose (SMBG) groups according to the method of monitoring blood glucose. Nearest-neighbor matching propensity score matching (PSM) was used to balance covariates at a ratio of 1:2.

Results: Compared with the first 6 days during the study period, the index of glycemic variability, such as the mean largest amplitude of glycemic excursions (LAGE), average daily risk range (ADRR) and glucose management indicators (GMI) during the last 6 days were improved (all p < 0.05). The fasting blood glucose before delivery in the FSL-CGM group was lower than that in the SMBG group (p < 0.05). In the normal weight subgroup, the FSL-CGM group had a lower gestational weight gain (GWG) than the SMBG group (p < 0.05). The incidence of neonatal hypoglycemia was higher in the SMBG group than in the FSL-CGM group (p < 0.05).

Conclusions: This study demonstrated that FSL-CGM helps reduce maternal glycemic variability and the incidence of neonatal hypoglycemia. Additionally, FSL-CGM may contribute to appropriate gestational weight gain during pregnancy.

Trial registration: ClinicalTrials.gov identifier, NCT05003154.

Introduction: Individuals with both obesity and type 2 diabetes mellitus (T2DM) are at heightened risk for developing cardiovascular and kidney-related complications. Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, has shown promising effects on heart health and renal function. This study aims to evaluate the influence of empagliflozin on these outcomes among Chinese patients suffering from obesity and T2DM.

Methods: This study included 500 adults with obesity and T2DM who were treated with empagliflozin for at least 6 months. Demographic information, clinical data, and treatment records were collected. Primary outcomes included changes in cardiovascular parameters and renal function measured at 1 week and 1, 3, and 6 months after treatment initiation. Secondary outcomes included heart failure hospitalization, mortality, and safety events.

Results: Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) showed significant reductions after 6 months of empagliflozin therapy (p < 0.001). Renal function improved significantly, with a rise in estimated glomerular filtration rate (eGFR) and a decline in serum creatinine levels (p < 0.01). Glycated hemoglobin (HbA1c) levels initially increased after 1 week but continued to decrease thereafter (p < 0.001). Albuminuria modestly reduced over time, with significant decreases from baseline to 3 months (p < 0.01). Body weight was also significantly reduced after 6 months (p < 0.001). Major adverse cardiovascular events (MACE) occurred in 8.4% of patients, and 1.0% progressed to end-stage renal disease. Multivariate analysis identified higher HbA1c levels and lower DBP as significant predictors of MACE, while reduced eGFR and elevated albuminuria were significant predictors of chronic kidney disease (p < 0.05).

Conclusion: Empagliflozin significantly improved cardiovascular and renal outcomes in Chinese populations with obesity and T2DM, with sustained benefits observed over 6 months. Elevated HbA1c, lower DBP, increased albuminuria, and reduced eGFR were associated with higher risks of adverse events during treatment period, highlighting the necessity of careful monitoring in high-risk patients.