Diabetes, Obesity & Metabolism最新文献

Aims: Women with gestational diabetes (GDM) have increased lifetime risk of developing diabetes. We aim to determine the factors contributing to poor adherence of the postpartum oral glucose tolerance test (OGTT) and identify key predictors to postpartum dysglycaemia in our Asian cohort.

Methods: We conducted a retrospective cohort study of women with high-risk GDM (n = 561). High-risk women with GDM were defined as (1) women with diabetic-range glucose excursions on an antepartum OGTT, (2) women diagnosed GDM on early OGTT and (3) women requiring ≥20 units of insulin during antepartum period. We use logistic regression predictive models to associate maternal variables with postpartum OGTT attendance and glucose tolerance status postnatally.

Results: Between March 2020 to March 2024, 58.7% (n = 329) of women returned for postpartum OGTT. Predictors for attendance of postpartum OGTT were Chinese ethnicity (odds ratio [OR] 2.11, 95% confidence interval [CI] [1.14-3.89]), pre-pregnancy body mass index (BMI) (OR 0.95 [95% CI 0.90-0.99]), first GDM (OR 2.34 [95% CI 1.39-3.96]) and 2-h glucose threshold on antepartum OGTT (OR 0.87 [95% CI 0.76-0.99]). Ethnicity influences postnatal dysglycaemia outcomes in our cohort. Chinese women, compared to women of Malay ethnicity, had a 4.5-odds of persistent postpartum dysglycaemia. An antenatal HbA1c of ≥5.7% and an elevated 2-h post-OGTT glucose value significantly predict postpartum dysglycaemia independent of ethnicity.

Conclusion: Ethnicity-specific prediction models integrating antepartum OGTT and HbA1c predict postpartum dysglycaemia in a multiethnic Southeast Asian cohort. Using these predictive models, we could identify high-risk patients for early intervention.

Aims: The study aims to examine the outcome of replacement of prandial insulin with once-weekly subcutaneous semaglutide in people with type 2 diabetes reasonably controlled on multiple daily insulin injections (MDI).

Materials and methods: This single-centre, randomised, open-label trial enrolled a statistically predetermined sample of 60 adults with HbA1c ≤7.5% (58 mmol/mol) receiving MDI, with a total daily dose (TDD) ≤120 units/day. Participants were assigned 2:1 to subcutaneous semaglutide 1.0 mg plus insulin degludec, or to continue MDI. The primary outcome was percentage of subjects maintaining HbA1c ≤7.5% (58 mmol/mol) at Week 26.

Results: At Week 26, 90% of semaglutide and 75% of MDI subjects maintained HbA_1c ≤7.5% (≤58 mmol/mol) (p = 0.18). Mean changes (95% CI) in HbA_1c, weight and percentage body weight for semaglutide versus MDI, respectively, were -0.5% (-0.7, -0.3) versus 0.0% (-0.3, 0.3; p = 0.009); -8.9 kg (-9.9, -7.8) versus 1.5 kg (-0.1, 3.1; p < 0.001); and -8.6% (-9.6, -7.6) versus 1.4% (0.0, 2.8; p < 0.001). Insulin TDD decreased 56.0% (-62.3, -49.7) with semaglutide and increased 6.7% (-2.5, 16.0) with MDI (p < 0.001). Among semaglutide subjects, 58% reduced insulin TDD > 50%, 97.5% stopped prandial insulin and 45% lost >10% body weight. Participant treatment satisfaction scores trended higher with semaglutide. Hypoglycaemia frequency was similar between groups.

Conclusions: In people with type 2 diabetes well controlled (HbA_1c ≤7.5% [≤58 mmol/mol]) on MDI ≤120 units/day, replacing multiple daily injections of prandial insulin with once-weekly subcutaneous semaglutide can maintain and even improve HbA_1c, lower body weight and lessen the burden of management.

Aims: This study aimed to assess the safety, pharmacokinetics and pharmacodynamics of noiiglutide (SHR20004), a novel glucagon-like peptide-1 receptor agonist, in Chinese obese participants without diabetes mellitus (DM).

Materials and methods: This phase 1, randomised, double-blind, placebo-controlled study enrolled adult participants with body mass index (BMI) ≥28 kg/m². The study used a titration method, each subject received daily noiiglutide injection for 3-6 weeks, until reaching the final dose of 0.18, 0.24, 0.30 or 0.36 mg per day. Each dose group consisted of 10 participants, with eight receiving noiiglutide and two receiving placebos. Safety assessments were conducted throughout the study, and pharmacokinetics and pharmacodynamics were evaluated.

Results: Most treatment-emergent adverse events were of mild to moderate in severity, with no serious adverse event or adverse event led to withdraw. Blood concentration of noiiglutide reached a steady state after daily administration for 4 days, with no significant accumulation. Mean elimination half-life (t_1/2) was between 9.90 and 11.8 h at steady state. At the end of treatment, the mean weight loss compared to baseline for the placebo group and each treatment group was -1.89, -3.26, -5.45, -4.35 and -7.46 kg respectively. The weight and BMI reductions observed in each noiiglutide treatment group were greater than those in the placebo group and exhibited an increasing trend with extended administration duration.

Conclusions: Daily administration of noiiglutide using a titration method was well tolerated by Chinese obese participants without DM and showed potential therapeutic effect for weight loss.

Aims: To assess the efficacy and safety of cofrogliptin for impaired glucose tolerance (IGT).

Methods: In this multicenter, double-blind, placebo-controlled phase 2 trial, IGT patients were randomized 1:1:1 to receive cofrogliptin 10 mg, cofrogliptin 25 mg or placebo once biweekly. The primary endpoint was the change from baseline in glucose total AUC_{0-3 h} during meal tolerance test (MTT) at week 12.

Results: Among 261 subjects screened, 99 were enrolled. At week 12, significant mean reductions from baseline in glucose total AUC_{0-3 h} during MTT were observed in cofrogliptin groups (10 mg: -1.75 mmol h/L, p = 0.01; 25 mg: -1.54 mmol h/L, p = 0.02) versus placebo (0.36 mmol h/L). Significant benefits were also seen with cofrogliptin for secondary endpoints of the change from baseline in C_max of glucose during MTT 0-3 h at week 12, and the change from baseline in glucose total AUC_{0-3 h} and C_max of glucose during OGTT 0-3 h at week 10 versus placebo. Additionally, more cofrogliptin-treated patients achieved normoglycaemia versus placebo at week 10. The incidence of AEs was generally comparable in all groups, and all of AEs were mild or moderate. No serious AEs or severe hypoglycaemia were reported.

Conclusion: A 12-week treatment with cofrogliptin provided significant glucose-lowering, and was safe, well tolerated.

Aim: To assess weight loss and cardiorenal outcomes by baseline body mass index (BMI) in VERTIS CV.

Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. These post hoc analyses evaluated cardiometabolic and cardiorenal outcomes (a composite of death from CV causes or hospitalization for heart failure [HHF], CV death, HHF and an exploratory composite kidney outcome including ≥40% estimated glomerular filtration rate [eGFR] decrease) by baseline BMI, using conventional clinical categories and Cox proportional hazards models.

Results: In total, 8246 adults were randomized (mean age 64.4 years, diabetes duration 13.0 years, BMI 32.0 kg/m², 61% with BMI >30 kg/m²). Absolute body weight reduction was greater with ertugliflozin versus placebo at 3 and 5 years in the overall population (p < 0.001) and across BMI subgroups. Ertugliflozin increased the proportion of participants achieving ≥5% and ≥10% body weight reduction (ertugliflozin 34.9% and 13.6%, placebo 19.4% and 4.1%; odds ratio [95% confident interval, CI], 2.21 [1.76-2.77] and 3.65 [2.39-5.57], respectively) at 5 years. No significant difference was observed in the effect of ertugliflozin on HHF across BMI subgroups (P_interaction = 0.61). Similarly, no significant difference was observed in the effect of ertugliflozin on the kidney composite outcome across BMI subgroups (P_interaction = 0.39). Results were similar for other CV outcomes, and safety was consistent with the known ertugliflozin profile.

Conclusion: Weight loss was observed across baseline BMI and was sustained over 5 years of follow-up. The effects of ertugliflozin on HHF and kidney composite were consistent across baseline BMI.

Aim: To measure the impact of type 1 and 2 diabetes mellitus (T1D and T2D) on the QoL of a person's family members/partner and assess if there is any difference in family impact.

Methods: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with diabetes completing the Family Reported Outcome Measure-16 (FROM-16).

Results: Two hundred and sixty-one family members/partners (mean age = 57.9 years, SD = 13.8; females = 68.2%) of people with diabetes (mean age = 57.7, SD = 20.6; females = 38.3%; T1D n = 100; T2D n = 161) completed the FROM-16. The overall FROM-16 mean score was 10.47, SD = 7.8, suggesting a moderate effect on the QoL of family members of people with diabetes. A quarter (24.5%) of family members experienced a 'very large effect' or 'extremely large effect' on their QoL. The family impact of T1D (mean FROM-16 = 12.61, SD = 7.9) was greater than that of T2D (mean = 9.15, SD = 7.5, p < 0.01), with being 'female' and 'parents of children and adolescents' rendered as significant predictors of greater impact. Family members of T2D had a lower risk of experiencing a high family impact (FROM-16 score >16) compared with T1D (RR 0.561, 95% CI 0.371-0.849).

Conclusions: Compared to T2D, family members of T1D experience a greater impact on their QoL, particularly those caring for children and adolescents. These findings have clinical and resource implications, indicating a need to assess this impact as a part of routine diabetes care to support impacted family members. The FROM-16 could assess this impact in routine practice and further facilitate referral of family members to appropriate support services.