Diabetes Therapy最新文献

Introduction: Daily insulin administration can be burdensome for people with type 2 diabetes (PwT2D) and can impact treatment adherence. This study investigated preferences for once-weekly, long-acting basal insulin for treatment of PwT2D.

Methods: An online discrete-choice experiment was administered to PwT2D in the USA. Qualitative interviews informed the selection of six attributes: reduction in A1c level after 6 months, amount of time spent in optimal blood sugar range each day, number of serious low blood sugar events, number of nighttime low blood sugar events, change in weight because of the insulin over 6 months, and frequency of administration. Each participant completed eight questions offering a choice between two long-acting insulins; questions varied according to an experimental design. A fixed treatment choice question asked about preferences for daily versus weekly insulin, holding other treatment features constant. Data were analyzed using random-parameters logit models, and heterogeneity was explored through subgroup analyses.

Results: Four hundred sixty-six PwT2D completed the survey (mean age, 57; mean A1c, 7.5%; 59.0% female); 33.3% of these were currently on a basal/bolus regimen, 34.3% used basal only, and 32.4% were insulin naive. Respondents placed the most importance on avoiding a 10-pound weight change and equal importance on the largest change in the number of serious and nighttime low blood sugar events per year and achieving the longest time in range included in the choice questions. There was significant heterogeneity in preferences by experience: insulin-naive respondents had stronger preferences for scheduled and flexible weekly insulin over daily insulin; 67.6% preferred flexible weekly over daily insulin, all else being equal.

Conclusion: PwT2D valued insulin efficacy and reducing treatment-related adverse events, with heterogeneity in the relative importance of administration frequency. All else being equal, respondents preferred weekly over daily basal insulin. These findings provide insights into the preferences of PwT2D considering weekly long-acting insulin.

Despite the growing evidence supporting the outpatient use of continuous glucose monitoring (CGM) for improving glycaemic control and reducing hypoglycaemia, there is a need for a detailed understanding of the specific features of CGM devices that best meet individual patient needs. This expert opinion, based on a comprehensive literature review and the personal perspectives of clinicians, aims to provide the healthcare professionals (HCPs) with a comprehensive framework for selecting CGM devices. It evaluates the current state of CGM technology, categorizing features into essential features, major drivers of choice, and additional/useful features. Moreover, the practical model presented outlines a patient's journey with CGM, emphasising the importance of aligning device features with patient needs. This includes understanding the patient's lifestyle, clinical conditions, and personal preferences to optimize CGM use and improve diabetes management outcomes.

Introduction: A bidirectional relationship has been observed between type 2 diabetes mellitus and sarcopenia, especially among older adults. While previous studies have reported that imeglimin improves mitochondrial function, they have not assessed its effects on muscle strength in patients with type 2 diabetes. Therefore, we aimed to investigate the effects of imeglimin on muscle strength in patients with type 2 diabetes.

Methods: In this prospective cohort study, we recruited consenting patients with type 2 diabetes (20-75 years). Changes in lean body mass (LBM), fat mass, quadriceps muscle strength, and grip strength from baseline (week 0) to week 24 were evaluated and compared between patients treated with imeglimin therapy (group I) and those who did not take imeglimin (controls, group C).

Results: We recruited 27 patients treated with imeglimin (group I) and 29 controls (group C), and 50 of them completed the study (group I: n = 23; group C: n = 27). The change in LBM, total body fat mass, or skeletal muscle index from baseline to week 24 did not differ significantly between the two groups. However, group I exhibited a significantly higher percent change in quadriceps knee extension strength from baseline to week 24 than group C (13 ± 19% and 2.1 ± 14%, p = 0.022). Conversely, the difference in percent change in grip strength was not significant. Multivariable analysis showed that imeglimin use was significantly associated with a percent change in quadriceps knee extension strength, independent of age, sex, body mass index, and skeletal mass index (β = 0.325, p = 0.0014).

Conclusions: Imeglimin positively affected muscle strength in patients with type 2 diabetes without altering LBM. Therefore, imeglimin exerts a unique effect on skeletal muscles in humans. Further randomized controlled trials are needed to validate these findings.

Trial registration: This research was registered in the University Hospital Medical Information Network (UMIN, UMIN000054715).

Introduction: Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes mellitus (T2DM), is a leading cause of blindness and has detrimental effects on patients' quality of life. We compared the risk of DR diagnosis with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM in Japan.

Methods: This Japanese retrospective cohort study used the JMDC Claims Database (data collected from January 2015 to September 2022). Patients with T2DM and no record of microvascular or macrovascular diseases who were newly treated with an SGLT2i (23,061 patients) or a DPP-4i (53,986 patients) were matched 1:1 using propensity score (10,166 per matched group). Incidence rates (IRs) and cumulative IRs of DR diagnosis were calculated for each treatment group; hazard ratio (HR) and its 95% confidence interval (CI) were calculated using Cox proportional hazard models to compare the risk between the groups.

Results: The IR of DR diagnosis was 46.23 and 57.12 per 1000 person-years in the SGLT2i and DPP-4i groups, respectively, with a significantly lower risk in the SGLT2i group than in the DPP-4i group (HR 0.83, 95% CI 0.75-0.92, P = 0.0003).

Conclusions: In this study, the risk of DR diagnosis was lower with SGLT2i compared with DPP-4i in patients with T2DM without microvascular and macrovascular diseases in Japan. Findings suggest that early SGLT2i treatment may be beneficial in preventing DR development in early-stage T2DM. Graphical abstract available for this article.

Introduction: The shortage of general practitioners (GPs) and the increasing prevalence of type 2 diabetes create significant pressure on primary healthcare services. To enable that medical services are available to all that need it, innovative solutions are needed. One of those, a Short Message Service (SMS)-supported basal insulin titration service is investigated in this study. The primary objective was to determine the percentage of subjects who achieved stable fasting blood glucose (FBG) within their individual target range with this service after week 16.

Methods: This single-arm, 16-week study aimed to enroll 111 adults diagnosed with type 2 diabetes that needed insulin. The study subjects measured their FBG 4 consecutive days to establish a baseline, then received SMS prompts for daily FBG measurements and evening insulin injections until their FBG stabilized within the target range. Adjusting the insulin based on the FBG. Once stabilization was achieved, subjects continued with their optimal insulin dose for the remainder of the study. Sixteen weeks after the baseline, subjects measured FBG for 4 days before visit 4, where these values were read by the healthcare provider.

Results: Out of the planned 111 subjects, only 30 were enrolled, with one withdrawal prior to service activation. Challenges in subject recruitment were attributed to the COVID-19 outbreak, limited eligibility, competing studies, and new medications delaying insulin initiation. Subjects were on average 59.97 years old, had an HbA1c of 9.29% a FBG of 205.64 mg/dl, and had diabetes for 10 years. Among the 29 subjects who started the service, 72% achieved successful titration at visit 4, with a median time of 49 days. Notable improvements were observed in HbA1c levels (decreased by 1.58%) and FBG levels (decreased by 64 mg/dl) over the 16-week study period. No adverse events or device-related issues were reported.

Conclusions: Despite recruitment challenges, guided basal insulin titration holds promise for insulin therapy initiation in individuals. The findings emphasize the potential of tele-medical approaches, specifically through remote messaging, in managing diabetes and improving therapy adherence.

Introduction: Bone fragility is a critical issue in the treatment of elderly people with type 2 diabetes (T2D). In the Canagliflozin Cardiovascular Assessment Study, the subjects with T2D who were treated with canagliflozin showed a significant increase in fracture events compared to a placebo group as early as 12 weeks post-initiation. In addition, it has been unclear whether sodium-glucose co-transporter 2 (SGLT2) inhibitors promote bone fragility. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to prospectively evaluate the short-term effect of the SGLT2 inhibitor luseogliflozin on bone strength and microarchitecture in elderly people with T2D.

Methods: This was a single-center, randomized, open-label, active-controlled pilot trial for ≥ 60-year-old Japanese individuals with T2D without osteoporosis. A total of 22 subjects (seven women and 15 men) were randomly assigned to a Lusefi group (added luseogliflozin 2.5 mg) or a control group (added metformin 500 mg) and treated for 48 weeks. We used the second-generation HR-pQCT (Xtreme CT II®, Scanco Medical, Brüttisellen, Switzerland) before and 48 weeks after the treatment to evaluate the subjects' bone microarchitecture and estimate their bone strength.

Results: Twenty subjects (Lusefi group, n = 9; control group, n = 11) completed the study, with no fracture events. As the primary outcome, the 48-week changes in the bone strength (stiffness and failure load) estimated by micro-finite element analysis were not significantly different between the groups. As the secondary outcome, the changes in all of the cortical/trabecular microarchitectural parameters at the radius and tibia from baseline to 48 weeks were not significantly different between the groups.

Conclusions: In the pilot trial, we observed no negative effect of 48-week luseogliflozin treatment on bone microarchitecture or bone strength in elderly people with T2D.

Trial registration: UMIN-CTR no. 000036202 and jRCT 071180061.

The Tandem t:slim X2 insulin pump is a second-generation automated insulin delivery system with Control-IQ technology. It consists of an X2 insulin pump, an integrated Dexcom sensor, and an embedded 'Control-IQ' algorithm, which predicts glucose levels 30 min in the future, adapting the programmed basal insulin rates to get glucose levels between 112.5 and 160 mg/dl (8.9 mmol/l). The system delivers automatic correction boluses of insulin when glucose levels are predicted to rise > 180 mg/dl (10 mmol/l). It has been commercially available since 2016. We reviewed the current evidence about the psychological, safety, and exercise-related outcomes of this device in children, adolescents, and young adults living with type 1 diabetes. We screened 552 papers, but only 21 manuscripts were included in this review. Fear of hypoglycemia is significantly reduced in young people with diabetes and their parents. Interestingly, diabetes-related distress is decreased; thus, the system is well accepted by the users. The sleeping quality of subjects living with diabetes and their caregivers is improved to a lesser extent as well. Despite the small number of data, this system is associated with a low rate of exercise-related hypoglycemia. Finally, evidence from the literature shows that this system is safe and effective in improving psychological personal outcomes. Even if further steps toward the fully closed loop are still mandatory, this second-generation automated insulin delivery system reduces the burden of diabetes. It properly addresses most psychological issues in children, adolescents, and young adults with type 1 diabetes mellitus; thus, it appears to be well accepted.

Introduction: ISIS 449884, a 2'-O-methoxyethyl antisense oligonucleotide that targets the glucagon receptor (GCGR), has demonstrated an ability to reduce hepatic glucose output and lower the blood glucose level. The primary objective of this study was to investigate the safety and efficacy of ISIS 449884 as an add-on to metformin in a population of Chinese patients with type 2 diabetes mellitus (T2DM).

Method: This was a multicenter, placebo-controlled (2:1), randomized, double-blind, parallel-enrollment, multiple-dose phase II study in Chinese patients with T2DM. A total of 90 patients who were uncontrolled by stable metformin monotherapy were randomized into three cohorts. Thirty subjects were enrolled in each cohort and received injections of ISIS 449884 (50 mg or 60 mg weekly or 100 mg every other week) or a corresponding volume of placebo (0.25 mL and 0.3 mL weekly or 0.5 mL every other week) subcutaneously in a 2:1 ratio for 16 weeks.

Results: The primary efficacy endpoint was analyzed in 88 subjects (ISIS 449884, n = 59; placebo, n = 29). The corrected LS mean change from baseline in glycated hemoglobin (HbA1c) at week 17 in the pooled ISIS 449884 treatment group was - 1.31% (95% CI - 1.66%, - 0.96%), and that in the pooled placebo group was 0.15% (95% CI - 0.37%, 0.66%). The LS mean difference between the two groups was - 1.46% (95% CI - 1.92%, - 1.00%, P < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 53/60 subjects (88.3%) and 25/30 subjects (83.3%) in the pooled ISIS 449884 treatment group and the pooled placebo group, respectively, with similar incidences. Drug-related TEAEs occurred in 41/60 subjects (68.3%) and 9/30 subjects (30.0%), respectively. TEAEs of grade 3 or higher occurred in 5/60 (8.3%) subjects and 2/30 (6.7%) subjects, respectively, and none of them were drug related.

Conclusions: The ISIS 449884 injection add-on to metformin significantly reduced HbA1c in patients with T2DM uncontrolled by stable metformin monotherapy and showed an acceptable benefit/risk profile.

Clinical trial registration: www.chinadrugtrials.org.cn , CTR20191096.

Introduction: Semaglutide, a glucagon-like peptide 1 receptor agonist (GLP1RA), is available in both parenteral and oral preparations. Studies of injectable preparations have convincingly demonstrated its beneficial effect on major adverse cardiac events (MACE). This predictive analysis was undertaken to forecast early termination of the SOUL trial (oral semaglutide) as well as the primary events.

Methods: SOUL is a multicenter, double-blind, placebo-controlled randomized controlled trial (RCT) evaluating the reduction in MACE associated with oral semaglutide versus placebo in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. A sample of 9642 participants will be followed for 5 years and 5 months. A random-effects model meta-analysis, pooling hazard ratios from previous RCTs, was conducted using R software to inform the predictive model. The background CV event rates from the placebo arms of previous RCTs with semaglutide were matched with the pre-adjudicated assumptions of the SOUL trial to create the predictive model. The truncated trial duration, MACE, and its individual components in the intervention and placebo arms were estimated. The predicted difference between the two groups was estimated using the chi-squared test.

Results: A pooled analysis of 10,013 patients revealed a significant reduction in the number of MACEs associated with semaglutide (HR 0.79, 95% CI 0.69-0.91). Predictive analysis indicated that 1225 events would be achieved by 3.78 years, suggesting premature termination.

Conclusion: The mathematical model based on the meta-analysis predicts that the SOUL study on oral semaglutide will be terminated early, with oral semaglutide showing benefits in terms of MACE compared to placebo. If the SOUL study corroborates the findings of this model, it may not only form the basis for the calculation of power but also define the duration of such studies, reducing costs and easing the process of designing cardiovascular outcome trials (CVOTs).

Protocol registration: INPLASY202460061.

Introduction: The transition from paediatric to adult diabetes care (TPA) of children/adolescents with type 1 diabetes (T1D) represents a unique challenge and remains a critical phase in the T1D care pathway. This study aims to describe and understand the experience of the transition process from a participant's perspective in young adults who are living in France with T1D and to measure their satisfaction.

Methods: An online questionnaire was presented to people with T1D in France on a global online participant community platform. The questionnaire was developed by a scientific committee including paediatric and adult diabetologists and refined by a group of participants. Thematic qualitative analysis was performed on the responses.

Results: A total of 104 respondents were included in the survey (mean age 24.4 years [95% CI 23.8-25.0]; 61.5% female). The mean age at the time of transition was 18.4 years (95% CI 17.8-18.9), and 56% of respondents had their first adult diabetology follow-up in the same institution. During TPA, of the 76 participants who experienced personal issues, 74% experienced at least one issue with their diabetes management in the months following the transition. In the following months, 61% experienced new or unexpected problems in monitoring their diabetes after transition and 44% reported unusual glycaemic imbalances, including hypoglycaemia (8%) and hyperglycaemia (9%) requiring hospitalisation. Presence of personal issues during TPA was significantly associated with occurrence of problems with diabetes management or glycaemic imbalance. Three factors identified for a successful transition were (i) early meeting with the 'adult' diabetes care team, (ii) letting the participants choose the right age to leave paediatric clinic and (iii) having good diabetes control at the beginning of the TPA process.

Conclusion: Most young adults with T1D report experiencing issues around TPA with significant consequences on their disease management. Hence, it is necessary to identify these issues to better support them and improve diabetes management during this phase.