Mean HbA1c Reduction Research Articles

Association between intensity of glycemic control with GLP-1 receptor agonists and risk of atherosclerotic cardiovascular disease: a systematic review and meta-regression

Abstract Background Several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown to reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (DM). However, this reduction has not been consistent among different GLP-1 RAs. We conducted a systematic review and meta-regression analyses to evaluate the association between the intensity of glycemic control achieved byGLP-1 RAs therapy in patients with type 2 DM and the reduction of MACE as well as to identify potential mechanisms involved. Methods Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through November 2022. Studies were considered eligible if they were cardiovascular outcomes randomized trials (CVOTs) comparing GLP-1 RAs versus placebo in type 2 DM patients. Trials including non-diabetic patients and GLP-1 RAs refused by European Medicines Agency or US Food and Drug Administration were excluded. The outcome of interest was 3-point MACE (CV death, MI, or stroke). Random-effects meta-analyses and meta-regression evaluated associations between glycemic control withGLP-1 RAs and study outcomes. Secondary meta-regression analyses were performed for body weight and blood pressure (BP) variation. Results Overall, 8 CVOTs were included, with a total of 60080 patients (30694 treated withGLP-1 RAs). GLP-1 RAs were associated with a lower incidence of 3P-MACE (RR 0.876; 95% CI 0.821-0.935, p<0.001). Mean HbA1C reduction was 0.57% in patients treated withGLP-1 RAs vs. placebo. Meta-regression showed that higher reductions of HbA1C levels were associated with lower risk of 3P-MACE (Log RR -0.286 [95% CI-0.512; -0.056], p=0.015), which translates into an estimated relative risk reduction of 25% for each 1% reduction in HbA1C (Figure 1A). There was a non-significant association between glycemic control and each of the 3P-MACE outcomes analysed separately. Body weight reduction was also associated with a lower risk of 3P-MACE (Log RR -0.067 [95% CI-0.134; 0.001], p=0.053), despite not meeting statistical significance (Figure 1B). Systolic BP decrease was not associated with reduced risk of 3P-MACE. Conclusions The better the glycemic control withGLP-1 RAs in type 2 DM patients, the greater the reduction in 3P-MACE. Body weight reduction may also play a potential role.Figure 1

Effectiveness of dapagliflozin as an insulin adjunct in type 1 diabetes: a semi-mechanistic exposure-response model.

Introduction: Dapagliflozin-induced improvement of glycemic control in patients with inadequately controlled type 1 diabetes (T1D) is complicated by the delicate balance between blood glucose and exogenous insulin. In this work, we developed a semi-mechanistic population exposure-response model using pooled patient-level data to characterize the joint effect of dapagliflozin and insulin on average daily glucose concentrations and glycated hemoglobin (HbA1c) levels in patients with T1D. Methods: A non-linear mixed-effects model was developed in Monolix (Lixoft, France) and R software (R Project, www.r-project.org) using pooled patient-level data from phase 2 and phase 3 trials (NCT01498185, NCT02460978, NCT02268214). Results: Because of the apparent lack of association between bolus insulin dose and glucose concentrations measured by continuous glucose monitoring the model was able to capture the quantitative link between basal, but not bolus, insulin dose and plasma glucose. Even so, this association remained flat, with a 50% decrease in the basal insulin dose from pretreatment level, resulting in ∼5% increase in glucose exposure. Therefore, dapagliflozin efficacy was not significantly affected by the insulin dose adjustment, with 24-week HbA1c reduction on 10-mg dapagliflozin treatment changing from -0.5 [95% CI: -0.55, -0.45] to -0.42 [95%CI: -0.48, -0.36] after adjustment. At the same time, the analysis revealed ∼2-fold steeper slope of glucose-HbA1c relationship in dapagliflozin-treated patients vs. control group, suggesting the presence of additional dapagliflozin treatment-related benefits, not explained by the dapagliflozin-mediated ∼4% increase in plasma hemoglobin levels. Finally, the efficacy of 5 and 10-mg doses, represented by the mean HbA1c reduction at week 24 of dapagliflozin treatment, was shown to be notably greater than the 1- and 2.5-mg doses. Discussion: This research is an attempt to deconvolute and reconstruct dapagliflozin-HbA1c dose-response relationship in T1D by accounting for the drug's action on both daily insulin dose and plasma glucose on a subject-level. While the model is able to adequately capture the observed data, it also revealed that the variability in CGM is poorly approximated by the variability in insulin dose alone. Furthermore, the slope of CGM/HbA1c relationship may differ depending on the population and treatment scenarios. As such, a deeper dive into the physiological mechanisms is required to better quantify the intricate network of glycemic response under dapagliflozin treatment.

Effectiveness of Technology-Enabled, Low Carbohydrate Dietary Interventions, in the Prevention or Treatment of Type 2 Diabetes Mellitus in Adults: A Systematic Literature Review of Randomised Controlled and Non-Randomised Trials.

Evidence suggests that low carbohydrate dietary (LCD) approaches can improve glycaemic control and may result in type 2 diabetes mellitus (T2DM) remission. This systematic literature review (SLR) aimed to assess the effectiveness of technology-enabled LCD interventions in the management of people with prediabetes or T2DM. Data sources included Medline, Embase, CINAHL, and Web of Science. Randomised (RCTs) or non-randomised (non-RCTs) controlled trials investigating the effect of technology-enabled LCDs (<130 g/day) or very low carbohydrate diets (VLCDs < 50 g/day) on glycosylated haemoglobin A1c (HbA1c) for at least three months and published in English between 2009 and 2023 were included. Risk of bias assessment, data extraction, and synthesis were conducted using standard tools and procedures. Six studies (two RCTs and four non-RCTs, total sample, n = 1519) were identified and included in the SLR. Two studies examining LCDs reported significant reductions in mean HbA1c (0.4% and -1.2%) and weight loss (-3.8 kg and -7.5 kg) at one year. Three studies examining VLCDs reported significant reductions in mean HbA1c (-0.8% to -1.3%) and weight loss (-12 kg to -14 kg) up to two years. Technology-enabled LCD or VLCD interventions can be a novel approach in helping people with prediabetes or T2DM self-manage their condition and possibly achieve remission. However, further research is required to determine the sustainability, effectiveness, and safety of this approach.

Real-World Hemoglobin A1c Changes, Prescribing Provider Types, and Medication Dose Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

Given the lack of real-world data on oral semaglutide use outside clinical trials, the purpose of this study was to describe dose, prescriber specialty, and change in hemoglobin A1c (HbA1c) after 6months of oral semaglutide treatment for patients with type 2 diabetes mellitus (T2DM). This was a retrospective study among adult patients with T2DM with ≥ 1 claim for oral semaglutide between November 1, 2019`1-June 30, 2020. Patients had continuous health plan enrollment ≥ 12months prior to (pre-index) and ≥ 6months following (post-index) the date of the first oral semaglutide claim (index). Dose at initiation and specialty of the prescribing provider were captured. Change in HbA1c between the last post- and pre-index HbA1c measurement was calculated. Patients were stratified by pre-index HbA1c ≥ 9% (poorly controlled) and HbA1c < 9%. A total of 744 HbA1c < 9% and 268 poorly controlled patients were included in the study. Most patients had an initial oral semaglutide dose of 7mg (49.3%) or 3mg (42.9%), prescribed most frequently by a primary care provider (27.8%). Mean HbA1c reduction was 0.8% (p < 0.001). Patients with poorly controlled T2DM had greater HbA1c reductions than patients with HbA1c < 9% (2.0% versus 0.4%, p < 0.001). Patients persistent with oral semaglutide (≥ 90days continuous treatment) had a mean HbA1c reduction of 0.9% (p < 0.001); persistent patients with poorly controlled T2DM had a mean reduction of 2.5%. Patients with T2DM in this study experienced significant reductions in HbA1c within 6months following initiation of oral semaglutide. Patients with a higher starting HbA1c experienced greater HbA1c reductions. The initial dose of oral semaglutide was higher than prescribing instructions indicated for more than half of the study patients.

Glycemic and Economic Outcomes in Elderly Patients with Type2 Diabetes Initiating Dulaglutide Versus Basal Insulin in a Real-World Setting in the United States: The DISPEL-Advance Study.

Treatments like glucagon-like peptide-1 receptor agonists carry low hypoglycemia risk and are recommended for elderly patients with type2 diabetes (T2D), while some routine treatments, like insulin, increase hypoglycemia risk. The DISPEL-Advance (Dulaglutide vs Basal InSulin in Injection Naïve Patients with Type2 Diabetes: Effectiveness in ReaL World) study compared glycemic outcomes, healthcare resource utilization, and costs in elderly patients with T2D who initiated treatment with dulaglutide versus those initiating treatment with basal insulin. This observational, retrospective cohort study used data from the Optum Research Database. Medicare Advantage patients (≥ 65years) with T2D were assigned to dulaglutide or basal insulin cohorts based on pharmacy claims and propensity score matched on demographic and baseline characteristics. Change in HbA1c, 12-months follow-up HbA1c, and follow-up all-cause and diabetes-related healthcare resource utilization and costs were compared. Propensity score matching yielded well-balanced cohorts with 1891 patients each (mean age: dulaglutide, 72.09years; basal insulin, 72.56years). The dulaglutide cohort had significantly greater mean HbA1c reduction from baseline to follow-up than basal insulin cohort (- 0.95% vs - 0.69%; p < 0.001). The dulaglutide cohort had significantly lower mean all-cause and diabetes-related medical costs (all-cause: $8306 vs $12,176; diabetes-related: $4681 vs $7582 respectively; p < 0.001) and lower mean all-cause total costs ($18,646 vs $20,972, respectively; p = 0.007) than basal insulin cohort. The dulaglutide cohort had significantly lower all-cause and diabetes-related total costs per 1% change in HbA1c than basal insulin cohort (all-cause: $19,729 vs $30,334; diabetes-related: $12,842 vs $17,288, respectively; p < 0.001). Elderly patients with T2D initiating dulaglutide had greater HbA1c reduction, lower mean all-cause medical and total costs, lower diabetes-related medical costs, and lower total all-cause and diabetes-related costs per 1% change in HbA1c than patients initiating basal insulin. Future studies assessing medications that do not increase hypoglycemia risk could help inform therapeutic strategies in elderly patients.

The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes (TROPHIES): Final, 24-month analysis of time to first significant treatment change, treatment persistence and clinical outcomes.

To present the final results of the TROPHIES study (The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes). The prospective, real-world TROPHIES study included patients with type 2 diabetes initiating their first injectable glucose-lowering medication (GLM), dulaglutide or liraglutide, in France, Germany and Italy. The primary endpoint was the time spent on dulaglutide or liraglutide until a significant treatment change over 24 months. Other endpoints measured persistence with treatment, clinical outcomes (glycated haemoglobin [HbA1c] and weight) and treatment patterns. Kaplan-Meier estimates of time to first significant treatment change and persistence with treatment were generated. Propensity-score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances in the comparison between cohorts. The 286 of 1014 patients (28.2%) in the dulaglutide cohort and 448 of 991 patients (45.2%) in the liraglutide cohort had a significant treatment change over 24 months. By IPTW analysis, dulaglutide-initiating patients were less likely to have a significant treatment change (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.46-0.63) and more likely to be persistent with treatment (HR 0.69, 95% CI 0.56-0.86) over 24 months than liraglutide-initiating patients. Dulaglutide and liraglutide yielded similar HbA1c (-11.80 mmol/mol [1.08%] and -11.91 mmol/mol [1.09%]) and weight (-3.5 kg and -3.3 kg) reductions from baseline to 24 months. Few changes in patterns of treatment with other GLMs were observed in the two cohorts. Dulaglutide-initiating patients had a longer time spent without any significant treatment change and higher persistence than those initiating liraglutide. Treatment with either glucagon-like peptide-1 receptor agonist yielded similar and clinically meaningful reductions in HbA1c and body weight.

SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study

Aims/hypothesisInsulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium–glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes.MethodsWe performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy.ResultsWe identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA1c (−2.6 mmol/mol [−0.2%] with SGLT2i and −5.4 mmol/mol [−0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m2 vs −7.2 ml/min per 1.73 m2, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort.Conclusions/interpretationBoth SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.Graphical

Retatrutide as a Novel Treatment for Obesity and Type 2 Diabetes

Retatrutide is a triple hormone agonist of the receptors of glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide (GIP) and glucagon that can be administered subcutaneously once a week. Different doses and escalation schedules of retatrutide were evaluated in 2 phase 2 American trials of subjects with obesity (n=338) and type 2 diabetes (n=281). In the obesity trial of 48 week-duration, percentage change in body weight from baseline after 24 weeks and 48 weeks were the primary and secondary outcomes respectively. At 24 weeks, the mean percentage decrease in weight ranged from 7.2% to 17.5% across retatrutide groups versus 1.6% with placebo. At 48 weeks, the decrease was 8.7% to 24.2% versus 2.1% with placebo. In the diabetes trial, the primary endpoint was a change in glycated hemoglobin (HbA1c) values from baseline to week 24. This trial included an active treatment group receiving dulaglutide 1.5mg once weekly. Secondary endpoints included change in HbA1c and body weight at 36 weeks. At 24 weeks, mean HbA1c reductions were 0.43% to 2.02% with retatrutide, 1.4% with dulaglutide and 0.01% with placebo. At 36 weeks, mean percentage weight reductions were 3.2% to 16.9% with retatrutide, 2.0% with dulaglutide and 3.0% with placebo. While the decrease in HbA1c levels reached a plateau at 24 weeks, weight loss in the 2 studies was progressive without evidence of attenuation effect up to the end of follow-up at 36-48 weeks. The most common adverse effects of retatrutide were gastrointestinal (GI) such as nausea, diarrhea, vomiting and constipation reported by 13-50% in the retatrutide groups compared with 35% in the dulaglutide group, and 13% in the placebo group. Discontinuation rates due to adverse effects were also higher with retatrutide being 16-17% compared with 2% with dulaglutide and 0-4% with placebo. In summary, retatrutide is highly effective drug in causing substantial weight loss and HbA1c reduction. Yet, tolerance to this drug seems sub-optimal. Phase 3 trials are urgently needed to clarify efficacy and safety of retatrutide.

787-P: Glucose and Weight Outcomes Associated with Oral Semaglutide in the Real-World—Initial Results from the Association of British Clinical Diabetologists’ (ABCD) Audit

Semaglutide is the first glucagon like peptide-1 receptor agonist (GLP1-RA) available in an oral preparation. Weight and HbA1c outcomes with injectable semaglutide in the real-world are well established. The aim of this analysis is to assess weight and HbA1c response to oral semaglutide. Methods: Data were extracted from the secure online ABCD audit tool. Individuals were included if baseline and follow-up weight and/or HbA1c data were available. Change in HbA1c, body mass index (BMI) and weight from baseline was assessed using a multivariate linear regression model and change in the numbers achieving an endpoint HbA1c≤7.5% [58mmol/mol] were assessed using Chi2 tests in Stata 16. Results: Data were available for 350 individuals with baseline mean±SD HbA1c 9.2%±1.7 [76.6mmol/mol±18.3], weight 101.8kg±21.9, BMI 34.3kg/m2±6.9, median diabetes duration 11years (IQR 6-16) and age 59 years (IQR 51-68); 63.0% were male and 79.7% were white. Median follow-up was 0.5years (IQR 0.3-0.8). Significant reductions in HbA1c of 0.7% (95%CI 0.4, 0.9; P&amp;lt;0.001) [7.4mmol/mol; 95%CI 4.7, 10.0; P&amp;lt;0.001] were observed. Weight decreased by 3.3kg (95%CI 2.3, 4.3; P&amp;lt;0.001) and BMI fell by 1.1kg/m2 (95%CI 0.6, 1.6; P&amp;lt;0.001). Twice as many people achieved a HbA1c≤7.5% at follow-up compared to baseline (28.6% [52/182] vs 14.3% [26/182]) - this change was statistically significant (P&amp;lt;0.001). Conclusion: In the real-world, oral semaglutide is associated with statistically significant and clinically meaningful reductions in HbA1c, weight and BMI. The numbers achieving a HbA1c≤7.5% also increased. In the light of this, further data collection and analysis should be undertaken, including comparisons between oral and injectable GLP1-RAs and analysis of switches between them Disclosure T.S.J.Crabtree: Speaker's Bureau; Abbott Diabetes, Novo Nordisk, Lilly, Sanofi, Insulet Corporation. K.Adamson: None. S.Krishnasamy: Other Relationship; Novo Nordisk, Sanofi, Eli Lilly and Company, AstraZeneca. M.Khine: None. P.De: Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Takeda Canada, Daiichi Sankyo, Napp Pharmaceuticals Limited, Lilly Diabetes. R.Peter: None. R.E.Ryder: Other Relationship; Novo Nordisk, Speaker's Bureau; GI Dynamics, BioQuest. Funding Novo Nordisk

907-P: Glycaemic Outcomes Associated with Omnipod DASH Use in the Real World—Results from the Association of British Clinical Diabetologists (ABCD) Omnipod Worldwide Audit

Introduction: The ABCD Omnipod® Worldwide Audit launched in 2021 with the aim of capturing routine clinical outcomes from users in the real-world. This analysis reports glucose outcomes, including comparisons between pump-naïve and established pump-users starting on Omnipod DASH® Insulin Management System. Methods: Individuals were included in the analysis if relevant baseline and follow-up data were available. Change in HbA1c, time-in-range (TIR, 70-180mg/dL), time below range (TBR, &amp;lt;70mg/dL) and total daily dose of insulin were assessed using paired T-tests. For glucose outcomes, stratified analyses were performed to compare the outcomes between those new to pump therapy (“new”) and those already established (“established”). Results: Over a median follow-up of 2.3years (IQR 1.2-3) we included 235 individuals from the UK with baseline mean±SD HbA1c 8.1±1.4%; age 36.0±16.5years; diabetes duration 21.7±14.9years; 34.0% (n=82/235) were new to pump therapy. Across the whole population HbA1c reduced by 0.3% (95%CI 0.1, 0.5; P&amp;lt;0.01). Stratified by previous therapy, HbA1c reductions were statistically significant in the “new” group (0.5%; 95%CI 0.1, 0.8; P=0.01). TIR, TBR and HbA1c levels were maintained in those in the “established” group. Total daily dose decreased from 41.4units to 36.9units (-4.4; 95%CI 0.8, 8.1; P=0.018) between baseline and follow-up. Of those asked to rate on a 7-point Likert scale, 82/84 (97.6%) stated Omnipod DASH had improved their quality of life and 83/86 (96.5%) would recommend the system to other people with diabetes. Conclusion: In individuals new to pump therapy, Omnipod DASH is associated with clinically meaningful reductions in HbA1c, reduced insulin requirements and improved quality of life. Individuals switching to Omnipod DASH from other pumps maintained previous HbA1c levels, TIR and TBR. Disclosure T.S.J.Crabtree: Speaker's Bureau; Abbott Diabetes, Novo Nordisk, Lilly, Sanofi, Insulet Corporation. E.G.Wilmot: Advisory Panel; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Roche Diabetes Care, Embecta, Consultant; Springer Healthcare, Research Support; Abbott Diabetes, Diabetes UK, Insulet Corporation, Novo Nordisk, NIH - National Institutes of Health, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Ypsomed AG, Glooko, Inc. M.Haq: None. N.Hasan: None. D.M.Williams: None. E.R.Gatdula: None. E.Chinnasamy: None. J.Varghese: None. G.Modgil: None. R.E.Ryder: Other Relationship; Novo Nordisk, Speaker's Bureau; GI Dynamics, BioQuest. Funding Insulet Corporation

1061-P: Food Recording and HbA1c Improvement —GluCare.Health Remote Monitoring Program Compared with Traditional Care in Patients with Obesity

Introduction: Technology is intended to assist with diagnosing, treating, and monitoring patients remotely. All studies reported positive findings between technology and weight loss. Food record has been used to monitor patients with obesity, but its impact on outcomes is still little known (1). The GluCare Health care model is centered on the use of Continuous Metabolic Monitoring (CMM) and behavioral change to address metabolic diseases in a continuous manner. The app also allows for nutrition intervention through meal logging and feedback from dietitians to improve understanding of macronutrient quality and quantity. Overall, the GluCare CMM program aims to provide continuous patient supervision and support through personalized lifestyle coaching and behavioral change. Material and Methods: Thirty participants were enrolled during 2022 at GluCare Health, Dubai (UAE). Participants were male and female aged 18 years or older with a starting body mass index (BMI) of &amp;gt;25kg/m². All the participants were on treatment using the GLP-1 analogue. Fifteen participants opted for the GluCare Health program and fifteen opted for traditional care. Outcomes: BMI and HbA1c reduction in each group after 3 months follow-up and description of number of food logs per opt-in patient. Results : On opt-in GluCare program, BMI average reduction was 2.89 kg/m² and mean HbA1c reduction was statistically significant (p= 0.002) with mean difference of 17% of reduction meanwhile on the opt-out group, BMI average reduction was 1.21 kg/m² and the HbA1c reduction was not statistically significant (p= 0.117) with 3.4% of reduction. The average of food records per opt-in patient/monthly was 71.29. Conclusion: Food monitoring and personalized dietary remote orientation by specialist healthcare providers are relevant tools to reduce HbA1c and manage obesity effectively. Disclosure B.Demircan: None. M.Caccelli: None. Y.Said: None. V.Munirathinam: None. C.Palsky: None. I.Almarzooqi: None. A.Hashemi: None.

Real-world study of ethnic differences in glycaemic control and clinical characteristics among insulin-naïve people with type 2 diabetes initiating biphasic insulin aspart 30/70: A retrospective, observational cohort study in England.

This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin-naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England. Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin-naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index. In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %-point changes [95% CI of -2.32 (-2.36; -2.28) (White); -1.91 (-2.02; -1.80) (South Asian); -2.55 (-2.69; -2.40) (Black); and -2.64 (-3.24; -2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m2 : White, 0.92 (0.86; 0.99); South Asian, 0.60 (0.41; 0.78); Black, 1.41 (1.16; 1.65); and Chinese, 0.32 (-0.67; 1.30)]. In the overall population, hypoglycaemic event rates increased from 0.92 events per 100 patient-years before the index to 3.37 events per 100 patient-years post index; event numbers were too low to be analysed by subgroup. Among insulin-naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.

THE INFLUENCE OF GLP-1RAS (ORAL SEMAGLUTIDE) ON TENSIONAL CONTROL IN DIABETIC PATIENTS WITH CHRONIC RENAL DISEASE

Objective: GLP-1 receptor agonists (GLP-1RAs) represent one of the pharmacological groups of choice for the diabetic management of patients with cardiovascular disease and chronic kidney disease (CKD). Their hypotensive effect has not been sufficiently evaluated in association with the usual antihypertensive drugs. The main objective is to study the hypotensive effect of oral semaglutide at a maintenance dose of 7mg per day in a cohort of patients with stage 3b CKD (glomerular filtration rate -GFR- 44 to 30ml/min by CKD-EPI) with poor diabetic control and without previous treatment with GLP-1 receptor agonists or iSGLT2. Design and method: Sixteen patients of both sexes were selected and divided into two follow-up arms of eight patients each. In one arm, the combination of oral semaglutide with an angiotensin receptor blocker (ARB) (such as losartan at a maintenance dose of 50-100mg per day) is evaluated, and in the other, dietary measures are intensified together with ARB at the same doses. After 4 months of treatment, the primary and secondary variables were assessed: body weight, glycosylated haemoglobin (HbA1c), renal function and albuminuria (albumin/creatinine ratio - ACC). Results: Mean age was similar in both groups (69 vs 70 years). The reduction in mean blood pressure (BP) values obtained with standardised measurements in a nephrology consultation in the semaglutide + ARB arm was -12mmHg (systolic) and -5mmHg (diastolic) compared to those in the ARB arm alone (-5mmHg systolic and -3mmHg diastolic), with statistical significance (p&lt;0.05). The other comparative variables between the two groups were: reduction in body weight (-2.5kg vs -0.5kg, p&lt;0.05); reduction in mean HbA1c (-1.2% vs -0.1%, p&lt;0.05); changes in eGFR (+2ml/min/1.73m2 vs -3ml/min/1.73m2, p&gt;0.05) and mean reduction in ACC (-257mg/g vs +12mg/g, p&lt;0.05). Conclusions: Orally administered GLP-1 receptor agonists (semaglutide) are drugs with a hypotensive potential complementary to renin angiotensin system inhibitors in diabetic renal patients. This property, together with their antiproteinuric effect, makes them an ideal choice in situations of hypertension and moderate renal dysfunction. Larger, controlled studies are needed to measure the renal effect alongside the various antihypertensive groups.

Efficacy and safety of luseogliflozin in Caucasian patients with type 2 diabetes: results from a phase III, randomized, placebo-controlled, clinical trial

IntroductionMost data demonstrating the efficacy and safety of luseogliflozin (luseo) in people with type 2 diabetes mellitus (T2DM) originate from the Japanese population. This study evaluated luseo versus placebo (PCB)...

Use of Fixed-dose Combination Therapy with Remogliflozin and Vildagliptin as an Add-on Drug in Improving the Glycemic Control of Type 2 Diabetes Mellitus: An Observational Study

Objective To evaluate whether a fixed dose combination (FDC) with remogliflozin and vildagliptin as an add-on therapy can improve the glycemic control in the management of type 2 diabetes mellitus and also the non-glycemic effects on physical profile, blood pressure, lipids, and insulin resistance. Materials and Methods An observational study that included 50 poorly controlled diabetics from April 2021 to September 2021. Patients were divided into two groups – those who were prescribed this FDC by their treating physician as an add-on drug were formed as group 1 ( n = 28). Comparison group was age-matched patients who received other standard anti-diabetic medications, categorized as group 2 ( n = 22). Fasting and postprandial sugars were done at baseline, the third and sixth month; glycated hemoglobin, body mass index, blood pressure, and lipids were done at baseline and the sixth month. Changes in blood sugar levels and glycated hemoglobin (HbA1C) at the third and sixth month from the baseline were compared using the Mann-Whitney U test. P-value less than 5% was considered statistically significant. Results A statistically significant reduction in mean HbA1c was noted in group 1 [–1.80 (−3.20, −0.15)] when compared to group 2 [0.50 (0.05, 0.80)] at the end of the third month. At the end of the sixth month, a significant reduction in the HbA1c level was noted in group 1 [(7.83 ± 0.87 %) when compared to baseline (10.3 ± 1.75%)]. Change in PPBS value at the third month from baseline was also statistically significant between groups 1 and 2 (−62.0 mg%, 19.0, P = 0.003). With respect to the body mass index and blood pressure, we did not find any significant difference. Conclusion The fixed drug combination improves glycemic control by significantly reducing mean HbA1c at the third and sixth month from baseline and there was no significant effect on body mass index, blood pressure, and lipids.

A Meta-Analysis of Randomized Trial Outcomes for the t:slim X2 Insulin Pump with Control-IQ Technology in Youth and Adults from Age 2 to 72.

Objective: To evaluate the effect of hybrid-closed loop Control-IQ technology (Control-IQ) in randomized controlled trials (RCTs) in subgroups based on baseline characteristics such as race/ethnicity, socioeconomic status (SES), prestudy insulin delivery modality (pump or multiple daily injections), and baseline glycemic control. Methods: Data were pooled and analyzed from 3 RCTs comparing Control-IQ to a Control group using continuous glucose monitoring in 369 participants with type 1 diabetes (T1D) from age 2 to 72 years old. Results: Time in range 70-180 mg/dL (TIR) in the Control-IQ group (n = 256) increased from 57% ± 17% at baseline to 70% ± 11% during follow-up, and in the Control group (n = 113) was 56% ± 15% and 57% ± 14%, respectively (adjusted treatment group difference = 11.5%, 95% confidence interval +9.7% to +13.2%, P < 0.001), an increase of 2.8 h/day on average. Significant reductions in mean glucose, hyperglycemia metrics, hypoglycemic metrics, and HbA1c were also observed. A statistically similar beneficial treatment effect on time in range 70-180 mg/dL was observed across the full age range irrespective of race-ethnicity, household income, prestudy continuous glucose monitor use, or prestudy insulin delivery method. Participants with the highest baseline HbA1c levels showed the greatest improvements in TIR and HbA1c. Conclusion: This pooled analysis of Control-IQ RCTs demonstrates the beneficial effect of Control-IQ in T1D across a broad spectrum of participant characteristics, including racial-ethnic minority, lower SES, lack of prestudy insulin pump experience, and high HbA1c levels. The greatest benefit was observed in participants with the worst baseline glycemic control in whom the auto-bolus feature of the Control-IQ algorithm appears to have substantial impact. Since no subgroups were identified that did not benefit from Control-IQ, hybrid-closed loop technology should be strongly considered for all youth and adults with T1D. Clinical Trials Registry: clinicaltrials.gov; NCT03563313, NCT03844789, and NCT04796779.

A Prospective Observational Study of Comparison, Safety, and Efficacy of Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes Mellitus in A Tertiary Care Hospital

Aims: The purpose of the study was to determine the safety and efficacy of Dipeptidyl Peptidase 4-Inhibitor as mono-therapy and in combination therapy. The impact of age, disease duration and gender on the efficacy of DPP-4 inhibitors were also studied. Materials and Methods: A prospective observational study was conducted among patients with type 2 diabetes mellitus. The study consisted of 6 groups: Metformin+Glimepiride, Metformin+Teneligliptin, Glimepiride+Teneligliptin, Metformin only, Teneligliptin only and Glimepiride only. Fasting and Post Prandial Blood Sugar and HbA1c were monitored before and after 6 months of therapy. Results: In combination therapy, the adverse effects were higher in Glimepiride and Teneligliptin group followed by Metformin and Glimepiride and Metformin and Teneligliptin. The mean FBS reduction was 21.57 mg/dl, 28.32 mg/dl, and 20.08mg/dl in Metformin+Glimepiride, Metformin+Teneligliptin and Glimepiride+Teneligliptin, respectively. The mean Post-Prandial Blood Sugar reduction was 27.63mg/dl, 42.78mg/dl, 34.13mg/dl in Metformin+Glimepiride, Metformin+Teneligliptin and Glimepiride+Teneligliptin, respectively. The mean HbA1c reduction was 1.30%, 1.41%, and 0.80% in Metformin+Glimepiride, Metformin+Teneligliptin and Glimepiride+Teneligliptin, respectively. Conclusion: Metformin and Teneligliptin combination therapy and Teneligliptin monotherapy were safe and efficacious compared to all other oral hypoglycemic drugs under study. There was no significant impact of gender, BMI class and disease duration on the drug’s efficacy.

Use of iGlarLixi for the Management of Type2 Diabetes in Japanese Clinical Practice: Prior Treatment Subgroup Analysis of the SPARTA Japan Study.

iGlarLixi, a fixed-ratio combination of insulin glargine 100U/mL and the glucagon-like peptide1 receptor agonist (GLP-1 RA) lixisenatide, is one option for treatment intensification in individuals with type2 diabetes (T2D) who are unable to achieve targeted glycaemic control with their current glucose-lowering agent. Real-world data on the impact of prior treatment on the effectiveness and safety of iGlarLixi may be useful to guide individualised treatment decisions. This analysis of the 6-month, retrospective, observational SPARTA Japan study compared glycated haemoglobin (HbA1c), body weight and safety for pre-specified subgroups defined by prior treatment: post oral antidiabetic agent (OAD), GLP-1 RA, basal insulin (BI) + OADs (BOT), GLP-1 RA + BI or multiple daily injections (MDI). The post BOT and MDI subgroups were further divided on the basis of prior dipeptidyl peptidase4 inhibitor (DPP-4i) use, and the post MDI group was divided on the basis of whether participants continued bolus insulin. Of the 432 participants in the full analysis set (FAS), 337 were included in this subgroup analysis. Across subgroups, mean baseline HbA1c ranged from 8.49% to 9.18%. iGlarLixi significantly (p < 0.05) reduced mean HbA1c from baseline in all but the post GLP-1 RA + BI group. At 6months, these significant reductions ranged from 0.47% to 1.27%. Prior DPP-4i exposure had no impact on the HbA1c-lowering effect of iGlarLixi. Mean body weight decreased significantly in the FAS (0.5kg) and the post BOT (1.2kg) and MDI (1.5 and 1.9kg) subgroups but increased in the post GLP-1 RA subgroup (1.3kg). iGlarLixi treatment was generally well tolerated, with very few participants discontinuing because of hypoglycaemia or gastrointestinal events. In participants with suboptimal glycaemic control on various regimens, 6months of iGlarLixi treatment improved HbA1c in all but one prior treatment subgroup (GLP-1 RA + BI), and was generally well tolerated. UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

Real world evidence of clinical predictors of glycaemic response to glucose-lowering drugs among Chinese with type 2 diabetes.

To examine whether simple clinical features can predict the 1-year glycaemic response to glucose-lowering drugs (GLDs) among Chinese with type 2 diabetes. We used data from a diabetes risk assessment and complication screening programme and electronic medical records. We used linear regression models to examine the association between clinical features and 1-year glycaemic response to GLDs. Use of metformin (n=15,433), sulphonylureas (SU) (n=15,190), dipeptidyl peptidase-4 inhibitor (DPP-4i) (n=7947), thiazolidinedione (TZD) (n=4107), and sodium-glucose cotransporter 2 inhibitors (SGLT-2i) (n=1883) were associated with a mean reduction of HbA1c ranging from 0.7% to 1.3% at one year. Men had a greater response to SU but a poorer response to metformin and TZD. Older age predicted a better response to all GLDs but not SGLT-2i, whereas increasing diabetes duration was associated with a poorer response to all GLDs except for DPP-4i. Obese patients responded greater to TZD and SGLT-2i but poorer to SU than those with normal weight. Patients with a higher level of triglycerides to high-density lipoprotein cholesterol ratio had a greater glycaemic response to TZD but a smaller response to SU and DPP-4i. Glycaemic response to GLDs differed considerably by clinical features among Chinese patients with type 2 diabetes.

Effectiveness of Diabetes Self-Management Education on Distress and HbA1C among Indian Type 2 Diabetes Mellitus Patients: A Randomized Controlled Trial.

The interrelationship of diabetes with mental illness has increased in recent years. Diabetes-related distress is the emotional burden, stress, and worries associated with diabetes, which does not reach the threshold for depressive disorder. A diabetes self-management education (DSME) is a structured educational approach to improve glycemic control and diabetes-related distress. This study aimed to assess the effectiveness of DSME in comparison with usual diabetes care in improving glycemic control and diabetes-related distress. This is a single-center, parallel randomized controlled trial. A total of 106 participants were recruited for both intervention and control groups with 53 participants each. The control group received only routine outpatient department (OPD) care. The intervention group received DSME in addition to routine OPD care. Diabetes-related distress and HbA1C were assessed after 3 months. The data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) version 25. Per-protocol analysis was done. Of 127 patients screened, 106 met the eligibility criteria and were randomized. At 3-month follow-up, the reduction in mean HbA1C, fasting blood sugar (FBS), postprandial blood sugar (PPBS), and diabetes distress were significant in the intervention group compared with the control group (p 0.001). The mean HbA1C reduction in the intervention group was significant (mean difference: -1.3, SD: 0.4). The mean DDS had decreased significantly in the intervention group from 2 to 1.2 (mean difference: -0.8, SD: 0.1). The DSME was effective in improving the glycemic control, diabetes-related distress, and self-care among type 2 diabetes (T2DM) mellitus patients.