HbA1c kinetics as a prognostic marker of ophthalmic risk in GLP-1 receptor agonist therapy

Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy has been associated with inadequate bowel preparation (IBP) during colonoscopy, but the role of baseline body mass index (BMI) remains unclear. We aim to assess whether baseline BMI modifies the association between GLP-1RA use and bowel preparation adequacy and lesion detection, hypothesizing a BMI-dependent effect modification. We conducted a retrospective cohort study of 51,268 patients (46,883 controls, 4,385 GLP-1RA treated) undergoing colonoscopy. Patients were grouped by BMI category from normal or overweight to class III obesity. Multivariable logistic regression models incorporating treatment × BMI interaction terms were used to formally test for effect modification. Primary outcomes were IBP, adenoma detection, and sessile serrated polyp detection. Analysis was adjusted for age, sex, race, diabetes, and gastrointestinal medications. GLP-1RA use demonstrated significant BMI-dependent effect modification for IBP (global likelihood ratio test P = 0.001). In normal or overweight patients, GLP-1RA therapy was associated with increased odds of IBP (odds ratio 1.66; 95% confidence interval 1.37-2.02; P < 0.001). This effect progressively attenuated with increasing BMI and was negligible in class III obesity. GLP-1RA therapy did not demonstrate an additional adverse impact on adenoma or sessile serrated polyp detection rates compared with patients in similar BMI categories not receiving the therapy. GLP-1RA therapy increased IBP risk primarily in normal and overweight patients, with minimal effect in severe obesity. BMI stratification may inform personalized colonoscopy preparation strategies in GLP-1RA-treated patients.

To compare 1-year changes in estimated 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk following metabolic and bariatric surgery (MBS) versus glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy among adults with obesity. Obesity is a major driver of ASCVD through adverse metabolic and inflammatory pathways. Metabolic and bariatric surgery and GLP-1 receptor agonists represent the most effective contemporary treatments for obesity and are increasingly used to mitigate cardiovascular risk. However, their comparative effects on integrated short-term and lifetime ASCVD risk in real-world clinical practice remain incompletely characterized. We conducted a retrospective cohort study of adults with obesity (body mass index ≥30kg/m²) who underwent MBS or initiated GLP-1RA therapy between 2020 and 2023 within a large tertiary health care system in the United States. Participants were identified from electronic health records and followed for 12 months. Primary outcomes were 1-year changes in estimated 10-year and lifetime ASCVD risk. Secondary outcomes included percent total body weight loss, blood pressure, and lipid parameters. Multivariable linear regression models were used to adjust for baseline body mass index and baseline ASCVD risk. The final cohort included 812 patients, of whom 579 underwent MBS and 233 initiated GLP-1RA therapy. At baseline, patients receiving GLP-1RAs were older and had higher estimated ASCVD risk. At 1 year, reductions in 10-year ASCVD risk were similar between groups (-0.8% vs. -1.1%; P=.36). In contrast, lifetime ASCVD risk decreased significantly more following MBS than GLP-1RA therapy (-8.6% vs. -1.7%; P<.001). MBS was associated with greater percent total body weight loss (-27.8% vs. -11.1%; P<.001) and more favorable lipid changes, including larger reductions in low-density lipoprotein cholesterol and greater increases in high-density lipoprotein cholesterol. After adjustment, MBS remained independently associated with a greater reduction in lifetime ASCVD risk compared with GLP-1RA therapy (β -6.92; 95% CI -9.22 to -4.62). In this real-world cohort, both MBS and GLP-1RA therapy were associated with improvements in estimated cardiovascular risk, but MBS conferred substantially greater reductions in lifetime ASCVD risk, accompanied by superior weight loss and lipid improvements. These findings highlight the complementary roles of surgical and pharmacologic therapies in obesity management and may inform strategies to optimize long-term cardiovascular risk reduction.

Background and aims:Although landmark clinical trials have demonstrated an increased risk for genitourinary infection (GUI) after initiation of sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy that led to an FDA label warning, real world findings have been inconsistent and evidence specifically in older adults is lacking. The objective of the study was to examine the incidence of GUI in patients aged 65 years or older initiated on SGLT2i compared with glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy at a large academic health system.Methods:A retrospective population-based cohort study was conducted using electronic health records of patients aged 65 years and older with a diagnosis of type 2 diabetes mellitus. Patients newly initiated on SGLT2i or GLP1-RA therapy with estimated glomerular filtration rate (eGFR) ⩾30 mL/min per 1.73 m² and active within the health system for at least 1 year prior to initiation were included. We compared the incidence of inpatient, emergency room, or outpatient diagnosis of GUI (bacterial and mycotic) within 6 months of SGLT2i or GLP1-RA initiation. A chi-square or Fisher’s exact test were used to analyze between-group differences for categorical variables, while a t-test was used for continuous variables. A Cox proportional hazards model was used to estimate the impact of confounding variables on the primary outcome.Results:One hundred and thirty-three patients were initiated on SGLT2i therapy and 341 patients newly initiated on GLP1-RA therapy. After adjusting for differences in age, A1c, body mass index, eGFR, race and sex, there was no statistically significant difference in GUI incidence within 6 months of SGLT2i versus GLP1-RA initiation (3.8% versus 6.5%, adjusted hazard ratio: 0.784, 95% confidence interval 0.260–2.367).Conclusion:We found no increased risk of composite GUI within 6 months of initiating SGLT2i compared with GLP1-RA therapy. These real-world data in older adults add to previous findings, which suggest no increased risk of urinary tract infection with SGLT2i initiation.Plain language summaryA class of antidiabetic medications and risk for genitourinary infections in older adults with type 2 diabetesOlder adults with type 2 diabetes often benefit from a class of antidiabetic medications known as sodium-glucose cotransporter-2 inhibitors (SGLT2is) which help to lower blood glucose, decrease risk for cardiovascular disease and prevent kidney disease progression. However, there is concern that these medications may increase risk for urinary tract infections and/or genital fungal infections in older adults based on clinical trial evidence. Our study evaluated the real-world occurrence of these safety events in patients aged 65 years or older who were newly started on these medications. We compared these patients with a group of patients newly started on an alternative class of antidiabetic agents which are not expected to increase risk for infections, known as glucagon-like peptide-1 receptor agonists (GLP1-RA). In our study, we included 133 patients who started an SGLT2i and 341 patients who started a GLP1-RA at a large teaching hospital. We evaluated the occurrence of infection up to 6 months after initiation of these mediations. We found no significant difference in infection rate between these two groups. We conclude in the study that the use of SGLT2i in older adults was not associated with increased risk for urinary tract infections or genital fungal infections when compared with GLP1-RA use.

Idiopathic intracranial hypertension (IIH) is strongly associated with obesity with weight reduction as a central component to management. The relative effectiveness of bariatric surgery (BS) vs glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy remains uncertain. This study aimed to assess the short-term and long-term effectiveness of GLP-1RA therapy vs BS for symptom control in patients with IIH. This multicenter retrospective cohort study used the TriNetX Research Network. Adults aged 18 years or older with IIH and body mass index (BMI) ≥40 who underwent BS or initiated GLP-1RA therapy were included. Propensity score-matched cohorts were created to balance demographics, comorbidities, symptoms, and medication use. The primary outcomes were persistence or recurrence of IIH-related symptoms (headache, papilledema, visual deficits). Secondary outcomes included BMI change, nausea/vomiting, lumbar punctures, cerebrospinal fluid shunting, venous sinus stenting, and use of carbonic anhydrase inhibitors (CAIs) or topiramate. Outcomes were assessed at 3 to 18 months and >18 months postintervention. Among 3185 eligible patients (1982 GLP-1RA; 1203 BS), 946 matched pairs had 3 to 18 months of follow-up and 963 matched pairs had >18 months. At 3 to 18 months, BS achieved greater BMI reduction (mean 35.6 vs 40.5, P < .01) and lower rates of papilledema (hazard ratio [HR]: 4.65 [1.89, 11.43], P < .01), CAI use (HR: 2.86 [1.37, 5.99], P < .01), and topiramate use (HR: 1.71 [1.06, 2.77], P = .02). However, other outcomes were comparable. At >18 months of follow-up, the 2 arms were comparable in time-to-event analyses, although GLP-1RA patients had higher hazards of nausea/vomiting (HR: 1.78 [1.15, 2.77], P = .01) and CAI use (HR: 2.37 [1.09, 5.16], P = .03). BS achieved greater early weight loss and symptom improvement, while GLP-1RA therapy provided comparable outcomes in long-term. BS remains the most effective intervention for rapid benefit, but GLP-1RAs may represent a durable nonsurgical alternative, supporting individualized treatment selection based on comorbidities, preferences, cost, and surgical candidacy.

The use and overall benefit of glucagon-like peptide-1 (GLP-1) receptor agonist therapy for hospitalized patients with type 2 diabetes mellitus (DM) with chronic kidney disease (CKD) has limited data regarding impact and safety. We studied the impact and safety of GLP-1 receptor agonist therapy in hospitalized DM patients with CKD. Retrospective study of 51 patients using either dulaglutide (n = 3) or liraglutide (n = 48). Glomerular filtration rate (GFR) groups of stages 3 to 5 and 1 and 2 were compared. The primary outcome was total amount of insulin within the last 24 hours in the hospital. The secondary outcomes were glucose management and safety. Mean insulin total amount within the last 24 hours in the hospital significantly differed (P = 0.01) between the GFR groups, with the GFR stages 3 to 5 group (mean 0.5, standard deviation 0.36) having a lower mean insulin level than the GFR stages 1 and 2 group (mean 0.8, standard deviation 0.45). Point-of-care glucose reached the target of 140 to 180 mg/dL within the last 24 hours in hospital, with increased odds for the GFR stages 3 to 5 group as compared with the GFR stages 1 and 2 group (odds ratio 4.08, 95% confidence interval 1.05-15.83, P = 0.04). For both GFR groups, there were minimal adverse events. Almost all of them continued GLP-1 receptor agonist therapy at discharge (94.1%). The use of GLP-1 receptor agonist therapy had better outcomes in patients with GFR stages 3 to 5 as compared with GFR stages 1 and 2. There were minimal adverse events reported for both GFR groups. This study suggests that the off-label use of GLP-1 receptor agonists for hospitalized DM patients with CKD may be useful.

Background:The peri-coronary fat attenuation index (FAI) is a novel imaging biomarker of inflammation. This study aimed to investigate the association between combination therapy with sodium–glucose transporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) and coronary artery inflammation, as assessed by the peri-coronary FAI, in patients with type 2 diabetes mellitus (T2DM).Methods:This retrospective analysis included 292 patients with T2DM who underwent coronary computed tomography angiography (CCTA) at Hebei General Hospital. Patients were divided into three groups: (1) non-SGLT-2i/GLP-1RA users (non-users, n = 125): Patients not receiving SGLT-2i or GLP-1RA therapy; (2) SGLT-2i/GLP-1RA monotherapy group (mono-tx, n = 124): Patients treated with either SGLT-2i or GLP-1RA alone; (3) SGLT-2i + GLP-1RA combination therapy group (combo-tx, n = 43): Patients receiving concurrent SGLT-2i and GLP-1RA therapy. Clinical parameters, laboratory biomarkers, and the peri-coronary FAI of patients were collected and comparatively analyzed among the three groups. Finally, multivariate linear regression models were constructed to elucidate the independent association between combined GLP-1RA and SGLT-2i therapy and the peri-coronary FAI.Results:One-way analysis of variance (ANOVA) revealed significant differences in the peri-coronary FAI among the three therapy groups. Specifically, compared with the non-user group, the combo-tx group had significantly lower peri-coronary FAI values in the left circumflex artery (LCX) and left anterior descending artery (LAD). Compared with the mono-tx group, the combo-tx group also had a significantly lower LCX FAI. Multivariate regression analysis further confirmed that combination therapy was independently associated with a lower FAI in the LAD, LCX, and right coronary artery (RCA). Subgroup analysis revealed a significant interaction by sex in the association between treatment regimen and LCX FAI.Conclusion:The combined use of SGLT-2 inhibitors and GLP-1RAs may be associated with a decrease in the peri-coronary FAI in patients with T2DM, suggesting a potential role in reducing coronary inflammation. Thus, this combination therapy might offer advantages over monotherapy.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischemic stroke and examined trends and disparities. Using nationwide Czech registry data (2015-2024), we identified patients with incident nonfatal MI or ischemic stroke and confirmed T2D. GLP-1RA users-initiating therapy within 12 months post-event-were propensity score-matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality. GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126,845 MI survivors, 28,206 had T2D; the matched cohort comprised 2,271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR:0.7; 95%CI:0.52-0.93), all-cause (HR:0.61;95%CI:0.47-0.80) and cardiovascular death (HR:0.54, 95%CI:0.36-0.80). Among 177,115 stroke survivors, 73,750 had T2D; the matched cohort comprised 2,235 patients (385 GLP-1RA; median follow-up 27 months). GLP-1RA use was associated with lower risk of MACE (HR:0.71; 95%CI:0.54-0.94), all-cause (HR:0.59;95%CI:0.46-0.76) and cardiovascular death (HR:0.55; 95%CI:0.37-0.81). GLP-1RA therapy after MI or stroke in T2D was associated with substantially lower risks of MACE, cardiovascular and all-cause death in real-world practice. Utilization remained low, particularly among women and older adults, underscoring the need for broader and more equitable implementation in secondary prevention.

BackgroundRecent large clinical trials have demonstrated cardiovascular benefits of similar overall magnitude for sodium–glucose cotransporter-2 inhibitor (SGLT-2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in subjects with type 2 diabetes. We sought to identify subgroups based on baseline characteristics with a differential response to either SGLT-2i or GLP-1RA.MethodsPubMed, Cochrane CENTRAL, and EMBASE were searched from 2008 to 2022 for SGLT-2i or GLP-1RA randomized trials that reported 3-point major adverse cardiovascular events (3P-MACE). Baseline clinical and biochemical characteristics included age, sex, body mass index (BMI), HbA1c, estimated glomerular filtration rate (eGFR), albuminuria, preexisting cardiovascular disease (CVD), and heart failure (HF). Absolute and relative risk reductions (ARR and RRR) regarding incidence rates for 3P-MACE with a 95% confidence interval were calculated. The association of average baseline characteristics in each study with the ARR and RRR for 3P-MACE was investigated by meta-regression analyses (random-effects model, assuming inter-study heterogeneity). Meta-analysis was also conducted to investigate whether the efficacy of SGLT-2i or GLP-1RA on 3P-MACE reduction could differ according to the patient’s characteristics (e.g., HbA1c above/below cutoff).ResultsAfter a critical assessment of 1,172 articles, 13 cardiovascular outcome trials with a total of 111,565 participants were selected. In meta-regression analysis, the more patients with reduced eGFR in the studies, the greater ARR by SGLT-2i or GLP-1RA therapy. Similarly, in the meta-analysis, SGLT-2i therapy tended to be more effective in reducing 3P-MACE in people with eGFR < 60 ml/min/1.73 m2 than in those with normal renal function (ARR − 0.90 [–1.44 to − 0.37] vs. − 0.17 [–0.34 to − 0.01] events/100 person-years). Furthermore, people with albuminuria tended to respond better to SGLT-2i therapy than those with normoalbuminuria. However, this was not the case for the GLP-1RA treatment. Other factors including age, sex, BMI, HbA1c, and preexisting CVD or HF did not affect the efficacy of either SGLT-2i or GLP-1RA treatment on the ARR or RRR of 3P-MACE.ConclusionsBecause decreased eGFR [significant] and albuminuria [trend] were found to predict a better efficacy for SGLT-2i in 3P-MACE reduction, this class of drug should be preferred in such patients. However, GLP-1RA may be considered for patients with normal eGFR because it showed better efficacy than SGLT-2i in this subgroup [trend].

Greater adherence to medications has been broadly demonstrated to be associated with improved clinical outcomes. However, there is limited real-world evidence on adherence to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes mellitus (T2DM). This retrospective cohort study used United States administrative claims data to compare adherence to GLP-1RAs in T2DM patients initiating exenatide once weekly (QW), exenatide twice daily (BID), or once-daily liraglutide (initiated therapy = index therapy). Patients were included if they had T2DM, were GLP-1RA-naïve, initiated a GLP-1RA from 02/01/2012-01/31/2013 (date of initiation = index), were ≥18 years at index, and had continuous enrollment for 12 months before (baseline) to 6 months after index (follow-up). Study outcome was index GLP-1RA adherence (proportion of days covered [PDC] during follow-up, dichotomized at ≥80% vs. <80%, and at ≥90% vs. <90%). Multivariable logistic regressions compared adherence between the GLP-1RAs, adjusting for potential confounders. Sensitivity analyses were performed separating liraglutide by dose (1.2 mg/1.8 mg). Study sample included 4,041 exenatide QW, 4,586 exenatide BID, and 14,211 liraglutide (6,641 1.2 mg, 7,570 1.8 mg) patients. Median unadjusted PDC values were 0.783 for exenatide QW, 0.500 exenatide BID, 0.722 liraglutide, 0.761 liraglutide 1.2 mg, and 0.683 liraglutide 1.8 mg. Compared with patients treated with either exenatide BID or liraglutide, patients treated with exenatide QW had a statistically significantly greater multivariable-adjusted odds of achieving adherence of ≥80% (odds ratio vs. exenatide QW (OR) = 0.41 for exenatide BID; 0.80, liraglutide; 0.87, liraglutide 1.2 mg; 0.75, liraglutide 1.8 mg) and ≥90% (OR = 0.31 for exenatide BID; 0.60 liraglutide; 0.66 liraglutide 1.2 mg; 0.56 liraglutide 1.8 mg) (all P < 0.001). Patients initiating exenatide QW had significantly higher adjusted odds of adherence compared with patients initiating other GLP-1RAs. Given differences in adherence across the GLP-1RAs, research correlating these factors with clinical and economic outcomes is warranted.

To assess whether clinical characteristics and simple biomarkers of β-cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes. We prospectively studied 620 participants with type 2 diabetes and HbA1c ≥58 mmol/mol (7.5%) commencing GLP-1RA therapy as part of their usual diabetes care and assessed response to therapy over 6 months. We assessed the association between baseline clinical measurements associated with β-cell failure and glycemic response (primary outcome HbA1c change 0-6 months) with change in weight (0-6 months) as a secondary outcome using linear regression and ANOVA with adjustment for baseline HbA1c and cotreatment change. Reduced glycemic response to GLP-1RAs was associated with longer duration of diabetes, insulin cotreatment, lower fasting C-peptide, lower postmeal urine C-peptide-to-creatinine ratio, and positive GAD or IA2 islet autoantibodies (P ≤ 0.01 for all). Participants with positive autoantibodies or severe insulin deficiency (fasting C-peptide ≤0.25 nmol/L) had markedly reduced glycemic response to GLP-1RA therapy (autoantibodies, mean HbA1c change -5.2 vs. -15.2 mmol/mol [-0.5 vs. -1.4%], P = 0.005; C-peptide <0.25 nmol/L, mean change -2.1 vs. -15.3 mmol/mol [-0.2 vs. -1.4%], P = 0.002). These markers were predominantly present in insulin-treated participants and were not associated with weight change. Clinical markers of low β-cell function are associated with reduced glycemic response to GLP-1RA therapy. C-peptide and islet autoantibodies represent potential biomarkers for the stratification of GLP-1RA therapy in insulin-treated diabetes.

Due to the high efficiency of glucagon-like peptide-1 (GLP-1) receptor agonists therapy in only a part of patients, the search for predictors of response to the treatment is a relevant problem. Purpose. The purpose is to compare the efficacy of liraglutide and exenatide therapy in obese patients with type 2 diabetes mellitus (T2DM) and to evaluate the predictors of response to glycated hemoglobin (HbA1c), weight and lipids reduction. Material and methods. The study included 47 patients with type 2 diabetes and obesity who received GLP-1 receptor agonists therapy. 26 patients were treated with liraglutide, 21 patients were treated with exenatide. We measured the parameters of carbohydrate and lipid metabolism, the levels of hormones involved in glucose and lipids metabolism and in appetite regulation. Blood pressure was measured. These parameters were evaluated at baseline and after 24 weeks of treatment. Results. Patients receiving exenatide therapy showed a tendency towards more frequent HbA1c level reduction by 1% or more (60% versus 30.4%, p = 0.07). The effects of liraglutide and exenatide on weight and waist circumference were comparable. When assessing the predictors of response to the therapy, a more pronounced decrease in HbA1c level (by 1% or more) was in the patients with a higher initial HbA1c level (8.7 (8.2; 9.7) versus 8.2 (6.9; 8.7)%, p = 0.04), as well as with a higher initial GLP-1 level (0.12 (0.05; 0.17) versus 0.040 (0.01; 0.09) ng/ml.) A more significant decrease in the triglycerides (TG) level was detected in patients with a higher level of glucose-dependent insulinotropic peptide (GIP) before therapy (409 (316.0; 431.4) pg/ml in patients who reduced TG level by 30% or more and 331.5 (324.9; 367.1) pg/ml in patients with a lower decrease in TG level). Among the studied parameters, no predictors of body mass reduction were revealed. Conclusion. Measurement of HbA1c, GLP-1, GIP level may be useful to predict the efficacy of GLP-1 receptor agonists therapy.

IntroductionOnce-weekly semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog for the treatment of type 2 diabetes (T2D) that has been associated with greater reductions in glycated hemoglobin (HbA1c) and body weight versus GLP-1 receptor agonists dulaglutide, exenatide extended-release (ER), liraglutide and lixisenatide in the SUSTAIN trial program and a network meta-analysis (NMA). The aim of the present study was to assess the long-term cost-effectiveness of semaglutide versus all available GLP-1 receptor agonists in Denmark, using a clinically orientated treatment approach.MethodsOutcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline characteristics and treatment effects were sourced from the corresponding SUSTAIN trials and the NMA. Patients were assumed to initiate GLP-1 receptor agonist therapy and subsequently treatment-intensify according to clinical treatment guidelines, with addition of basal insulin and switching to basal-bolus insulin occurring when HbA1c exceeded recommended targets. Patients were assumed to receive a GLP-1 receptor agonist plus basal insulin therapy once HbA1c levels reached 7.5% and a basal-bolus insulin regimen once HbA1c exceeded 8.0%. Costs were captured in 2017 Danish kroner (DKK), with future costs and outcomes discounted at 3% per annum.ResultsPrimary analyses indicated that semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.11 and 0.34 quality-adjusted life years, respectively, versus dulaglutide, achieved at cost savings of DKK 289 and DKK 13,416, respectively. Supporting analyses indicated that both doses of semaglutide were either cost-effective or dominant versus exenatide ER, liraglutide 1.2 mg and 1.8 mg and lixisenatide.ConclusionSemaglutide represents a cost-effective alternative to other GLP-1 receptor agonist therapies available in Denmark, demonstrating clinical benefits versus dulaglutide, exenatide ER, liraglutide and lixisenatide for the treatment of patients with T2D.FundingNovo Nordisk A/S.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s13300-019-0630-6) contains supplementary material, which is available to authorized users.

Older adults with type 2 diabetes mellitus (T2DM) are at high risk of both cardiovascular complications and cognitive decline, with major implications for independence and self-management. Endothelial dysfunction and impaired angiogenic capacity may play a key role. This study investigated the association between circulating angiogenic T cells (Tang cells) and cognitive function in older adults with T2DM and explored the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. A cross-sectional study was conducted on 154 T2DM patients aged 60-80 years, treated either with GLP-1 receptor agonist (GLP-1RA) plus metformin or metformin alone. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Circulating CD3+CD31+CXCR4+ Tang cells were quantified by flow cytometry. Propensity score matching was applied to control for age, body weight and HbA1c. In the overall cohort, higher Tang cell levels were significantly associated with better cognitive performance (MoCA, r = 0.423; MMSE, r = 0.428; both P < 0.001). After matching, 35 patients in each treatment group were included in the comparative analysis. The GLP-1RA + MET group showed significantly higher circulating Tang cell levels than the MET group, both in absolute counts and as percentage of CD3+ T cells (P < 0.001). Circulating Tang cell levels are positively associated with cognitive function in older adults with T2DM. GLP-1RA therapy is associated with higher Tang cell levels compared with metformin alone, suggesting a potential association with mechanisms related to endothelial repair in diabetes-related cognitive impairment in older age.

BACKGROUND. The search for new effective methods of treatment and prevention of COVID-19 in patients with type 2 diabetes mellitus (T2DM) remains an urgent task for the healthcare system.AIM. To evaluate the efficacy and safety of initiating of glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy in T2DM patients hospitalized with COVID-19.MATERIALS AND METHODS. The inclusion criteria were history of T2DM, BMI&gt; 27 kg/m2, confirmed diagnosis of COVID-19. The intervention group of 53 patients started dulaglutide therapy (1,5 mg once weekly) during the first 24 hours of admission, the control group consisted of 50 patients, who proceeded with glucose-lowering therapy. We evaluated the effect of therapy on carbohydrate metabolism, laboratory and clinical parameters, the outcome of COVID-19 and the safety of therapy (hypoglycemic events, side effects).RESULTS. There were no differences found in the degree of decrease in the level of glycemia in the compared groups: fasting plasma glucose (FPG) on day 7 of hospitalization– 8,2 [6,0;9,8] mmol/L vs 8,1 [6,5;9,8] mmol/L (p=0,935), mean daily glycemia (MDG) — 9,7 [8,3;11,8] mmol/L vs 11,1 [8,7;12,8] mmol/L (p=0,182). Therapy of dulaglutide had a positive effect on inflammatory markers: CRP (15,8 vs 24,4 mg/l, p=0,035), LDH (261,6 vs 326,1 U/l, p=0,016) and the level of lymphocytes (1,2 vs 0,9 x 10*9/L, p=0,049) and on clinical parameters: saturation, the need for oxygen therapy and the risk of severe course according to the NEWS2 scale. The death rate in the group receiving GLP-1RA is 3,5 times lower compared to the control group (5,7% vs 20,0%, p=0,038). The initiation of dulaglutide therapy in patients with T2DM hospitalized with COVID-19 reduced the chance of death and transfer to mechanical ventilation by 4,2 times compared to the control group (OR = 0,24, 95% CI: 0,062–0,931). GLP-1RA therapy in patients with COVID-19 and T2DM is safe in terms of hypoglycemic events and side effects.CONCLUSIONS. The initiation of GLP-1RA therapy leads to a decrease in FPG and MDG, comparable with the control group. The start of GLP-1RA therapy in hospitalized patients with COVID-19 and T2DM reduces the chance of death, favorably affecting on laboratory and clinical parameters.

Background: The potential benefits and risks of combination sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy versus (vs.) monotherapy, remain a subject of debate to reduce metabolic and cardiovascular outcomes in patients with diabetes mellitus. This study aims to systematically review and meta-analyze the available evidence from randomized controlled trials (RCTs). Methods: A comprehensive search identified relevant RCTs comparing combination therapy with SGLT-2i and GLP-1RA to monotherapy or placebo. The primary outcome was the incidence of major adverse cardiovascular events (MACE) (all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and hospitalization for heart failure (hHF)). Secondary outcomes included changes in metabolic parameters and adverse events. Random-effects meta-analysis estimated risk ratios, mean difference, and 95% confidence intervals (CI). Results: The meta-analysis included 11 RCTs with 42,851 participants, of which 2,870 on combination therapy, and the rest on SGLT-2i (37.1%), GLP-1RA (20.1%) monotherapies or placebo (42.8%). Combination therapy had a significantly lower risk of MACE vs. GLP-1RA monotherapy (RR=0.81, 95% CI 0.65;1.00) and placebo (RR=0.73, 95% CI 0.61;0.88). Combination therapy also had a lower risk of hHF vs. GLP-1RA, SGLT-2, and placebo monotherapies (RR=0.37, 95% CI 0.22;0.65), (RR=0.37, 95% CI 0.19;0.75), and (RR=0.43, 95% CI 0.24;0.75), respectively. Combination therapy was showed greater weight loss and HbA1c reduction vs. SGLT-2i monotherapy (MD=-2.03, 95% CI -2.85;-1.21 and MD=-0.74, 95% CI -1.21;-0.27), respectively, while no difference vs. GLP-1RA monotherapy. Incidence of nausea and diarrhea was higher with combination therapy vs. SGLT-2i monotherapy (MD=3.34, 95% CI 1.74;6.43 and MD=1.75, 95% CI 1.10;2.77), respectively. Conclusion: Combination SGLT-2i and GLP-1RA therapy may provide superior cardiovascular, weight, and HbA1c outcomes vs. monotherapy, despite higher gastrointestinal adverse events. These results impact the management of patients with metabolic and cardiovascular diseases, and highlighting the need for further research to optimize combination therapy.