Diabetes Therapy最新文献

Introduction: Insulin resistance (IR) is a major feature of type 2 diabetes mellitus (T2DM) and plays a crucial role in the accelerated progression of diabetic kidney disease (DKD). It has been found that surrogates of IR are of high value in assessing IR status. This study aims to evaluate the associations between surrogates of IR and DKD in T2DM.

Methods: A total of 1026 patients with T2DM from January 2021 to February 2022 were selected in our final analysis. Logistic regression analysis and the receiver operating characteristic (ROC) curve analysis were performed to assess the correlation between IR surrogates and DKD.

Results: The levels of triglyceride glucose-waist circumference (TyG-WC), triglyceride glucose-waist to height ratio (TyG-WHtR), visceral adiposity index (VAI), and lipid accumulation product (LAP) were significantly higher in the microalbuminuria group and macroalbuminuria group compared with the normoalbuminuria group (P < 0.05). The results of multivariate logistic regression analysis showed that the highest quartile of triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), triglyceride glucose (TyG) index, TyG-WHtR, TyG-WC, LAP, and VAI were significantly correlated with DKD (all P < 0.05). The ROC curves and results showed that TyG area under the curve (AUC) > VAI AUC > TG/HDL-C AUC > TyG-WHtR AUC > LAP AUC > 0.7 > TyG-WC AUC > metabolic index of insulin resistance (METS-IR) AUC > 0.6 > triglyceride glucose-body mass index (TyG-BMI) AUC > 0.5.

Conclusions: The predictive value of IR surrogates for DKD in T2DM varies. TG/HDL-C, TyG, TyG-WHtR, LAP, and VAI can effectively predict DKD and are expected to be simple and economic biological indicators of DKD risk.

Type 2 diabetes mellitus (T2DM) is a global health priority, with an estimated 629 million people projected to be affected by the year 2045. T2DM significantly increases the risk of atherosclerotic cardiovascular disease and other complications. Hyperglycaemia imprints early molecular and cellular changes, often termed "metabolic memory", predisposing individuals to long-term microvascular and macrovascular complications, even after glycaemic normalisation. T2DM remission is increasingly recognised as an achievable target, offering substantial benefits such as reduced morbidity, improved quality of life, and preservation of beta-cell function. Among therapeutic options, metabolic surgery (MS) demonstrates the most significant impact, particularly for long-term outcomes. MS induces profound hormonal changes, including increased glucagon-like peptide 1 (GLP-1) levels and improved bile acid metabolism, alongside reductions in ectopic fat in the liver and pancreas, which improve insulin sensitivity and secretion. However, intensive lifestyle and pharmacological interventions, such as GLP-1 receptor agonists and glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 dual agonists like tirzepatide, also show promise, particularly when implemented early in the disease course. Predictors of sustained remission include younger age, shorter diabetes duration, lower baseline HbA1c, absence of insulin use, fewer medications and greater total weight loss percentage. Emerging tools such as the DiaRem score, machine learning models, and biomarkers like FGF-21 enhance patient stratification and predict remission likelihood. This narrative review explores the mechanisms and therapeutic options for T2DM remission, evaluates their impact on long-term outcomes and highlights the importance of early, multidisciplinary, and personalised interventions to optimize remission and improve metabolic health.

Introduction: The expanding range of therapeutic options for type 2 diabetes (T2D) calls for a reassessment of clinical scenarios in which existing glucose-lowering therapies might be substituted with the oral glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide (OS). In light of the numerous unresolved questions, a panel of experts was convened to develop practical guidance for clinicians using the Delphi consensus method.

Methods: A panel of 13 experts formulated 31 statements addressing the following clinical scenarios: switch from injectable GLP-1 RA to OS; switch from sodium-glucose cotransporter 2 inhibitor to OS; switch from insulin to OS; switch from dipeptidyl peptidase 4 inhibitor (DPP4i) to OS; switch from "old" oral therapies (i.e., sulfonylureas, glinides, pioglitazone, acarbose) to OS. A panel of 28 diabetologists from the Emilia-Romagna region evaluated each statement by assigning a relevance score on a 9-point scale via a dedicated online platform. The RAND/UCLA Appropriateness Method was employed to determine the presence of disagreement among panelists.

Results: Panelists showed agreement for all 31 statements, all considered relevant. Panelists agreed that in many circumstances OS can represent a valuable alternative to injectable GLP-1 RAs, other oral glucose-lowering drugs, and insulin. The selection of OS is justified by its proven effectiveness in reducing glycated hemoglobin and body weight, as well as its positive impact on cardiovascular outcomes and all-cause mortality. Furthermore, OS can allow a simplification of therapy in patients treated with insulin.

Conclusion: In an ever-evolving therapeutic landscape, OS therapy stands as a valuable option in the management of patients with T2D.

Introduction: Patients with type 2 diabetes mellitus (T2DM) who cannot achieve normal glycosylated hemoglobin (HbA1c) levels are sometimes given the combined therapeutic regimen of polyethylene glycol loxenatide (PEG-Loxe) + basal insulin. The aim of this study was to investigate the efficacy and safety of PEG-Loxe combined with basal insulin in patients with T2DM.

Methods: This retrospective, real-world study included patients with T2DM aged ≥ 18 years for whom basal insulin therapy was ineffective, whose HbA1c levels were between 7.0% and 11.0%, and who were on either continued basal insulin dose adjustment or who had received PEG-Loxe + basal insulin combined therapy for at least 24 weeks. The primary endpoint was change in HbA1c level after 24 weeks treatment. Secondary endpoints included HbA1c achievement target rate, change in fasting plasma glucose and body weight, respectively, and change in HbA1c stratified by sex, age, disease duration, and baseline HbA1c level.

Results: Overall, 307 patients were identified. After propensity score matching, 44 patients each were included in the basal insulin and PEG-Loxe + basal insulin group. After 24 weeks, a significant difference in Hb1Ac reduction between the groups (P = 0.003) was observed. Also, patients treated with PEG-Loxe + basal insulin combined therapy experienced greater body weight reduction compared those treated with basal insulin only (intergroup difference: - 3.2 kg; 95% confidence interval [95% CI] - 5.4, - 1.0]; P = 0.005). There was a significant intergroup difference in weight reduction in patients with body mass index ≥ 28 kg/m² (- 8.4 kg; 95% CI - 13.9, - 3.0; P = 0.004). HbA1c levels in female patients aged < 65 years with HbA1c ≥ 8.5% and with a disease duration ≥ 10 years were significantly different between the two treatment groups (P < 0.005). Hypoglycemic events occurred in 10.4% of patients treated with PEG-Loxe + basal insulin with no cases of level 3 hypoglycemia.

Conclusion: PEG-Loxe + basal insulin combined therapy was safe and effective in patients with T2DM who did not achieve optimal glycemic control with insulin therapy alone.

Trial registration: ClinicalTrials.gov identifier: ChiCTR2400086699.

Introduction: People with chronic kidney disease (CKD) and type 2 diabetes (T2D) have an increased risk of kidney failure and cardiovascular disease. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) have shown cardiorenal protective effects. The objective of this multinational, multidatabase study was to describe the incidence of kidney and cardiovascular outcomes in separate, non-mutually exclusive cohorts of patients with CKD and T2D who initiated either an SGLT2i or a GLP-1 RA.

Methods: Data describing adults (≥ 18 years) with T2D and CKD who were new users of either SGLT2i or GLP-1 RA from 2012 to 2019 were assessed from population-based Danish National Health Registers (DNHR) and Valencia Health System Integrated Database (VID), hospital-based Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex), and US Optum^® de-identified Electronic Health Record dataset (Optum^® EHR). Crude incidence rates (IRs) and 95% confidence intervals (CIs) for primary outcomes (kidney failure, acute coronary syndrome, stroke, new-onset congestive heart failure, new-onset atrial fibrillation) and cumulative incidence by follow-up time for primary and secondary outcomes (laboratory measurements of kidney function) were estimated.

Results: SGLT2i cohorts comprised 12,501 patients in DNHR, 22,404 in VID, 811 in J-CKD-DB-Ex, and 54,308 in Optum^® EHR. GLP-1 RA cohorts comprised 10,696 in DNHR, 8317 in VID, 219 in J-CKD-DB-Ex, and 78,934 in Optum^® EHR. Baseline clinical profile differences were observed for GLP-1 RA and SGLT2i new users, and crude IRs of kidney and heart failure tended to be higher in the GLP-1 RA cohorts than in the SGLT2i cohorts across data sources.

Conclusion: Understanding the incidence of kidney failure and cardiovascular outcomes in people receiving antidiabetic medications with cardiorenal protective effects is important for future studies aiming to compare the incidence of kidney and cardiovascular outcomes related to new and existing CKD treatments.

Introduction: Obesity prevalence has increased in Finland and is prevalent in patients with type 2 diabetes (T2D). Also, hyperglycemia in patients with T2D is partially attributed to obesity. We aimed to examine the time trends of body mass index (BMI) and glycated hemoglobin (HbA1c) control across different BMI categories among Finnish patients with T2D.

Methods: Regional data on the electronic health records (EHRs) covering all public healthcare services in North Karelia, Finland, were used to conduct this retrospective study. Annual patients with T2D from 2012 to 2022 were identified from the EHRs. In each study year, patients with ≥ 1 measurement of BMI and HbA1c were included. Linear and logistic regression analyses estimated with generalized estimating equations were performed to evaluate the time trends.

Results: The annual number of patients for analyses ranged from 5149 to 10,216 during 2012-2022. The unadjusted mean BMI declined slightly over time but increased after age adjustment (all p < 0.05). In the age-stratified analysis adjusted for sex and diabetes duration, mean BMI increased over time in patients aged 45-64 years (all p < 0.05). Furthermore, the increasing time trend in age-adjusted BMI among the study patients persisted after adjusting for sex, diabetes duration, and antidiabetic medication use (p < 0.05). Overall, patients in the higher BMI categories had higher HbA1c levels and were less likely to achieve the HbA1c target from 2012 to 2022. When examining time trends of HbA1c control, HbA1c control improved over time in patients with the highest level of BMI, coinciding with a greater increase in new antidiabetic medication use compared with the lowest BMI group (p < 0.05 for calendar year × obesity class III interaction).

Conclusion: Our findings suggest that weight management requires increased attention among Finnish patients with T2D and is especially important for better glycemic control.

Introduction: The ONWARDS programme assessed the efficacy and safety of once-weekly insulin icodec (icodec) versus once-daily basal insulin comparators in type 2 diabetes (T2D) or type 1 diabetes (T1D). This post hoc exploratory analysis of ONWARDS 1-6 assessed the impact of icodec during and around hospitalisation.

Methods: ONWARDS 1-6 were randomised, two-arm, phase 3a trials (ClinicalTrials.gov: NCT04460885; NCT04770532; NCT04795531; NCT04880850; NCT04760626; NCT04848480). Adults with T2D (ONWARDS 1-5; n = 3765) and T1D (ONWARDS 6; n = 582) received icodec or once-daily comparators (insulin degludec, insulin glargine U100, insulin glargine U300). Hospitalised cases were analysed for: hospitalisation duration, icodec dose, self-measured blood glucose, glycated haemoglobin (HbA_1c) levels, and clinically significant and severe hypoglycaemia before, during, and after hospitalisation.

Results: Across trials, a similar number of participants receiving icodec (n = 152/2172) and once-daily comparators (n = 156/2175) were hospitalised. Median duration of hospital stay was similar between treatment groups (icodec, 5.0 days; once-daily comparators, 6.0 days); icodec dose remained fairly stable around hospitalisation. Most hospitalised participants completed the trial without permanently discontinuing treatment (icodec, 84.9%; once-daily comparators, 90.4%). Mean HbA_1c levels remained relatively stable over assessed time points for both treatment groups. Six participants receiving icodec (one with T2D; five with T1D) and three receiving once-daily comparators (one with T2D; two with T1D) reported clinically significant or severe hypoglycaemia during hospitalisation.

Conclusions: Similar numbers of hospitalisations were reported in both treatment arms. Icodec treatment was continued during hospitalisation in most participants and did not appear to have an impact on glycaemic management or hypoglycaemia. This analysis suggests that once-weekly icodec could be managed in a similar way to once-daily basal insulin analogues during hospitalisation.

Trial registration: ClinicalTrials.gov identifiers, NCT04460885 (ONWARDS 1), NCT04770532 (ONWARDS 2), NCT04795531 (ONWARDS 3), NCT04880850 (ONWARDS 4), NCT04760626 (ONWARDS 5), NCT04848480 (ONWARDS 6).

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.