Diabetes Therapy最新文献

People living with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at risk of CKD progression and kidney failure. This is a summary of the FIDELITY pooled analysis where two clinical trials (FIDELIO-DKD and FIGARO-DKD) were performed to investigate the safety and efficacy of finerenone in people with T2D and CKD. The data from these two studies were combined and analyzed and it was found that those who took finerenone on top of standard-of-care medicine had a 14% reduced risk of having a cardiovascular event and 23% reduced risk of having a kidney event versus those who took placebo. Those who took finerenone were also more likely to have high blood potassium, but this was mostly manageable.A graphical abstract and translations of all content (Chinese, Japanese, German, Spanish, Brazilian-Portuguese, French) are available for this article.

Introduction: Type 2 diabetes (T2D) represents a remarkable disease burden in Japan, and the cost-effectiveness of pharmacotherapy is an important consideration. In this study, we compared the long-term effects of the type of initial medication, as well as the initial frequency of clinic visits, on the occurrence of T2D-related complications. Additionally, we compared the medical costs associated with each treatment pattern.

Methods: We analyzed electronic health record data collected from multiple primary care clinics in Japan. Patients were selected based on being primarily prescribed either biguanides (BG) or DPP-4 inhibitors (DPP-4i) during a 3-month baseline period, both of which are commonly used as first-choice medications in Japan. We then followed the onset of T2D-related complications and conducted survival analyses. Additionally, we calculated the accumulated medical costs up to the onset of an event or loss to follow-up, and summarized the annual costs per patient for each treatment pattern.

Results: A total of 416 Japanese patients with T2D who initiated treatment between January 2015 and September 2021 were included. The median follow-up period was 2.69 years. The survival analysis showed that the use of DPP-4is and frequent visits from the beginning of treatment did not offer a benefit in suppressing the onset of complications later on. On the other hand, it was found that the annual medical costs for the group using DPP-4i with frequent visits were about 1.9 times higher than for the group using BGs with less frequent visits.

Conclusions: The results suggest that for Japanese patients with T2D, the use of BGs along with relatively long follow-up intervals in the beginning of treatment can remarkably reduce medical costs while providing a level of complication suppression equivalent to that of the use of DPP-4is or frequent visits.

Introduction: The association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of urogenital infections remains controversial. This study aimed to investigate the association between SGLT2 inhibitors and the incidence of perineal soft tissue infections, including Fournier's gangrene (FG), genital bacterial infections, and urinary tract infections (UTIs), using administrative claims data in Japan.

Methods: In this retrospective cohort study, we utilized the JMDC Claims Database. The study included patients aged 18 years or older diagnosed with type 2 diabetes mellitus, identified by a diagnostic code, who received new prescriptions for SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP-4) inhibitors between April 2014 and August 2020. Using one-to-one propensity score (PS) matching, we compared the incidence of perineal soft tissue infections, including FG, genital bacterial infection, and UTIs between groups treated with SGLT2 and DPP-4 inhibitors. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using the Cox proportional hazards model.

Results: We identified 34,897 patients in the SGLT2 inhibitor group and 135,311 patients in the DPP-4 inhibitor group. After one-to-one PS matching, 31,665 pairs were generated. The mean age of the patients was 51 years, with approximately 70% being male. The use of SGLT2 inhibitors was associated with a decreased risk of UTI (HR 0.90, 95% CI 0.83-0.98) and an increased risk of genital bacterial infection (HR 1.23, 95% CI 1.03-1.46) compared to DPP-4 inhibitors. However, no significant association was observed with perineal soft tissue infection (HR 1.05, 95% CI 0.61-1.81).

Conclusions: SGLT2 inhibitors were associated with a reduced risk of UTI and an increased risk of genital bacterial infection. They showed no significant association with perineal soft tissue infection when compared to DPP-4 inhibitors. Future research should explore broader demographics, focusing on the elderly and achieving gender balance, to gain a comprehensive understanding of infection risks.

Introduction: This study aimed to evaluate glycemic outcomes in subphenotypes of type 2 diabetes (T2D) with HbA1c > 7.0%, previously on basal insulin (pre-BI) alone (≥ 42 U/day) or on basal-bolus therapy (pre-BB), and who were switched to either basal insulin glargine 300 U/mL (IGlar-300) or 100 U/mL (IGlar-100), with or without pre-prandial insulin.

Methods: Participants from EDITION 2 (pre-BI, n = 785), and EDITION 1 (pre-BB, n = 792) trials were assigned retrospectively to subphenotypes of T2D: severe insulin deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity diabetes (MOD), and severe insulin resistant diabetes (SIRD). Key efficacy and safety parameters were analyzed at baseline, and after 26 weeks, for IGlar-300 and IGlar-100 pooled groups according to subphenotypes. Outcomes were also compared with insulin-naïve subphenotypes on oral antihyperglycemic drugs (OADs) from the EDITION 3 trial (pre-OAD, n = 858).

Results: Pre-BI and pre-BB treated subphenotypes with SIDD had a higher mean HbA1c (8.9% and 9.1%) at baseline compared to those of MARD (7.7% and 7.8%) and MOD (8.1% and 8.2%) and after 26 weeks remained above target HbA1c (7.7% and 8.0%) despite mean glargine doses of 0.7 to 1.0 U/kg/day and pre-prandial insulin use in the pre-BB SIDD subgroup. Pre-BB treated individuals with MARD and MOD achieved lower HbA1c levels (6.9% and 7.2%) than the pre-BI groups (7.3% and 7.5%) despite similar mean FPG levels (123-130 mg/dL). Only 19-22% of participants with SIDD achieved HbA1c < 7.0% compared to 33-51% with MARD and MOD, respectively. Pre-BI and pre-BB treated subphenotypes experienced more hypoglycemia than pre-OAD treated subphenotypes.

Conclusion: Individuals with T2D assigned post hoc to the SIDD subphenotype achieved suboptimal glycemic control with glargine regimens including basal-bolus therapy, alerting clinicians to improve further diabetes treatment, particularly post-prandial glycemic control, in individuals with SIDD.

Introduction: Insulin efsitora alfa (efsitora) is a basal insulin with a flat pharmacokinetic profile and long half-life, enabling weekly dosing. These attributes may provide stable glucose levels. This exploratory phase 1 study aimed to assess the hypoglycemic risk during experimental conditions that mimic situations encountered in daily life.

Methods: This was a single-site, open-label, two-period, fixed-sequence study in participants with type 2 diabetes (T2D) previously treated with basal insulin. The incidence, duration, and nadir glucose of hypoglycemia were assessed after treatment with efsitora versus insulin glargine (glargine) during three provocation conditions: 24-h prolonged fasting, prolonged fasting with exercise, and double dosing of study insulin.

Results: The 54 enrolled adults (BMI 21.8-39.7 kg/m², HbA1c 6.5-9.4%) achieved stable fasting glucose before undergoing provocation. Most hypoglycemic events were level 1 (≥ 54 to < 70 mg/dL) and resolved spontaneously or after oral glucose. The incidences of level 1 hypoglycemia for efsitora and glargine were not significantly different: for prolonged fasting, the incidences were 44.7 vs. 42.6% and the difference in proportion was 2.1% (95% CI: - 17.2, 21.4); for prolonged fasting with exercise, the corresponding values were 65.9 vs. 50.0% and 15.9% (- 3.0, 34.8); for double dosing, the corresponding values were 68.1 vs. 61.7% and 6.4% (- 12.8, 25.6). Level 2 hypoglycemia (< 54 mg/dL) was infrequent during both treatments and all provocations. No severe hypoglycemia was observed. Mean nadir glucose (range 62.8-66.3 mg/dL) and hypoglycemia duration (range 76.6-115.2 min) were also similar for the two treatments, depending on the provocation.

Conclusion: Overall, weekly efsitora did not increase the incidence, duration, or severity of hypoglycemia compared to daily glargine during provocation periods in patients with T2D.

Trial registration: ClinicalTrials.gov identifier NCT04957914.

Continuous glucose monitoring (CGM) is now advocated for the clinical management of individuals with type 1 diabetes (T1D). However, this glucose monitoring strategy is not routinely used in type 2 diabetes (T2D), given the large population, significant cost implications and relatively limited supporting evidence. T2D is a more heterogenous condition compared with T1D with various glucose lowering therapies that do not necessarily require CGM to ensure within target glucose levels. While all individuals with T2D may benefit from CGM at certain time points, the whole T2D population does not necessarily require this technology continuously, which should be prioritized based on patient benefit and cost effectiveness. In this pragmatic opinion piece, we describe the rationale and evidence for CGM use in different subgroups of individuals with T2d, divided according to the stage of the condition, glycemic therapies, presence of diabetes complications, or associated co-morbidities. We discuss a total of 16 T2D subgroups and provide a clinical view on CGM use in each, based on current evidence while also highlighting areas of knowledge gaps. This work provides health care professionals with a simple guide to CGM use in different T2D groups and gives suggestion for future studies to justify expansion of this technology.

People living with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in this population. CVD risk increases with each uncontrolled risk factor, even in individuals with good glycaemic control. Recommendations for assessing CVD risk in the T1D population are extended from those for type 2 diabetes (T2D) even though the physiopathology and underlying mechanisms of atherosclerosis in T1D are poorly understood and differ from those in T2D. Unlike the assessment of microvascular complications, which is well established in T1D, this is far from being the case for the comorbidities and risk associated with CVD. Aside from classical cardiovascular comorbidities, carotid ultrasound can be useful to stratify CVD risk. The utilization of specific risk scales such as the Steno Type 1 Risk Engine can help to more accurately classify cardiovascular risk in these individuals. The cornerstones of the management of cardiovascular risk in T1D are the promotion of the Mediterranean diet, tight glycaemic control (glycated haemoglobin (HbA1c) < 7%), blood pressure < 130/80 mmHg in most patients, and low-density lipoprotein (LDL) cholesterol < 100 mg/dL in moderate-risk individuals, < 70 mg/dL in high-risk individuals, and < 55 mg/dL in very high-risk individuals. Conventional medical follow-up of patients with T1D should be individualized (approximately 2-3 visits per year), and a carotid ultrasound evaluation is recommended every 5 years in the absence of significant preclinical atherosclerosis or more often in those with severe preclinical atherosclerosis. Antithrombotic therapy is recommended in those receiving secondary prevention, those with stenosis > 50% in any arterial bed, and those with an impaired ankle-brachial index. This document is a proposal of a practical approach for the evaluation, classification, and management of CVD risk in individuals living with T1D.

Introduction: In this phase 4, multicentre, prospective, non-interventional PIONEER REAL Netherlands study, we assessed clinical outcomes associated with once-daily oral semaglutide use in real-world clinical practice in adults living with type 2 diabetes (T2D) naïve to injectable glucose-lowering medication.

Methods: Participants initiated on oral semaglutide were followed for 34-44 weeks. Change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS) was the primary endpoint; secondary endpoints included change in body weight (BW) from BL to EOS, the proportion of participants with HbA1c < 7.0% at EOS and the composite endpoints of HbA1c reduction ≥ 1.0%-points with BW reduction ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ status/change). Safety was evaluated in all participants who initiated oral semaglutide treatment.

Results: Oral semaglutide was initiated in 187 participants; 94.1% completed the study and 78.6% remained on treatment at EOS. At BL, 54.0% of participants were male, mean age was 58.8 years, mean duration of T2D was 8.7 years and mean body mass index was 35.1 kg/m²; mean HbA1c was 8.6% and mean BW was 103.1 kg. Significant improvements from BL to EOS were observed for HbA1c and BW (estimated change [95% confidence interval]: - 1.16%-points [- 1.48 to - 0.85]; p < 0.0001, and - 5.84 kg [- 6.88 to - 4.80]; p < 0.0001, respectively). At EOS, 47.5% of participants had an HbA1c level < 7.0%; 41.8% and 35.5% of participants achieved composite endpoints of HbA1c reduction ≥ 1.0%-points plus BW reduction ≥ 3% or ≥ 5%, respectively. DTSQ status and change scores improved by 2.1 (p = 0.0003) and 10.8 points (p < 0.0001), respectively. Oral semaglutide was easy or very easy to consume for 81.5% of participants. Adverse events were mostly mild/moderate, with gastrointestinal disorders being the most common.

Conclusion: In this real-world population, we reported clinically significant reductions in HbA1c and BW, improved treatment satisfaction and no new safety concerns. A graphical abstract is available with this article.

Clinical trial registration: NCT04601740.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have attracted much attention because of their significant hypoglycemic and weight-loss effects. Previous preparations can only be subcutaneously injected. Oral administration of GLP-1RAs semaglutide helps to broaden treatment options, but its safety in the real world still needs to be observed. This study is based on FDA adverse event reporting system (FAERS) database to mine adverse drug events (ADE) of oral semaglutide, and provide references for the clinical safe use of this drug.

Methods: To analyze the signal quality of oral semaglutide, which is a drug used in the FAERS database from the third quarter of 2019 to the third quarter of 2023, we collected ADE data and performed data mining by using disproportionate analysis. Then, we standardized the data and used a variety of signal-quantification techniques, including reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian belief propagation neural network (BCPNN), and multiple empirical Bayesian gamma Poisson contractions (MGPS), for further analysis.

Results: We screened 2398 reports on the use of semaglutide tablets, involving a total of 5653 ADE. These reports were mainly submitted by consumers, and the reporting country was mainly the United States. A total of 23 system organ classes (SOC) and 93 preferred terms (PT) were mined for the signals of semaglutide tablets. The three most common SOC were gastrointestinal disorders, general disorders and administration site conditions, and investigations. At the PT level, metabolism and nutrition disorders exhibit the highest number of signals, with the top three being thyroid cyst, acute cholecystitis, and ketosis. Gastrointestinal disorders rank second, primarily involving eructation, pancreatitis, impaired gastric emptying, and regurgitation. In addition, vith nerve paralysis occurs and the signal intensity is high.

Conclusions: Our study provides a deeper and broader understanding of the safety of oral semaglutide. The results of the ROR, PRR, BCPNN, and MGPS algorithms exhibit high consistency, with metabolism and nutrition-related disorders having the highest number of signals. The conclusions align with the technical specifications of the product. Notably, other unexpected effects are reported, including acute cholecystitis, paralysis of the abducens nerve, and positional vertigo.

Introduction: The triglyceride-glucose index (TyG) has been identified as a dependable and simple indicator marker of insulin resistance (IR). Research has demonstrated a correlation between macrovascular complications and TyG. However, limited research exists regarding the relationship between TyG and diabetic microvascular complications. Consequently, the objective of this study is to investigate the association between TyG and diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN).

Methods: This is a cross-sectional, observational study. A total of 2048 patients from Tongren Hospital, Shanghai Jiao Tong University School of Medicine were enrolled. The primary outcomes are DKD and DPN. Quantile regression analysis was employed to investigate the implicit factors of TyG quartiles. Subsequently, based on implicit factors, logistic regression models were constructed to further examine the relationship between TyG and DKD and DPN.

Results: In the baseline, TyG exhibited higher values across patients with DKD, DPN, and co-existence of DKD and DPN (DKD + DPN) in type 2 diabetes (T2D). Univariate logistic regressions demonstrated a significant association between an elevated TyG and an increased risk of DKD (OR = 1.842, [95% CI] 1.317-2.578, P for trend < 0.01), DPN (OR = 1.516, [95% CI] 1.114-2.288, P for trend < 0.05), DKD + DPN (OR = 2.088, [95% CI] 1.429-3.052, P for trend < 0.05). Multivariable logistic regression models suggested a statistically significant increase in the risk of DKD (OR = 1.581, [95% CI] 1.031-2.424, p < 0.05), DKD + DPN (OR = 1.779, [95% CI] 1.091-2.903, p < 0.05) after adjusting the implicit factors of TyG quartiles. However, no significant relationship was observed between TyG and DPN in the multivariable regression analysis.

Conclusions: Elevated TyG was significantly associated with an increased risk of DKD in T2D, but no significant relationship was shown with DPN. This finding provided further evidence for the clinical significance of integrating TyG into the initial assessment of diabetic microvascular complications.