Change In HbA1c Research Articles

Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD

ObjectivesCurrently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes. Research design and methodsData were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI. Paired biopsies from interventional studies (n = 421) were used to assess the impact of change in weight, HbA1c and active vs. placebo treatment on improvements in steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis. ResultsIn the discovery cohort (n = 687), risk of severe steatosis, NASH and advanced fibrosis correlated positively with HbA1c, after adjustment for obesity and age. These data were endorsed in a separate validation cohort (n = 170). Predictive modelling using HbA1c and age was non-inferior to the established non-invasive biomarker, Fib-4, and allowed the generation of HbA1c, age, and BMI adjusted risk charts to predict NAFLD severity. Following intervention, reduction in HbA1c was associated with improvements in steatosis and NASH after adjustment for weight change and treatment, whilst fibrosis change was only associated with weight change and treatment. ConclusionsHbA1c is highly informative in predicting NAFLD severity and contributes more than BMI. Assessments of HbA1c must be a fundamental part of the holistic assessment of patients with NAFLD and, alongside age, can be used to identify patients with highest risk of advanced disease.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Glucagon-like peptide-1 receptor agonist therapy effects on glycemic control and weight in a primary care clinic population.

Glucagon-like peptide-1 receptor agonist (GLP-1a) medications have been shown in randomized controlled trials (RCTs) to have consistent and impressive effectiveness in lowering hemoglobin A1c (HbA1c) and weight, but limited data exist on the efficacy of GLP-1a medications in clinical practice. We studied the association between GLP-1a therapy and changes in weight and HbA1c in a real-world patient population. In this retrospective cohort study of patients seen in a primary care clinic between 2012 and 2021, we examined the change in weight and HbA1c over 12 months in a cohort of patients with at least one prescription for a GLP-1a. Within this cohort, treatment was defined as having ≥2 GLP-1a prescriptions at a therapeutic dosage separated by ≥10 months. The cohort included 693 patients of whom 393 (57%) were treated with GLP-1a therapy. The treatment group had a mean change in body mass index (BMI) of -0.83 kg/m2 (±2.88) compared to -0.70 kg/m2 (±2.99) in the without GLP-1a group (p = 0.57). Treated patients had a mean change in HbA1c of -1.00% (±2.07) compared to -0.83% (±1.92) in the without GLP-1a group (p = 0.27). For treated and without GLP-1a patients, respectively, the proportion of patients with a decrease in BMI was 65 versus 64% (p = 0.86), and the proportion with a decrease in HbA1c was 73 versus 69% (p = 0.28). In clinical practice, GLP-1a therapy was associated with more modest reductions in weight and HbA1c than shown in prior RCTs. As GLP-1a use continues to expand throughout primary care, the real-world impact of this pharmacotherapy will require further evaluation.

Efficacy and safety of insulin glargine 300 U/mL in people with type 2 diabetes in China: The INITIATION study.

To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) in people with suboptimally controlled type 2 diabetes (T2D) in China. INITIATION (NCT05002933) was a prospective, interventional, multicentre, single-arm, phase IV study conducted in China. Individuals with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin (insulin experienced) were included. The primary endpoint was the change in HbA1c from baseline to week 24. Safety assessments included hypoglycaemia and adverse events (AEs). In total, 568 participants were enrolled and 562 initiated Gla-300 treatment (189 in the insulin-naïve subgroup; 373 in the insulin-experienced subgroup). At week 24, the mean ± standard error (SE) change in HbA1c from baseline was -0.91% ± 0.05% (-9.9 ± 0.5 mmol/mol; P < .0001). Significant HbA1c reductions were also observed in the insulin-naïve (mean ± SE change: -1.38% ± 0.09% [-15.1 ± 1.0 mmol/mol]) and insulin-experienced (-0.68% ± 0.05% [-7.4 ± 0.5 mmol/mol]) subgroups (both P < .0001). During the 24-week treatment period, the incidence of confirmed hypoglycaemia (plasma glucose ≤ 3.9 mmol/L) was 39.7% for all hypoglycaemia and 13.3% for nocturnal hypoglycaemia; the incidence of severe hypoglycaemia was low (0.5%). Overall, treatment-emergent AEs (TEAEs) were reported in 126 participants (22.4%), with no serious treatment-related TEAEs. Gla-300 was effective in improving glycaemic control and had a relatively low risk of hypoglycaemia in people with suboptimally controlled T2D who were insulin naïve or switching from another basal insulin in China.

Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-controlled Study

PurposeThe purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin. MethodsIn this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA1c from baseline at 24 weeks across the groups. FindingsFor the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA1c of 7.9%. After 24 weeks, HbA1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of −0.38% and −0.83%, respectively, compared with the PBO group. The proportion of patients with HbA1c levels <7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone. ImplicationsThe addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. ClinicalTrials.gov identifier: NCT04885712.

PIONEER REAL Sweden: A Multicentre, Prospective, Real-World Observational Study of Oral Semaglutide Use in Adults with Type2 Diabetes in Swedish Clinical Practice.

The study was designed to assess outcomes with once-daily oral semaglutide in adults with type2 diabetes (T2D) naïve to injectable glucose-lowering agents, in Swedish clinical practice. In this non-interventional, multicentre study, participants initiated oral semaglutide and were followed for 34-44weeks. The primary endpoint was glycated haemoglobin (HbA1c) change from baseline to end of study (EOS). Secondary endpoints included body weight (BW) change from baseline to EOS, proportion of participants achieving HbA1c < 7%, and proportion achieving both a HbA1c reduction ≥ 1% and BW reduction of ≥ 3% or ≥ 5%, at EOS. Participants completed Diabetes Treatment Satisfaction Questionnaires (DTSQ status/change) and a dosing conditions questionnaire. A total of 187 participants (mean age 62.5years) initiated oral semaglutide. Baseline mean HbA1c and BW were 7.8% (n = 177) and 96.9kg (n = 165), respectively. Estimated mean changes in HbA1c and BW were - 0.88%-points (95% confidence interval [CI] - 1.01 to - 0.75; P < 0.0001) and - 4.72% (95%CI - 5.58 to - 3.86; P < 0.0001), respectively. At EOS, 64.6% of participants had HbA1c < 7%, and 22.9% achieved HbA1c reduction of ≥ 1% and BW reduction of ≥ 5%. DTSQ status and change scores improved by 1.44 (P = 0.0260) and 12.3 points (P < 0.0001), respectively. Oral semaglutide was easy or very easy to consume for 86.4% of participants. Most common adverse events (AEs) were gastrointestinal disorders; nine participants (4.8%) had serious AEs; one (0.5%) experienced severe hypoglycaemia. In this real-world study population, we observed significant reductions in HbA1c and BW in people living with T2D when prescribed semaglutide tablets as part of routine clinical practice in Sweden, with improved treatment satisfaction among participants and no new safety concerns. NCT04601753.

Efficacy and safety of oral semaglutide in older patients with type 2 diabetes: a retrospective observational study (the OTARU-SEMA study)

BackgroundOral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world.MethodsWe retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65–74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity.ResultsWe studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (− 13.1 ± 7.5 mmol/mol and − 3.0 ± 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = −0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = −0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4).ConclusionsOral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of ≥ 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence.

Effect of Replacing Sucrose in Beverages with Nonnutritive Sweetener Sucralose on Cardiometabolic Risk Factors Among Asian Indian Adults with Type2 Diabetes: A 12-Week Randomized Controlled Trial.

Country-specific evidence-based research is crucial for understanding the role of nonnutritive sweeteners (NNS) in managing type2 diabetes (T2D). The main aim of this study was to explore the effect of replacing sucrose with sucralose in coffee/tea in Asian Indians with type2 diabetes (T2D). This 12-week, parallel-arm randomized controlled trial included 210 participants with T2D, assigned to the intervention group, where sugar/sucrose in coffee or tea was substituted with sucralose, or the control group, where sugar/sucrose was continued. Lifestyle factors remained unchanged. The primary outcome was change in HbA1c. Secondary outcomes were changes in body weight (BW), body mass index (BMI), waist circumference (WC), lipid profiles, and inflammatory markers. At the end of 12weeks, no change was observed in HbA1c, fasting plasma glucose, lipid profile, and inflammatory markers between or within groups. There was a small but significant reduction in BW (- 0.5kg [95%CI - 1.0, - 0.1]; p = 0.02), BMI (- 0.2kg/m2 [- 0.4, 0.0]; p = 0.03), and WC (- 0.8cm [- 1.4, - 0.3]; p = 0.002) in the intervention group. Improvements were also observed in lipid accumulation product (p = 0.01), visceral adiposity index (p = 0.04), triglyceride/glucose index (p = 0.04), total energy intake (p = 0.04), and carbohydrate intake (p < 0.0001). In Asian Indians with T2D, replacing about 60kcal of added sucrose with sucralose in coffee/ tea had no benefit on glycemia but resulted in a small reduction in body weight, body mass index, and waist circumference. Clinical Trials Registry of India (CTRI/2021/04/032686).

Effect of High-Intensity Interval Training on Blood Glucose Levels in Patients with Type 2 Diabetes Mellitus: A Literature Review

Diabetes Mellitus (DM) is a chronic and progressive disease characterized by elevated blood glucose levels. This study aims to investigate the effect of High-Intensity Interval Training on blood glucose levels in patients with type 2 diabetes mellitus through a literature review. The comprehensive search in the database resulted in 7,737 articles: Pubmed (2,610), Science Direct (4,724), Scopus (282), and Springer (121), and only 11 articles met the criteria for further review. A comprehensive analysis of the included studies reveals the effect of HIIT on blood glucose levels in type 2 DM patients, which can be observed through changes in blood glucose levels and HbA1c following exercise. In conclusion, our findings suggest that HIIT could be an essential intervention for managing blood glucose in Type 2 DM patients.

The effect of USM-IAM-based counselling vs standard counselling on insulin adherence, FBS and HbA1c among patients with uncontrolled type 2 diabetes mellitus (T2DM): a randomised controlled trial

BackgroundMany patients with T2DM on insulin are not optimally controlled despite receiving standard diabetes education counselling. Poor insulin adherence may be a contributing factor. We developed and evaluated a new module [Universiti Sains Malaysia-Insulin Adherence Module (USM-IAM)] on insulin-treated patients with poorly controlled diabetes.MethodsEligibility criteria are those diagnosed with T2DM, aged between 18 and 65 years, with HbA1c between 8 and 15% and on insulin therapy for 1 year. Patients were randomly allocated to receive either the USM-IAM-based counselling or the standard counselling (SC) at baseline and the second visit. Patients were instructed to adjust insulin doses based on blood glucose levels. Outcomes were changes in adherence score, FBS and HbA1c levels from baseline to 3 months and baseline to sixth month.ResultsNinety patients were randomised to each group. The baseline sociodemographic and clinical characteristics were homogenous among groups. Ninety patients were analysed for each group. Adherence score changes between baseline to 3 months were − 8.30 (− 11.47, − 5.14) in USM-IAM-based counselling group (USM-IAM) and − 7.64 (− 10.89, − 4.40) in standard counselling group (SCG), between baseline to sixth month were − 10.21 (− 13.40, − 7.03) in USM-IAM and − 10.79 (− 14.64, − 6.97) in SCG. FBS changes between baseline to 3 months were 1.374 (0.25, 2.50) in USM-IAM and 0.438 (− 0.66, 1.54) in SCG, and between baseline to sixth month were 1.713 (0.473, 2.95) in USM-IAM and 0.998 (− 0.02, 2.01) in SCG. HbA1c changes between baseline to 3 months were 1.374 (0.25, 2.50) in USM-IAM and 0.547 (0.12, 0.98) in SCG, and between baseline to sixth month were 1.03 (0.65, 1.41) in USM-IAM and 0.617 (0.20, 1.03) in SCG. Between-subjects effects for all outcomes were not statistically significant.ConclusionBoth groups had significant improvements in adherence score and HbA1c with time, with higher improvement in patients receiving the USM-IAM. FBS reductions were significant in the intervention group but not in the control group.Trial registrationThis study protocol is registered with Clicaltrials.gov with ID NCT05125185 dated 17th November 2021.

Evaluation of remote pharmacist intervention on type 2 diabetes hemoglobin A1c reduction in an accountable care organization

Background The value of clinical pharmacists for ambulatory internal medicine clinics is well recognized, including their role in hemoglobin A1c (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM). However, there is a lack of data evaluating the clinical impact of remote, referral-based pharmacy programs. Methods This multicenter, cohort, retrospective chart review study analyzed the impact of pharmacist interventions on blood glucose control in patients aged 18 years and older who were diagnosed with T2DM with an HbA1c of 8.5% or greater and referred to the clinical pharmacy team for medication evaluation. Primary care providers may have accepted or rejected pharmacist recommendations. The primary study outcome was the mean change in HbA1c from baseline to follow-up at 2 to 5 months. Secondary outcomes included appropriate use of American Diabetes Association–indicated secondary prevention and any occurrence of glycemia-related events (i.e., T2DM-related emergency room visits or hospitalizations). Results At the conclusion of the study, the mean change in HbA1c from baseline to follow-up at 2 to 5 months was −2.7% and −0.6% for the accepted and rejected intervention groups, respectively (t = −2.94, P = 0.0068). Conclusions The results of this study suggest that remote pharmacist intervention significantly improves blood glucose control in adults with T2DM.

Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial

Aims/hypothesisThe aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment.MethodsThe Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS).ResultsOf 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were –2 (–4, –1) mmol/mol, –8 (–9, –6) mmol/mol and –11 (–12, –9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were –0.2 (–0.3, –0.1), –0.7 (–0.8, –0.6) and –1.0 (–1.1, –0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] –0.9 [–1.4, –0.4] kg, –2.3 [–2.8, –1.8] kg and –3.3 [–3.8, –2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity.Conclusions/interpretationSignificantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials.Trial registrationClinicalTrials.gov NCT04017832.FundingThis trial was funded by Novo Nordisk A/S, Søborg, Denmark.Graphical

Effect of switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL (Gla-300) in Brazilian people with type 1 diabetes

BackgroundLow adherence to the number of insulin injections and glycemic variability are among the challenges of insulin therapy in type 1 diabetes (T1D). The TOP1 study investigated the effect of switching from twice-daily (BID) basal insulin to once daily (OD) insulin glargine 300 U/mL (Gla-300) on glycemic control and quality of life.MethodsIn this 28-week, phase 4 trial, people with T1D aged ≥ 18 years, who were treated with BID basal insulin in combination with prandial rapid-acting insulin for at least 1 year, and had HbA1c between 7.5% and 10.0%, were switched to Gla-300 OD as basal insulin. The present study aimed to evaluate the impact of this change on HbA1c, glycemic profile, treatment satisfaction and safety. The change in HbA1c from baseline to Week 24 was the primary endpoint.ResultsOne hundred and twenty-three people with T1D (mean age 37 ± 11 years; 54.5% female) were studied. The disease duration was 20.0 ± 9.8 years, baseline HbA1c and fasting plasma glucose (FPG) were 8.6 ± 0.7% and 201 ± 80.3 mg/dL, respectively. After switching from BID to OD insulin regimen, no significant change in HbA1c was observed from baseline to Week 24 (p = 0.873). There were significant reductions in fasting self-monitoring blood glucose (SMBG) from baseline to Week 24 (175 ± 42 vs. 156 ± 38 mg/dL; p < 0.0001), and in glycemic profile (8-point SMBG) at several time points. There was a significant decrease in the proportion of patients with at least one hypoglycemic event (p = 0.025), in numbers of hypoglycemic events per patient-years of any type (p = 0.036), symptomatic (p = 0.007), and confirmed ≤ 70 mg/dL events (p = 0.049) from run-in to the last 4 weeks on treatment. There were significant improvements in treatment satisfaction (p < 0.0001), perceived hyperglycemia (p < 0.0001) scores and satisfaction with the number of injections between post-run-in and Week 24, and a significant decrease in fear of hypoglycemia.ConclusionsSwitch from BID basal insulin to OD Gla-300 as part of basal bolus therapy in T1D resulted in similar glycemic control as measured by HbA1c, but provided significant improvements in SMBG, daily glucose profile, a lower incidence of hypoglycemia and increased patient satisfaction.Trial registrationNCT03406000.

Dual add-on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study.

To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.

Trajectories of BMI before and after diagnosis of type 2 diabetes in a real-world population.

Few studies have examined the clinical characteristics associated with changes in weight before and after diagnosis of type 2 diabetes. Using a large real-world cohort, we derived trajectories of BMI before and after diabetes diagnosis, and examined the clinical characteristics associated with these trajectories, including assessing the impact of pre-diagnosis weight change on post-diagnosis weight change. We performed an observational cohort study using electronic medical records from individuals in the Scottish Care Information Diabetes Collaboration database. Two trajectories were calculated, based on observed BMI measurements between 3 years and 6 months before diagnosis and between 1 and 5 years after diagnosis. In the post-diagnosis trajectory, each BMI measurement was time-dependently adjusted for the effects of diabetes medications and HbA1c change. A total of 2736 individuals were included in the study. There was a pattern of pre-diagnosis weight gain, with 1944 individuals (71%) gaining weight overall, and 875 (32%) gaining more than 0.5 kg/m2 per year. This was followed by a pattern of weight loss after diagnosis, with 1722 individuals (63%) losing weight. Younger age and greater social deprivation were associated with increased weight gain before diagnosis. Pre-diagnosis weight change was unrelated to post-diagnosis weight change, but post-diagnosis weight loss was associated with older age, female sex, higher BMI, higher HbA1c and weight gain during the peri-diagnosis period. When considering the peri-diagnostic period (defined as from 6 months before to 12 months after diagnosis), we identified 986 (36%) individuals who had a high HbA1c at diagnosis but who lost weight rapidly and were most aggressively treated at 1 year; this subgroup had the best glycaemic control at 5 years. Average weight increases before diagnosis and decreases after diagnosis; however, there were significant differences across the population in terms of weight changes. Younger individuals gained weight pre-diagnosis, but, in older individuals, type 2 diabetes is less associated with weight gain, consistent with other drivers for diabetes aetiology in older adults. We have identified a substantial group of individuals who have a rapid deterioration in glycaemic control, together with weight loss, around the time of diagnosis, and who subsequently stabilise, suggesting that a high HbA1c at diagnosis is not inevitably associated with a poor outcome and may be driven by reversible glucose toxicity.

Changes in daily intake of nutrients and foods including confectionery after the initiation of empagliflozin in Japanese patients with type 2 diabetes: a pilot study

IntroductionIt is unclear how dietary intake changes after sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is started in patients with type 2 diabetes.MethodsWe performed a non-controlled, open-label study that enrolled 51 patients with type 2 diabetes. The patients were newly administered empagliflozin, and their dietary habits were examined using a self-administered diet history questionnaire at the beginning of the study and after 24 weeks. We investigated the association of changes in HbA1c and body weight with changes in energy, nutrient, and food group intakes.ResultsAt 24 weeks after the start of the study, HbA1c improved significantly and body weight decreased. In the food group, only the intake of confectionery increased, and there were no significant differences in the association between changes in HbA1c and body weight and changes in energy, nutrient, and food group intakes after 24 weeks. However, a significant negative correlation was found between change in HbA1c after 4 weeks and change in energy intake after 24 weeks, and principal component analysis showed an association between change in HbA1c levels after 4 weeks and change in energy intake and some food group intakes including confectionery after 24 weeks.ConclusionIn this study, after 24 weeks of treatment with empagliflozin, only intake of confectionery increased. Early assessment by dietitians after initiation of SGLT2i treatment might be important because our data suggested that the reduction in blood glucose levels after the start of empagliflozin was associated with a subsequent increase in energy intake.Trial registrationUniversity Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on September 5, 2016 (registration ID, UMIN000002309|| http://www.umin.ac.jp/ctr/).

Study protocol for a prospective, multicentre study of hypercortisolism in patients with difficult-to-control type 2 diabetes (CATALYST): prevalence and treatment with mifepristone

IntroductionEven with recent treatment advances, type 2 diabetes (T2D) remains poorly controlled for many patients, despite the best efforts to adhere to therapies and lifestyle modifications. Although estimates vary, studies...

Improvement in Glycemic Indices and Point in Range by Addition or Switch to IDegAsp–Real-World Evidence

Abstract Aim and Objectives: This study aimed to evaluate the effectiveness of insulin degludec/insulin aspart (IDegAsp) in uncontrolled type 2 diabetes mellitus (T2DM) patients in clinical practice settings. Materials and Methods: This study includes a retrospective analysis of uncontrolled T2DM patients on oral antidiabetic drugs and/or insulin (basal, bolus, or premix) and initiated on IDegAsp and in a subgroup of patients who switched from insulin glargine to IDegAsp. Clinical endpoints were mean change in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and % point in range (PIR) before and after treatment with IDegAsp. Descriptive statistics were applied to analyze the data, and statistical significance was set at P ≤ 0.05. Results: A total of 540 patients with T2DM were initiated on IDegAsp, among which 85 switched from insulin glargine (U100/300) to IDegAsp. In 6 months, overall, the mean change in glycemic variables HbA1c, FPG, and PPG was –0.3%, –21 mg/dL, and –36 mg/dL, and among those who switched from insulin glargine to IDegAsp, it was –0.4%, –18 mg/dL, and –49 mg/dL, respectively, and the difference was statistically significant (P &lt; 0.05). Self-monitored blood glucose, 1 month before and from 4 to 6 months after initiation of IDegAsp was assessed in overall 43 patients. The % PIR before breakfast and before dinner (BBF+BD) was 68% and 69% (95% CI –4.413 to 4.902) respectively. Furthermore, among those who switched from insulin glargine to IDegAsp (n = 25), BBF + BD increased from 67% to 77% (95% CI –10.35 to 10.65). Conclusion: Our results show clinically significant improvements in glycemic variables and PIR in patients treated with IDegAsp and especially in patients who switched from insulin glargine (U100/300) to IDegAsp.

The Effect of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists on the Lipid Profile of Diabetic Patients Using Statins: A Retrospective Cohort Study in the Diabetic Center of King Salman Bin Abdulaziz Hospital, Saudi Arabia.

Background Dyslipidemia is a common complication of type 2 diabetes mellitus (T2DM), which is the leading cause of morbidity and mortality in developed countries, including Saudi Arabia. Injectable glucagon-like peptide-1 receptor agonists (GLP-1RA) are recent therapies found to be effective in treating dyslipidemia in diabetic patients by acting similarly to the body's internal glucagon peptide hormone, regulating blood sugar levels and reducing triglycerides and low-density lipoprotein (LDL) levels. Aim of the study This retrospective cohort study aimed to investigate the effect of GLP-1RA on the lipid profile of dyslipidemia diabetic patients who were not controlled using statins. Methods Data were collected from the medical records of male and female diabetic patients with dyslipidemia (uncontrolled by statins) who were administered to the diabetic center of King Salman Bin Abdulaziz Hospital in Riyadh, Saudi Arabia, and received GLP-1RA (dulaglutide) from June 2023 to August 2023. The primary endpoint was the change in triglycerides and LDL-C levels after three months of using dulaglutide, and the secondary endpoints included the change in body weight, BMI, and HbA1c%. Descriptive analysis was conducted to present numerical and categorical data. The Wilcoxon signed-ranktest was used to compare numerical data before and after using dulaglutide. Ethical considerations were taken into account by ensuring anonymous data collection and obtaining IRB approval before data collection. Results The study included 102 patients with a median (interquartile range (IQR)) age of 59 (14) years. Females constituted 55.2% of the population. Obesity (96.1%), hypertension (71.6%), and retinopathy (13.7%) were the most commonly reported comorbidities. The study showed a significant reduction in body weight, BMI, HbA1c, hemoglobin, mean corpuscular volume (MCV), serum LDL-C, and triglyceride concentrations after three months of using dulaglutide (p<0.001). Conclusion Our study results confirm the positive effect of the GLP-1RA (dulaglutide) on the lipid profile of diabetic patients with dyslipidemia uncontrolled by statins.

Effects of basic carbohydrate counting versus standard dietary care for glycaemic control in type 2 diabetes (The BCC Study): a randomised, controlled trial

BackgroundClinical guidelines recommend basic carbohydrate counting (BCC), or similar methods to improve carbohydrate estimation skills and to strive for higher consistency in carbohydrate intake potentially improving glycaemic control. However, evidence for this approach in type 2 diabetes (T2D) is limited.ObjectiveTo examine the efficacy of a structured education program in BCC as add-on to standard dietary care on glycaemic control in individuals with T2D.MethodsThe BCC Study was a randomized, controlled, open-label, parallel-group trial. Individuals with T2D aged 18-75 years with glycated haemoglobin A1c (HbA1c) 53–97 mmol/mol (7.0–11.0%) were randomly assigned (1:1) to BCC or standard dietary care. The primary outcomes were differences in changes in HbA1c or glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) between groups after six months of intervention.ResultsBetween September 2018 and July 2021, 48 participants were randomly assigned, 23 to BCC and 25 to standard dietary care. Seven participants did not receive the allocated intervention. From a baseline-adjusted mean of 65 mmol/mol (95% CI 62-68 [8.1%, 7.8-8.4]), HbA1c changed by −5 mmol/mol (−8 to −1 [−0.5%, −0.7 to −0.1]) in BCC and -3 mmol/mol (−7 to 1 [−0.3%, −0.6 to 0.1]) in standard care with an estimated treatment effect of −2 mmol/mol (−7 to 4 [−0.2%, −0.6 to 0.4]); p = 0.554. From a baseline-adjusted mean of 4.2 mmol/l (3.7 to 4.8), MAGE changed by −16% (−33 to 5) in BCC and by −3% (−21 to 20) in standard care with an estimated treatment effect of −14% (−36 to 16); p = 0.319. Only median carbohydrate estimation error in favour of BCC (estimated treatment difference −55% (−70 to −32); p < 0.001) remained significant after multiple testing adjustment.ConclusionsNo glycaemic effects were found but incorporating BCC as a supplementary component to standard dietary care led to improved skills in estimating carbohydrate intake among individuals with T2D.