New Perspectives in Management of Cardiovascular Risk Among People With Diabetes.

Following the publication of results from multiple landmark cardiovascular outcome trials of antihyperglycemic medications over the past 8 years, there has been a major shift in the focus of care for people with type 2 diabetes, from control of hyperglycemia to managing cardiovascular risk. Multiple international cardiology and diabetes society guidelines and recommendations now endorse sodium-glucose cotransporter-2 inhibitors and glucagon-like protein-1 receptor agonists as first-line therapies to mitigate cardiovascular risk. The most recent publication is the 2023 European Society of Cardiology guideline on the management of cardiovascular disease in those with type 2 diabetes that, for the first time, recommends use of both classes of medications for the mitigation of cardiovascular risk for those with or at high risk for atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. Here, we review the evidence behind contemporary society guidelines and recommendations for the management of type 2 diabetes and cardiovascular risk.

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). METHODS: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. RESULTS: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. CONCLUSIONS: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

People living with type 2 diabetes (T2D) are more likely to develop problems with their heart or blood circulation, known as cardiovascular disease (CVD), than people who do not have T2D. However, it can be difficult to predict which people with T2D are most likely to develop CVD. This is because current approaches, such as blood tests, do not identify all people with T2D who are at an increased risk of CVD. In this study we reviewed published papers that investigated the differences between people with T2D who experienced CVD compared to those who did not. We found some indicators that could potentially be used to determine which people with T2D are most likely to develop CVD. More studies are needed to determine how useful these are. However, they could potentially be used to enable clinicians to provide targeted advice and treatment to those people with T2D at most risk of developing CVD.

Who eats last? Intra-household gender inequality in food allocation among children in educationally backward areas of India.

The practice of women eating after men is a common gender-inequitable food allocation mechanism among adults in Indian households and has been associated with poor health and nutritional outcomes for women. However, empirical evidence on whether a similar practice of girls eating after boys is prevalent among children is scarce. Using primary data from a household survey conducted in educationally backward areas of four Indian states, we provide new evidence of this practice among children. Almost 28 per cent of the sample households follow the mealtime custom of girls eating after boys. Scheduled Tribes and households with higher incomes are less likely to follow this practice. Other relevant factors include children's relative ages by sex and an interplay between family size and children's sex composition. While our findings may not be generalizable, they suggest an intersectionality between gender and other dimensions of inequality, namely social identity and economic class.

CROI 2023: Metabolic and Other Complications of HIV Infection.

Comorbid conditions have major impacts on the health, quality of life, and survival of people with HIV, particularly as they age. The 2023 Conference on Retroviruses and Opportunistic Infections (CROI) featured excellent science related to specific comorbidities, such as cardiovascular disease (CVD), cancer, and obesity. Studies investigating factors that may contribute to CVD, such as mental health disorders, antiretroviral therapies, and activation of hormonal pathways, were featured prominently. Other studies sought to understand the epidemiology of non-AIDS-defining cancers in people with HIV. As at previous CROI conferences, weight gain attributable to antiretroviral therapies was a major theme, and several abstracts focused on the important question of whether weight decreases after discontinuation of antiretroviral therapy (ART) regimens associated with weight gain. This review focuses on abstracts presented at CROI 2023 in these areas, highlighting those with the most clinical impact.

Diabetes risk and provision of diabetes prevention activities in 44 low-income and middle-income countries: a cross-sectional analysis of nationally representative, individual-level survey data.

BACKGROUND: The global burden of diabetes is rising rapidly, yet there is little evidence on individual-level diabetes prevention activities undertaken by health systems in low-income and middle-income countries (LMICs). Here we describe the population at high risk of developing diabetes, estimate diabetes prevention activities, and explore sociodemographic variation in these activities across LMICs. METHODS: We performed a pooled, cross-sectional analysis of individual-level data from nationally representative, population-based surveys conducted in 44 LMICs between October, 2009, and May, 2019. Our sample included all participants older than 25 years who did not have diabetes and were not pregnant. We defined the population at high risk of diabetes on the basis of either the presence of impaired fasting glucose (or prediabetes in countries with a haemoglobin A1c available) or overweight or obesity, consistent with the WHO Package of Essential Noncommunicable Disease Guidelines for type 2 diabetes management. We estimated the proportion of survey participants that were at high risk of developing diabetes based on this definition. We also estimated the proportion of the population at high risk that reported each of four fundamental diabetes prevention activities: physical activity counselling, weight loss counselling, dietary counselling, and blood glucose screening, overall and stratified by World Bank income group. Finally, we used multivariable Poisson regression models to evaluate associations between sociodemographic characteristics and these activities. FINDINGS: The final pooled sample included 145 739 adults (86 269 [59·2%] of whom were female and 59 468 [40·4%] of whom were male) across 44 LMICs, of whom 59 308 (40·6% [95% CI 38·5-42·8]) were considered at high risk of diabetes (20·6% [19·8-21·5] in low-income countries, 38·0% [37·2-38·9] in lower-middle-income countries, and 57·5% [54·3-60·6] in upper-middle-income countries). Overall, the reach of diabetes prevention activities was low at 40·0% (38·6-41·4) for physical activity counselling, 37·1% (35·9-38·4) for weight loss counselling, 42·7% (41·6-43·7) for dietary counselling, and 37·1% (34·7-39·6) for blood glucose screening. Diabetes prevention varied widely by national-level wealth: 68·1% (64·6-71·4) of people at high risk of diabetes in low-income countries reported none of these activities, whereas 49·0% (47·4-50·7) at high risk in upper-middle-income countries reported at least three activities. Educational attainment was associated with diabetes prevention, with estimated increases in the predicted probability of receipt ranging between 6·5 (3·6-9·4) percentage points for dietary fruit and vegetable counselling and 21·3 (19·5-23·2) percentage points for blood glucose screening, among people with some secondary schooling compared with people with no formal education. INTERPRETATION: A large proportion of individuals across LMICs are at high risk of diabetes but less than half reported receiving fundamental prevention activities overall, with the lowest receipt of these activities among people in low-income countries and with no formal education. These findings offer foundational evidence to inform future global targets for diabetes prevention and to strengthen policies and programmes to prevent continued increases in diabetes worldwide. FUNDING: Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program and the EU's Research and Innovation programme Horizon 2020.

Association of marijuana, tobacco and alcohol use with estimated glomerular filtration rate in women living with HIV and women without HIV.

OBJECTIVE: Marijuana, tobacco and alcohol use are prevalent among people with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women with HIV (WWH) and women without HIV. DESIGN: We undertook a repeated measures study of 1043 WWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women. METHODS: We quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009 to 2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors. RESULTS: Marijuana use of 1-14 days/month versus 0 days/month was associated with 3.34 ml/min per 1.73 m 2 [95% confidence interval (CI) -6.63, -0.06] lower eGFR and marijuana use of >0.02-1.6 marijuana-years versus 0-0.2 marijuana-years was associated with 3.61 ml/min per 1.73 m 2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of seven or more drinks/week versus no drinks/week was associated with 5.41 ml/min per 1.73 m 2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7-4.27 drink-years and >4.27 drink-years versus 0-0.7 drink-years were associated with 2.85 ml/min per 1.73 m 2 (95% CI 0.55, 5.15) and 2.26 ml/min per 1.73 m 2 (95% CI 0.33, 4.20) higher eGFR, respectively. CONCLUSION: Among a large cohort of WWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR.

Precision Prognostics for Cardiovascular Disease in Type 2 Diabetes: A Systematic Review and Meta-analysis.

Background Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with type 2 diabetes (T2D). Methods We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Results Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Conclusions Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

COVID-19 and (mis)understanding public attitudes to social security: Re-setting debate.

The Covid-19 pandemic has seen emerging debate about a possible shift in 'anti-welfare commonsense' i.e. the orthodoxy previously described in this journal as solidifying negative public attitudes towards 'welfare'. While a shift in attitudes might be ascribed to the circumstances of the crisis it would still be remarkable for such a strongly established orthodoxy to have changed quite so rapidly. It is appropriate, therefore, to reflect on whether the 'anti-welfare' orthodoxy was in fact as unequivocal as claimed? To address this question, challenges to the established orthodoxy that were emerging pre-pandemic are examined along with the most recently available survey data. This leads to discussion of broader issues relating to understanding attitudes: methodology; 'messiness' and ambivalence of attitudes; attitudes and constructions of deservingness; and following or leading opinion. It is argued that the 'anti-welfare' orthodoxy has always been far more equivocal than claimed, with consequent implications for anti-poverty action and re-setting debate.

Omega-3 Fatty Acids in Cardiovascular Disease and Diabetes: a Review of Recent Evidence.

PURPOSE OF REVIEW: Omega-3 fatty acids (n-3 FA) lower triglycerides, have anti-inflammatory properties, and improve metabolism. Clinical evidence of cardiovascular benefit with omega-3 fatty acids is mixed. We discuss mechanisms providing biological plausibility of benefit of omega-3 fatty acids in cardiovascular risk reduction and review clinical trials investigating the benefits of prescription omega-3 fatty acids in dyslipidemia, atherosclerotic cardiovascular disease (ASCVD), and diabetes. RECENT FINDINGS: Although early trials showed no benefit of omega-3 fatty acids in ASCVD, the REDUCE-IT trial noted significant risk reduction in ASCVD events with highly purified EPA (icosapent ethyl) use which has changed the landscape for currently available therapeutic options. However, other large trials like STRENGTH and VITAL, which used different formulations of prescription omega-3 fatty acids, did not note significant cardiovascular risk reduction. Thus the effectiveness of omega-3 fatty acids for cardiovascular disease prevention is an ongoing topic of debate. A relative paucity of studies examining benefits for glycemic outcomes in persons with diabetes exists; however, few studies have suggested lack of benefit to date. Significant residual cardiovascular risk exists for individuals with hypertriglyceridemia. Prescription omega-3 fatty acids are more commonly used for CV risk reduction in these patients. Clinical guideline statements now recommend icosapent ethyl use for selected individuals with hypertriglyceridemia to reduce cardiovascular events given recent evidence from the REDUCE-IT trial. Nonetheless, data from other large scale trials has been mixed, and future research is needed to better understand how different preparations of omega-3 may differ in their cardiovascular and metabolic effects, and the mechanisms for their benefit.

Employment trajectories and mental health-related disability in Belgium.

OBJECTIVES: An individual's quality of employment over time has been highlighted as a potential determinant of mental health. With mental ill-health greatly contributing to work incapacities and disabilities in Belgium, the present study aims to explore whether mental health, as indicated by registered mental health-related disability, is structured along the lines of employment quality, whereby employment quality is assessed over time as part of individuals' labour market trajectories. METHODS: Using administrative data from the Belgian Crossroads Bank for Social Security over 16 quarters between 2006 and 2009, transitions between waged jobs of varying quality (based on dimensions of income, working time, employment stability and multiple jobholding), self-employment, and unemployment are considered among individuals in the labour force aged 30-40 at baseline (n = 41,065 women and 45,667 men). With Multichannel Sequence Analysis and clustering, we constructed ideal types of employment trajectories. Fitting Cox regressions, we then evaluated individuals' hazard of experiencing a disability from a mental disorder between 2010 and 2016. RESULTS: Our analysis highlights various gender-specific trajectories. Among both genders, individuals exposed to near-constant unemployment over the initial 4 years showed the highest hazard of subsequent mental health-related disability compared to a group characterised by stable full-time employment, single jobholding, and above-median income. Trajectories involving a higher probability of subsidised and non-standard employment and (potential) spells of unemployment and lower relative income were also strong predictors of cause-specific disabilities. Health selection and confounding might, however, be contributing factors. CONCLUSIONS: Our study shows a gradient of mental disorders resulting in a disability along trajectory types. Our findings highlight the predictive power of labour market trajectories and their employment quality for subsequent mental disorder-related disability. Future research should examine the mechanisms, including selection effects in this association.

CROI 2022: metabolic and other complications of HIV infection or COVID-19.

Comorbid conditions have a major impact on the health, quality of life, and survival of people with HIV, particularly as this population ages. The 2022 Conference on Retroviruses and Opportunistic Infections (CROI) featured excellent science related to specific comorbidities, such as cardiovascular disease, type 2 diabetes, cancer, and frailty. The role of systemic inflammation in the pathogenesis of cardiovascular disease was an important theme, with strong evidence regarding the impact of microbial translocation. Other studies examined functional impairment, frailty, and potential important contributors, such as concomitant medications and sleep disturbances. The ANCHOR (Anal Cancer/High-grade Squamous Intraepithelial Lesions Outcomes Research) study provided crucial evidence that treatment of high-risk anal lesions reduces the incidence of anal cancer, which has important implications in the prevention of this devastating comorbidity. In addition, numerous presentations demonstrated the importance of comorbid conditions in COVID-19 outcomes in people with HIV and described persistent symptoms after acute SARS-CoV-2 infection has resolved. This review focuses on the abstracts presented at CROI 2022 in these areas, highlighting those with the most clinical impact.

Coronary Endothelial Dysfunction in People Living With HIV Is Related to Body Fat Distribution.

BACKGROUND: People living with HIV (PLWH) on antiretroviral therapy (ART) are at increased risk of atherosclerotic disease. Abnormal adipose distribution is common in PLWH and may contribute to atherosclerosis. Because coronary artery endothelial function (CEF) is impaired in early atherosclerosis, predicts future cardiovascular events, and is reduced in PLWH, we investigated associations between body fat distribution and CEF in PLWH. SETTING: Prospective cohort study. METHODS: PLWH on stable ART underwent MRI to quantify CEF, measured as change in coronary cross-sectional area from rest to that during isometric handgrip exercise, an endothelial-dependent stressor. Abdominal visceral and subcutaneous fat area (axial L4 level) and liver fat fraction were quantified using MRI. Linear regression was used to determine associations between CEF and independent variables. RESULTS: Among 84 PLWH (52 ± 11 years; 33% women), mean cross-sectional area change was 0.74 ± 11.7%, indicating impaired CEF. On univariable regression analysis, CEF was inversely related to waist circumference (R = -0.31, P = 0.014), hip circumference (R = -0.27, P = 0.037), and subcutaneous fat area (R = -0.25, P = 0.031). We did not observe significant relationships between CEF and liver fat fraction, waist/hip ratio, or visceral fat area. On multivariable regression adjusted for age, sex, and race, CEF was associated with waist circumference, hip circumference, subcutaneous fat, and liver fat fraction. CONCLUSION: Waist and hip circumference and subcutaneous fat area are associated with impaired CEF, an established metric of abnormal vascular health in PLWH on stable ART, and may contribute to the increased rate of heart disease in this population.

Cardiovascular Disease in Patients with Diabetes: A Comparison of Professional Society Guidelines.

In this review, we compare major points given in the 2021 American Diabetes Association and the 2020 American Association of Clinical Endocrinologists/American College of Endocrinology guidelines, in particular, the assessment and management of cardiovascular risk in patients with diabetes with a focus on dyslipidemia, blood pressure, and pharmacotherapy in diabetes.

Trends in Insulin Types and Devices Used by Adults With Type 2 Diabetes in the United States, 2016 to 2020.

Importance: Despite rising costs and public scrutiny devoted to insulin, less is known regarding recent trends in its ambulatory use in the United States. Objective: To characterize trends in ambulatory insulin use, overall and based on insulin characteristics, among adults with type 2 diabetes in the United States from January 1, 2016, through December 31, 2020. Design, Setting, and Participants: This serial cross-sectional study included patients whose data were collected in IQVIA's National Disease and Therapeutic Index (NDTI), a 2-stage, all-payer, nationally representative audit of outpatient care. Approximately 4800 physicians each calendar quarter completed a form for 2 consecutive days regarding visits for each of their patients, including diagnoses, treatments, and demographic information. Data were collected from January 2016 through December 2020. Exposures: Ambulatory use of insulin. Main Outcomes and Measures: Nationally representative projections for ambulatory use of insulin (ie, treatment visits), overall and aggregated by insulin molecule (insulins regular, neutral protamine Hagedorn [NPH], lispro, glulisine, glargine, detemir, degludec, and aspart), delivery devices (vials/syringes or pens), therapeutic class (short-acting, rapid-acting, long-acting, intermediate-acting, and premixed insulin), insulin type (human, analog, and biosimilar), and date of approval (newer: before 2010; and older: after 2010). Results: There were 27 860 691 insulin treatment visits between 2016 and 2020. Among all patient encounters that indicated use of insulin in 2020, 1 989 154 (43.9%) were among those aged 60 to 74 years; 2 372 629 (52.4%) among men; 2 646 247 (58.4%) among White patients; 811 639 (17.9%) among Black patients; and 701 912 (15.5%) among Hispanic patients. Insulin glargine was the most frequently used insulin from 2016 to 2020, accounting for approximately half of treatment visits (eg, 2020: 2.6 of 4.9 million visits; 95% CI, 2.1-3.1 million). Among insulin classes, long-acting insulin accounted for approximately two-thirds of treatment visits during this period (eg, 2020: 3.7 million visits; 95% CI, 3.0-4.4 million). Treatment visits for insulin pens increased from 36.1% in 2016 (2.2 of 6.0 million visits; 95% CI, 1.7-2.7 million) to 58.7% in 2020 (2.9 million visits; 95% CI, 2.3-3.5 million), while use of insulin vials/syringes declined in parallel. Analog insulin use predominated and accounted for more than 80% of total treatment visits across all years (eg, 2020: 4.3 million visits; 95% CI, 3.4-5.1 million). Newer insulins were increasingly used, from 18.1% of total treatment visits in 2016 (1.1 million visits; 95% CI, 0.8-1.4 million) to 40.9% in 2020 (2.0 million visits; 95% CI, 1.5-2.5 million). The use of biosimilar insulin, which was first approved in 2015, increased from 2.6% in 2017 (0.1 of 5.3 million visits; 95% CI, 0.04-0.2 million) to 8.2% in 2020 (0.4 million visits; 95% CI, 0.2-0.6 million) of total insulin treatment visits. The total number of insulin treatment visits declined from a peak of 6.0 million visits in 2016 to a nadir of 4.9 million visits in 2020 (approximately 18% decline). Conclusions and Relevance: In this study, ambulatory insulin use in the United States during the past 5 years remained dominated by the use of insulin analogs and insulin pen delivery devices, with increasing uptake of newer products as they have been brought to market.

Short Communication: Plasma Lymphocyte Activation Gene 3 and Subclinical Coronary Artery Disease in the Multicenter AIDS Cohort Study.

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.

Short Communication: Plasma Lymphocyte Activation Gene 3 and Subclinical Coronary Artery Disease in the Multicenter AIDS Cohort Study.

Chronic inflammation, including among people with HIV (PWH), elevates immune cell expression of lymphocyte activation gene 3 (LAG3); however, low plasma LAG3 predicts cardiovascular disease (CVD) events in the general population. The associations among LAG3 plasma levels, subclinical atherosclerosis, inflammation, and HIV infection have not been well described. We measured plasma LAG3 in 704 men with and without HIV from the multicenter AIDS cohort study, who underwent coronary computed tomography angiography. HIV serostatus was not independently associated with LAG3 after adjustment for sociodemographic and CVD risk factors. Current smoking status and African American race were associated with lower LAG3, and age and sTNFαRI concentration were associated with greater LAG3. LAG3 was not associated with coronary artery stenosis. Thus, no difference was found in plasma LAG3 concentration by HIV serostatus, and no association between LAG3 and subclinical coronary atherosclerosis in men with and without HIV was observed.

CROI 2021: Metabolic and Other Complications of HIV Infection or COVID-19.

Comorbid conditions have a major impact on the health, quality of life, and survival in people with HIV, particularly as they age. The 2021 Conference on Retroviruses and Opportunistic Infections featured excellent science related to specific comorbidities as well as multimorbidity. A number of presentations related to comorbidities in women with HIV reflected a new wave of research aimed at understanding how the epidemiology and pathogenesis of comorbidities may differ by sex. Weight gain related to antiretroviral therapy was also a major theme of the comorbidity abstracts presented at the meeting. Several presentations demonstrated the importance of comorbid conditions in COVID-19 outcomes in people with HIV and described persistent symptoms after acute SARS-CoV-2 infection has resolved, a nascent topic that will expand over time. This review focuses on research presented at the conference in these areas, highlighting those with the most clinical impact.

Ambulatory noninsulin treatment of type 2 diabetes mellitus in the United States, 2015 to 2019.

OBJECTIVE: To examine trends in the noninsulin drug treatment of type 2 diabetes, including first- and second-line therapies on top of metformin, from 2015 to 2019. PARTICIPANTS AND METHODS: We conducted a descriptive analysis of cross-sectional data using the IQVIA National Disease and Therapeutic Index, a nationally representative audit of ambulatory physician practices in the United States. We focused on the use of noninsulin pharmacological treatments for type 2 diabetes among individuals aged 35 years and older between January 1, 2015 and December 31, 2019. The main outcome was type 2 diabetes visits where a prescription drug was used ("treatment visit"). RESULTS: Ambulatory diabetes visits decreased from 30.1 million treatment visits in 2015 to 29.5 million treatment visits in 2019. Among treatment visits where a single drug was prescribed, the use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by glucagon-like peptide-1 (GLP-1) receptor agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT2) inhibitors increased from 7.3% to 19.5%. Among treatment visits where metformin plus another drug was prescribed, the share of second-line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulphonylurea use declined from 45.2% to 32.7%, use of SGLT2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 receptor agonists increased from 9.8% to 18.2%. CONCLUSIONS: Significant changes in the landscape of ambulatory care for diabetes have taken place during the past 6 years, including moderate declines in metformin monotherapy, moderate declines in second-line sulphonylurea use, and large increases in SGLT2 use. These changes underscore the dynamic nature of drug utilization for diabetes in the United States, and reflect the effects of emerging evidence, evolving clinical guidelines and evolving regulatory and payment policies.