Reduction In HbA1c Research Articles

The effect of vitamin D supplementation on markers of insulin resistance in women with polycystic ovarian syndrome: a systematic review.

Insulin resistance (IR) is a common pathology in women with polycystic ovarian syndrome (PCOS) involved in increased rates of cardiometabolic disease such as diabetes and cardiovascular disease. Low serum vitamin D is often associated with insulin resistance but there is no consensus on whether vitamin D supplementation can ameliorate markers of IR in PCOS. We assessed evidence on the effects of vitamin D supplementation (≥ 1000 IU/day), without the use of additional supplements or other pharmacological treatments known to affect IR, on markers of IR and glycemic control in women with PCOS. A systematic search was conducted using PubMed, Medline and Web of Science databases from January 2000 up to November 2023. Randomized controlled trials that assessed the effects of vitamin D supplementation in women with PCOS, on fasting glucose, fasting insulin, glycated haemoglobin (HbA1c) or homeostatic model assessment for insulin resistance (HOMA-IR) were included. 9 studies were identified. Study populations ranged from 28 to 180 participants, with mean ages ranging from 22 to 30 years. Daily vitamin D doses ranged from 1714-12,000 IU. Of the included studies, 3 reported statistically significant reductions in fasting glucose, 2 reported reductions in fasting insulin, 2 reported reductions in HOMA-IR, none reported reductions in HbA1c and 5 reported no differences in any of the relevant outcomes. In conclusion, in RCTs of vitamin D supplementation in women with PCOS, the majority of studies do not report statistically significant improvements in fasting glucose, fasting insulin, HbA1c or HOMA-IR. However, as a minority of studies report some statistically significant results, further investigation may be warranted. PROSPERO ID: CRD42023486144.

Empagliflozin add‐on therapy is superior to metformin monotherapy in diabetic patients with NAFLD: An open‐label, single‐center, pilot clinical trial

AbstractBackgroundThe prevalence of non‐alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, inflammation, and advanced fibrosis, is high among type‐2 diabetes mellitus (T2DM) patients. Empagliflozin (EMPA), a sodium‐glucose cotransporter‐2 inhibitor, has been well established to improve glycemic status in T2DM. However, evidence of the desirable effects of EMPA, when added to the standard treatment in diabetics with coexisting NAFLD, has yet to be determined.ObjectiveThe main objective of the current study is to explore the benefits of EMPA on hepatic fat content in patients with T2DM and NAFLD, who received metformin (MET) monotherapy.MethodsIn this open‐label clinical trial study, 60 patients with T2DM and NAFLD were assigned to either the MET + EMPA or MET group in an up‐titrated manner for 24 weeks. Anthropometric characteristics, blood glucose indices, lipid profile, liver enzymes, and steatosis grades were measured at baseline and 24 weeks after the intervention.ResultsThe results showed that in patients with a mean age of 53.26 ± 7.64 who received MET+ EMPA, all the parameters had a greater decrease than the MET group. In addition, the reduction of FBS, BS, HbA1C, TG, and ALT had a statistically significant difference between the two groups after 24 weeks follow‐up (p < 0.05). Notably, in the MET+ EMPA group, there was a substantial improvement in steatosis grades based on the fibroscan and ultrasound modality results.ConclusionThe EMPA add‐on therapeutic schedule in uncontrolled T2DM patients with NAFLD significantly ameliorated steatosis stages, liver function, anthropometric features, and biochemical parameters.

The Endogenous Inhibitor of CETP, apoC1, Remains Ineffective In Vivo after Correction of Hyperglycemia in People with Type 1 Diabetes.

ApolipoproteinC1 (apoC1) is the main physiological inhibitor of the cholesterol ester transfer protein (CETP). Increased CETP activity is associated with macrovascular complications in patients with type 1 diabetes (T1D). ApoC1 has lost its ability to inhibit CETP in patients with T1D, and in vitro glycation of apoC1 increases CETP activity, suggesting that hyperglycemia could be a factor implicated in the loss of the inhibitory effect of apoC1 on CETP. Thus, we aimed to see whether improvement of glycemic control might restore apoC1 inhibitory effect on CETP. We studied 98 patients with T1D and HbA1c > 9% at baseline and 3 months after improvement of glycemic control by a medical intervention (insulin introduction or changes in multi-injection therapy or pump therapy introduction/therapeutic education for all patients). CETP activity was assessed by a radioactive method and plasma apoC1 levels were measured by ELISA. The different isoforms of apoC1 were determined by mass spectrometry. CETP activity was not significantly modified after improvement of glycemic control, despite a significant reduction in mean HbA1c (8.7 ± 1.7 vs. 10.8 ± 2, p < 0.0001). No association between plasma apoC1 and CETP activity was observed in patients with T1D at baseline, nor at 3 months, even in the subgroup of patients with optimal control (3-month HbA1c < 7%). We did not find any glycated form of apoC1 using mass spectrometry in people with T1D. Hyperglycemia in vivo does not seem to be a major factor implicated in the loss of apoC1 ability to inhibit CETP activity observed in T1D. Other factors, such as qualitative abnormalities of lipoproteins, could be involved. Our data emphasize the fact that hyperglycemia is not the only factor involved in lipid abnormalities and macrovascular complications in T1D. Clinical trial reg. no. NCT02816099 ClinicalTrials.gov.

Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial

Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes. This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A1c (HbA1c) 7·0-10·0% (53·0-85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. The primary endpoint was the change in HbA1c from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed. Between Aug 12, 2022, and May 7, 2024, of 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA1c decreased from 7·88% (62·66 mmol/mol) at baseline to 7·41% (57·5 mmol/mol) at week 26 with efsitora and from 7·94% (63·3 mmol/mol) at baseline to 7·36% (56·9 mmol/mol) at week 26 with degludec. Mean HbA1c change from baseline to week 26 was -0·51% with efsitora and -0·56% with degludec (estimated treatment difference 0·052%, 95% CI -0·077 to 0·181; p=0·43), confirming a non-inferiority margin of 0·4% for efsitora compared with degludec. Rates of combined level 2 (<54 mg/dL [3·0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14·03 vs 11·59 events per patient year of exposure; estimated rate ratio 1·21, 95% CI 1·04 to 1·41; p=0·016) during weeks 0-52, with the highest rates during weeks 0-12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0-52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group. In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA1c reduction compared with daily insulin degludec. Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycaemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes. Eli Lilly and Company.

Comparative effects of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors on heart failure with preserved ejection fraction in diabetic patients: a meta-analysis

BackgroundHeart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients.MethodsWe conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors’ impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP). ResultsTwelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001).ConclusionsGLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects.

Mindfulness-based group intervention for adolescents with type 1 diabetes: initial findings from a pilot and feasibility randomized controlled trial.

To evaluate feasibility/acceptability of a virtual, group mindfulness-based intervention (MBI) adapted for pediatric type 1 diabetes (T1D). This two-way controlled trial randomized adolescents 1:1 to MBI (n = 20) or health education (HE; n = 22) groups lasting 6-7 weeks. Eligibility included 12-17 years, T1D ≥ 1 year, and elevated scores on PROMIS depression or anxiety measures. Recruitment, retention, and session attendance were tracked to measure feasibility. Acceptability was measured via youth-reported post-session surveys. Adolescents completed depression, anxiety, and diabetes-specific surveys at baseline, immediately post-program, and 3 months post-program completion. HbA1c values approximating these timeframes were obtained from chart review. 55% of screened participants were eligible to participate, and 100% of eligible youth enrolled. There was 93% study retention and 96% session attendance rates. Survey data were 100% complete at baseline, and 93% complete at post-program and 3-month follow-ups; 83% and 78% of MBI participants rated sessions as at least somewhat enjoyable and helpful, respectively, and 91% and 82% of HE participants rated sessions as at least somewhat enjoyable and helpful, respectively. Mean scores showed declines in depression, anxiety, disordered eating, diabetes distress, and HbA1c in both groups across time, with trends toward potential greater reductions in depression and HbA1c in MBI. This pilot provides preliminary evidence that virtual MBI and HE groups adapted for adolescents with T1D are feasible to deliver and acceptable, with potential improvement in psychosocial, behavioral, and diabetes-specific outcomes. Whether MBI is more effective for targeting negative affect and glycemic control in the context of adolescent T1D requires testing in a full-scale efficacy trial.

The impact of time-restricted eating on beta-cell function in adults with type 2 diabetes: a randomized cross-over trial.

Time-restricted eating (TRE) which consists of restricting the eating window to typically 4-8h (while fasting for the remaining hours of the day) has been proposed as a non-pharmacological strategy with cardio-metabolic benefits but little is known about its metabolic impact in type 2 diabetes (T2DM). We evaluated whether TRE can improve pancreatic beta-cell function and metabolic status in overweight individuals with early T2DM. In a randomized cross-over trial, 39 participants [mean 2.9 years of diabetes duration, baseline glycated hemoglobin (HbA1c) 6.6% ± 0.7% and body mass index (BMI) 32.4 ± 5.7 kg/m2] were randomized to either an initial intervention consisting of 6-weeks of TRE (20h-fasting/4h-eating) or standard lifestyle. The primary outcome of beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2) derived from an oral glucose tolerance test. Trial registration: clinicaltrials.gov NCT05717127. As compared to standard lifestyle, TRE induced a 14% increase in ISSI-2 (+14.0 ± 39.2%, p = 0.03) accompanied by 14% reduction of hepatic insulin resistance as evaluated by HOMA-IR [-11.6% (-49.3-21.9), p = 0.03]. Fasting glucose did not differ between interventions, but TRE yielded a significant reduction in HbA1c (-0.32 ± 0.48%, p <0.001). These metabolic improvements were coupled by a reduction of body weight of 3.86% (-3.86 ± 3.1%, p <0.001) and waist circumference of 3.8 cm (-3.8 ± 7.5 cm, p = 0.003). TRE improved beta-cell function and insulin resistance in overweight patients with early diabetes, accompanied by beneficial effects on adiposity.

A comprehensive assessment of the association between common drugs and psychiatric disorders using Mendelian randomization and real-world pharmacovigilance database

Medications prescribed for chronic diseases can lead to short-term neuropsychiatric symptoms, but their long-term effects on brain structures and psychiatric conditions remain unclear. We comprehensively analyzed the FDA Adverse Event Reporting System database and conducted drug target Mendelian Randomization (MR) studies on six categories of common drugs, 477 brain imaging-derived phenotypes (IDPs) and eight psychiatric disorders. Genetic instruments were extracted from expression quantitative trait loci (eQTLs) in blood, brain, and other target tissues, protein quantitative trait loci (pQTLs) in blood, and genome-wide association studies (GWAS) of hemoglobin and cholesterol. Summary statistics for brain IDPs, psychiatric disorders, and gut microbiome were obtained from the BIG40, Psychiatric Genomics Consortium, and MiBioGen. A two-step MR and mediation analysis were employed to screen possible mediators of drug-IDP effects from 119 gut microbiota genera and identify their mediation proportions. Among 19 drug classes, six drugs were found to be associated with higher risks of psychiatric adverse events, while 11 drugs were associated with higher risks of gastrointestinal adverse events in the FAERS analysis. We identified ten drug-psychiatric disorder associations, 202 drug-IDP associations, 16 drug-microbiota associations, and four drug-microbiota-IDP causal links. For example, PPARG activation mediated HbA1c reduction caused a higher risk of bipolar disorder (BD) II. Genetically proxied GLP-1R agonists were significantly associated with an increase in the volume of the CA3-head of the right hippocampus and the area of the left precuneus cortex, both of which have been shown to correlate with cognition in previous studies. Common drugs may affect brain structure and risk of psychiatric disorder. Oral medications in particular may exert some of these effects by influencing gut microbiota. This study calls for greater attention to be paid to the neuropsychiatric adverse effects of drugs and encourages drug repurposing. National Natural Science Foundation of China (grant No. 82330035, 82130043, 82172685, and 82001223), National Natural Science Foundation of Hunan Province (grant No. 2021SK1010), and the Science Foundation for Distinguished Young Scholars of Changsha (grant No. kq2209006).

Machine learning assessment of vildagliptin and linagliptin effectiveness in type 2 diabetes: Predictors of glycemic control.

Differential effects of linagliptin and vildagliptin may help us personalize treatment for Type 2 Diabetes Mellitus (T2DM). The current study compares the effect of these drugs on glycated hemoglobin (HbA1c) in an artificial neural network (ANN) model. Patients with T2DM who received either vildagliptin or linagliptin, with predefined exclusion criteria, qualified for the study. Two input variable datasets were constructed: with or without imputation for missing values. The primary outcome was HbA1c readings between 3 to 12 months or the reduction in HbA1c levels. The cohort comprised 191 individuals (92 vildagliptin and 99 linagliptin). Linagliptin group had significantly higher disease burden. For imputed dataset, HbA1c was lower with linagliptin at 3 to 12 months (7.442 ± 0.408 vs. 7.626 ± 0.408, P < 0.001). However, there was a small yet significant difference in HbA1c reduction favoring vildagliptin over linagliptin (-1.123 ± 0.033 vs. -1.111 ± 0.043, P < 0.001). LDL level, uric acid, and the drug group were identified as predictors for HbA1c levels. In the non-imputed dataset HbA1c at 3 to 12 months was lower with linagliptin (median ± IQR: 7.489 ± 0.467 vs. 7.634 ± 0.467, P-value < 0.001). However, both linagliptin and vildagliptin exhibited similar reductions in HbA1c levels (both median ± IQR of -1.07 ± 0.02). Predictors for HbA1c levels included eGFR level and the drug group. Linagliptin effectively lowers HbA1c levels more than vildagliptin including in patients with comorbidities. DPP4-I choice is a constant predictor of HbA1c in all models.

The Portfolio Diet and HbA1c in Adults Living with Type 2 Diabetes Mellitus: A Patient-Level Pooled Analysis of Two Randomized Dietary Trials.

(1) Background: The Portfolio Diet, a dietary pattern of cholesterol-lowering foods, is also rich in low glycemic index (GI) foods. While strong evidence supports clinically meaningful reductions in cholesterol, evidence on the relationship between the Portfolio Diet and diabetes management is lacking. (2) Objective: To evaluate the relationship between the Portfolio Diet and glycated hemoglobin (HbA1c) as a determinant of glycemic control among adults living with type 2 diabetes mellitus (T2DM). (3) Methods: Patient-level data was pooled from two randomized dietary trials of low glycemic index interventions compared to high cereal fibre control diets in adults living with T2DM where HbA1c was collected (clinicaltrials.gov identifiers: NCT00438698, NCT00438698). Dietary exposure was assessed using weighed 7-day diet records. Adherence to the Portfolio Diet and its pillars (nuts and seeds, plant protein, viscous fibre, plant sterols, monounsaturated fatty acid [MUFA] oils) was determined using the validated clinical Portfolio Diet Score (c-PDS). Multiple linear regression was used to assess the association between change in the c-PDS and change in HbA1c over 6-months with covariate adjustments. (4) Results: A total of 267 participants, predominantly White (67%) and male (63%), were included, with a mean ± standard error age of 62 ± 0.5 years, baseline BMI of 30.2 ± 0.3 kg/m2, HbA1c of 7.08 ± 0.03%, and a c-PDS of 4.1 ± 0.3 points out of 25. Change in the c-PDS was significantly associated with a change in HbA1c (β: -0.04% per point, 95% CI: -0.07, -0.02, p = 0.001). A 7.5-point (30%) increase in the c-PDS was associated with a 0.3% reduction in HbA1c. Of the individual pillars, a 1-point change in nut and seeds intake (β: -0.07%, 95% CI: -0.12, -0.02, p = 0.009) or in plant protein intake (β: -0.11%, 95% CI: -0.18, -0.03, p = 0.009) was associated with a change in HbA1c. Further analysis of plant protein intake revealed that an increase in dietary pulse intake, a particularly low-GI food, was significantly associated with a reduction in HbA1c (β: -0.24% per 1-cup points cooked pulses (226 g) or 2 c-PDS points, 95% CI: -0.45, -0.03, p = 0.028). (5) Conclusions: Among adults living with T2DM, the Portfolio Diet was associated with lower HbA1c over a 6-month period, predominantly driven by two pillars: nuts and seeds and plant protein, particularly dietary pulses. These data have implications for including the Portfolio Diet in dietary recommendations for glycemic control in T2DM. A trial demonstrating the direct causal effect of the Portfolio Diet in a diverse group is warranted.

The effectiveness of telemonitoring and integrated personalized diabetes management in people with insulin-treated type 2 diabetes mellitus.

To evaluate the effectiveness of integrated personalized diabetes management (iPDM) through telemedicine (tele-iPDM) with regard to glycaemic control. A 6-month single-centre, open-label, prospective randomized controlled trial enrolled insulin-treated patients with type 2 diabetes, aged 18-65 years with glycated haemoglobin (HbA1c) levels of 7.5%-10.5%. The tele-iPDM group received insulin adjustment by investigators through a cloud-based telemonitoring platform for 6 months (blood glucose monitoring reviewed weekly from Weeks 0 to 12 and then monthly from Weeks 13 to 24). The control group performed self-monitoring and insulin adjustment. The primary outcome was the difference in HbA1c change from baseline between the two groups at 24 weeks. Secondary outcomes included changes in HbA1c at 12 weeks, fasting plasma glucose, body weight, body mass index (BMI), the percentage of individuals achieving HbA1c <7% at 24 weeks, the percentage of individuals with an HbA1c reduction of >0.5% at 24 weeks, and incidences of hypoglycaemic events. A total of 151 participants were enrolled, with a mean age of 53.36 ± 8.08 years and a mean diabetes duration of 12.38 ± 8.47 years. The baseline HbA1c was 8.47 ± 0.76%. The mean HbA1c decreased from baseline to 12 and 24 weeks in both groups. At 12 weeks, HbA1c reduction from baseline was -1.2% (95%CI -1.42 to -0.98) in the tele-iPDM group and -0.57% (95%CI -0.79 to -0.36) in the control group. The mean difference in HbA1c between the tele-iPDM and usual care groups at 12 weeks was -0.63% (95%CI -0.94 to -0.32; p < 0.001). At 24 weeks, HbA1c reduction from baseline was -1.14% (95%CI -1.38 to -0.89) in the tele-iPDM group and - 0.49% (95%CI -0.73 to -0.25) in the control group. The mean difference in HbA1c between the tele-iPDM and usual care groups was -0.65% (95%CI -0.99 to -0.30; p < 0.001). There were no significant differences in body weight, BMI, or hypoglycaemic events between the two groups. Telemonitoring can support the iPDM care model in individuals with insulin-treated type 2 diabetes. It improves the efficiency of diabetes care, enhances glycaemic control at 12 weeks, and sustains glycaemic control at 24 weeks.

The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response: a retrospective cohort study.

Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 ± 1.8 vs. -2.1 ± 1.9, p-value= 0.934, respectively), and weight (-6.1 ± 5 vs. -6.2 ± 4.4kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses.

Real-world impact of adding a glucagon-like peptide-1 receptor agonist compared with basal insulin on metabolic targets in adults living with type 2 diabetes and chronic kidney disease already treated with a sodium-glucose co-transporter-2 inhibitor: The Impact GLP-1 CKD study.

To compare the effectiveness of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with adding basal insulin among adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) already treated with a sodium-glucose co-transporter-2 inhibitor (SGLT2i) and not reaching their glycaemic control targets. A retrospective analysis of the Canadian LMC Diabetes Registry was conducted. Adults who initiated a GLP-1 RA were matched 1:1 to adults who initiated basal insulin in a T2D and CKD population. Changes in metabolic outcomes were evaluated at 26-52 weeks following the therapy start date. Propensity score matching was used to match participants who initiated a GLP-1 RA to participants who initiated basal insulin (n = 153/cohort). A significantly greater reduction in HbA1c at 26-52 weeks of follow-up was observed in the GLP-1 RA cohort compared with the basal insulin cohort (-1.3% ± 1.4% vs. -1.1% ± 1.4%, P = .03). Weight was significantly reduced (-3.4 ± 3.7 vs. 2.6 ± 4.5 kg, P < .001), and the estimated glomerular filtration rate decline slowed significantly (-0.3 ± 8.2 vs. -2.4 ± 10.4 mL/min/1.73m2, P = .02), but the change in albuminuria was not significantly different (-5.7 ± 38.1 vs. -0.5 ± 38.3 mg/mmol, P = .47) at follow-up in the GLP-1 RA group compared with the basal insulin group. No differences in self-reported hypoglycaemic events per week and therapy discontinuations were reported between the cohorts. The study shows the real-world effectiveness of GLP-1 RA therapy for T2D and CKD. GLP-1 RAs provided superior reductions in HbA1c and weight, and greater kidney protection, compared with basal insulin among adults with T2D and CKD already treated with an SGLT2i.

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.

Health outcomes of telemonitoring of patients with type-2 diabetes mellitus: One-year results from a randomized controlled trial (Optimizing care of Patients via Telemedicine In Monitoring and aUgmenting their control of diabetes Mellitus).

Telehealth increases care accessibility to patients with type-2 diabetes mellitus but the duration of its implementation to sustain optimal glycaemic control remains unclear. This study aimed to assess the health outcomes of these patients using the Optimizing care of Patients via Telemedicine In Monitoring and aUgmenting their control of diabetes Mellitus (OPTIMUM) home tele-monitoring (HTM) system 6 months post-intervention, compared to standard care. An open-labelled randomized controlled trial involving 330 participants with type-2 diabetes mellitus, aged 26-65 years, and suboptimal glycaemic control (HbA1c = 7.5%-10%) was conducted. Intervention group received OPTIMUM HTM for 6 months followed by usual care for another 6 months, while control group received usual care for 12 months. OPTIMUM HTM includes in-app video-based tele-education, tele-monitoring of the blood pressure, capillary glucose and weight via Bluetooth devices and mobile applications, followed by algorithm-based tele-management by the OPTIMUM HTM team. Assessments using self-care inventory scale and medication adherence were administered for both groups at baseline, 6-month, and 12-month timepoints. Complete data from 156 (intervention) and 159 (control) participants, with comparable demographic profiles, were analysed. Both groups showed a significant reduction in HbA1c from baseline (p < 0.001). From 6-month to 12-month time-points, the intervention group was twice as likely to maintain their HbA1c ≤ 8% (adjusted odds ratio = 2.02, 95%CI = 1.18-3.49; p < 0.011). The intervention group demonstrated higher scores for self-care behaviours (adjusted odds ratio = 3.83 [95%CI = 1.68-5.97], p = 0.001) and not skipping medications (adjusted odds ratio = 2.32 [95%CI = 1.09-4.97], p = 0.030) at 12 months. The OPTIMUM HTM system enabled patients to maintain their glycaemic control beyond the intervention period. The favourable outcomes could be the effect of telehealth in sustaining self-care behaviour and medication adherence.

The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis.

The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability. Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis. With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses. Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

Effect of Verapamil on Glycemic Control in Type 2 Diabetic Hypertensive Patients in Saudi Arabia: A Quasi Experimental Study.

Type 2 diabetes is a common chronic disease that continues to increase in prevalence globally and is a major healthcare burden. Diabetes and hypertension frequently occur concurrently, and the use of antihypertensive agents is common in diabetic patients. One antihypertensive agent, verapamil, has tentatively shown potentially positive effects on glycemic control in assorted pre-clinical models. To evaluate the effect of verapamil on glycemic control in hypertensive type 2 diabetic patients. Type 2 diabetic hypertensive patients were recruited from King Fahad Medical City, Riyadh, KSA, to receive oral verapamil therapy. Blood pressure and glycometabolic parameters, including fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), C-peptide, and homeostatic model assessment insulin resistance (HOMA-IR), were monitored at baseline and after 6 months of verapamil therapy. Thirty-five patients (16 male, 19 female) with a mean age of 57.2 years were recruited. The use of verapamil was associated with non-significant decreases in HbA1c, FPG, C-peptide, and HOMA-IR. However, a sub-group of 17 participants showed a decrease in HbA1c that was ≥0.5%. Univariate logistic regression showed that baseline BMI, HOMA-IR, and C-peptide were significantly (P < 0.05) associated with HbA1c reductions of ≥0.5%. Verapamil is metabolically neutral and allows the stabilization of glycometabolic parameters in type 2 diabetic individuals. Additional research exploring the mechanism behind the variable response to verapamil therapy is warranted.

Effectiveness of shared decision-making for glycaemic control among type 2 diabetes mellitus adult patients: A systematic review and meta-analysis.

In diabetes care and management guidelines, shared decision-making (SDM) implementation is explicitly recommended to help patients and health care providers to make informed shared decisions that enable informed choices and the selection of treatments. Despite widespread calls for SDM to be embedded in health care, there is little evidence to support SDM in the management and care of diabetes. It is still not commonly utilized in routine care settings because its effects remain poorly understood. Hence, the current systematic review and meta-analysis aimed to evaluate the effectiveness of SDM for glycaemic control among type 2 diabetes adult patients. Literature sources were searched in MEDLINE, PubMed, Cochrane library and HINARI bibliographic databases and Google Scholar. When these records were searched and reviewed, the PICO criteria (P: population, I: intervention, C: comparator, and O: outcome) were applied. The extracted data was exported to RevMan software version 5.4 and STATA 17 for further analysis. The mean differences (MD) of glycated hemoglobin (HbA1c) were pooled using a random effect model (REM), and sub-group analysis were performed to evaluate the effect size differences across the duration of the follow-up period, modes of intervention, and baseline glycated hemoglobin level of patient groups. The sensitivity analysis was performed using a leave-one-out meta-analysis to quantify the impact of each study on the overall effect size in mean difference HbA1c%. Finally, the statistically significant MD of HbA1c% between the intervention groups engaged in SDM and control groups received usual care was declared at P ˂0.05, using a 95% confidence interval (CI). In the database search, 425 records were retrieved, with only 17 RCT studies fulfilling the inclusion criteria and were included in the meta-analysis. A total of 5416 subjects were included, out of which 2782(51.4%) were included in trial arms receiving SDM and 2634(48.6%) were included in usual diabetes care. The Higgins (I2) test statistics were calculated to be 59.1%, P = 0.002, indicating statistically significant heterogeneity was observed among the included studies, and REM was used as a remedial to estimate the pooled MD of HbA1c% level between patients who participated in SDM and received usual care. As a result, the pooled MD showed that the SDM significantly lowered HbA1c by 0.14% compared to the usual care (95% CI = [-0.26, -0.02], P = 0.02). SDM significantly decreased the level of HbA1c by 0.14% (95% CI = -0.28, -0.01, P = 0.00) when shared decisions were made in person or face-to-face at the point of care, but there was no statistically significant reduction in HbA1c levels when patients were engaged in online SDM. In patients with poorly controlled glycaemic level (≥ 8%), SDM significantly reduced level of HbA1c by 0.13%, 95% CI = [-0.29, -0.03], P = 0.00. However, significant reduction in HbA1c was not observed in patients with ˂ 8%, HbA1c baseline level. Overall, statistically significant reduction of glycated hemoglobin level was observed among T2DM adult patients who participated in shared decision-making compared to those patients who received diabetes usual care that could lead to improved long-term health outcomes, reducing the risk of diabetes-related complications. Therefore, we strongly suggest that health care providers and policy-makers should integrate SDM into diabetes health care and management, and further study should focus on the level of patients' empowerment, health literacy, and standardization of decision supporting tools to evaluate the effectiveness of SDM in diabetes patients.

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.