Clinical evolution of patients with AF and diabetes mellitus in the COVID-19 pandemic. REFADI Registry

Introduction and objectives: To analyze the evolution of patients with atrial fibrillation (AF) and diabetes in the mid-term follow-up during the COVID-19 pandemic and to describe its impact on this population. Method(s): Multicenter and prospective registry that included patients with AF and diabetes attended in cardiology clinics. A multivariate analysis was performed to determine the variables associated with the occurrence of clinical events and mortality. Recruitment was performed in February-December 2019. Result(s): The evolution of 633 patients, 96,2% of those included in the REFADI registry with a median follow-up of 835 days was analyzed (mean age 73.8 +/- 8.5 years, 54.3% male, CHA2DS2-VASc 4,34 +/- 1,4, HAS-BLED 2,47 +/- 0,96) were analyzed. The proportion of anticoagulated patients remained constant (95.6% vs 94.5%;P = .24). There was a decrease in the prescription of vitamin K antagonists (from 31.4% to 19.7%;P < .01), and an increase in the use of direct anticoagulants (from 62.0% to 70.3%;P < .01). During the follow-up there was an increase in the prescription of SGLT2 inhibitors (from 20.0% to 25.5%;P < .01) and GLP1 agonists (from 4.2% to 9.1%;P < .01). During this period, 17.2% of patients died, the majority from cardiovascular causes, 6.4% from COVID-19, 2.8% from stroke, and 1.8% from hemorrhage. Older age, lower ejection fraction, lower hemoglobin levels, and especially lower direct anticoagulants prescription were associated with mortality. Conclusion(s): Patients with AF and diabetes have a high thromboembolic risk and a high risk of developing complications, especially of cardiovascular origin.Copyright © 2023 Sociedad Espanola de Cardiologia

Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach.

In Covid-19, variations in fasting blood glucose are considered a distinct risk element for a bad prognosis and outcome in Covid-19 patients. Tirazepatide (TZT), a dual glucagon-like peptide-1 (GLP-1)and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist may be effective in managing Covid-19-induced hyperglycemia in diabetic and non-diabetic patients. The beneficial effect of TZT in T2DM and obesity is related to direct activation of GIP and GLP-1 receptors with subsequent improvement of insulin sensitivity and reduction of body weight. TZT improves endothelial dysfunction (ED) and associated inflammatory changes through modulation of glucose homeostasis, insulin sensitivity, and pro-inflammatory biomarkers release. TZT, through activation of the GLP-1 receptor, may produce beneficial effects against Covid-19 severity since GLP-1 receptor agonists (GLP-1RAs) have anti-inflammatory and pulmoprotective implications in Covid-19. Therefore, GLP-1RAs could effectively treat severely affected Covid-19 diabetic and non-diabetic patients. Notably, using GLP-1RAs in T2DM patients prevents glucose variability, a common finding in Covid-19 patients. Therefore, GLP-1RAs like TZT could be a therapeutic strategy in T2DM patients with Covid-19 to prevent glucose variability-induced complications. In Covid-19, the inflammatory signaling pathways are highly activated, resulting in hyperinflammation. GLP-1RAs reduce inflammatory biomarkers like IL-6, CRP, and ferritin in Covid-19 patients. Therefore, GLP-1RAs like TZ may be effective in Covid-19 patients by reducing the inflammatory burden. The anti-obesogenic effect of TZT may reduce Covid-19 severity by ameliorating body weight and adiposity. Furthermore, Covid-19 may induce substantial alterations in gut microbiota. GLP-1RA preserves gut microbiota and prevents intestinal dysbiosis. Herein, TZT, like other GLP-1RA, may attenuate Covid-19-induced gut microbiota alterations and, by this mechanism, may mitigate intestinal inflammation and systemic complications in Covid-19 patients with either T2DM or obesity. As opposed to that, glucose-dependent insulinotropic polypeptide (GIP) was reduced in obese and T2DM patients. However, activation of GIP-1R by TZT in T2DM patients improves glucose homeostasis. Thus, TZT, through activation of both GIP and GLP-1, may reduce obesity-mediated inflammation. In Covid-19, GIP response to the meal is impaired, leading to postprandial hyperglycemia and abnormal glucose homeostasis. Therefore, using TZT in severely affected Covid-19 patients may prevent the development of glucose variability and hyperglycemia-induced oxidative stress. Moreover, exaggerated inflammatory disorders in Covid-19 due to the release of pro-inflammatory cytokines like IL-1ß, IL-6, and TNF-α may lead to systemic inflammation and cytokine storm development. Besides, GIP-1 inhibits expression of IL-1ß, IL-6, MCP-1, chemokines and TNF-α. Therefore, using GIP-1RA like TZT may inhibit the onset of inflammatory disorders in severely affected Covid-19 patients. In conclusion, TZT, through activation of GLP-1 and GIP receptors, may prevent SARS-CoV-2-induced hyperinflammation and glucose variability in diabetic and non-diabetic patients.

Association between use of novel glucose-lowering drugs and COVID-19 hospitalization and death in patients with type 2 diabetes: a nationwide registry analysis.

AIMS: Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. METHODS AND RESULTS: Patients with T2DM registered in the Swedish National Patient Registry and alive on 1st February 2020 were included. "Incident severe COVID-19" was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA and DPP-4i to analyze the associations between their use and I) incident severe COVID-19, II) risk of 30-day mortality in patients hospitalized for COVID-19.Among 344,413 patients, 39,172 (11%) were treated with SGLT2i, 34,290 (10%) with GLP-1 RA and 53,044 (15%) with DPP-4i; 9,538 (2.8%) had incident severe COVID-19 by 15th May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i were also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA. CONCLUSION: SGLT2i and DPP-4i use was associated with higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA.

Obesity and COVID-19: insights from two pandemics.

This review article discusses the pathophysiological mechanisms of the development of coronavirus infection in obese patients. It has been shown that obesity is considered as the most important risk factor for the development of many comorbid diseases, including severe forms and deaths as a result of a new coronavirus infection. The higher incidence and severity of a new coronavirus infection in obese patients is based on a complex of factors, the main of which are an increase in cardiovascular risk, including a tendency to thrombosis, a decrease in the efficiency of the respiratory system, impaired immune response, and the presence of chronic inflammatory state. The article discusses non-drug approaches and issues of pharmacological therapy in patients with obesity in the context of a pandemic of a new coronavirus infection. It is shown that the implementation of national quarantine measures has led to an increase in physical inactivity, the level of stress and a change in the eating behavior of the population, closing a vicious circle and contributing to an increase in body weight. For this reason, the efforts of physicians of therapeutic specialties should be directed primarily to increasing resistance to infection among obese patients and combating physical inactivity. The main groups of drugs that can be used to combat lipotoxicity are listed. It was noted that infectious disease doctors and endocrinologists can use those groups of drugs that affect the most vulnerable pathogenetic triggers for the development of obesity and comorbidities: hunger and satiety processes, decreased insulin sensitivity, development of lipotoxicity and chronic inflammation. It has been proven that the range of positive effects of new antihyperglycemic drugs from the groups of type 1 glucagon-like peptide agonists and type 2 sodium-glucose transporter inhibitors, combined with a well-studied efficacy and safety profile, represents a new opportunity for the treatment of obesity in the context of a coronavirus infection pandemic.Copyright © 2022 Authors. All rights reserved.

Top 20 Research Studies of 2021 for Primary Care Physicians

This article summarizes the top 20 research studies of 2021 identified as POEMs (patient-oriented evidence that matters) that did not address the COVID-19 pandemic. Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prevent adverse cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and also reduce all-cause and cardiovascular mortality. Most older adults (mean age, 75 years) with prediabetes do not progress to diabetes. Among patients in this age group with type 2 diabetes treated with medication, an A1C level of less than 7% is associated with increased risk of hospitalization for hypoglycemia, especially when using a sulfonylurea or insulin. For patients with chronic low back pain, exercise, nonsteroidal anti-inflammatory drugs, duloxetine, and opioids were shown to be more effective than control in achieving a 30% reduction in pain, but self-discontinuation of duloxetine and opioids was common. There is no clinically important difference between muscle relaxants and placebo in the treatment of nonspecific low back pain. In patients with chronic pain, low- to moderate-quality evidence supports exercise, yoga, massage, and mindfulness-based stress reduction. For acute musculoskeletal pain, acetaminophen, 1,000 mg, plus ibuprofen, 400 mg, without an opioid is a good option. Regarding screening for colorectal cancer, trial evidence supports performing fecal immunochemical testing every other year. For chronic constipation, evidence supports polyethylene glycol, senna, fiber supplements, magnesium-based products, and fruit-based products. The following abdominal symptoms carry a greater than 3% risk of cancer or inflammatory bowel disease: dysphagia or change in bowel habits in men;rectal bleeding in women;and abdominal pain, change in bowel habits, or dyspepsia in men and women older than 60 years. For secondary prevention in those with established arteriosclerotic cardiovascular disease, 81 mg of aspirin daily appears to be effective. The Framingham Risk Score and the Pooled Cohort Equations both overestimate the risk of cardiovascular events. Over 12 years, no association between egg consumption and cardiovascular events was demonstrated. Gabapentin, pregabalin, duloxetine, and venlafaxine provide clinically meaningful improvements in chronic neuropathic pain. In patients with moderate to severe depression, initial titration above the minimum starting dose of antidepressants in the first eight weeks of treatment is not more likely to increase response. In adults with iron deficiency anemia, adding vitamin C to oral iron has no effect. In children with pharyngitis, rhinosinusitis, acute bronchitis, or acute otitis media, providing education combined with a take-and-hold antibiotic prescription results in 1 in 4 of those children eventually taking an antibiotic.Copyright © 2022 American Academy of Family Physicians.

Dipeptidyl Peptidase-4 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, and Sodium-Glucose Cotransporter-2 Inhibitors and COVID-19 Outcomes.

PURPOSE: It has been reported that dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have a role in modulation of inflammation associated with coronavirus disease 2019 (COVID-19). This study assessed the effect of these drug classes on COVID-19-related outcomes. METHODS: Using a COVID-19 linkable administrative database, we selected patients aged ≥40 years with at least 2 prescriptions of DPP-4i, GLP-1 RA, or SGLT-2i or any other antihyperglycemic drug and a diagnosis of COVID-19 from February 15, 2020, to March 15, 2021. Adjusted odds ratios (ORs) with 95% CIs were used to calculate the association between treatments and all-cause and in-hospital mortality and COVID-19-related hospitalization. A sensitivity analysis was performed by using inverse probability treatment weighting. FINDINGS: Overall, 32,853 subjects were included in the analysis. Multivariable models showed a reduction of the risk for COVID-19 outcomes for users of DPP-4i, GLP-1 RA, and SGLT-2i compared with nonusers, although statistical significance was reached only in DPP-4i users for total mortality (OR, 0.89; 95% CI, 0.82-0.97). The sensitivity analysis confirmed the main results reaching a significant reduction for hospital admission in GLP-1 RA users and in-hospital mortality in SGLT-2i users compared with nonusers. IMPLICATIONS: This study found a beneficial effect in the risk reduction of COVID-19 total mortality in DPP-4i users compared with nonusers. A positive trend was also observed in users of GLP-1 RA and SGLT-2i compared with nonusers. Randomized clinical trials are needed to confirm the effect of these drug classes as potential therapy for the treatment of COVID-19.

Role of Glucagon-like Peptide-1 (GLP-1) Agonists in the Management of Diabetic Patients with or without COVID-19

Glucagon-like peptide 1 (GLP-1) is a gut-derived hormone released after a meal, which alleviates hyperglycemia, increases beta-cell survival, reduces body weight, and reduces inflammation. These thrilling effects motivated clinical studies to discover the potential use of GLP-1 receptor agonists (GLP-1 RAs) in the management of T2D. GLP-1 RAs are potential anti-diabetic agents that can reduce blood pressure, glucose levels, HbA1c and, weight loss without hypoglycemia risk. This manuscript reviews the importance of GLP-1 RAs and their role in the management of T2D with or without COVID-19 infection. Hence, this manuscript can help physicians and researchers to choose the most appropriate drugs for the individualized treatment of subjects. Copyright © 2022 Mirzaei et al.

Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19.

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.

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Quicker administration may not increase use of antimicrobals... Update on cancer, cytokines, and COVID-19 vaccines... Dulaglutide efficacious in pediatric patients with type 2 diabetes... AMVUTTRA approved by FDA for polyneuropathy... Global society announces support for new bill for insulin access... [ FROM AUTHOR] Copyright of Nursing is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Tirzepatide (Mounjaro) for Type 2 Diabetes

The FDA has approved tirzepatide (Mounjaro - Lilly), a peptide hormone with activity at both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, to improve glycemic control in adults with type 2 diabetes. Tirzepatide, which is injected subcutaneously once weekly, is the fi rst dual GIP/GLP-1 receptor agonist to become available in the US. Selective GIP receptor agonists are not available in the US;GLP-1 receptor agonists have been available for years. Copyright © 2022, Medical Letter Inc.. All rights reserved.

Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes: Protocol for a Kidney End Points Real-world Study (COMBi-KID Study).

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are both considered to be part of standard care in the management of glycemia in type 2 diabetes. Recent trial evidence has indicated benefits on primary kidney end points for individual drugs within each medication class. Despite the potential benefits of combining SGLT2is and GLP-1RAs for glycemia management, according to national and international guideline recommendations, there is currently limited data on kidney end points for this drug combination. OBJECTIVE: The aims of the study are to assess the real-world effects of combination SGLT2i and GLP-1RA therapies for diabetes management on kidney end points, glycemic control, and weight in people with type 2 diabetes who are being treated with renin-angiotensin system blockade medication. METHODS: This retrospective cohort study will use the electronic health records of people with type 2 diabetes that are registered with general practices covering over 15 million people in England and Wales and are included in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network. A propensity score-matched cohort of prevalent new users of SGLT2is and GLP-1RAs and those who have been prescribed SGLT2is and GLP-1RAs in combination will be identified. They will be matched based on drug histories, comorbidities, and demographics. A repeated-measures, multilevel, linear regression analysis will be performed to compare the mean change (from baseline) in estimated glomerular filtration rate at 12 and 24 months between those who switched to combined therapy and those continuing monotherapy with an SGLT2i or GLP-1RA. The secondary end points will be albuminuria, serum creatinine level, glycated hemoglobin level, and BMI. These will also be assessed for change at the 12- and 24-month follow-ups. RESULTS: The study is due to commence in March 2022 and is expected to be complete by September 2022. CONCLUSIONS: Our study will be the first to assess the impact of combination SGLT2i and GLP-1RA therapy in type 2 diabetes on primary kidney end points from a real-world perspective. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/34206.

REGULATION OF INTESTINAL ACE2 EXPRESSION BY THE BILE ACID RECEPTOR GPBAR1 IS MEDIATED BY A GPBAR1/GLP-1/GLP-1R AXIS

Background: ACE2 is a carboxypeptidase homolog to the dipeptidase ACE but with different substrate specificity;while ACE principally acts as a carboxydipeptidase (peptidyldipeptidase) removing the C-terminal dipeptide from Ang I to form Ang II, ACE2 functions exclusively as a carboxypeptidase removing a single C-terminal amino acid from Ang II generating Ang- (1-7) or, much less efficiently, from Ang I forming Ang-(1-9). ACE and ACE2 than playing a key role in regulating the renin–angiotensin–aldosterone system (RAAS). In the normal lung, ACE2 mRNA is mainly expressed by type II alveolar epithelial cells and endothelial cells, but the level of expression increases in response to inflammation while is downregulated in response to SARS-CoV infection. ACE2, mRNA and protein, is highly expressed in the gastrointestinal tract, with the higher expression detected in epithelial cells of the ileum and the colon where mediates the absorption of amino acids. ACE2 expression in the intestine undergoes regulation in response to a variety of factors including intestinal microbiota and inflammation. Furthermore, previous studies have suggested that insulinotropic factor glucagon like peptide (GLP)-1 might regulate ACE2 expression in the heart, suggesting a potential interaction of GLP1 with ACE2. GPBAR1, G Protein Bile Acid Receptor, is robustly expressed in the gastrointestinal tract and its activation in the intestine promotes the release of GLP-1. Aim: to investigate the possible interaction between bile acids via GPBAR1 and the expression of ACE2 in the gastrointestinal tract. Materials and Methods: HT29 cells treated with TNF-α + IL-1β and mouse models of colitis were used to assess ACE2 expression and treatment with BAR501, a GPBAR1 agonist, was used to investigate its modulation. Results: The inflammatory stimulus increased the expression of Ace2 in HT29 cells and in colon of mice according to the data obtained in human samples from patient with IBD. GPBAR1 agonism by BAR501 relieved inflammation both in vitro and in vivo but in vitro this effect induced down-regulation of ACE2 while in vivo administration of BAR501 increased ACE2 expression. In mouse model of colitis, inflammation up-regulated also the GLP-1 gene expression that was further increased by BAR501 and instead, the administration of Exendina- 3, a GLP-1R antagonist was able to block the up-regulation of Ace2 expression exerted by BAR501. Conclusions: In conclusion, our results demonstrate that both in vivo and in vitro activation of GPBAR1 by a selective agonist exerts an anti-inflammatory effect. On the other hand, in vivo activation of GPBAR1 in the colon induces the release of GLP-1, which mediates some of the anti-inflammatory effects exerted by the receptor, and induces further upregulation of Ace2 by GPBAR1/GLP-1/GLP-1R axis.(Figure Presented)

COVID-19 Outcomes in Patients Who Started GLP1-RAs during Hospitalization

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been hypothesized to exert beneficial effects on COVID-19 outcomes due to their anti-inflammatory properties. In our COVID-19 ward, patients admitted for severe interstitial bilateral pneumonia due to SARS-COV2 infection and having type 2 diabetes (T2D) or in-hospital hyperglycemia (IHH) were treated with GLP-1 RAs in addition to standard therapy according to usual care. Aim of the present study was to evaluate if GLP-1 RAs therapy was related with outcomes. A retrospective analysis was performed to assess if the GLP1-RAs were associated with a lower risk of a composite outcome (death or admission to intensive care unit) . During the COVID-19 pandemics, 135 patients were admitted (61.5% men, age 66.3±13.7 years, 49.6% with T2D and 50.4% with IHH) , of whom 23.1% initiated GLP1-RA during the hospitalization (39.1% of patients with T2D and 7.6% of patients with IHH) . Almost all patients were treated with once-weekly subcutaneous semaglutide, while dulaglutide was administered in 2 cases. Overall, 26.3% of patients not treated vs. 7.1% of patients treated with GLP1-RAs reached the composite outcome (p=0.03) . At multivariate analysis adjusted for age, gender, T2D, history of cardio/cerebrovascular disease, hypertension, pulmonary disease, and dementia, the use of GLP-1 RAs was associated with a reduced risk of composite outcome of 80% (OR 0.20;95% confidence intervals 0.04-0.95) . Dementia resulted the only other independent correlate of the outcome. These preliminary results suggest that the addition of GLP1-RAs to standard care during hospitalization for SARS-CoV2 infection could play a role in improving clinical outcomes in patients with COVID-19 and T2D or IHH: at the best of our knowledge this is the first study showing such an effect when GLP1-RAs were started during hospitalization.

Efficacy of subcutaneous semaglutide compared to placebo for weight loss in obese, non-diabetic adults: a systematic review & meta-analysis.

BACKGROUND: Research on semaglutide's effect on weight loss has been largely focused on Type 2 Diabetics. No meta-analyses of semaglutide's efficacy in non-diabetic individuals have been conducted to date. Expanding the knowledge of semaglutide's outcome in non-diabetics may provide impactful changes at the clinical level. AIM: This systematic review and meta-analysis quantified the efficacy of subcutaneous semaglutide in treating obesity in non-diabetic adult patients compared to placebo. METHOD: Academic Search Premier, Cumulative Index to Nursing and Allied Health Literature (CINAHL) complete, MEDLINE with Full Text, Cochrane Central Register of Controlled Trials, medrxiv.org, and clinicaltrials.gov were systematically investigated using a predetermined search strategy from inception to August 21, 2021. Covidence.org was used to screen, select, and extract data by two independent reviewers. Individual study bias was assessed using the Cochrane Risk of Bias 2 tool. Data were exported to RevMan v5.4, where meta-analysis was conducted using a DerSimonian and Laird random-effects model. RESULTS: The initial search identified 332 relevant articles and ultimately retained four randomized controlled trials encompassing 2,882 participants with a BMI ≥ 27 kg/m2. Patients treated with semaglutide experienced a clinically significant reduction in mean body weight - 11.62 kg (95% CI: -13.03 to -10.21; P < 0.00001). CONCLUSION: This systematic review and meta-analysis validates the clinical efficacy of semaglutide for the treatment of obesity in the adult, non-diabetic population.

Heart failure in type 2 diabetes: results of a non-interventional cross-sectional study in Romania (FIND)

Background: Heart failure (HF) is a frequent comorbidity in type 2 diabetes (T2D) patients. Limited data on the prevalence of HF in T2D in Romanian clinical practice exist. Aim: This study addressed this knowledge gap by collecting recent information about HF prevalence in T2D. Method: FIND was a cross-sectional, observational study conducted in two large diabetes outpatient clinics from January to May 2020. Consecutive adult patients with T2D were enrolled upon expressing the written consent. Clinical data related to diabetes status was collected. The cardiology exam was performed as in clinical practice, after inclusion in the study. The cardiac assessment included natriuretic peptide testing, typical HF signs and symptoms, and echocardiography exam with left ventricle ejection fraction (LVEF) and structural abnormalities reported. Due to coronavirus disease-19 lockdown, the study was early terminated and some patients could not perform the cardiology exam. The per protocol population (PPP) included all T2D patients with cardiology exam conducted (270 out of 300 enrolled). Epidemiological methods have been used for the analysis of collected data with descriptive statistics. Results: The prevalence of HF was 30.7%. Most HF patients (83.1%) had preserved ejection fraction (LVEF ≥50%, HFpEF subgroup) and 16.9% mid-range ejection fraction (LVEF 40-49%, HFmrEF subgroup). The prevalence of HF typical symptoms was 57.0% in PPP group and 91.6% in HF subgroup. The echocardiography showed diastolic dysfunction (PPP: 87.3%, HF: 96.4%), cardiac structural changes (PPP: 64.8%, HF: 74.7%), and systolic dysfunction (PPP: 24.6%, HF: 41.0%). Natriuretic peptides were above the upper limit in 23.2% of PPP patients and 57.5% of the HF patients. The gender distribution was balanced (males: 50% in PPP, 50.6% in HF group). The mean age (SD) of patients was 63.8 (8.7), and 67.2 (7.8) years, with a mean duration of T2D (SD) of 11.1 (6.9), and 11.7 (7.0) years in PPP and HF groups, respectively. In the HF group, only 8.5% had a previous diagnosis of HF. In total, 98.2% of patients in PPP group received anti-diabetes treatment: metformin monotherapy (46.7%), oral anti-diabetes drugs combination (OAD) (26.7%), injectable GLP-1 receptor agonist (GLP-1 RA) (7.4%), and insulin (44.1%). Mean (SD) HbA1c levels were 7.9% (1.6) and 7.8% (1.6) in the PPP and HF groups, respectively. The prevalence of HF by anti-diabetes treatment was 29.6% in metformin only group, 30.6% in OAD group, 20.0% in GLP-1 RA group and 33.6% in insulin group. The treatment for HF following cardiac assessment included beta-blockers (82.4%), diuretics (52.7%), angiotensin converting enzymes inhibitors (47.3%), statins (31.1%), and angiotensin receptor blockers (25.7%). Discussion: FIND is the first study assessing the prevalence of HF in T2D in Romania. Almost one third of patients of the T2D patients had HF diagnosed by a cardiologist and for one in ten patients this was flagged only by the standard cardiologic exam at the time of study. HF prevalence rate was not influenced by diabetes duration or current diabetes treatment. An early clinical assessment of cardiovascular risk followed by tailored treatment approach to ensure cardioprotection and prevent complications is needed. Funding: AstraZeneca Romania.

Digital diabetes care: How well equipped are patients and what do they think about it

Aims: Covid-19 precipitated an abrupt shift to non-face- to- face (digital) consultation. Some believe that this was overdue and that digital is better for many patients. Our aim was to establish the extent to which people with diabetes were equipped to manage digital consultation and what they felt about it. Methods: We surveyed 1,000 people with diabetes (500 type 1, 500 type 2) from our local, largely deprived community with a user-approved questionnaire, tested for face validity and readability. Results: Response rate was 376/1000 (38%);132 (35%) type 1 diabetes, 218 (58%) type 2 diabetes, 1% other and 6% blank. Age of respondents was: ≤30, 0%;31-40, 4%;41-50, 7%;51-60, 12%;61-70, 17%;71-80, 52%;81-90, 3%;and blank, 5%. Treatment was: diet alone, 11%;diet and tablets, 39%;diet and insulin injections, 24%;diet, tablets and glucagon-like peptide-1 receptor agonist, 2%;insulin pump, 9%;and blank, 6%. Some 22% were attending the hospital clinic;74% not and 4% blank. Only 40% patients had access to a video calling device and only 35% had ever used it. Separate Likert scales showed: 79% strongly preferred or preferred face-to- face consultation, 17% strongly preferred or preferred telephone;and only 6% strongly preferred or preferred video consultation;66% recognised limitations in examination, weight and blood pressure checks with digital. Summary: Our survey, representative of type 1 and type 2 diabetes and of all treatment modalities but with underrepresentation of very young respondents, reveals that most patients did not have equipment for digital consultation and 79% preferred face-to- face consultation.

Development of a virtual glucagon-like peptide 1 analogue initiation service for people with type 2 diabetes within Forth Valley

Background: Prior to the covid-19 pandemic glucagon-like peptide (GLP-1) education was delivered face-to- face by diabetes specialist nurses. This service is now predominately virtual, with diabetes dietitians hosting online groups to deliver education. Aim: To evaluate the clinical outcomes of GLP-1 therapy education delivered online compared to face-to- face education sessions. Methods: Data were collated from 53 patients prior to the restrictions imposed by the covid-19 pandemic (Group A) and 53 patients who were educated virtually (Group B). The demographics of the patient group including duration of diabetes, gender, age, body mass index (BMI), Hba1c on referral and Hba1c change after four months of GLP-1 therapy were compared. Results: Group A was 45% male, with a mean age of 57 years, 10% had type 2 diabetes for over 10 years and 88% had a BMI between 30-39 kg/m2. The range of HbA1c at referral was 62-121mmol/ mol and mean improvement in HbA1c after 4 months of GLP-1 therapy in Group A was 24.3 ± 15.3mmol/mol. Group B was 55% male, with a mean age of 56 years, 43% had type 2 diabetes for over 10 years and 51% had a BMI of over 40 kg/m2. The range of HbA1c at referral was between 61-117mmol/ mol and the mean improvement in HbA1c after 4 months of GLP-1 therapy in Group B was 23.8 ± 17.5mmol/mol. Conclusions: The launch of virtual education for patients starting on GLP-1 therapy has been successful and maintained significant improvements in HbA1c after 4 months of treatment.

Risk of death in people with type 2 diabetes following SARS-CoV- 2 infection: A population level analysis of potential risk factors

Introduction: In this study we set out to determine the relative likelihood of death following covid-19 infection in people with type 2 diabetes when compared to those without type 2 diabetes. Methods: Analysis of digital health record data was performed relating to people living in the Greater Manchester conurbation (population 2.82 million) who had a recorded diagnosis of type 2 diabetes and subsequent covid-19 confirmed infection. Each individual with type 2 diabetes (n = 13,807) was matched with three covid-19 infected non-diabetes controls (n = 39583). Results: For type 2 diabetes individuals, their mortality rate after a covid-19 positive test was 7.7% vs 6.0% in matched controls;the relative risk (RR) of death was 1.28. From univariate analysis performed within type 2 diabetes individuals, likelihood of death following covid-19 recorded infection was lower in people taking metformin, sodium glucose cotransporter-inhibitor 2(SGLT-2i) or glucagon-like peptide-1( GLP-1) agonist. A lower estimated glomerular filtration rate (eGFR) was associated with a higher mortality rate, as was hypertension history. Likelihood of death following covid-19 infection was also higher in those people with diagnosis of COPD/severe enduring mental illness, and in people taking aspirin/ clopidogrel/insulin. Smoking in people with type 2 diabetes significantly increased mortality rate. In combined analysis of type 2 diabetes patients/controls, multiple regression modelling indicated that factors independently relating to higher likelihood of death (accounting for 26% of variance) were: type 2 diabetes/age/ malegender/social deprivation (higher Townsend index). Conclusion: Following confirmed infection with covid- 19 a number of factors are associated with mortality in type 2 diabetes individuals. Prescription of metformin, SGLT-2is or GLP-1 agonists + non-smoking status associated with reduced risk of death for people with type 2 diabetes. Age/male sex/social disadvantage associated with an increased risk of death.

Real-world use of once-weekly semaglutide in patients with type 2 diabetes: pooled analysis of data from four SURE studies by baseline characteristic subgroups.

INTRODUCTION: This post hoc pooled analysis of four real-world studies (SURE Canada, Denmark/Sweden, Switzerland and UK) aimed to characterize the use of once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The Semaglutide Real-world Evidence (SURE) studies had a duration of ~30 weeks. Changes in glycated hemoglobin (HbA1c) and body weight (BW) were analyzed for the overall population and the following baseline subgroups: GLP-1RA-naïve/GLP-1RA switchers; body mass index <25/≥25-<30/≥30-<35/≥35 kg/m2; age <65/≥65 years; HbA1c <7%/≥7-≤8%/>8-≤9%/>9%; T2D duration <5/≥5-<10/≥10 years. Data for patients achieving treatment targets were analyzed in the overall population and the baseline HbA1c ≥7% subgroup. RESULTS: Of 1212 patients, 960 were GLP-1RA-naïve and 252 had switched to semaglutide from another GLP-1RA. In the overall population, HbA1c was reduced from baseline to end of study (EOS) by -1.1% point and BW by -4.7 kg; changes were significant for all subgroups. There were significantly larger reductions of HbA1c and BW in GLP-1RA-naïve versus GLP-1RA switchers and larger reductions in HbA1c for patients with higher versus lower baseline HbA1c. At EOS, 52.6% of patients in the overall population achieved HbA1c <7%. No new safety concerns were identified in any of the completed SURE studies. CONCLUSIONS: In this pooled analysis, patients with T2D initiating OW semaglutide showed significant improvements from baseline to EOS in HbA1c and BW across various baseline subgroups, including patients previously treated with a GLP-1RA other than semaglutide, supporting OW semaglutide use in clinical practice. TRAIL REGISTRATION NUMBERS: NCT03457012; NCT03631186; NCT03648281; NCT03876015.