Change In HbA1c Research Articles

Residual risk post acute coronary syndroms after 1 year of cardiac rehabilitation. Can we improve it?

Abstract How much do we reduce residual risk with a cardiac rehabilitation program? What is left to do? Which would be the impact of a lower cholesterol threshold for the use of more potent lipid lowering drugs on residual risk? We explored these issues. Methods We retrospectively analyzed clinical and biochemical data from patients after 1 year of cardiac rehabilitation following an acute coronary event. Changes in residual risk of combined myocardial infarction, stroke and cardiovascular death, and its modification with optimization of treatment in patients with suboptimal lipid control, and with the use of PCSK9 inhibitors in those with a LDL-cholesterol over 70 mg/dl, were estimated using the SMART-REACH model calculator. Wilcoson and McNemar tests for paired-samples were used in the statistical análisis. Results 262 consecutive patients were included. Median age was 63.5 years, 80.5% men, 89.3% stented. Baseline use of high intensity statins was 90.8%. After 1 year, the use of Ezetimibe was doubled to 77.1%, empaglifozin to 26%, and PCSK inhibitors were used only in 5%, with a residual use of colchicine. Blood pressure and Cholesterol profile improved after 1 year, with no change in HbA1c. Absolute 10- years and life-long residual risk were reduced 4.8% (95%CI:3.6-5.9) and 6% (95%IC: 4.5-7.5) respectively (both p<0.001). LDL-cholesterol was >55 mg/dl with a suboptimal lipid lowering treatment in 29.8% of patients: an optimization to higher dose of rosuvastatin/atorvastatin plus ezetimibe would decrease absolute 10-years and life-long residual risk in 7.2% (95%CI: 4.9-9.4) and 9.9% (95%CI: 6.4-13.5%) respectively (both p<0.001). LDL-cholesterol remained > 70 mg/dl after higher dose of statin plus ezetimibe in 13.7% of patients: use of PCSK9 inhibitors in this group would reduce absolute 10-year and life-long residual risk in an additional 5.4% (95%CI:2.4-7,6;p=0,018) and 7% (95%CI: 3,8-10,1) compared to maximal dose of statins plus ezetimibe. Conclusions Cardiac rehabilitation programs reduce cardiac risk 1 year after an acute coronary event. Residual risk remain very high, and a significant proportion of patients do not reach recommended targets and optimal lipid lowering treatment. Optimization of lipid lowering drugs, and a lower LDL-cholesterol threshold for the use of PCSK9 inhibitors, would have a significant impact on residual risk.Changes in residual riskPCSK9-inhibitors in LDLchol >70 mg/dl

Nutritional management, skipping breakfast, glycemic control, and cardiovascular risk on type 2 diabetes mellitus

Abstract Background Meal timing is an emerging field that investigates the influence of eating patterns on circadian rhythm and general health. There is still disagreement in the literature as to whether eating windows could impact weight gain and biochemical markers. Purpose 1- Evaluate the impact of nutritional interventions on weight, body mass index (BMI), waist circumference (WC), fasting blood glucose (FG), glycated hemoglobin (HbA1c), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides, systolic blood pressure (SBP), and diastolic blood pressure (DBP), between 0th and 12th month in Type 2 Diabetes Mellitus (T2D); 2-Observe breakfast skipping and sleep disorders, and also analyze the influence of these data with possible changes in anthropometric and biochemical markers. Methods This experimental and observational study recruited 44 participants with T2D. The assessments were carried out in October 2022 and 2023. The nutritional assessment consisted of prescribing a personalized eating plan (Mediterranean diet and DASH). Statistical analysis: For the variables "breakfast habits", "nocturnal awakenings", and "sleep duration", the numbers of participants were converted into percentages of the total number of individuals. Parametric variables were compared using the paired t-test and non-parametric variables were compared by the Wilcoxon test. To evaluate the influence of the habit of eating breakfast and sleep disorders on quantitative variables, variations were calculated between the 0th and 12th month between participants who had or did not have the habit of eating breakfast and had or did not have sleep disorders. Parametric variables were compared using the unpaired t test and non-parametric variables using the Mann-Whitney test. Parametric data were presented as mean ± standard deviation and non-parametric data as median ± interquartile range, both accompanied by the dispersion of all repetitions. α<0.05 and P<0.05 were adopted. Results Significant reductions were found between the 0th and 12th month of FG, HbA1c, LDL-C, triglycerides, SBP, DBP, BMI, WC, and weight (p<0.0001). Regarding breakfast habits, in the 1st month, 77.3% of participants skipped this meal, reducing to 13.6% in the 12th month. For sleep duration, in the 1st month, 90.9% of participants slept less than 6 hours, reducing to 40.9% in the 12th month. For nocturnal awakenings, 70.5% of participants had at least 1 awakening in the 1st month, reducing to 54.5% in the 12th month. For influence analysis, no significant differences were found between changes in FG, HbA1c, LDL-C, triglycerides, SBP, DBP, BMI, WC, and weight on breakfast habit or sleep disorders, except for HDL-C and sleep disorders (p<0.005). Conclusion Nutritional management improved biochemical markers, reduced anthropometric data, regulated the eating window, reduced nocturnal awakenings, and optimized sleep duration in patients with T2D.

Intermittently scanned continuous glucosemonitoring compared with blood glucose monitoring is associated with lower HbA1c and a reduced risk of hospitalisation for diabetes-related complications in adults with type 2 diabetes on insulin therapies.

We assessed the impact of initiating intermittently scanned continuous glucose monitoring (isCGM) compared with capillary blood glucose monitoring (BGM) on HbA1c levels and hospitalisations for diabetes-related complications in adults with insulin-treated type 2 diabetes in Sweden. This retrospective comparative cohort study included adults with type 2 diabetes who had a National Diabetes Register initiation date for isCGM after 1 June 2017. Prescribed Drug Register records identified subgroups treated with multiple daily insulin injections (T2D-MDI) or basal insulin (T2D-B), with or without other glucose-lowering drugs. The National Patient Register provided data on hospitalisation rates. We identified 2876 adults in the T2D-MDI group and 2292 in the T2D-B group with an isCGM index date after 1 June 2017, matched with 33,584 and 43,424 BGM control participants, respectively. The baseline-adjusted difference in the change in mean HbA1c for isCGM users vs BGM control participants in the T2D-MDI cohort was -3.7 mmol/mol (-0.34%) at 6 months, and this was maintained at 24 months. The baseline-adjusted difference in the change in HbA1c for isCGM users vs BGM control participants in the T2D-B cohort was -3.5 mmol/mol (-0.32%) at 6 months, and this was also maintained at 24 months. Compared with BGM control participants, isCGM users in the T2D-MDI cohort had a significantly lower RR of admission for severe hypoglycaemia (0.51; 95% CI 0.27, 0.95), stroke (0.54; 95% CI 0.39, 0.73), acute non-fatal myocardial infarction (0.75; 95% CI 0.57, 0.99) or hospitalisation for any reason (0.84; 95% CI 0.77, 0.90). isCGM users in the T2D-B cohort had a lower RR of admission for heart failure (0.63; 95% CI 0.46, 0.87) or hospitalisation for any reason (0.76; 95% CI 0.69, 0.84). This study shows that Swedish adults with type 2 diabetes on insulin who are using isCGM have a significantly reduced HbA1c and fewer hospital admissions for diabetes-related complications compared with BGM control participants.

One-year outcomes of a digital twin intervention for type 2 diabetes: a retrospective real-world study

This retrospective observational study, building on prior research that demonstrated the efficacy of the Digital Twin (DT) Precision Treatment Program over shorter follow-up periods​​, aimed to examine glycemic control and reduced anti-diabetic medication use after one-year in a DT commercial program. T2D patients enrolled had adequate hepatic and renal function and no recent cardiovascular events. DT intervention powered by artificial intelligence utilizes precision nutrition, activity, sleep, and deep breathing exercises. Outcome measures included HbA1c change, medication reduction, anthropometrics, insulin markers, and continuous glucose monitoring (CGM) metrics. Of 1985 enrollees, 132 (6.6%) were lost to follow-up, leaving 1853 participants who completed one-year. At one-year, participants exhibited significant reductions in HbA1c [mean change: -1.8% (SD 1.7%), p < 0.001], with 1650 (89.0%) achieving HbA1c below 7%. At baseline, participants were on mean 1.9 (SD 1.4) anti-diabetic medications, which decreased to 0.5 (SD 0.7) at one-year [change: -1.5 (SD 1.3), p < 0.001]. Significant reductions in weight [mean change: -4.8 kg (SD 6.0 kg), p < 0.001], insulin resistance [HOMA2-IR: -0.1 (SD 1.2), p < 0.001], and improvements in β-cell function [HOMA2-B: +21.6 (SD 47.7), p < 0.001] were observed, along with better CGM metrics. These findings suggest that DT intervention could play a vital role in the future of T2D care.

Mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy in the treatment of obesity and type 2 diabetes mellitus

Objective: To evaluate the mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity and type 2 diabetes mellitus. Methods: The cohort of this retrospective observational study comprised 118 obese patients with body mass index (BMI) ≥40 kg/m2 with or without other related metabolic diseases and BMI of (27.5-40.0) kg/m2 with type 2 diabetes mellitus (T2DM) who had been treated with SADI-S. Patients who had undergone modified surgery or been followed up for less than 1 year were excluded. Clinical data of the included patients [56 men and 62 women aged (34.5±9.7) years], who had undergone SADI-S in China-Japan Union Hospital, Jilin University from October 2018 to August 2022, were collected. Their mean preoperative body mass was (125.9±25.0) kg and BMI (42.8±6.8) kg/m2. The 60 patients with T2DM had a mean fasting blood glucose of (9.9±3.2) mmol/L and HBA1c of (8.4±1.7) % before surgery. The main outcome measures were mid-term weight loss after surgery (body mass, BMI, excess weight loss, and total weight loss) 1, 2, 3, and 4 years after surgery and efficacy regarding diabetes mellitus (fasting blood glucose, glycated hemoglobin and diabetes remission rate at 1, 2, and 3 years after surgery). Outcomes were defined as follows. Complete remission: HbA1c <6% or fasting blood glucose <6 mmol/L without hypoglycemic medication; partial remission: HBA1c <6.5% or fasting blood glucose <7 mmol/L without hypoglycemic medication; significant improvement: HBA1c <7.0%, stable decrease of at least 1% compared with preoperative HBA1c, and postoperative dose of hypoglycemic medication significantly less; ineffective: no change in HBA1c and no reduction in dosage of hypoglycemic medication. Other outcome measures included intraoperative and postoperative adverse effects and postoperative nutritional indexes. Results: SADI-S was successful in all patients. There was no significant bleeding, conversion to open surgery, or perioperative death. The operation time was (186.1±41.5) minutes, and the postoperative hospital stay 6 (5-7) days. Surgical complications occurred in four patients, comprising peritoneal effusion, internal jugular vein thrombosis, anastomotic leakage, and gastric fistula. Body weight and BMI 1, 2, 3 and 4 years were significantly lower post- than pre-operatively (all P<0.05). Excess weight loss was (81.9±16.2) %, (82.2±15.5) %, (88.3±20.1) %, and (83.2±18.1) % at 1, 2, 3, and 4 years postoperatively, respectively. Total weight loss was (39.7±8.7) %, (40.6±10.6) %, (42.2±11.5) % and (45.4±10.2) %, respectively. The mean fasting blood glucose concentrations of the 60 patients with T2DM were (5.1±1.0) mmol/L, (5.0±0.7) mmol/L, and (5.4±0.9) mmol/L 1, 2 and 3 years postoperatively, respectively. The values for glycosylated hemoglobin were (4.9±0.6) %, (4.8±0.5) %, and (5.1±0.8) %, respectively, all of which are significantly lower than preoperatively (all P<0.05). The complete remission rate of diabetes was 95.0% (38/40), 90.0% (36/40), and 9/13 1, 2, and 3 years postoperatively, respectively. Additionally, the partial remission rate and significant improvement rate were both 100%. Two years postoperatively, the incidence of anemia was 27.8% (10/36), of hypoproteinemia 11.8% (4/34), and of ferritin deficiency 25.8% (8/31), all of which were improved by conservative treatment such as blood transfusion, iron supplementation, and adjustment of diet. Conclusion: SADI-S has a significant mid-term beneficial effect on weight loss and diabetes remission status in patients with obesity and type 2 diabetes.

Eliciting medication preferences of patients with type 2 diabetes under different insurance coverages in China

ObjectiveTo understand the medication preference of type 2 diabetes mellitus (T2DM) patients with different insurance coverages, and to provide reference for improving the patient-centered clinical treatment decision.MethodsThis study used Discrete Choice Experiment (DCE) to elicit preferences of T2DM patients with different insurance coverages in China. A multistage stratified cluster-sampling procedure for data collection and a total of 1,409 valid respondent were conducted.ResultsSeven attributes have significant influence on the preference of T2DM patients with Urban Employee Basic Medical Insurance (UEBMI) and Urban and Rural Residents Basic Medical Insurance (URRBMI) (p &amp;lt; 0.05). T2DM patients with UEBMI pay the most attention to Gastrointestinal adverse events, while T2DM patients with URRBMI pay the most attention to the Treatment efficacy/reduction in HbA1c. Patients with different medical insurance have different willingness to pay for Cardiovascular benefits, Mode of administration and Weight change. When Gastrointestinal adverse events is changed from higher (40%) to none (0%), patients with UEBMI are willing to pay ¥523.49 more per month, while patients with URRBMI are only willing to pay ¥266.62; When the Treatment efficacy/reduction in HbA1c changes from poor (0.5%) to Highest (2.5%), patients with UEBMI are willing to pay ¥518.44 more per month, while patients with URRBMI are willing to pay ¥328.33 more per month. The Gastrointestinal adverse events and the Treatment efficacy/reduction in HbA1c are the primary factors for T2DM patients with UEBMI and URRBMI, followed by the Hypoglycemic risk.ConclusionPhysicians should consider patients’ medication preferences in clinical medication treatment of T2DM patients with different insurance coverages, make targeted treatment decisions, and improve patients’ medication compliance to achieve better treatment results.

Glucose-lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes.

Obesity is a major risk factor for diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D). This study investigated the effect of glucose lowering medication associated with weight change on DPN. Participants with T2D were grouped based on whether their glucose lowering medications were associated with weight gain (WG) or weight loss (WL). They underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function and corneal confocal microscopy (CCM) at baseline and follow-up between 4 and 7 years. Of 76 participants, 69.7% were on glucose lowering medication associated with WG, and 30.3% were on glucose lowering medication associated with WL. At baseline, participants in the WG group had a significantly longer duration of diabetes (p < .01), higher douleur neuropathique en 4 (DN4) score (p < .0001) and VPT (p = .01) compared with those in the WL group. Over a 56-month period, participants in the WG group showed no significant change in body weight (p = .11), HbA1c (p = .18), triglycerides (p = .42), DN4 (p = .11), VPT (p = .15) or Sudoscan (p = .43), but showed a decline in corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) (p < .0001). Participants in the WL group showed a reduction in weight (p = .01) and triglycerides (p < .05), no change in DN4 (p = .30), VPT (p = .31) or Sudoscan (p = .17) and a decline in the corneal nerve branch density (p < .01). Participants treated with glucose lowering medication associated with weight gain had worse neuropathy and greater loss of corneal nerves during follow-up, compared to patients treated with medication associated with weight loss.

Efficacy and safety of cofrogliptin once every 2 weeks in Chinese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, phase 3 trial.

We conducted a multicentre, randomized phase 3 trial in China to evaluate the efficacy and safety of cofrogliptin (HSK7653), a novel long-acting dipeptidyl peptidase-4 inhibitor, in patients with drug-naïve type 2 diabetes (T2D). Patients with inadequately controlled T2D were randomly assigned (1:1:1) to cofrogliptin 10 mg, cofrogliptin 25 mg or placebo, taken orally once every 2 weeks for a 24-week double-blind period. Eligible patients then received cofrogliptin 25 mg in a 28-week open-label extension. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. In total, 475 patients (median age: 54.0 years) were randomized and received at least one dose of cofrogliptin 10 mg (n = 158), cofrogliptin 25 mg (n = 158) or placebo (n = 159); 401 patients entered the open-label extension. At week 24, the least-squares (LS) mean difference (95% confidence interval [CI]) in HbA1c versus placebo was -0.63% (-0.81, -0.46) with cofrogliptin 10 mg and -0.59% (-0.77, -0.42) with cofrogliptin 25 mg (both p < 0.0001). The LS mean (standard error) change in HbA1c from baseline was maintained at the end of the study in patients given open-label cofrogliptin 25 mg for an additional 28 weeks: cofrogliptin 10 mg: -0.86% (0.07); cofrogliptin 25 mg: -0.74% (0.07); placebo: -0.89% (0.07). Over the entire study, common adverse events were hyperuricaemia, hyperlipidaemia, hypertriglyceridaemia, increased lipase, upper respiratory tract infection and urinary tract infection. Hypoglycaemic events did not significantly differ between groups. Cofrogliptin provided glycaemic control over 52 weeks and was generally well tolerated in patients with T2D. Registered on Clinicaltrials.gov with the registration number NCT04556851 (https://clinicaltrials.gov/study/NCT04556851).

Efficacy of Alogliptin/Metformin Fixed-Dose Combination Tablets and Vildagliptin/Metformin Fixed-Dose Combination Tablets on Glycemic Control in Real-World Clinical Practice for the Patients with Type 2 Diabetes: A Multicenter, Open-Label, Randomized, Parallel Group, Comparative Trial.

Background: This study was aimed to compare the efficacy of two combination tablets of dipeptidyl peptidase-4 (DPP-4) inhibitors and metformin with different dosages, alogliptin/metformin (AM) and vildagliptin/metformin (VM), on glycemic control in patients with type 2 diabetes (T2D). Methods: This was a prospective, multicenter, open-label, randomized, parallel group, comparative trial. After a run-in period of treatment with metformin alone, a total of 59 Japanese outpatients with T2D, aged 20-79 years with glycated hemoglobin (HbA1c) levels of 6.5%-10% were randomly assigned to 12-week AM treatment, alogliptin 25 mg/metformin 500 mg combination tablet orally once a day, or VM treatment, vildagliptin 50 mg/metformin 250 mg combination tablet orally twice a day. The primary endpoints were the changes in HbA1c and fasting plasma glucose (FPG) levels from baseline to week 12 between the two groups. Blinded intermittently scanned continuous glucose monitoring (isCGM) was performed between weeks 10 and 12. The incidence of adverse events during the study was also evaluated. Results: In all, 52 participants were analyzed. Significant decreases in HbA1c and FPG levels from baseline to week 12 were observed in both treatment groups. However, there were no significant differences between the AM and VM groups in the change in HbA1c level (-0.3% and -0.4%, P = 0.309) or the FPG level (-9.0 and -15.0 mg/dL, P = 0.789). The isCGM revealed that both treatments achieved the recommended glycemic target range. No adverse events, such as severe hypoglycemia, were observed in either group. Conclusions: We concluded that there were no significant differences in the efficacy of two combination tablets of DPP-4 inhibitors and metformin with different dosages on glycemic control in patients with T2D.

GLP-1 Receptor Agonists in Overweight and Obese Individuals With Type 1 Diabetes Using an Automated Insulin Delivery Device: A Real-World Study.

Automated insulin delivery (AID) systems have improved glycemic control in individuals with type 1 diabetes (T1D) but overweight and increased cardiovascular risk remain a challenge. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with improved cardiometabolic profile but are currently not approved for the treatment of T1D. Individuals with T1D at Steno Diabetes Center Copenhagen, Denmark, treated with AID and off-label GLP-1 RA for at least six months between January 2017 and May 2024 were included in a retrospective chart review study. Nineteen individuals with (median [range]) age 42 (24-60) years were included. At GLP-1 RA initiation, hemoglobin A1c (HbA1c) was 7.3% (6.1%-8.7%), HbA1c 56 (43-72) mmol/mol, body weight 91.5 (78.0-115.0) kg, and body mass index 35.4 (27.0-42.0) kg/m2. Time in range was 74% (29%-82%), time above range 25% (18%-71%) while time below range was 1% (0%-5%). After six months of treatment, body weight changed -11% (-22% to -3%; P = .001) and total daily insulin dose changed -15.1 (-32.5 to -8.2) IU (P = .004). There were no significant changes in HbA1c or other glucose measures. One person developed ketoacidosis caused by infusion set failure, but none reported severe hypoglycemia. Glucagon-like peptide-1 receptor agonist as add-on therapy for six months in individuals with obesity and AID-treated T1D led to considerable weight loss and a reduction in insulin dose.

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.

SGLT2 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. We 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 6months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12months. After 6months, 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 12months. 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. SGLT2i 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?

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

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.