Diabetes Therapy最新文献

Introduction: Type 2 diabetes mellitus (T2DM) is a highly heterogeneous disease with a varying risk of complications. The recent novel subgroup classification using cluster analysis contributed to the risk evaluation of diabetic complications. However, whether the subgroup classification strategy could be adopted to predict the risk of onset and progression of diabetic kidney disease (DKD) in Chinese individuals with T2DM remains to be elucidated.

Methods: In this retrospective study, 612 Chinese patients with T2DM were enrolled, and the median follow-up time was 3.5 years. The T2DM subgroups were categorized by a two-step cluster analysis based on five parameters, including age at onset of diabetes, body mass index (BMI), glycosylated hemoglobin (HbA1c), homeostasis model assessment 2 of insulin resistance (HOMA2-IR), and homeostasis model assessment 2 of β-cell function (HOMA2-β). Clinical characteristics across subgroups were compared using t-tests and chi-square tests. Furthermore, multivariate logistic regression models were adopted to assess the risk of albuminuria progression and renal function decline among different subgroups.

Results: The cohort was categorized into four groups: severe insulin-deficient diabetes (SIDD), with 146 patients (23.9%); mild insulin resistance (MIRD), with 81 patients (13.2%); moderate glycemic control diabetes (MGCD), with 211 patients (34.5%); and moderate weight insulin deficiency diabetes (MWIDD), with 174 patients (28.4%). The MIRD group exhibited an increased risk of progression from non-albuminuria to albuminuria as compared with the MWIDD group, with an adjusted odds ratio (OR) and 95% confidence interval (CI) of 2.92 (1.06, 8.04). The SIDD group had a higher risk of progression from micro-albuminuria to macro-albuminuria as compared with the MGCD group, with an adjusted OR and 95% CI of 3.39 (1.01, 11.41). There was no significant difference in the glomerular filtration rate (GFR) decline among all groups.

Conclusion: The present study offered the first evidence for risk evaluation of the development of DKD in the novel cluster-based T2DM Chinese subgroups. It suggested that the MIRD subgroup had a higher risk of DKD onset than the MWIDD subgroup. Meanwhile, the SIDD subgroup showed a higher risk of progression of albuminuria than the MGCD subgroup. This novel classification system could be effective in predicting the risk of DKD in Chinese patients with T2DM, which could facilitate the implementation of personalized therapeutic strategies.

Trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2300077183).

Introduction: Oral semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1RA) approved for improving glycemic control in adults with type 2 diabetes (T2D). The PIONEER REAL program evaluates clinical and patient-reported outcomes of oral semaglutide treatment as part of routine clinical practice across 13 countries. Here, data from Canada, Denmark, Italy, the Netherlands, Sweden, Switzerland, and the UK are pooled and analyzed to address treatment satisfaction as well as glycated hemoglobin (HbA_1C) and body weight changes in relevant subgroup analyses.

Methods: This pooled analysis encompasses seven country-specific, non-interventional, multicenter, phase 4, prospective, single-arm clinical studies assessing the use of oral semaglutide in adults with T2D. Primary endpoint was the change in HbA_1C from baseline to end of study (EOS), and secondary endpoints included changes in body weight and treatment satisfaction. For the analyses, results were stratified by age, T2D duration, and oral semaglutide dose at EOS as well as baseline HbA_1C, body weight, and body mass index.

Results: Oral semaglutide treatment was initiated by 1615 participants. At EOS, 1222 (76%) participants out of the 1483 (92%) who completed the study were on treatment. Estimated changes in HbA_1C and body weight from baseline to week 38 were - 1.0%-point (95% CI - 1.08 to - 0.97; P < 0.0001) and - 5.0% (CI - 5.37 to - 4.72; P < 0.0001). Treatment satisfaction increased significantly during the study. Shorter T2D duration interacted with higher HbA_1C reduction and body weight loss. Interaction was also observed between higher baseline HbA_1C and more pronounced decrease in HbA_1C. No significant interactions were detected between clinical outcomes and age or physician setting.

Conclusion: The PIONEER REAL pooled analysis shows that people initiating oral semaglutide treatment experience improved glycemic control and body weight loss across age groups and T2D duration. This occurs regardless of specialist or primary care practice setting and is accompanied by an increased treatment satisfaction.

Clinical trial registrations: NCT04559815 (Canada), NCT04537637 (Denmark), NCT05230615 (Italy), NCT04601740 (the Netherlands), NCT04601753 (Sweden), NCT04537624 (Switzerland), NCT04862923 (UK).

Introduction: Newer incretin-based therapies for type 2 diabetes (T2D) have the potential to substantially reduce glycated hemoglobin (HbA1c) and weight with a low associated risk of hypoglycemia. This study aimed to assess the percentage of participants randomized to tirzepatide or comparator who achieved the composite endpoint of HbA1c ≤ 6.5% and weight reduction ≥ 10% without hypoglycemia across prespecified baseline characteristics: T2D duration (≤ 5, > 5-10, or > 10 years), sex, HbA1c (≤ 8.5% or > 8.5%), age (< 65 or ≥ 65 years), and body mass index (< 30, 30 to < 35, or ≥ 35 kg/m²).

Methods: This post hoc analysis of SURPASS-1 through -5 evaluated adult study participants with T2D treated with tirzepatide 5, 10, or 15 mg versus placebo or active comparator. Missing HbA1c and weight values were imputed from mixed models for repeated measures. Logistic regression was used to compare tirzepatide versus comparators for the percentage of participants reaching the composite endpoint.

Results: Across subgroups, the composite endpoint was achieved by a median of approximately 30%, 45%, and 54% of participants who received tirzepatide 5, 10, and 15 mg, respectively; this was consistent across baseline subgroups, except that a greater percentage of women than men achieved the composite endpoint. The most common treatment-emergent adverse events were gastrointestinal in nature.

Conclusions: In this post hoc analysis, tirzepatide achieved the composite outcome of glycemic control and weight loss with no hypoglycemia, irrespective of baseline characteristics. This may help clinicians as they select suitable treatment in diverse populations.

Trial registration: ClinicalTrials.gov: NCT03954834, NCT03987919, NCT03882970. NCT03730662, and NCT04039503.

Introduction: There are limited data on the prevalence of cardiovascular risk factors/diseases (diabetes, obesity, hypertension, and dyslipidemia) and their composite scores reflecting overall cardiovascular health among young (< 50 years old) married couples.

Methods: We have an established longitudinal prospective cohort of postpartum women with a history of hyperglycemia [pre-existing diabetes (PED; n = 101), overt diabetes in pregnancy (ODiP; n = 92), gestational diabetes (GDM; n = 643)], and normoglycemia (n = 183) in pregnancy and their spouses (n = 819). In this study, we report data from baseline cross-sectional evaluation of these 819 young couples regarding the burden of cardiovascular risk factors/diseases, their concordance and associations.

Results: The mean (SD) age was 33.5 (4.9) years for women and 36.9 (5.4) years for men, and the evaluation was performed at a median (IQR) postpartum interval of 30 (20-45) months. Diabetes, hypertension, obesity, and dyslipidemia were present in 25.0%, 6.9%, 25.6%, and 4.0% of women and 15.8%, 20.2%, 14.3%, and 8.2% of men, respectively. Among men, dysglycemia (diabetes/prediabetes) and adverse cardiovascular score (average/poor) showed a significant trend in progression according to the antenatal categories of their partner (highest in DIP, intermediate in GDM, and lowest in normoglycemia). The concordance was higher for adverse cardiovascular score (58.5%), overweight/obesity (48.7%), and dysglycemia (42.4%) compared to prehypertension/hypertension (29.2%) and hypercholesterolemia (8.2%). The odds ratios were significant for all associations evaluated, except for elevated blood pressure, being strongest (OR > 2.0) for overweight/obesity and adverse cardiovascular score.

Conclusions: Nearly three in five young couples evaluated in the study showed concordance for adverse cardiovascular scores. The cardiovascular risk in men increased in a graded manner across the increasing severity of antenatal glycemic categories of their partners.

Introduction: The high risk of cardiovascular events in people with type 2 diabetes increases with age. The cardiovascular effects of once-weekly subcutaneous and once-daily oral semaglutide versus placebo in people with type 2 diabetes at high cardiovascular risk were investigated in the SUSTAIN 6 and PIONEER 6 cardiovascular outcomes trials, respectively. It is unknown whether the effects of semaglutide are age dependent.

Methods: This post hoc analysis evaluated cardiovascular, metabolic, and safety outcomes with semaglutide versus placebo in age subgroups (≤ 60; > 60 to ≤ 65; > 65 to ≤ 70; and > 70 years) pooled from SUSTAIN 6 and PIONEER 6. Major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), changes from baseline in glycated hemoglobin A_1c (HbA_1c) and body weight, and adverse events were analyzed.

Results: Semaglutide reduced major adverse cardiovascular events and its components versus placebo across age subgroups (most hazard ratios < 1.0; p_interaction > 0.05). The treatment difference in HbA_1c reduction was greater in those aged ≤ 60 years than in older subgroups (p_interaction = 0.01). Reductions in body weight with semaglutide versus placebo were consistent across age subgroups (p_interaction = 0.124). Serious adverse events or severe hypoglycemic episodes did not differ between semaglutide and placebo across age subgroups.

Conclusion: Semaglutide consistently reduced major adverse cardiovascular events and body weight versus placebo across age subgroups; its safety profile did not differ with age. These results suggest that relaxing HbA_1c targets based solely on age may not always be required for people with type 2 diabetes.

Trial registration: SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) are registered at ClinicalTrials.gov.

Introduction: Diabetes is associated with a high economic burden in China; therefore, strategies to prevent diabetes, improve glycaemic control, delay disease-related complications and maintain quality of life are essential. This study was conducted to evaluate trends in treatment patterns and glycaemic control in people with type 2 diabetes (T2D) in real-world clinical practice in Tianjin, China.

Methods: This retrospective, cross-sectional, multicentre study analysed data from adults with T2D living in Tianjin, China between 2015 and 2019, based on information obtained from a regional electronic medical record database. Temporal trends in treatment patterns and glycaemic control were assessed using linear regression (continuous variables), and Cochran-Armitage (two categories) or Cochran-Mantel-Haenszel (≥ 3 categories) tests.

Results: Between 2015 and 2019, data from 312,203 individuals treated at 75 hospitals were included. Over this period, there was an upward trend in the prevalence of hypertension, hyperlipidaemia, obesity, cardiovascular disease, stroke and retinopathy each year (all P < 0.001). The use of metformin or dipeptidyl peptidase-4 inhibitors increased, while thiazolidinedione, alpha-glucosidase inhibitor and glinide use decreased; the use of basal insulin (BI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), GLP-1 RAs + BI, bolus insulin and BI + bolus insulin increased, whereas the use of premixed insulin showed a downward trend (all P < 0.001). From 2015 to 2019, an increased proportion of individuals achieved glycated haemoglobin (HbA1c) < 7% (< 53 mmol/mol; 28.1-33.7%), fasting plasma glucose (FPG) < 7 mmol/l (21.7-26.9%) and postprandial glucose (PPG) < 10 mmol/l (22.0-48.2%; all P < 0.001). There was no change in the proportion of individuals with an FPG ≥ 7 mmol/l and a PPG ≥ 10 mmol/l, while the prevalence of residual hyperglycaemia increased (P < 0.001).

Conclusions: Glycaemic control improved between 2015 and 2019 in people with T2D in Tianjin, China; however, there is an unmet need for more effective glycaemic control.

Introduction: Previous studies have shown that iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, provides effective glycemic control in people with type 2 diabetes (T2D). The SIMPLIFY Japan study assessed the impact of switching from multiple daily insulin injections (MDI) to once-daily iGlarLixi on health-related quality of life (HRQOL) and glycemic parameters in Japanese people with moderately controlled T2D.

Methods: This 24-week, prospective, observational cohort study enrolled Japanese adults with T2D who switched from MDI therapy to iGlarLixi. Data were collected at baseline, 12, and 24 weeks; changes in Diabetes Therapy-Related Quality of Life (DTR-QOL) questionnaire score, glycated hemoglobin (HbA1c), body weight and self-reported treatment adherence were evaluated; the primary endpoint was change in DTR-QOL at 24 weeks.

Results: Sixty-six participants were enrolled and 61 were included in the full analysis set. Significant improvements were observed in total DTR-QOL score from baseline to week 24 (mean change + 10.8 points; P < 0.001), with higher scores observed in individual domains related to social/daily activities, treatment satisfaction, and reductions in treatment-related anxiety (P < 0.05). A small HbA1c increase was noted at week 24 (P < 0.001), while this did not appear to adversely affect HRQOL or treatment satisfaction. A significant reduction in body weight was observed at week 12 (mean change - 0.7 kg; P = 0.046). Self-reported treatment adherence increased from baseline to week 24, with the proportion of participants who never missed an insulin injection increasing from 55.7 to 77.6%. At week 24, the incidence of hypoglycemia and gastrointestinal adverse events was 18.2 and 27.3%, respectively.

Conclusions: Switching from MDI to iGlarLixi therapy in Japanese people with T2D was associated with enhanced HRQOL (despite slight elevation in HbA1c) and improved treatment adherence, with a favorable safety profile. These findings support the beneficial role of iGlarLixi in the management of T2D in real-world Japanese clinical practice.

Study registration: Japan Registry of Clinical Trials (jRCT1041210151).

Introduction: The aim of this work was to assess the safety and effectiveness of concomitant iGlarLixi and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) use in adults with type 2 diabetes (T2D) who fasted during Ramadan.

Methods: Of the 420 eligible participants from the SoliRam study, 174 were using SGLT-2i in addition to iGlarLixi and 246 were not using SGLT-2i, referred to as SGLT-2i user and non-user, respectively. The primary endpoint was the proportion of participants experiencing ≥ 1 severe and/or symptomatic documented (< 70 mg/dl [< 3.9 mmol/l]) hypoglycemia.

Results: More than 50% of participants in both groups were male. The mean weight, glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG) were similar in both groups. Approximately half of participants in the SGLT-2i-user group and ~ 25% participants in the SGLT-2i-non-user group were on two oral anti-hyperglycemic drugs (OADs), whereas ~ 20% in the SGLT-2i-user group and ~ 1% of participants in the SGLT-2i-non-user group were on three OADs in addition to iGlarLixi. Around 35% and 55% of participants in the SGLT-2i-user and SGLT-2i-non-user groups, respectively, were taking concurrent sulphonylureas. About 97% of participants in both groups were able to fast for ≥ 25 days. The incidence of primary endpoint was low in both groups; SGLT-2i user: 0.6%, 4.2%, and 0.6% and SGLT-2i-non-user: 1.3%, 0.9% and 0% during pre-Ramadan, Ramadan, and post-Ramadan period, respectively. The incidence of severe and/or symptomatic documented (< 54 mg/dl [< 3.0 mmol/l]) hypoglycemia events was also low throughout the study, including during Ramadan. No severe hypoglycemia occurred during Ramadan in either group. Improvements in HbA1c and FPG, with a small reduction in weight, were observed from pre- to post-Ramadan in both groups. No serious adverse event was reported in either group.

Conclusions: Concomitant iGlarLixi and SGLT-2i therapy with or without other OADs was demonstrated to be safe in adults with T2D during Ramadan fast, with a low risk of hypoglycemia and improvements in glycemic outcomes.