Comparison of subcutaneous GLP-1 receptor agonists, semaglutide and dulaglutide, on HbA1c and weight loss outcomes: A systematic review

Background: The aim of this systematic review was to ascertain whether semaglutide is more effective than dulaglutide on outcomes of glycosylated haemoglobin (HbA1c) and weight loss in adults. The objectives were to identify studies that compared the subcutaneously administered formulations of the two drugs, compare changes in outcomes stated, analyse the data and evaluate each drugs’ effectiveness and determine which drug is more effective at achieving the outcomes. Methods: Studies were eligible for inclusion if they were published up to December 2023, written in the English language and involved adult participants only. Studies were excluded if they were of a qualitative methodology, contained paediatric samples, those that involved other subtypes of diabetes mellitus, including gestational diabetes and studies that investigated only semaglutide or dulaglutide. Two electronic databases, Medline and Embase, were searched up to 31 December 2023 for published studies with at least 3-month follow-up that compared semaglutide and dulaglutide on the outcomes of changes in HbA1c and weight. Included studies were assessed for risk of bias using the Cochrane Collaboration risk-of- bias tool v2.0 and the Risk of Bias in Non-randomised studies of Interventions tool, as appropriate. Data on the outcomes were then considered for appropriateness for statistical analyses. All included studies were deemed unsuitable for statistical analyses due to inconsistencies of implied data distributions and use of statistical methods and were therefore synthesised using descriptive statistics and a narrative analysis. Results: A total of 3 studies (1343 participants) met the inclusion criteria, where study 1 was a non- randomised cohort study, and study 2 and 3 were randomised controlled open-label studies. Statistical analysis was unable to be conducted without reducing the validity of the analysis, due poor use of statistics overall within all the studies. As a result, a narrative analysis was conducted. Both semaglutide and dulaglutide were shown to reduce HbA1c and weight from baseline, with semaglutide showing overall greater reductions in both HbA1c and weight reduction. Overall, participants on semaglutide were more likely to experience adverse events and discontinue treatment due to this. However, dulaglutide was found to have higher rates of serious adverse events and death related to treatment than semaglutide. Conclusions: Evaluation of the three studies showed that both GLP1-RAs are effective at reducing HbA1c and weight, with semaglutide achieving greater reductions in both outcomes overall. However, more robust and long-term studies needed on real-life populations to better determine the real-world, long-term efficacy and safety of these drugs. In addition, it was concluded that more needs to be done to increase research proficiency in healthcare, especially in the field of statistics. Better training should be sought on the conduction of statistical analyses and reporting of research, such as the reporting of normalised data, so readers and future systematic reviews may make robust comparisons between studies

Ethnic differences in insulin secretory function between black African and white European men with early type 2 diabetes

AimTo test the hypothesis that men of black (West) African ethnicity (black African men [BAM]) with early type 2 diabetes (T2D) would have greater insulin secretory deficits compared with white European men (WEM), following prediabetic hypersecretion.MethodsIn 19 BAM and 15 WEM, matched for age, body mass index and duration of diabetes, we assessed and modelled insulin secretory responses to hyperglycaemia stimulated intravenously (hyperglycaemic clamp) and orally (meal tolerance test).ResultsWith similar post‐challenge glucose responses, BAM had lower second‐phase C‐peptide responses to intravenous glucose (BAM 70.6 vs WEM 115.1 nmol/L/min [ratio of geometric mean 0.55, 95% confidence interval {CI} 0.37, 0.83]; P = .006) and to oral glucose (BAM 65.4 vs WEM 88.5 nmol/L/min [mean difference −23.2, 95% CI −40.0, −6.3]; P = .009). Peripheral insulin response in BAM to oral glucose was preserved (BAM 47.4 vs WEM 59.4 nmol/L/min [ratio of geometric mean 0.89, 95% CI 0.59, 1.35]; P = .566), with relative reductions in insulin clearance (BAM 506.2 vs WEM 630.1 mL/m2 BSA/min [mean difference −123.9, 95% CI −270.5, 22.6]; P = .095), associated with enhanced incretin responses (gastric inhibitory polypeptide incremental area under the curve: BAM 46.8 vs WEM 33.9 μg/L/min [mean difference 12.9, 95% CI 2.1, 23.7]; P = .021).ConclusionsIn early T2D, BAM had significantly lower insulin secretory responses to intravenous and oral stimulation than WEM. Lower insulin clearance, potentially driven by increased incretin responses, may act to preserve peripheral insulin concentrations. Tailoring early management strategies to reflect distinct ethnic‐specific pathophysiology may improve outcomes in this high‐risk population

Black African men with early type 2 diabetes have similar muscle, liver and adipose tissue insulin sensitivity to white European men despite lower visceral fat

AIMS/HYPOTHESIS: Type 2 diabetes is more prevalent in black African than white European populations although, paradoxically, black African individuals present with lower levels of visceral fat, which has a known association with insulin resistance. Insulin resistance occurs at a tissue-specific level; however, no study has simultaneously compared whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men. We hypothesised that, in those with early type 2 diabetes, black (West) African men (BAM) have greater hepatic and adipose tissue insulin sensitivity, compared with white European men (WEM), because of their reduced visceral fat.METHODS: Eighteen BAM and 15 WEM with type 2 diabetes underwent a two-stage hyperinsulinaemic-euglycaemic clamp with stable glucose and glycerol isotope tracers to assess tissue-specific insulin sensitivity and a magnetic resonance imaging scan to assess body composition.RESULTS: We found no ethnic differences in whole body, skeletal muscle, hepatic or adipose tissue insulin sensitivity between BAM and WEM. This finding occurred in the presence of lower visceral fat in BAM (3.72 vs 5.68 kg [mean difference -1.96, 95% CI -3.30, 0.62]; p = 0.01). There was an association between skeletal muscle and adipose tissue insulin sensitivity in WEM that was not present in BAM (r = 0.78, p < 0.01 vs r = 0.25 p = 0.37).CONCLUSIONS/INTERPRETATION: Our data suggest that in type 2 diabetes there are no ethnic differences in whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men, despite differences in visceral adipose tissue, and that impaired lipolysis may not be contributing to skeletal muscle insulin resistance in men of black African ethnicity.© 2021, The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0

Associations between pancreatic lipids and <i>β</i>-cell function in Black African and White European men with type 2 diabetes

Context: Intrapancreatic lipid (IPL) has been linked with beta-cell dysfunction. Black populations suffer disproportionately from type 2 diabetes (T2D) and show distinctions in beta-cell function compared to Whites.Objective: We aimed to quantify IPL in White European (WE) and Black West African (BWA) men with early T2D, and to investigate relationships between IPL and beta-cell insulin secretory function (ISF).Design, Setting and Participants: We performed a cross-sectional assessment of 18 WE and 19 BWA middle-aged men with early T2D as part of the South London Diabetes and Ethnicity Phenotyping (Soul-Deep) study.Main Outcome Measures: Participants underwent Dixon magnetic resonance imaging to determine IPL in the pancreatic head, body, and tail, and subcutaneous and visceral adipose tissue volumes. Modelled first-phase and second-phase ISF were comprehensively determined using c-peptide measurements during a 3-hour meal tolerance test and a 2-hour hyperglycemic clamp test.Results: WE men had higher mean IPL than BWA men (P=0.029), mainly due to higher IPL in the pancreatic head in WE men (P=0.009). Mean IPL was inversely associated with orally stimulated first-phase ISF in WE but not BWA men (WE: r=-0.554, P=0.026; BWA: r=-0.183, P=0.468); there was no association with orally stimulated second-phase ISF in either WE or BWA men. No significant associations were found between mean IPL and intravenously stimulated ISF.Conclusions: IPL is lower in BWA than WE men with early T2D, and the lack of inverse association with orally stimulated first phase ISF in BWA men indicates that IPL may be a less important determinant of the development of T2D in BWA compared to WE men.</p

Ethnic and racial differences in children and young people with&nbsp;respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER Initiative

BackgroundChildren from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health.MethodsWe conducted a retrospective cohort study of individuals &lt;21 years seeking care at 24 health systems across the U.S, using electronic health record (EHR) data. Our cohort included those with a positive SARS-CoV-2 molecular, serology or antigen test, or with a COVID-19, multisystem inflammatory disease in children, or PASC diagnosis from February 29, 2020 to August 1, 2022. We identified children/youth with at least 2 codes associated with respiratory and neurologic PASC. We measured associations between sociodemographic and clinical characteristics and respiratory and neurologic PASC using odds ratios and 95% confidence intervals estimated from multivariable logistic regression models adjusted for other sociodemographic characteristics, social vulnerability index or area deprivation index, time period of cohort entry, presence and complexity of chronic respiratory (respectively, neurologic) condition and healthcare utilization.FindingsAmong 771,725 children in the cohort, 203,365 (26.3%) had SARS-CoV-2 infection. Among children with documented infection, 3217 children had respiratory PASC and 2009 children/youth had neurologic PASC. In logistic regression models, children &lt;5 years (Odds Ratio [OR] 1.78, 95% CI 1.62-1.97), and of Hispanic White descent (OR 1.19, 95% CI 1.05-1.35) had higher odds of having respiratory PASC. Children/youth living in regions with higher area deprivation indices (OR 1.25, 95% CI 1.10-1.420 for 60-79th percentile) and with chronic complex respiratory conditions (OR 3.28, 95% CI 2.91-3.70) also had higher odds of respiratory PASC. In contrast, older (OR 1.57, 95% CI 1.40-1.77 for those aged 12-17 years), non-Hispanic White individuals and those with chronic pre-existing neurologic conditions (OR 2.04, 95% CI 1.78-2.35) were more likely to have a neurologic PASC diagnosis.InterpretationRacial and ethnic differences in healthcare utilization for neurologic and respiratory PASC may reflect social drivers of health and inequities in access to care.FundingNational Institutes of Health

A nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID‐19

AimsTo investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.Materials and methodsRetrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.ResultsIn total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.ConclusionsHospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA

Rare presentation of collapse and cardiomyopathy in phaeochromocytoma

Summary A phaeochromocytoma is a rare neuroendocrine tumour derived from the chromaffin cells of the adrenal medulla. Tumours can produce excessive amounts of catecholamines. The presenting symptoms can vary but often include the classic triad of episodic headaches, sweating and palpitations. Due to catecholamine excess, patients can develop cardiomyopathy. Bradycardia and collapse could be the result of sinus node dysfunction or transient dysregulation of the autonomic nervous system. Patients with co-existing diabetes can have improvement or resolution of their diabetes after successful adrenalectomy. We report a case of an 87-year-old lady who initially presented with sweating, palpitations and collapse, resulting in a permanent pacemaker insertion. She was later found to have a large adrenal incidentaloma with subsequent markedly elevated plasma metanephrine levels. She later presented with chest pain and in acute pulmonary oedema with normal coronary arteries visualised on coronary angiogram. After surgical excision of her phaeochromocytoma, her diabetes resolved with her HbA1c improving from 68 to 46 mmol/mol, with no further requirement for diabetic medications. Her pulmonary oedema improved with no ongoing need for diuretic therapy. This case highlights that phaeochromocytomas can affect multiple systems and there should be a very high index of suspicion in patients presenting with sweating, palpitations, hypertension and a history of diabetes and even in those with collapse. Learning points There should be a high index of suspicion for phaeochromocytomas in patients with palpitations, diaphoresis, anxiety, hypertension and diabetes. Rarely phaeochromocytomas can present as bradycardia and collapse due to sinus node dysfunction or transient autonomic dysregulation and that should be considered in older patients. Catecholamine cardiomyopathy can occur in phaeochromocytoma with potential resolution after successful surgical excision. Diabetes can resolve after successful surgical treatment of a phaeochromocytoma. </jats:sec