Reduction In HbA1c Research Articles

Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: Results From a Pragmatic Cluster Randomized Controlled Trial.

This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health). A total of 600 adults with type 2 diabetes who met one or more of the following criteria in the last 90 days were enrolled: HbA1c ≥8% and/or LDL cholesterol ≥100 mg/dL and/or systolic blood pressure (SBP) ≥140 mmHg. Participants at MAC clinics received in-person and telephone self-management support from a specially trained MA health coach for 12 months. Electronic medical records were used to examine clinical outcomes in the overall sample. Behavioral and psychosocial outcomes were evaluated in a subsample (n = 300). All clinical outcomes improved significantly over 1 year in the overall sample (P < 0.001). The reduction in HbA1c was significantly greater in the MAC versus UC group (unstandardized Binteraction = -0.06; P = 0.002). A significant time by group by site interaction also showed that MAC resulted in greater improvements in LDL cholesterol than UC at Neighborhood Healthcare relative to Scripps Health (Binteraction = -1.78 vs. 1.49; P < 0.05). No other statistically significant effects were observed. This was the first large-scale pragmatic RCT supporting the real-world effectiveness of MAC for type 2 diabetes in U.S. primary care settings. Findings suggest that this team-based approach may be particularly effective in improving diabetes outcomes in FQHC settings.

Could Online Education Replace Face-to-Face Education in Diabetes? A Systematic Review.

Diabetes Self-Management Education and Support (DSMES) is a critical component of diabetes care. This study aims to examine the effect of online-based educational interventions on diabetes management compared to face-to-face interventions. A systematic review was conducted by searching three databases for studies in English or Spanish between December 2023 and March 2024. The inclusion criteria were studies that compared face-to-face DSMES with online interventions. The follow-up duration of the trials ranged from 1 to 12months. Multidisciplinary teams delivered online DSMES through various means, including Short Message Service (SMS), telephone calls, video calls, websites, and applications. Online DSMES was found to be comparable to face-to-face interventions in terms of glycated hemoglobin (HbA1c) levels in people with type 1 diabetes (T1D). In contrast, online interventions that focus on weight management in people with type 2 diabetes (T2D) have shown a significant reduction in HbA1c compared to face-to-face interventions. Online DSMES was found to be superior in terms of quality of life and cost-effectiveness in both T1D and T2D. None of the analyzed studies explored the differences between individual and group methodologies. The current evidence indicates that online DSMES services provide at least comparable biomedical benefits to face-to-face interventions, suggesting that online interventions could be incorporated into clinical practice as a complement or reinforcement. However, further research is needed to explore the potential benefits and effectiveness of online group sessions in DSMES.

Latest Trends of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-i) for Heart Failure (HF) and Chronic Kidney Disease (CKD)

Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) have been effective for heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes (T2D). Among SGLT2-i, empagliflozin and dapagliflozin were compared for clinical effect, with empagliflozin showing a lower composite of all-cause mortality or hospitalization with a hazard ratio (HR) of 0.90. In the EMPA-ELDERLY clinical trial, empagliflozin demonstrated better HbA1c reduction and weight reduction without affecting muscle strength or mass in elderly patients with T2D. The American College of Physicians (ACP) published “Newer Pharmacologic Treatments in Adults with Type 2 Diabetes” in April 2024. The potential mechanisms for the anti-inflammatory effects of SGLT2-i will be clarified in the future.

Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia.

Diabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices. A multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered. Data from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 ± 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of -1.47% (95% CI -1.76, -1.17), weight loss of -4.23 kg (95% CI -5.34, -3.12), and albumin/creatinine ratio of -18.6 mg/g (95% CI -60.2, -5.9). Approximately half the treated patients achieved a level of HbA1c ≤7% by the end of follow-up. Adverse events were rare and consistent with clinical trial safety profiles. In Colombia, administering semaglutide subcutaneously once a week over a 1-year period led to an average weight loss of 4.2kg and a decrease of 1.4% in HbA1c.

Gut hormone multi-agonists for the treatment of type 2 diabetes and obesity: advances and challenges.

The rapidly rising incidence of obesity, coupled with type 2 diabetes mellitus (T2DM), is a growing concern. Glucagon-like peptide 1 (GLP-1), an endogenous peptide secreted by enteroendocrine L-cells, demonstrates exceptional pharmacological potential for the treatment of T2DM and obesity, primarily through its pivotal roles in regulating glucose homeostasis, stimulating glucose-dependent insulin secretion, and promoting satiety. Considering its proven efficacy in glucoregulation and weight loss, GLP-1 receptor agonists (GLP-1RAs) have emerged as a revolutionary breakthrough in the arena of diabetes management and weight control. Additional gastrointestinal hormones, such as glucose-dependent insulinotropic peptide (GIP) and glucagon, exhibit structural similarities to GLP-1 and work synergistically to lower blood glucose levels or aid in weight loss. Today, various classes of gut hormone receptor multiple agonists are steadily progressing through development and clinical trials, including dual GLP-1/glucagon receptor agonists (first discovered in 2009), dual GLP-1/GIP receptor agonists (first described in 2013), and triple GLP-1/GIP/glucagon receptor agonists (initially designed in 2015). The GLP-1/GIP receptor co-agonist, tirzepatide, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of T2DM, outperforming basal insulin or selective GLP-1RAs by providing superior HbA1c reductions. Remarkably, tirzepatide also facilitated unprecedented weight loss of up to 22.5% in non-diabetic individuals living with obesity. This result is comparable to those achieved with certain types of bariatric surgery. Therefore, the advent of gut hormone multi-agonists signifies the dawn of an exciting new era in peptide-based therapy for obesity and T2DM. This review offers a comprehensive summary of the various types of gut hormone multiple agonists, including their discovery, development, action of mechanisms, and clinical effectiveness. We further delve into potential hurdles, limitations, and prospective advancements in the field.

The efficacy and safety of iGlarLixi versus IDegAsp in Chinese people with type 2 diabetes suboptimally controlled with oral antidiabetic drugs: The Soli-D randomized controlled trial.

To compare the efficacy and safety of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs). In Soli-D, a 24-week, multicentre, open-label, study, insulin-naïve adults were randomized 1:1 to once-daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium-glucose co-transporter-2 inhibitors. The primary endpoint was non-inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed. At week 24, iGlarLixi showed non-inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: -0.20 [95% confidence interval {CI}: -0.33, -0.07]; P < .001 for non-inferiority; [97.5% CI: -0.35, -0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of -1.49 kg in favour of iGlarLixi (97.5% CI: -2.32, -0.66; P < .001). Event rates (per person-year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported. In Chinese people with T2D suboptimally controlled with OADs, once-daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp.

Efficacy and safety of albiglutide, a once-weekly glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes: A systematic review and meta-analysis.

No meta-analysis has holistically analyzed and summarized the therapeutic efficacy and safety of albiglutide in type 2 diabetes (T2D). This meta-analysis addresses this knowledge gap. Randomized controlled trials involving patients with T2D receiving albiglutide in the intervention arm and either a placebo or an active comparator in the control arm were searched through electronic databases. The primary outcome was the change from baseline (CFB) in glycated hemoglobin (HbA1c); secondary outcomes included CFB in fasting plasma glucose, body weight, and adverse events (AE). From 443 initially screened articles, data from 12 randomized controlled trials involving 6423 subjects were analyzed. Albiglutide, at both doses, outperformed placebo in terms of HbA1c reductions (for albiglutide 30 mg: mean differences -1.04%, 95% confidence interval [CI] [-1.37--0.72], P < .00001, I2 = 89%; and for albiglutide 50 mg: mean differences -1.10%, 95% CI [-1.45--0.75], P < .00001, I2 = 90%). Higher proportions of subjects achieved HbA1c < 7% in the albiglutide arm than in placebo (for albiglutide 30 mg: odds ratio 6.26, 95% CI [2.50-15.70], P < .0001, I2 = 82%; and for albiglutide 50 mg: odds ratio 5.57, 95% CI [2.25-13.80], P = .0002, I2 = 84%). Albiglutide had glycemic efficacy comparable to other glucose-lowering drugs. CFB in body weight was similar with albiglutide and placebo. AE profile, including gastrointestinal AE, was identical with albiglutide and placebo, except for higher drug-related AE and injection-site reaction with albiglutide. Albiglutide provides reassuring data on good glycemic efficacy, tolerability, and safety over an extended period of clinical use in patients with T2D. Albiglutide 30 mg has comparable efficacy and safety profiles to albiglutide 50 mg.

Effectiveness of Jena DM® Herbal Formulation as Complementary Therapy to Conventional Oral Hypoglycemic Agents in Type-2 Diabetes Mellitus: A Quasi-experimental Study.

There is vast preclinical evidence that indicates that extracts from several Artemisia plant species have significant antidiabetic benefits. However, clinical evidence is limited to this effect. We sought to evaluate the effectiveness ofJena DM® (anArtemisia annua-based poly-herbal formulation) on glycemic control (Hb A1C) and insulin metabolism (HOMA), when administered as a complementary therapy in type-2 diabetes mellitus (T2DM). This study was supported by a research grant (JRD005) from Jena Herbals (U) Ltd, which is a local herbal medicines manufacturing facility in Uganda. We conducted a 12-week quasi-experimental study, involving 118 patients under routine follow-up at a diabetes and endocrinology clinic. Random assignment to either conventional or experimental study groups was done using a random number generator (Microsoft Excel version 16.0). Participant sociodemographic and clinical data as well as whole blood samples (3-5 mL) were obtained at scheduled clinic visits. Medication adherence was assessed using the Hill-Bone Scale, and adverse drug events (ADEs) using the Naranjo causality and the National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) scales. Group differences in glycemic control (HbA1C), fasting serum insulin (FSI) indices (% HOMA2-B, HOMA-IR), and other cardiometabolic parameters were assessed using independent samples t-test, and Pearson chi-square statistical tests were used. A p-value <0.05 was considered statistically significant. Ethical approvals were obtained before the study commencement. 12-week daily complementary therapy withJena DM® showed no significant effect on Hb A1C reduction (0.1 (95% CI: -0.56, 0.80) %;p=0.798); however, we observed a significant reduction in total body weight (2.0 (95% CI: 0.73, 3.28) kg;p=0.002). The overall frequency of self-reported ADEs including dizziness was significantly higher among patients that usedJena DM® (p=0.001).Epigastric pain was the most severe ADE necessitating clinical management. There was no significant difference in the homeostatic model assessment for insulin resistance (HOMA2-IR) between study groups. In contrast to a few studies that previously showed significanthypoglycemic effects ofArtemisia-basedextracts, this study did not show a statistically significant reduction on HbA1C during a 12-week complementary use ofJena DM® in patients withT2DM. Based on the findings of this study, future research should evaluate the long-term effects ofJena DM® on body weight, overall insulin metabolism, and the subsequent effect on glycemic control in T2DM.

Population-Based Study on the Implementation of Flash Glucose Monitoring and Severe Hypoglycemia in Adults With Type 1 Diabetes.

Objective: We analyzed the effect of implementing a flash glucose monitoring (FGM) technology in a public health care system with universal coverage on the rate of severe hypoglycemia requiring urgent care in adults with type 1 diabetes mellitus (T1DM). Methods: Using a comprehensive regional dataset, we extracted emergency care codes with hypoglycemia in individuals with T1DM who initiated the use of FGM in Andalucia, Spain, from January 1, 2020, to December 31, 2021. Severe hypoglycemia was defined as a confirmed blood glucose <70 mg/dL, which required the urgent dispatch of an emergency medical service (EMS) for onsite management. We compared hypoglycemic events reported in the 12 months before and after the initiation of FGM to determine the population incidence rates. Results: A total of 13,616 participants with a mean age of 43.7 ± 13.5 years were included. The follow-up periods were 23.4 and 24.8 months before and after FGM. There were 969 and 737 cases of hypoglycemia before and after the initiation of FGM. The baseline incidence rate was 358.58 episodes per 10,000 person-years, which decreased to 260.9 at the end of the follow-up (rate-ratio 0.72 [0.66; 0.80]). The reduction in hypoglycemia was significant in individuals aged ≥60 years (rate-ratio 0.40 [0.28; 0.55]) and males (0.64 [0.56; 0.72]). In addition, there was a reduction in the overall median HbA1c of -0.35% (95% CI [-0.38; -0.33], P < 0.001). Conclusion: The implementation of FGM systems in a public health care system as a provision for adults with T1DM was associated with significant reductions in the rate of severe hypoglycemic events that required urgent EMS care.

Efficacy and safety of glucagon-like peptide-1 receptor agonists on prediabetes: a systematic review and meta-analysis of randomized controlled trials

BackgroundPrediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is thought to be lifestyle modification. Pharmacological therapy, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), were not well addressed in the literature and were only evaluated in trials as secondary and exploratory outcomes with a limited sample size. Here, GLP-1RAs are evaluated as a comprehensive therapy approach for patients with prediabetes.MethodsA comprehensive search of Web of Science, SCOPUS, PubMed, and Cochrane was performed on May 5, 2023, to retrieve randomized controlled trials (RCTs) comparing the effect of GLP-1RAs to placebo and/or lifestyle modification on prediabetes reversion to normoglycemia, prevention of overt diabetes, glycemic control, anthropometric parameters, and lipid profiles. Review Manager (RevMan) version 5.4 was used. The quality of RCTs was assessed using the revised version of the Cochrane Risk of Bias Tool. GRADE was performed to evaluate the certainty of evidence.ResultsTwelve trials involving 2903 patients in the GLP-1RAs group and 1413 in the control group were included in the meta-analysis. Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43), P < 0.00001]. Significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL were observed in the GLP-1RAs arm (P < 0.05). However, higher incidences of gastrointestinal disorders were reported in the GLP-1RAs group (P < 0.05).ConclusionsGLP-1RAs combined with lifestyle modification proved to be a more effective therapy for managing prediabetic patients than lifestyle modification alone, with a tolerable safety profile. Future guidelines should consider GLP-1RAs as an adjunct to lifestyle modification in the management of prediabetic patients to provide better management and improve treatment adherence.

929-P: A Study to Evaluate Clinical and Metabolic Profile of Type 2 Diabetes Patients Receiving SGLT2 Inhibitors

Aim: The aim of the study was to determine the efficacy of SGLT2i and its impact on metabolic profile of type 2 diabetes (T2DM) patients with reference to serum glucagon and blood ketones. Methodology: The study was conducted in T2DM patients with inadequate glycemic control on a background therapy of either metformin and sulphonylurea (Group A) or metformin and DPP4 inhibitor(Group B) Blood samples were taken for estimation of fasting plasma glucose (FPG), post prandial plasma glucose (PPPG), HbA1c, beta-hydroxybutyrate (β-HB) and glucagon levels. Empagliflozin 10mg, was added to the existing anti-diabetic medication. The metabolic parameters were reassessed after 12 weeks. Results: At the end of 12 weeks glucagon levels increased significantly (28.8 ± 28.74 at baseline vs 108 ± 74 pg/ml; p&amp;lt;0.001). A significant increase in β-HB levels was also observed (0.1 ± 0.07 mmol/L at baseline versus 0.12 ± 0.07 mmol/L (p=0.03). FPG, PPPG and HbA1c decreased significantly by 30.33mg%, 53.16mg% and 1.05% respectively(p&amp;lt;0.01) In group A, FPG and PPPG decreased by 34.43 mg/dl and 51.71mg/dl respectively (p&amp;lt;0.001) with a mean HbA1c reduction of 1.09% (p&amp;lt;0.001) Serum glucagon and β-HB levels increased significantly [82.63 pg/ml (p&amp;lt;0.001) and 0.04 mmol/L (p&amp;lt;0.01) respectively]. In group B, there was decrease in FPG (mean difference 23.6mg %; p=0.003) and PPPG (mean difference 55.5mg%; p&amp;lt;0.001) at 12 weeks. HbA1c reduction of 0.99% was observed. (p=0.003) There was a significant increase in glucagon levels (mean difference +73.52 pg/ml; p&amp;lt;0.001). Conclusion: Addition of Empagliflozin to T2DM patients with inadequate glycemic control on either metformin and sulphonylurea or metformin and DPP4 inhibitors significantly improved efficacy. Plasma glucagon and β-HB levels increased with chronic empagliflozin treatment suggesting a change in substrate utilization towards fat. Disclosure S. Kandula: None. M.A. Meshram: None. A.C. Sonwane: None.

Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes: A Meta-Analysis.

This study aims to systematically review the efficacy and safety of oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) and provide a basis for the rational use of the drug in clinical practice. From the database's inception until February 2023, a systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Science and Technology Journal Database to identify randomized controlled trials (RCTs) comparing the efficacy of oral semaglutide at dosages of 3, 7, and 14 mg (trial group) against placebo or other positive control drugs (control group) for the treatment of T2DM. Following literature screening and data extraction, the bias risk assessment tool in the Cochrane reviewer handbook 5.1.0 was used to evaluate the literature quality. Meta-analysis was carried out with RevMan 5.4 software. A total of 10 RCTs with 9541 patients were included. The meta-analysis results revealed that compared with placebo or positive control drugs (empagliflozin, sitagliptin, liraglutide, and dulaglutide), oral semaglutide significantly reduced the hemoglobin A1c (HbA1c) in patients (compared to placebo, 3 mg [MD = -0.61%, 95% CI (-0.89, -0.34)], 7 mg [MD = -1.12%, 95% CI (-1.45, -0.79)], 14 mg [MD = -1.08%, 95% CI (-1.32, -0.85)]; compared to positive control drugs (7 mg [MD = -0.26%, 95% CI (-0.38, -0.15)], 14 mg [MD = -0.37%, 95% CI (-0.52, -0.23)]). Oral semaglutide also showed certain advantages over placebo or positive control drugs in terms of weight loss, HbA1c reduction achievement rate, fasting plasma glucose level, and body mass index with overall dose-dependent efficacy. The incidence of nausea, diarrhea, and vomiting caused by oral semaglutide was higher than that of the placebo or positive control drugs, and the incidence of appetite decrease or constipation was higher than that of the placebo. Severe or symptomatic hypoglycemic episodes were reduced compared to positive control drugs. Oral semaglutide has definite clinical benefits of reducing blood glucose, body weight, reducing the risk of hypoglycemia, and with good safety.

Real-World Use of Oral Semaglutide in Adults with Type 2 Diabetes in the PIONEER REAL Netherlands Multicentre, Prospective, Observational Study.

In this phase 4, multicentre, prospective, non-interventional PIONEER REAL Netherlands study, we assessed clinical outcomes associated with once-daily oral semaglutide use in real-world clinical practice in adults living with type 2 diabetes (T2D) naïve to injectable glucose-lowering medication. Participants initiated on oral semaglutide were followed for 34-44weeks. Change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS) was the primary endpoint; secondary endpoints included change in body weight (BW) from BL to EOS, the proportion of participants with HbA1c<7.0% at EOS and the composite endpoints of HbA1c reduction≥1.0%-points with BW reduction≥3% or≥5% at EOS. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ status/change). Safety was evaluated in all participants who initiated oral semaglutide treatment. Oral semaglutide was initiated in 187 participants; 94.1% completed the study and 78.6% remained on treatment at EOS. At BL, 54.0% of participants were male, mean age was 58.8years, mean duration of T2D was 8.7years and mean body mass index was 35.1kg/m2; mean HbA1c was 8.6% and mean BW was 103.1kg. Significant improvements from BL to EOS were observed for HbA1c and BW (estimated change [95% confidence interval]:-1.16%-points [-1.48 to-0.85]; p<0.0001, and-5.84kg [-6.88 to-4.80]; p<0.0001, respectively). At EOS, 47.5% of participants had an HbA1c level<7.0%; 41.8% and 35.5% of participants achieved composite endpoints of HbA1c reduction≥1.0%-points plus BW reduction≥3% or≥5%, respectively. DTSQ status and change scores improved by 2.1 (p=0.0003) and 10.8 points (p<0.0001), respectively. Oral semaglutide was easy or very easy to consume for 81.5% of participants. Adverse events were mostly mild/moderate, with gastrointestinal disorders being the most common. In this real-world population, we reported clinically significant reductions in HbA1c and BW, improved treatment satisfaction and no new safety concerns. A graphical abstract is available with this article. NCT04601740.

Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial.

To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.

Insulin Inertia Among People With Type 2 Diabetes Mellitus in Qatar: The INERT-Q Study.

Achieving and maintaining adequate glycaemic control is critical to reduce diabetes-related complications. Therapeutic inertia is one of the leading causes of suboptimal glycaemic control. To assess the degree of inertia in insulin initiation and intensification in people with Type 2 diabetes mellitus (DM-2). We performed a retrospective longitudinal cohort study and followed DM-2 2 years before and 2 years after the start of insulin. The primary outcome was the proportion of patients who achieved glycaemic targets (HBA1c ≤ 7.5%) at 6th month, 1st year and 2nd year. We included 374 predominantly male subjects (62%). The mean age was 55.3 ± 11.3 years, the mean duration of DM-2 was 12.0 ± 7.3 years, 64.4% were obese, 47.6% had a microvascular disease, and 24.3% had a macrovascular disease. The mean HBA1c at -2nd year and -1st year was 9.2 ± 2.1% and 9.3 ± 2.0%, respectively. The mean HbA1C at the time of insulin initiation was 10.4 ± 2.1%. The mean HBA1c at 6th month, 12th month and 2nd year was 8.5 ± 1.8%, 8.4 ± 1.8% and 8.5 ± 1.7%, respectively. The proportion of subjects who achieved HBA1c targets at 6th month, 12th month and 2nd year was 32.9%, 31.0% and 32.9%, respectively. Multivariate logistic regression analysis showed that achieving HBA1c targets at 6th month and 1st year increases the odds of achieving HBA1c targets at 2nd year (OR 4.87 [2.4-9.6] p < 0.001) and (OR 6.2 [3.2-12.0], p < 0.001), respectively. In people with DM-2, there was an alarming delay in starting and titrating insulin. The reduction in HBA1c plateaued at 6th month. Earlier initiation and intensification of insulin therapy are critical to achieving glycaemic targets. More studies are needed to examine the causes of therapeutic inertia from physicians', patients' and systems' points of view.

Safety and effectiveness of SGLT2 inhibitors in a UK population with type 2 diabetes and aged over 70 years: an instrumental variable approach.

Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in people with type 2 diabetes aged over 70 years using causal analysis. Hospital-linked UK primary care data (Clinical Practice Research Datalink, 2013-2020) were used to compare adverse events and effectiveness in individuals initiating SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Analysis was age-stratified: <70 years (SGLT2i n=66,810, DPP4i n=76,172), ≥70 years (SGLT2i n=10,419, DPP4i n=33,434). Outcomes were assessed using the instrumental variable causal inference method and prescriber preference as the instrument. Risk of diabetic ketoacidosis was increased with SGLT2i in those aged ≥70 (incidence rate ratio compared with DPP4i: 3.82 [95% CI 1.12, 13.03]), but not in those aged <70 (1.12 [0.41, 3.04]). However, incidence rates with SGLT2i in those ≥70 was low (29.6 [29.5, 29.7]) per 10,000 person-years. SGLT2i were associated with similarly increased risk of genital infection in both age groups (incidence rate ratio in those <70: 2.27 [2.03, 2.53]; ≥70: 2.16 [1.77, 2.63]). There was no evidence of an increased risk of volume depletion, poor micturition control, urinary frequency, falls or amputation with SGLT2i in either age group. In those ≥70, HbA1c reduction was similar between SGLT2i and DPP4i (-0.3 mmol/mol [-1.6, 1.1], -0.02% [0.1, 0.1]), but in those <70, SGLT2i were more effective (-4 mmol/mol [4.8, -3.1], -0.4% [-0.4, -0.3]). Causal analysis suggests SGLT2i are effective in adults aged ≥70 years, but increase risk for genital infections and diabetic ketoacidosis. Our study extends RCT evidence to older adults with type 2 diabetes.

Improved HbA1c and body weight in GADA-positive individuals treated with tirzepatide: A post hoc analysis of SURPASS.

People with clinically diagnosed type 2 diabetes (T2D) but positive anti-glutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits. Assess glycated hemoglobin (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive versus GADA-negative participants with clinical T2D diagnosis. Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status. N/A. N = 3791. Tirzepatide (5, 10, 15 mg). Change from baseline in HbA1c at Weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4)by GADA status. In participants with confirmed GADA status, 3671 (96.8%) were GADA-negative and 120 (3.2%) were GADA-positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive versus GADA-negative participants (mean [SD] BMI 32.2 [6.1] versus 33.6 [6.3] kg/m2). At Week 40/42, both groups achieved robust reductions in HbA1c (-2.11% versus -2.32%) and BW (9.2 kg versus -9.6 kg) (p < 0.001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; p = 0.024) and BW reductions did not differ between groups (0.38 kg [-0.99, 1.75]; p = 0.588). In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.

Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled Trials

The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged <18 years. PubMed, Embase, Web of Science, and Cochrane Library were searched for all randomized controlled trials (RCTs) up to August 2023 comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data for meta-analysis. Fourteen RCTs were included in the meta-analysis with a total of 1,262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, p<0.001) than the control group. However, there was no difference in fasting plasma glucose [fasting plasma glucose (FPG); RD=-2.07 mg/dL, p=0.065] between the two groups. Nonetheless, the experimental group that received exenatide showed no significant reduction in HbA1c (p=0.253) and FPG (p=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28 kg, p=0.002) and body mass index (BMI) (RD=-1.63 kg/m2, p=0.002) compared to the control group. The experimental group was given liraglutide (RD=-2.31 kg, p=0.038) or exenatide (RD=-2.70 kg, p<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. However, for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81 kg/m2, p=0.260). For the experimental group using exenatide, BMI declined more significantly in the intervention group than in the control group (RD=-1.14 kg/m2, p<0.001). This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide was better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide was more effective than liraglutide.

A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes

An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) could provide additional benefits to patients with type 2 diabetes. To evaluate the effect of the 5:2 MR on glycemic control among patients with early type 2 diabetes compared with metformin and empagliflozin. The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized, open-label, active parallel-controlled clinical trial conducted between November 13, 2020, and December 29, 2022, in 9 centers across China. A total of 509 eligible patients underwent screening, out of which 405 were randomly assigned to 3 groups and included in the intention-to-treat analysis. Patients were randomly allocated in a 1:1:1 ratio to receive either metformin, empagliflozin, or 5:2 MR. The treatment was 16 weeks, with an 8-week follow-up. The primary end point was the change in hemoglobin A1c (HbA1c) level from baseline to 16 weeks. Secondary end points included changes in body weight, anthropometric measurements, and biochemical parameters. Of the 405 randomized participants (265 men [65.4%]; mean [SD] age, 45.5 [11.0] years; mean [SD] body mass index, 29.5 [4.1]; and mean [SD] HbA1c level, 7.9% [0.6%]), 332 completed the 16-week treatment. From baseline to week 16, participants in the 5:2 MR group showed the greatest reduction in HbA1c (least-squares mean [LSM], -1.9% [SE, 0.2%]), significantly greater than patients receiving metformin (LSM, -1.6% [SE, 0.2%]; adjusted LSM difference, -0.3% [95% CI, -0.4% to -0.1%]) and empagliflozin (LSM, -1.5% [SE, 0.2%]; adjusted LSM difference, -0.4% [95% CI, -0.6% to -0.2%]). At week 16, the mean weight loss in the 5:2 MR group (LSM, -9.7 kg [SE, 2.2 kg]) was greater than that in the metformin group (LSM, -5.5 kg [SE, 2.3 kg]) and empagliflozin group (LSM, -5.8 kg [SE, 2.3 kg]). This randomized clinical trial of Chinese adults with overweight or obesity and with early type 2 diabetes found that 5:2 MR could improve glycemic outcomes and weight loss in the short term compared with metformin or empagliflozin, making it a promising initial intervention and early management for type 2 diabetes. Chinese Clinical Trial Registry Identifier: ChiCTR2000040656.

Application of Mobile Telephony to Improve Medication Adherence in Type 2 Diabetes Patients

Therapeutic failure, poor quality of life and high economic costs have been linked to poor adherence to medication in Type 2 diabetes (T2D) patients. This paper aims to assess patients’ glycemic control, knowledge of T2D and adherence to medications, and evaluate the impact of mobile telephone-based intervention on these indices. A one-year retrospective review of pharmacy refill records was followed by a 6-months’ randomized controlled intervention conducted among 121 T2D patients in a secondary health care facility in Nigeria. Participants were assigned to control (n = 60) and intervention (n = 61) groups. The intervention comprised twice-weekly short message service (SMS) follow-up messaging to the intervention group alongside usual healthcare services. Control group received no SMS. Primary (HbA1c) and secondary (knowledge and adherence) outcome indicators were measured and compared pre- and post-intervention. The same copy of questionnaire was administered at baseline and post-intervention to both groups. Chi-square test was used to examine association of variables while two-sample t-test was conducted to compare mean pre- and post- intervention scores in both groups at p&lt;0.05. The study revealed that intervention significantly improved glycemic control (HbA1c reduction) (p = 0.01). For the control group, mean pre- and post- intervention knowledge scores were 2.798 and 3.118 respectively (t = 1.1368, p = 0.2705) while intervention group recorded 2.714 and 4.193 respectively (t = 5.6772, p&lt;0.001) on a 5-point Likert scale. Pre- and post- intervention adherence scores for control group were 3.804 and 4.013 respectively, (t = 0.2343, p = 0.8182) while intervention group had 3.430 and 6.859 respectively (t = 6.3216, p&gt;0.001) on the 8-point Morisky Medication Adherence Scale (MMAS-8). The study concluded that patients initially had poor glycemic control, fair knowledge of T2D and low adherence to medications. SMS intervention significantly improved all three indices. Policy reforms in healthcare financing is recommended for sustainable provision of mhealth follow-up in diabetes care.