Diabetes Therapy最新文献

Tirzepatide is the first dual long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist indicated for the treatment of type 2 diabetes in adults, for reducing excess body weight and maintaining long-term weight reduction in adults with obesity or overweight and at least one weight-related comorbid condition, and for treating obstructive sleep apnea in adults with obesity. Recent studies found beneficial effects on heart failure with preserved ejection fraction and on metabolic dysfunction-associated steatohepatitis; its effects on cardiovascular outcomes in people with type 2 diabetes, as well as on reducing morbidity and mortality in people with obesity/overweight, remain under investigation. Here, we review the mechanistic activity of tirzepatide and its effect on glycemic control, body weight, the cardiorenal system, and lipid metabolism.

Introduction: Ipragliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor approved in Japan as an adjunct to insulin therapy for the management of type 1 diabetes (T1D). Diabetic ketoacidosis (DKA) and severe hypoglycemia (SH) have been specified as important identified risks for ipragliflozin; however, real-world data on the incidences of these events are limited. We compared the incidences of initial DKA and SH in patients with T1D newly treated with ipragliflozin in combination with insulin versus those treated with insulin.

Methods: This post-marketing surveillance study used data from the JMDC Claims Database between June 2018 and December 2021. Using propensity score matching, patients with T1D were matched 1:10 to the ipragliflozin/insulin group and insulin group. For each treatment group, incidence rates (IRs) of DKA and SH were plotted on a Kaplan-Meier curve, and IRs per 1000 patient-years (PY) were calculated. The risks of DKA and SH were compared between the treatment groups by calculating the hazard ratios (HRs) and 95% confidence intervals (CIs) using a Cox proportional-hazards model.

Results: The incidence of DKA was not significantly different between the ipragliflozin/insulin and the insulin groups (log-rank p = 0.793); the IRs of DKA were 8.3 and 8.5 per 1000 PY, respectively (HR 0.902, 95% CI 0.418‒1.945; p = 0.792). The incidence of SH was significantly lower in the ipragliflozin/insulin group versus the insulin group (log-rank p = 0.001). The IRs of SH per 1000 PY were 6.6 and 21.7, respectively (HR 0.284, 95% CI 0.126‒0.637; p = 0.002).

Conclusions: Ipragliflozin/insulin combination therapy showed no difference in the incidence of DKA, but a lower incidence of SH, versus insulin therapy in patients with T1D in Japan. These results suggest that ipragliflozin treatment is not associated with increased incidences of initial DKA or SH; however, its use should be accompanied by appropriate monitoring, education, and risk mitigation strategies to minimize the occurrence of these events.

Introduction: Tirzepatide is recommended as a first-line injectable for people with type 2 diabetes (T2D), but there is a paucity of data on the use of basal insulin after tirzepatide in this population. This study aimed to evaluate glycemic control in people with T2D newly intensified with insulin glargine 300 U/ml (Gla-300) who had suboptimal HbA1c after treatment with tirzepatide.

Methods: DELIVER-T was a retrospective analysis of the US Optum's Clinformatics^® Data Mart from January 1, 2022 to August 31, 2024. People with T2D were included if they were insulin naïve and were previously treated with tirzepatide and then intensified with Gla-300. The primary analysis (Gla-300 switch/add-on group) included all those with a HbA1c > 7.0% at baseline who either switched from tirzepatide to Gla-300 or who added Gla-300 to tirzepatide. The primary endpoint was the change in HbA1c levels from baseline to 6 months. Secondary endpoints included reaching HbA1c target < 7.0% and any hypoglycemia.

Results: In total, 82 people had a HbA1c > 7.0% at baseline and were included in the primary analysis (Gla-300 switch/add-on group). The mean (SD) change in HbA1c from baseline to 6 months was - 1.3% (2.0; p = 0.0027) for the primary analysis (Gla-300 switch/add-on group). The proportion of participants reaching the target of HbA1c < 7.0% at 6 months was 26.8% (n = 22) for the primary analysis (Gla-300 switch/add-on group). No hypoglycemic events were captured in the database during the 6-month follow-up period.

Conclusions: In insulin-naïve people with T2D who had suboptimal HbA1c with tirzepatide, significant reductions in HbA1c and improvements in the percentage of people reaching HbA1c target of < 7.0% were observed with Gla-300. Infographic and video abstract available for this article. Please follow the digital features link under the abstract. A video abstract of the Deliver-T study, which evaluated glycaemic control in people with T2D previously treated with tirzepatide and newly intensified with insulin glargine 300 U/mL (Gla-300).

Introduction: Metformin is widely recommended as a first-line therapy for patients with type 2 diabetes; however, evidence supporting its effects on cardiovascular outcomes is limited and derived from older studies. Furthermore, there is little direct evidence that demonstrates the protective effect of metformin on renal events. By contrast, sodium-glucose cotransporter 2 (SGLT2) inhibitors have consistently shown benefits in reducing cardiovascular and renal events. This study aims to directly compare the effects of an SGLT2 inhibitor and metformin on the urinary albumin-to-creatinine ratio (UACR), which is a marker of diabetic nephropathy and endothelial dysfunction.

Methods: This article presents the study protocol for a multicenter, randomized, open-label, controlled trial that evaluates the efficacy of the SGLT2 inhibitor tofogliflozin versus metformin on UACR in patients with type 2 diabetes and diabetic kidney disease (DKD). A total of 120 participants with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m² and UACR between 30 and 2000 mg/gCr will be enrolled. Participants will be randomized (1:1) to receive either tofogliflozin or metformin and will be stratified using baseline UACR (< 300 or ≥ 300 mg/gCr), eGFR (< 60 or ≥ 60 mL/min/1.73 m²), and age (< 65 or ≥ 65 years).

Planned outcomes: The primary endpoint is the change in UACR from baseline at 52 weeks. The secondary endpoints include changes in UACR at 26 and 104 weeks (absolute and percentage changes); slope of eGFR decline; and changes in hemoglobin A1c, body weight, and blood pressure. If tofogliflozin demonstrates a superior reduction in albuminuria, SGLT2 inhibitors may be considered an alternative first-line therapy in selected patients with type 2 diabetes and DKD.

Trial registration: jRCTs031210339; Clinicaltrials.gov (NCT05469659).

Introduction: Once-weekly semaglutide has proven to be a safe and effective treatment for type 2 diabetes; however, clinical trial data on Asian populations are limited, warranting real-world data (RWD). In this study we assessed the effectiveness and safety of semaglutide in Japanese patients with type 2 diabetes using RWD.

Methods: A retrospective analysis was conducted at five diabetes centers in Japan between December 2019 and June 2022. Changes in hemoglobin A1C (HbA1c), body weight (BW), lipid parameters, liver/kidney function, and adverse events were assessed over 52 weeks. Subgroup analyses were stratified by glucagon-like peptide-1 receptor agonist (GLP-1RA)-naïve users versus prior GLP-1RA users (GLP-1RA switch group), baseline body mass index (BMI) (< 30 or ≥ 30 kg/m²), and alanine aminotransferase (ALT) level (≤ 30 or > 30 U/L).

Results: Of the 503 patients included in the study, 270 (mean age 53 years; 61.8% men; mean duration of diabetes 10.7 years) were included in the per-protocol analysis. Mean (± standard deviation) baseline HbA1c and BMI were 8.1 ± 1.5% and 31.7 ± 6.2 kg/m², respectively; 52% patients were prior GLP-1RA users. HbA1c level had fallen by approximately 0.9% at both 26 and 52 weeks after treatment initiation (p < 0.001), with BW reductions of - 3.2 kg at 26 weeks and - 4.3 kg at 52 weeks (p < 0.001). Lipid profiles and liver function improved significantly (p < 0.001). Compared to prior GLP-1RA users, GLP-1RA-naïve patients showed greater reductions in HbA1c level (- 1.2% vs. - 0.8%, p = 0.009) and BMI (- 1.6 vs. - 1.2 kg/m², p = 0.03). Patients with BMI ≥ 30 kg/m² had a larger reduction in BMI than those with BMI < 30  kg/m² (- 1.7 vs. - 1.1 kg/m², p = 0.002), and those with ALT > 30 U/L showed greater HbA1c reduction (- 1.2% vs. - 0.8%, p = 0.04) and improved liver function than those with ALT ≤ 30 U/L. Gastrointestinal adverse events occurred in 53.7% of patients, leading to discontinuation of treatment in 7.6%.

Conclusions: Once-weekly semaglutide improved glycemic control, BW, lipid profiles, and liver function in Japanese patients with type 2 diabetes in RWD and subgroup analyses, supporting a broad effectiveness range. The rate of gastrointestinal adverse events in the RWD was comparable to that in prospective clinical studies.

Registration: University hospital Medical Information Network Clinical Trial Registry No.: UMIN000050499).

Early gestational diabetes mellitus (eGDM) is a condition identified during early pregnancy, characterized by glucose levels that are neither normal nor high enough to meet the criteria for overt diabetes. eGDM is associated with adverse pregnancy and postpartum outcomes, but owing to its heterogeneity, management remains challenging. Women with eGDM can be categorized into distinct phenotypes: mild, moderate, and severe, based on glycemic levels, response to behavioral interventions, and associated risk factors. Additionally, some women with eGDM regress to normoglycemia, while others with early normoglycemia may develop gestational diabetes later ("potential GDM"). Precision medicine offers a tailored approach to managing eGDM, emphasizing individualized treatment plans to optimize outcomes and minimize harm. Future research should focus on refining diagnostic criteria, identifying phenotypes early, and implementing personalized management strategies. This commentary highlights the need for a nuanced understanding of eGDM to improve maternal and neonatal health.

Introduction: The True Vie I3 continuous glucose monitoring system (i3 CGM, Sinocare Meditech Inc., also approved in Europe as GlucoMen® iCan or iCan CGM system) is a new real-time continuous glucose monitoring system (CGM) intended for the management of diabetes mellitus. This pivotal study evaluated the performance of the factory-calibrated CGM system.

Methods: In this center-specific dataset, 35 adults with type 1 diabetes (T1D) and type 2 diabetes (T2D) wore sensors on the abdomen and arm for 15 days. Four in-clinic visits were scheduled, during which frequent comparator sampling of venous blood was performed every 5-15 min for up to 10 h, and a glucose manipulation was performed. CGM performance compared to Yellow Springs Instrument 2300 Stat Plus Glucose and Lactate Analyzer (Yellow Springs, OH) glucose analyzer was evaluated for abdomen and arm sensors separately, regarding mean absolute relative difference (MARD) and agreement rates (AR) stratified by glucose range and rate of change (RoC). Additionally, clinical accuracy, sensor attachment rate, pain, and safety were assessed. This single-center analysis was developed with the intention to provide European-and particularly German-data. The presented site was the highest-enrolling center in the study and, as such, can be considered representative of the overall study population-an assumption that the analysis confirmed.

Results: 20/20 AR and MARD were 95.5% and 9.4% for abdomen sensors, and 95.3% and 9.8% for arm sensors, respectively. Consensus error grid (CEG) analyses revealed that 100% of CGM-comparator pairs fell in zones A and B for abdomen and arm sensors. Accuracy of sensors remained stable throughout the wearing time. Adhesion rate was 100% for abdomen sensors and 97.1% for arm-worn sensors, without the use of any over-tape during the 15-day study period. Pain during insertion and removal was reported as minimal, and no unexpected safety issues were identified.

Conclusions: Data from a single study center showed that the performance of the i3 CGM is comparable to that published for other established CGM devices, and accuracy results were within limits specified for integrated continuous glucose monitoring systems (iCGM). The i3 CGM showed reliability, and its safety was validated during the 15 study days.

Trial registration: The study was registered under ClinicalTrials.gov (ID: NCT05806554).

Introduction: Although there is a recognized negative interplay between metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes (T2D), the extent to which comorbid MASH exacerbates T2D complications is not well understood. This real-world cohort study evaluated whether the coexistence of these diseases is associated with increased risk of microvascular and macrovascular complications.

Methods: We identified eligible adults with T2D from the Optum^® Clinformatics^® Data Mart Database (2016-2024). Presence of MASH was determined using International Classification of Diseases, Tenth Revision, Clinical Modification coding, requiring ≥ 1 primary inpatient or outpatient diagnosis code. Patients with T2D and MASH were matched 1:1 with patients with T2D without MASH using propensity score matching to balance baseline characteristics. Fine-Gray models were used to estimate subdistribution hazard ratios (sHR) comparing the risk of microvascular and macrovascular T2D complications between both groups, while accounting for death as a competing risk. Stratified analyses were performed by glycemic control (glycated hemoglobin < 7% and ≥ 7%) and age (< 65 and ≥ 65 years).

Results: The study comprised 7396 and 6207 matched pairs in the microvascular and macrovascular complications cohorts, respectively. In this T2D population, mean (standard deviation) follow-up was 2.8 (2.0) years for patients with MASH and 2.4 (1.8) years for patients without MASH in both cohorts. Compared with patients with T2D without MASH, those with T2D and MASH had increased hazards of microvascular (sHR 1.19 [95% confidence interval (CI) 1.12-1.26]) and macrovascular complications (sHR 1.15 [95% CI 1.08-1.23]). A similar trend was observed for the stratified subgroup analyses.

Conclusion: Patients with T2D and MASH had higher hazards of microvascular and macrovascular complications versus those with T2D without MASH. These findings suggest that the presence of MASH accelerates T2D-related complications, creating a clinical imperative for integrated screening and management approaches to identify this high-risk population among patients with T2D.

Introduction: Traditional Indian cereal-based breakfast items have high glycemic index (GI) contributing to postprandial (PP) glucose spikes. Use of diabetes-specific protein supplement (DSPS) may reduce glycemic excursions. The study aimed to evaluate the effect of partially replacing breakfast with DSPS (Protinex Diabetes Care) on PP glycemic response.

Methods: Forty-two persons with type 2 diabetes mellitus (T2DM) participated in this randomized, controlled, open-label, crossover study. Participants consumed a test breakfast (DSPS in 200 ml milk + reduced portion of popular Indian savory breakfast (upma/poha)) or isocaloric control breakfast (upma/poha) for 5 days, with 3-day washout. PP glucose and insulin were assessed on the first day of intervention at baseline, 30, 60, 90, 120, 150, and 180 min after breakfast to calculate incremental area under the curve (iAUC0-3h) and delta peak (ΔCmax). During in-home use, macronutrient intake was assessed using dietary recalls, and glycemic variability (GV) was assessed using continuous glucose monitoring (CGM).

Results: Glucose iAUC0-3h and ΔCmax were 59% and 46% lower in test vs control, respectively. Insulin iAUC0-3h and ΔCmax did not differ significantly. During the test period, protein intake was significantly higher by 8.8 g; mean amplitude of glycemic excursions (MAGE)-a GV metric-was significantly lower. There were no gastrointestinal or adverse events. DSPS was well accepted by participants.

Conclusions: DSPS as a partial breakfast replacement improves blood glucose control without significantly impacting insulin response. In a real-world setting, DSPS enhances protein intake and reduces GV. These findings support DSPS as a practical, well-tolerated strategy for improving glycemic control and macronutrient intake balance in people with T2DM.

Trial registration: The trial was registered with Clinical Trials Registry India (CTRI) CTRI/2024/08/072006 and has been registered in the International Clinical Trials Registry Platform (ICTRP).

Continuous glucose monitoring (CGM) has transformed diabetes management by providing continuous, high-resolution insight into glucose dynamics. Initially developed for type 1 diabetes, CGM now demonstrates substantial clinical and behavioral benefits for individuals with type 2 diabetes across diverse therapeutic settings. This narrative review synthesizes current evidence on the expanding role of CGM in optimizing glycemic control and promoting patient-driven lifestyle modification.Across randomized and real-world studies, CGM consistently improves glycosylated hemoglobin, increases time in range, and reduces glycemic variability, regardless of insulin use. Beyond metabolic outcomes, CGM enhances treatment satisfaction, psychological well-being, and self-efficacy, particularly when combined with structured education and feedback. By enabling individuals to visualize real-time glucose responses to daily behaviors, CGM serves as a powerful catalyst for sustained behavioral change and personalized self-management.In addition to its therapeutic applications, CGM also provides diagnostic insight by revealing unrecognized glucose excursions that conventional monitoring may miss, facilitating earlier identification of dysglycemia in at-risk individuals. Yet significant barriers persist, including device costs, limited insurance coverage, and the difficulty of translating raw data into actionable insights for patients and clinicians.In conclusion, CGM has evolved from a glucose-monitoring device to a comprehensive platform that supports both clinical decision-making and behavioral empowerment, bridging the continuum from diabetes prevention to long-term management.