Change In HbA1c Research Articles

Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study.

The aim was to investigate the effects of lotiglipron, a once-daily, oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity. A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study. In total, 901 participants were treated with at least one dose of the study drug (T2D cohort: n = 512, obesity cohort: n = 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least squares mean decreases up to -1.44% (90% confidence interval [CI]: -1.63, -1.26) (lotiglipron 80 mg), versus placebo, -0.07% (90% CI: -0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to -7.47% (90% CI: -8.50, -6.43) (lotiglipron 200 mg, five-step titration), versus placebo, -1.84% (90% CI: -2.85, -0.83). Across cohorts, the most frequently reported treatment-emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four-step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort). The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at-risk population unsuccessful and therefore clinical development of lotiglipron terminated. GOV: NCT05579977.

Comparing the effects of time-restricted eating on glycaemic control in people with type 2 diabetes with standard dietetic practice: A randomised controlled trial

AimsTo test the efficacy of time-restricted eating (TRE) in comparison to dietitian-led individualised dietary guidance to improve HbA1c in people with Type 2 diabetes mellitus. MethodsIn a parallel groups design, 51 adults (35–65 y) with Type 2 diabetes mellitus and overweight/obesity (HbA1c ≥6.5% (48 mmol/mol), BMI ≥25-≤40 kg/m2) commenced a six-month intervention. Following baseline, participants were randomised to TRE (1000–1900 h) or DIET (individualised dietetic guidance) with four consultations over four months. Changes in HbA1c (primary), body composition, and self-reported adherence (secondary) were analysed using linear mixed models. A non-inferiority margin of 0.3% (4 mmol/mol) HbA1c was set a priori. ResultsForty-three participants (56 ± 8 y, BMI: 33 ± 5 kg/m2, HbA1c: 7.6 ± 0.8%) completed the intervention. HbA1c was reduced (P=0.002; TRE: −0.4% (−5 mmol/mol), DIET: −0.3% (−4 mmol/mol)) with no group or interaction effects; TRE was non-inferior to DIET (−0.11%, 95%CI: −0.50% to 0.28%). Body mass reduced in both groups (TRE: −1.7 kg; DIET: −1.2 kg) via ∼900 kJ/d spontaneous energy reduction (P<0.001). Self-reported adherence was higher in TRE versus DIET (P<0.001). ConclusionsWhen individualised dietary guidance is not available, effective, and/or suitable, TRE may be an alternative dietary strategy to improve glycaemic control in people with Type 2 diabetes mellitus.

Effects of SGLT2 inhibitors on the onset of esophageal varices and extrahepatic cancer in type 2 diabetic patients with suspected MASLD: a nationwide database study in Japan

Background & aimSGLT2 inhibitors (SGLT2i) improve hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) and MASLD. We aimed to investigate the impact of SGLT2i on the incidence of liver-related events and extrahepatic cancer compared to DPP4 inhibitors (DPP4i) in patients with T2DM and suspected MASLD using a medical claims database in Japan.MethodsWe conducted a retrospective study using a Japanese medical claims database. Among patients with T2DM who were prescribed SGLT2i or DPP4i (n = 1,628,656), patients with suspected MASLD were classified into SGLT2i (n = 4204) and DPP4i (n = 4204) groups. Effects of SGLT2i on the following outcomes were compared to DPP4i: (1) changes in HbA1c and ALT levels after 6 months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12 months.ResultsAfter 6 months, DPP4i significantly decreased HbA1c levels compared to SGLT2i. In contrast, SGLT2i significantly decreased ALT levels compared to DPP4i. SGLT2i significantly decreased FIB-4 index compared to DPP4i over 12 months. Although no significant difference was observed in the incidence of overall liver-related events between the two groups, SGLT2i significantly reduced the incidence of esophageal varices (HR 0.12, 95%CI 0.01–0.95, P = 0.044). Moreover, SGLT2i significantly suppressed the incidence of extrahepatic cancer (HR 0.50, 95%CI 0.30–0.84, P = 0.009) compared to DPP4i.ConclusionSGLT2i was more beneficial than DPP4i in improving the hepatic inflammation and fibrosis indices. Moreover, SGLT2i suppressed the incidence of esophageal varices and extrahepatic cancer compared to DPP4i. SGLT2i may suppress life-threatening events in patients with T2DM and suspected MASLD.

The risk of diabetes and HbA1c deterioration during antipsychotic drug treatment: A Danish two-cohort study among patients with first-episode schizophrenia.

Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c). We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before. In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication. This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES.

The Effects of the AGE Inhibitor Pyridoxamine on Bone in Older Women with Type 2 Diabetes: a Randomized Clinical Trial.

Type 2 diabetes (T2D) patients have reduced bone turnover and increased fractures. Advanced glycation endproducts (AGEs) impair osteoblasts and are implicated in diabetic fractures. Pyridoxamine (PM) is a vitamin B6 metabolite which inhibits formation of AGEs. We hypothesized that PM treatment in older T2D patients, by inhibiting AGEs, would increase bone formation. Double-blind RCT. Academic center. Older T2D women (n=55). Oral PM 200 mg twice daily for one year. The primary outcome was the change in the bone formation marker P1NP. Other outcomes were changes in bone resorption, bone mineral density (BMD), HbA1c and skin autofluorescence (SAF), and in a bone biopsy sub-group, the correlation between bone fluorescent AGEs (fAGEs) and SAF. P1NP increased 23.0% with PM (95% CI: 9, 37; within-group p=0.028) vs. 4.1% with placebo (-9, 17; within-group p=0.576; between-groups p=0.056). BMD increased at the femoral neck (PM: 2.6±5% vs. placebo: -0.9±4%; between-groups p=0.007). Bone resorption markers and SAF did not change. HbA1c decreased (PM: -0.38 ± 0.7% vs. placebo: 0.05 ± 1.7%; between-groups p =0.04). Within the PM group, the HbA1c change correlated inversely with the % P1NP change (r =-0.50, p=0.034). Cortical bone biopsy fAGEs correlated with SAF (r=0.86, p=0.001). Adverse events were similar between groups. PM tended to increase P1NP in older T2D women, as well as increasing bone density and reducing HbA1c. Further studies are needed to investigate the potential of PM as a disease mechanism-directed approach to reduce fractures in T2D.

Pharmacometrics-Enhanced Bayesian Borrowing for Pediatric Extrapolation - A Case Study of the DINAMO Trial.

Bayesian borrowing analyses have an important role in the design and analysis of pediatric trials. This paper describes use of a prespecified Pharmacometrics Enhanced Bayesian Borrowing (PEBB) analysis that was conducted to overcome an expectation for reduced statistical power in the pediatric DINAMO trial due to a greater than expected variability in the primary endpoint. The DINAMO trial assessed the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycemic control (change in HbA1c over 26 weeks) in young people with type 2 diabetes (T2D). Previously fitted pharmacokinetic and exposure-response models for empagliflozin and linagliptin based on available historical data in adult and pediatric patients with T2D were used to simulate participant data and derive the informative component of a Bayesian robust mixture prior distribution. External experts and representatives from the U.S. Food and Drug Administration provided recommendations to determine the effective sample size of the prior and the weight of the informative prior component. Separate exposure response-based Bayesian borrowing analyses for empagliflozin and linagliptin showed posterior mean and 95% credible intervals that were consistent with the trial results. Sensitivity analyses with a full range of alternative weights were also performed. The use of PEBB in this analysis combined advantages of mechanistic modeling of pharmacometric differences between adults and young people with T2D, with advantages of partial extrapolation through Bayesian dynamic borrowing. Our findings suggest that the described PEBB approach is a promising option to optimize the power for future pediatric trials.

Is There a Correlation Between Preoperative HbA1c Change, Long-Term Weight Loss and Glycaemic Control in Patients With Type 2 Diabetes Undergoing Metabolic Surgery?

Introduction Optimisation of patients with type 2 diabetes mellitus (T2DM) prior to metabolic surgery aims to achieve tight glycaemic control by the time of surgery. Little is known about the influence of altering preoperative glycated haemoglobin (HbA1c) on postoperative weight loss and glycaemic control. The aim of this study was to determine whether a change in HbA1c during the preoperative period correlated with long-term weight maintenance and HbA1c in patients undergoing metabolic surgery. The quantity of glucose-lowering medication used prior to and following surgery was also examined. Methods A retrospective analysis was conducted on patients with T2DM who underwent metabolic surgery between 2013 and 2017. Preoperative HbA1c change was measured as a change in glycaemic control during the one-year pre-surgery. The primary outcomes were % excess weight loss (EWL) and HbA1c at five-year post-surgery. Secondary outcomes were % EWL and HbA1c at one-year post-surgery and the use of glucose-lowering medications post-surgery. The Pearson correlation coefficient (r) was used to determine the relationship between the pre-surgery HbA1c change and postoperative % EWL and HbA1c. A chi-squared test was used to calculate the statistical impact of changes in medication use post-surgery. Results Sixty-nine patients with complete data were included in the study. The mean change in HbA1cin the one-year pre-surgery, the one-year post-surgery and five-year post-surgery was -0.9% (1.5), -0.7% (1.2) and 0% (0 1.8), respectively. A change in HbA1cin the one-year pre-surgery did not correlate with % EWL at one-year and five-year post-surgery or with HbA1cat one-year and five-year post-surgery. At one-year and five-year post-surgery, there was a significant decrease in the proportion of patients requiring glucose-lowering medications compared to patient use prior to surgery (p < 0.001). Conclusion This study demonstrated a significant reduction in the proportion of glucose-lowering medication required long-term following metabolic surgery. Altering preoperative glycaemic control was not associated with long-term weight maintenance or glycaemic control.

8336 Glycemic Control and Associated Factors During Transition in Youths with Childhood-onset Type 2 Diabetes Mellitus

Abstract Disclosure: J. Yoo: None. H. Woo: None. M. Gu: None. J. Kim: None. Y. Lee: None. C. Shin: None. Y. Lee: None. Background: Childhood-onset type 2 diabetes has increased risk of early diabetes-related complications due to accelerated loss of pancreatic beta cell function. However, no second-choice anti-diabetic drug(such as GLP1 receptor agonists and SGLT2 inhibitors), other than metformin and insulin, is approved to be administered in pediatric patients with type 2 diabetes in South Korea. This study aimed to describe microvascular complications (nephropathy and eye disease) of youths with childhood-onset type 2 diabetes, investigate trends of glycemic control of patients and associated factors across transition period, and analyze change in glycemic control after adding 2nd-choice drug. Method: Among the patients who were treated for type 2 diabetes at Seoul National University Hospital since 2001, 84 patients who were diagnosed under age 18 and reached at age 20 or more on July, 2023 were included. Data of HbA1c, diabetes duration, administered medication, and diabetic complications were collected. Changes in HbA1c from 19 to 22 years of age (transition period) were investigated, and sex, age at diagnosis, and glycemic control at age 19 were analyzed as associated factors. Result: The average age of diagnosis and last follow-up was 14 years and 24.9 years respectively, and the median duration of diabetes was 9.6 years. At the last follow-up, complications developed in 28 patients (33.7%), and the prevalence was 25.3% for nephropathy and 20.6% for eye disease. At the occurrence of complications, the median diabetes duration was 6.2 years for microalbuminuria and 11.3 years for ophthalmic complications. During the transition period, HbA1c showed a significant decline from 8.3% to 7.7% (p=0.007). During this phase HbA1c decreased more significantly in the female (vs. male), in the patients with diagnostic age &amp;lt;15 years (vs. &amp;gt;15 years old), and patients with HbA1c 7% or above at 19-year-old visit(vs. &amp;lt; 7%). During entire follow-up, 59 patients (70%) received diabetes drugs other than metformin and insulin. At diagnosis, the proportion of patients treated with insulin accounted for 55%. At last visit, only few patients were maintained with metformin alone, and most patients required insulin or 2nd-choice antidiabetic drug. Analysis of HbA1c changes in 59 patients with the addition of 2nd-choice drug showed a decrease to 8.5% after 1 year (p=0.006) and to 8.1% at the last visit(p=0.017). Conclusion: Diabetic complications were observed in one-thirds of youths with type 2 diabetes at last follow-up in this study. Glycemic control during transition period to adulthood showed improvement, and factors that influence HbA1c improvement included female, younger age at diagnosis, and better glycemic control at age 19. There is a need to lower the insurance age criteria of South Korea for 2nd-choice antidiabetic drugs, considering that glycemic control significantly improved after adding the 2nd-choice drugs. Presentation: 6/1/2024

SGLT-2 Inhibitors Versus GLP-1 Receptor Agonists Effects on Kidney and Clinical Outcomes in Veterans with Type 2 Diabetes.

The primary aim compared kidney endpoints between patients with type 2 diabetes (T2D) 36 months after initiation on a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a GLP-1 receptor agonist (GLP-1RA). Secondary aims compared estimated glomerular filtration rate (eGFR), hemoglobin A1c (HbA1c), weight, and urine albumin-to-creatinine ratio (UACR) changes. We conducted a retrospective cohort study of propensity score matched veterans with T2D, baseline eGFR>20mL/min/1.73m2, and initiated on a SGLT2i vs GLP-1RA between 4/1/2009-9/1/2020. Cox proportional hazard models were constructed to evaluate effectiveness between both groups on composite endpoint (decline of >=40% in eGFR from baseline, ESRD event, and all-cause mortality) and its components adjusting for baseline characteristics. Spline models were constructed to evaluate eGFR change and linear mixed effects models were constructed to evaluate changes in HbA1c, weight, and UACR. We used an intent-to-treat (ITT) approach as our main analysis followed by a per-protocol (PP) approach excluding veterans who discontinued or switched therapy during the study period. A total of 29,146 propensity score matched veterans were included in SGLT2i and GLP-1RA groups (14,573 per group). In the ITT and PP analyses, veterans initiated on SGLT2i had a 35% (HR=0.65; 95% CI: 0.62, 0.68) and 34% (HR=0.66; 95% CI: 0.62, 0.69) reduction in the hazard of experiencing the composite endpoint compared to veterans initiated on GLP-1RA adjusting for baseline characteristics, respectively. Between 6-36 months, we found an improved chronic eGFR slope with SGLT2i compared to GLP-1RA in both ITT and PP analyses; +1.19 mL/min/1.73 m2 (95% CI: 0.93, 1.45) and +1.29 mL/min/1.73m2 (95% CI: 1.01, 1.57), respectively. The annual difference in chronic eGFR slope in both ITT and PP analyses were +0.97 mL/min/1.73m2/year (95% CI: 0.82, 1.11) and +1.08 mL/min/1.73m2/year (95% CI: 0.92, 1.25). Improved HbA1c, weight loss and UACR were reported for both groups. In this real-world study, veterans with T2D initiated on SGLT2i were associated with reduced hazard of experiencing mortality, worsening eGFR, or developing ESRD and improved glycemic, metabolic, and renal endpoints compared to GLP-1RA use.

Efficacy and safety of visepegenatide as an add-on therapy to metformin in patients with type 2 diabetes: a randomised, double-blind, parallel, placebo-controlled, phase 3 study

Visepegenatide, a once-weekly glucagon-like peptide-1 receptor agonist injection, demonstrated effective glycaemic control and good tolerability without the requirement of dose titration in the two completed phase 2 studies. We aimed to evaluate the efficacy and safety of visepegenatide in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin monotherapy in this phase 3 clinical study. This multicentre phase 3 clinical study included a 24-week, randomised, placebo-controlled, double-blind period followed by a 28-week open-label extended treatment period. Patients (N=620) aged ≥18 and≤75 years with glycated haemoglobin (HbA1c) ≥7.0% and ≤10.5% [≥53.0 and≤91.27mmol/mol], were randomized in a 1:1 ratio to receive visepegenatide 150-μg or placebo once-weekly subcutaneous injection during the double-blind period. Subsequently, the patients in the placebo group were switched to visepegenatide treatment (placebo→visepegenatide group), and the patients in the visepegenatide group continued the same treatment during the open-label extended treatment period. The primary endpoint was the change in HbA1c from baseline to week24. At week 24, the placebo-adjusted least squares mean (LSM) change of HbA1c was-0.57% (95% CI-0.71 to-0.43) with visepegenatide (p<0.001). The proportion of patients achieving HbA1c<7.0% and ≤6.5% [<53 and≤48mmol/mol] was higher in the visepegenatide group versus the placebo group (115 [40.5%] vs 50 [17.9%]; p<0.001, and 60 [21.1%] vs 17 [6.1%]; p<0.001). Visepegenatide demonstrated a significant reduction in fasting plasma glucose and 2-h postprandial glucose compared with placebo. Trends in the improvement of these variables were maintained during the open-label extended treatment period. No severe gastrointestinal adverse event or severe hypoglycaemia was reported during the 52-week study period. Once-weekly injection of visepegenatide 150μg as an add-on treatment to metformin therapy significantly improved glycaemic control and was generally well tolerated in Chinese patients with T2DM who were inadequately controlled with metformin monotherapy. The study was funded by PegBio Co., Ltd, Suzhou, China.

The effectiveness of continuous glucose monitoring with remote telemonitoring-enabled virtual educator visits in adults with non-insulin dependent type 2 diabetes: A randomized trial

AimsEstimate the effectiveness of continuous glucose monitoring (CGM) with remote telemonitoring-enabled virtual diabetes educator visits for improving glycemic management in adults with type 2 diabetes, not on insulin. MethodsParticipants with type 2 diabetes, not on insulin, and HbA1c > 7.0 % were enrolled in an open-label randomized trial of 6 weeks of CGM with telemonitoring versus enhanced usual care. Both groups received educator visits. HbA1c was assessed at 12 weeks. ResultsOf 105 participants (mean age 57.3 years, 49.5 % females, mean baseline HbA1c 8.0 %), 86 remained at follow-up. Change in HbA1c was −0.69 % (CGM) versus −0.33 % (enhanced usual care). Adjusting for baseline HbA1c, CGM was superior (0.65 % greater HbA1c reduction [95 % CI 0.17–1.12 %], p = 0.008). CGM participants were 92 % (RR = 1.92, 1.19–3.06, p = 0.007) more likely to have an HbA1c reduction ≥ 0.5 %, lost more weight (difference in weight reduction 2.17 kg, 0.22–4.11, p = 0.029) and were more satisfied with their treatment. No treatment-related adverse events were observed. ConclusionsCGM with virtual diabetes educator visits is effective, safe, and acceptable in adults with type 2 diabetes not on insulin and should be considered as an alternative to drug therapy for improving blood glucose.

Role of Gluten-Free Diet on HbA1c Level in Children with Type 1 Diabetes Mellitus and Celiac Disease

Background: Due to autoimmune mechanisms, celiac disease (CD) may affect patients with type 1 diabetes mellitus (T1DM) more than the general population. Objectives: We evaluated the effect of a gluten-free diet (GFD) on HbA1c levels in patients with both type 1 diabetes and CD. Methods: In this cross-sectional study, biochemical and clinical information was gathered from 174 children with T1DM from January 2013 to January 2019. Results: We assessed 174 children with T1DM (93 girls and 81 boys). Celiac disease was diagnosed in 18 out of 174 cases (10.34%). Height and weight percentiles showed significant differences between children with CD and those without CD (P = 0.015 and P = 0.026, respectively). The average HbA1c in the celiac group was 8.61 ± 2.20 (95% CI: 5.1 - 12.1) prior to GFD therapy. HbA1c was assessed six and twelve months following the initiation of the GFD and was found to be 8.32 ± 1.46 (95% CI: 6 - 9.8) and 8.37 ± 1.67 (95% CI: 6.1 - 10.2), respectively. No significant change in HbA1c was observed before and after therapy (P = 0.501). Conclusions: Diabetic children with CD exhibit lower weight and height compared to those without CD. Gluten-free diet therapy in patients with CD did not affect HbA1c levels.

Efficacy and safety of GLP-1 analog ecnoglutide in adults with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups had statistically significant HbA1c reductions from baseline of −1.81%, −1.90%, and −2.39%, respectively, compared to −0.55% for placebo (P < 0.0001). At end of treatment, 71.9% of the 1.2 mg group had HbA1c ≤ 6.5% versus 9.1% on placebo, and 33.3% had body weight reductions ≥5% versus 3.0% for placebo. Ecnoglutide was generally safe and well tolerated. China Drug Trials Registry CTR20211014.

Initiation of Intermittently Scanned Continuous Glucose Monitoring Is Associated With Reduced Hospitalization for Acute Diabetes Events and Cardiovascular Complications in Adults With Type 1 Diabetes.

We assessed the impact of intermittently scanned continuous glucose monitoring (isCGM) compared with blood glucose monitoring (BGM) on rates of hospitalization for metabolic and vascular complications of diabetes and on HbA1c levels for adults with type 1 diabetes. This retrospective study using data from the Swedish National Diabetes Register and the Swedish National Patient Register comprised adults with type 1 diabetes and an isCGM initiation date after 1 June 2017 and matched control individuals using BGM. Hospital admission rates were calculated per 100 person-years of follow-up. We identified 11,822 adults with type 1 diabetes and an isCGM index date after 1 June 2017 and HbA1c baseline values 3-8 months prior to the index date. Compared with 3,007 BGM users, isCGM users had a significantly lower relative risk of hospitalization for hypoglycemia (0.32; 95% CI 0.14, 0.74), diabetic ketoacidosis (0.55; 0.35, 0.87), stroke (0.48; 0.37, 0.64), acute myocardial infarction (0.64; 0.46, 0.91), atrial fibrillation (0.59; 0.38, 0.94), heart failure (0.25; 0.16, 0.39), peripheral vascular disease (0.21; 0.07, 0.62), kidney disease (0.48; 0.35, 0.66), or hospitalization for any reason (0.32; 0.29, 0.35). Compared with BGM users, change in mean HbA1c for isCGM users was -0.30% (-3.3 mmol/mol) at 6 months and -0.24% (-2.6 mmol/mol) at 24 months (both P < 0.001). This study shows that adults with type 1 diabetes in Sweden who initiate isCGM have significantly reduced hospitalization rates for acute diabetes events, kidney disease, and cardiovascular complications, along with improved glucose control, compared with BGM users.

Effect of structured individual and combined education on blood glucose regulation in type 2 diabetes mellitus

Abstract Although various approaches have been used in diabetes self-management education (DSME) programs, the effect of DSME programs on glycemic control is controversial. This study aimed to compare the effects of structured individual education and combined education on glycemic regulation in type 2 diabetes mellitus (T2DM). This study included T2DM patients who applied to the Ust Kaynarca Diabetes Center between 1 January 2018 and 11 March 2020. All data were retrospectively evaluated from hospital information systems. Patients who received only individual education were defined as the individual education group (IEG), and patients who received both individual and group education were defined as the combined education group (CEG). A total of 496 T2DM patients, with 248 (50.0%) in the IEG and 248 (50.0%) in the CEG, were included in the study. The change in HbA1c (ΔHbA1c) value for the IEG was 1.0% (2.5%), while the ΔHbA1c value for the CEG was 1.9% (2.8%) (P &amp;lt; 0.001). When factors affecting the glycemic control were evaluated, it was determined that the type of education [odds ratio (OR) = 2.295, P &amp;lt; 0.001], gender (OR = 1.799, P = 0.007), presence of hyperlipidemia (OR = 0.559, P = 0.032) and presence of medications added to treatment (OR = 1.558, P = 0.041) were effective on glycemic control. Combined education, in which individual and group education are conducted together, is more effective than individual education in glucose regulation.

Effect of time restricted eating versus current practice in dietetics on glycaemic control and cardio-metabolic outcomes in individuals at risk of developing type 2 diabetes: Protocol for a multi-centre, parallel group, non-inferiority, randomised controlled trial

BackgroundTime restricted eating (TRE) is a dietary strategy that may improve metabolic health. However, no studies have compared TRE with current practice (CP) in dietetics. HypothesisTRE will not be inferior to CP to improve glycaemic control in individuals at risk of type 2 diabetes (T2D). MethodsThis parallel group, randomised, non-inferiority, controlled trial randomised 247 participants by site and glycated haemoglobin (HbA1c) into TRE or CP (1:1) for 12 months. Participants were aged 35–70 years, with a body mass index (BMI) >25 but <45 kg/m2, and score ≥15 on the Australian type 2 diabetes risk (AUSDRISK) assessment, without a diagnosis of T2D. Study visits were balanced between groups and all participants received five consultations at 0, 0.5, 1, 2 and 3 months. TRE followed a self-selected 9 h eating window (≥0600 and ≤1900), whereas CP followed Australian dietary guidelines. OutcomesThe primary endpoint is the estimate of group mean difference (TRE vs CP) of HbA1c at 4 months in a covariate linear regression adjusting for stratification factors and sex. Secondary efficacy outcomes at 4 and 12 months are changes in fasting glucose, fasting insulin, HOMA-IR and nocturnal glucose by continuous glucose monitor incremental area under the curve and change in HbA1c at 12 months. Other endpoints are exploratory and will not be adjusted for multiplicity. ConclusionsWe will determine whether TRE is an alternate strategy to current practice in dietetics to improve glucose control.Trial registration:NCT04762251; 21 Feb 2021.

Effect of probiotics on glycemic control and lipid profiles in patients with type 2 diabetes mellitus: a randomized, double blind, controlled trial.

This double-blind, placebo-controlled, randomized (1:1) clinical trial was conducted at the West China Hospital, Sichuan University, from March to September 2017. Eligible participants included adults aged 18 years and older, living in the community, diagnosed with type 2 Diabetes Mellitus according to ADA guidelines, capable of self-managing their diabetes, and able to visit the study site for follow-up. The intervention group received 25 ml of a probiotic beverage containing with over 10^8 CFU/mL of Lactobacillus, administered four times daily. An equal volume of inactivated Lactobacillus was administered to the control group and the control group was administered the same volume of inactivated Lactobacillus. This study aimed to evaluate the effectiveness of probiotics on glycemic control and other diabetes-related outcomes in patients with type 2 diabetes patients. The primary outcomes were changes in HbA1c and FBG levels post-intervention. Investigators, participants, and study site personnel were blinded to the treatment allocation until the conclusion of the study. This double-blind, randomized, placebo-controlled clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR-POR-17010850). Of the 490 participants screened, 213 were randomized to either the probiotics group (n = 103) or the placebo group (n = 110). After 16 weeks of follow-up, the probiotic group showed reductions in HbA1c [-0.44 (-0.66 to -0.22)] and FBG [-0.97 (-1.49 to 0.46)] post-intervention, similar to the placebo group with reductions in HbA1c [-0.33 (-0.52 to -0.15)] and FBG [-0.90 (-1.32 to -0.47)], but these changes were not statistically significant in PP and ITT analyses (P>0.05). Adverse events were similarly distributed among groups, indicating comparable safety profiles. Overall, 16-week probiotic supplementation showed no beneficial effects on glycemic control, lipid profiles, or weight. https://www.chictr.org.cn/showproj.html?proj=18421, identifier ChiCTR-POR-17010850.

HbA1c and Liver Fat Following 16 Weeks of Fasted versus Fed Exercise Training in Adults with Type 2 Diabetes.

Exercise-nutrient timing is of interest for people with type 2 diabetes (T2D) as a potential method to optimize glycemic control. However, the optimal nutritional environment for exercise is not well understood over the long term. The Fasted Exercise for Type 2 Diabetes (FED) Trial compared 16 weeks of fasted versus postprandial morning exercise on glycated hemoglobin (HbA1c) and liver proton density fat fraction (PDFF). Twenty adults with T2D were recruited and randomized to complete exercise after an overnight fast versus after their morning meal. Participants walked three mornings per week, progressing to 180 minutes per week over 16 weeks. Groups were balanced with 5 males and 5 females each. Sixteen participants completed the trial (8 in each group, 50% female). Age, HbA1c, and PDFF were 59.8 ± 9.0 years, 7.2 ± 0.7%, and 9.3 ± 4.1%, respectively. On average, both groups completed 98% of their walking sessions but there was no change in HbA1c (-0.2%, p = 0.588). However, one participant from each group had changes in their glucose lowering medication during the trial and, when excluded, the fasted training group had greater improvements in HbA1c compared to the postprandial group (-0.3% versus 0.0%, p = 0.033). There was no difference in changes in liver PDFF between groups (-1.6% versus 0.3%, p = 0.221) but visceral fat and intramuscular fat decreased to a greater extent following fasted exercise. Although our study had a small sample size, it suggests that exercise after an overnight fast can have high adherence and represents an option for people with T2D to improve longer-term indicators of glycemia and ectopic fat depots.

Abstract B012: Randomized phase II trial of two different nutritional approaches for patients receiving treatment for their advanced pancreatic cancer: initial results of safety and feasibility of the medically supervised ketogenic diet

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by stromal fibrosis, hypoxia, and nutritional deprivation. Nutritional metabolic interventions may fundamentally change the tumor microenvironment and improve outcomes. A ketogenic diet (KD) (lower carbohydrate, moderate protein, higher fat) can significantly reduce glucose and insulin and stimulate ketogenesis. Triplet chemotherapy with gemcitabine/cisplatin/nab-paclitaxel has been associated with a median OS 16.4 months, PFS 10.1 months in patients with metastatic PDAC in the first-line setting. Recently, KD plus triplet chemotherapy was shown to inhibit murine pancreatic KPC tumor growth and prolong animal survival over chemotherapy alone (Yang et al, Med, 2022). Tumor growth inhibition was associated with glucose depletion, altered TCA substrate use and NADH elevation. Methods: In this Phase II trial, patients with treatment-naive metastatic PDAC were randomized to triplet chemotherapy with a medically supervised ketogenic diet (MSKD) or continuing their usual diet (non-MSKD). The MSKD is supported by Virta Health, who offers tracking of daily ketone (beta-hydroxybutyrate, BHB) and glucose levels, a web-based application, education, and communication with a remote care team to ensure sustained nutritional ketosis (BHB 0.5–3.0mM). Patients with BMI &amp;lt; 18, type 1 DM or history of DKA were excluded. Primary endpoint was PFS. Secondary endpoints: DCR (PR+CR+SD ≥ 9 weeks), change in CA 19-9 (CA125, CEA if not CA 19-9 expressers), average fasting insulin levels, HbA1c, body weight, gut microbiome, serum metabolites, QOL (QLQ- C30). Results: A total of 36 patients with untreated metastatic PDAC were enrolled. Among 32 evaluable patients (median age 65.9 years; 53% male), 16 were randomized to each arm. Both groups had similar baseline weight, HgbA1c, insulin and BHB levels (all p&amp;gt;0.05). Nine patients had type 2 DM; 6 required insulin. In the MSKD group, 15/16 achieved nutritional ketosis at any point during the study, with mean BHB of 0.57 mM (95% CI 0.40–0.73) and median proportion of days in ketosis of 39.4% (range 0-95.8%) by daily ketone tracking. Lab data showed significantly higher mean ± SD maximum change in BHB in the MSKD (0.5 ± 0.9 mmol/L) versus non-MSKD (–0.2 ± 0.3 mol/L) group (p = 0.018). There were no significant differences between groups in maximum change in weight, HbA1C, or insulin (all p &amp;gt; 0.05). The most common MSKD-related adverse events were Gr 1-2 fatigue (n=4), constipation (n=3), weight loss (n=3), and none stopped MSKD due to adverse events.Conclusion: A medically supervised ketogenic diet is feasible in patients with metastatic PDAC receiving triplet chemotherapy, with median proportion of days in ketosis of 39.4% and an acceptable safety profile. The MSKD is associated with comparable changes in insulin and HgbA1c levels compared to the non-MSKD diet, and sustained ketosis does not result in significantly greater weight loss. MSKD warrants further prospective exploration and analyses of the primary endpoint and correlative studies are ongoing. Citation Format: Gayle S Jameson, Erkut Borazanci, Diana L Hanna, Caroline GP Roberts, Meredith S Pelster, Richard C Frank, Angela T Alistar, Julia E Wiedmeier-Nutor, Sandra D Algaze, Brandon Fell, Sarah J Hallberg, Denise J Roe, Betsy C Wertheim, Derek Cridebring, Joshua D Rabinowitz, Stephen Gately, Daniel D Von Hoff, Drew W Rasco. Randomized phase II trial of two different nutritional approaches for patients receiving treatment for their advanced pancreatic cancer: initial results of safety and feasibility of the medically supervised ketogenic diet [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B012.

Semaglutide use in people with obesity and type 2 diabetes from real-world utilization data: An analysis of the All of US Program.

To analyse data from the All of Us Research Program to evaluate the real-world application and long-term effectiveness of semaglutide in treating type 2 diabetes and obesity patients in a large population. We identified patients prescribed semaglutide and analysed differences in route of administration and the time on semaglutide. For individuals diagnosed with obesity, we measured changes in body mass index (BMI) and weight from baseline, while measured changes in HbA1c for those patients with type 2 diabetes. We also examined the occurrence of newly diagnosed common adverse events from taking semaglutide. For 3739 semaglutide patients, those on injectable semaglutide (3364 patients) averaged 301.54 days on the medication, with 20.36% having no end date, while those on oral semaglutide (435 patients) averaged 172.48 days, with 24.60% having no end date. We found average decreases of 1.54 kg/m2 in BMI, 4.65 kg in weight and 0.75% in HbA1c for semaglutide users. The decreases were larger in participants taking injectable formulation, probably because of higher starting values. Over time, improvements in these outcomes diminished, but the values remained significantly lower than baseline levels. Approximately only 1.0% of patients reported newly diagnosed common adverse events. Consistent with clinical trial findings, this real-world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c, albeit to smaller magnitudes than observed in clinical trials. These findings provide valuable insights into real-world experience and the long-term effectiveness of semaglutide.