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Tirzepatide (TZP) is a novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist in development for T2D. In a continuous glucose monitoring (CGM) sub-study of SURPASS-3 (NCT03882970) , participants with T2D on metformin with or without SGLT-2 inhibitors spent up to 91% of time in range (71-180 mg/dL) for TZP (5, 10, 15 mg) vs. 75% for insulin degludec (IDeg) (p Disclosure R.M.Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. A.Bartee: None. M.Zeytinoglu: Employee; Eli Lilly and Company. R.Bray: Employee; Eli Lilly and Company. S.Allen: None. K.Brown: Employee; Eli Lilly and Company.

Context Breast cancer is increasing in prevalence in parallel with rising rates of obesity worldwide. Obesity is recognized as a leading modifiable risk factor for the development of breast cancer; however, this association varies considerably by clinicopathologic features, and the underlying mechanisms are complex. Evidence Acquisition Pubmed literature search using combinations of “obesity,” “breast cancer risk,” “diet,” “exercise,” “weight gain,” “weight loss,” “adipose tissue inflammation,” “crown-like structure,” “immune markers,” “metformin,” “gliflozins,” “SGLT-2i,” “GLP1-RA,” and related terms. Evidence Synthesis Elevated body mass index and weight gain are associated with increased risk of postmenopausal, hormone receptor–positive breast cancer. Emerging evidence suggests that adverse measures of body composition in individuals of any weight can also confer increased breast cancer risk. Mechanistically, various factors including altered adipokine balance, dysfunctional adipose tissue, dysregulated insulin signaling, and chronic inflammation contribute to tumorigenesis. Weight loss and more specifically fat mass loss through lifestyle and pharmacologic interventions improve serum metabolic and inflammatory markers, sex hormone levels, and measures of breast density, suggesting a link to decreased breast cancer risk. Conclusion Incorporating markers of metabolic health and body composition measures with body mass index can capture breast cancer risk more comprehensively. Further studies of interventions targeting body fat levels are needed to curb the growing prevalence of obesity-related cancer.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a recent class of medication approved for the treatment of type 2 diabetes (T2D). Previous meta-analyses have quantified the benefits and harms of SGLT2Is; however, these analyses have been limited to specific outcomes and comparisons and included trials of short duration. We comprehensively reviewed the longer-term benefits and harms of SGLT2Is compared to placebo or other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov from inception to July 2019 for randomized controlled trials of minimum 52 weeks’ duration that enrolled adults with T2D, compared an SGLT2I to either placebo or other anti-hyperglycemic medications, and reported at least one outcome of interest including cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. We conducted random effects meta-analyses to provide summary estimates using weighted mean differences (MD) and pooled relative risks (RR). The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Fifty articles describing 39 trials (vs. placebo, n = 28; vs. other anti-hyperglycemic medication, n = 12; vs. both, n = 1) and 112,128 patients were included in our analyses. Compared to placebo, SGLT2Is reduced cardiovascular risk factors (e.g., hemoglobin A1c, MD − 0.55%, 95% CI − 0.62, − 0.49), macrovascular outcomes (e.g., hospitalization for heart failure, RR 0.70, 95% CI 0.62, 0.78), and mortality (RR 0.87, 95% CI 0.80, 0.94). Compared to other anti-hyperglycemic medications, SGLT2Is reduced cardiovascular risk factors, but insufficient data existed for other outcomes. About a fourfold increased risk of genital yeast infections for both genders was observed for comparisons vs. placebo and other anti-hyperglycemic medications. DISCUSSION: We found that SGLT2Is led to durable reductions in cardiovascular risk factors compared to both placebo and other anti-hyperglycemic medications. Reductions in macrovascular complications and mortality were only observed in comparisons with placebo, although trials comparing SGLT2Is vs. other anti-hyperglycemic medications were not designed to assess longer-term outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07227-0.

BACKGROUND: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov (inception–July 2019) for randomized controlled trials ≥ 52 weeks’ duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80–0.90), macrovascular complications (including stroke, RR 0.86, 0.78–0.95), and mortality (RR 0.89, 0.84–0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. DISCUSSION: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07105-9.

Denosumab (DMAB) is a potent antiresorptive treatment used for treatment of osteoporosis and low bone mineral density (BMD) in those at high risk for fracture. In postmenopausal women with osteoporosis, DMAB treatment for 10 years has been studied, with results showing continued gains in BMD, sustained fracture risk reduction, and low risk of adverse events. However, upon discontinuation of DMAB, there is a rapid reversal of effect, with increase in bone turnover, loss of BMD, and in a subset of patients, a greater risk for multiple vertebral fractures.

Background: Several large randomized trials suggest GLP-1RAs may reduce mortality in addition to lowering A1c in patients with T2D. Treatment algorithms from the ADA/EASD now recommend a GLP-1RA be initiated in patients with T2D who either have or are at high risk of atherosclerotic cardiovascular (CV) disease, regardless of A1c level. To better quantify the efficacy and safety of GLP-1RAs, we conducted a systematic review and meta-analysis of all randomized trials of this drug class. Methods: We searched PubMed and Scopus (inception to June 2019) for randomized trials of at least 52 weeks duration enrolling adults with T2D that compared GLP-1RAs with placebo. Outcomes included microvascular/macrovascular complications, mortality, change in cardiovascular risk factors, and adverse events. Continuous outcomes were calculated with standardized mean differences, and binary outcomes were calculated using odds ratios. Pooled analyses were performed with fixed and random effects models. Heterogeneity was assessed using the I2 statistic. Results: See Table for results. Conclusions: Patients with T2D who received GLP-1RAs when compared to placebo had a significantly lower rate of major adverse CV events and A1c. These findings support the current ADA/EASD treatment recommendations. Subsequent cost effectiveness analyses will help further inform healthcare policy decisions. Disclosure J. Alexander: None. E.M. Staab: None. W. Wan: None. M. Franco: None. A.C. Knitter: None. C.C. Thomas: None. V.G. Press: Consultant; Self; Humana, Vizient Inc. M. Zeytinoglu: None. R. Skandari: None. K.E. Gunter: None. B. Bindon: None. S. Jumani: None. S.D. Bolen: None. N.M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. E. Huang: None. L.H. Philipson: None. N. Laiteerapong: None. Funding American Diabetes Association (1-18-JDF-037 to N.L.); National Institutes of Health (P30DK092949)

Background: Several large randomized trials suggest SGLT2Is may reduce mortality in addition to lowering A1c in patients with T2D. Treatment algorithms from the ADA and EASD now recommend a SGLT2I be initiated in patients with T2D who have chronic kidney disease or heart failure, regardless of A1c level. To better quantify the efficacy and safety of SGLT2Is, we conducted a systematic review and meta-analysis of all randomized trials of this drug class. Methods: We searched PubMed and Scopus (inception to June 2019) for randomized trials of at least 52 weeks duration enrolling adults with T2D that compared SGLT2Is with placebo. Outcomes included microvascular/macrovascular complications, mortality, change in cardiovascular (CV) risk factors, and adverse events. Continuous outcomes were calculated with standardized mean differences, and binary outcomes were calculated using odds ratios. Pooled analyses were performed with fixed and random effects models. Heterogeneity was assessed with the I2 statistic. Results: See Table for results. Conclusions: Patients who received SGLT2Is when compared to placebo had significantly lower rates of heart failure and A1c. These findings support the current ADA/EASD treatment recommendations. Subsequent cost effectiveness analyses will help further inform healthcare policy decisions. Disclosure J. Alexander: None. E.M. Staab: None. W. Wan: None. M. Franco: None. A.C. Knitter: None. C.C. Thomas: None. V.G. Press: Consultant; Self; Humana, Vizient Inc. M. Zeytinoglu: None. R. Skandari: None. K.E. Gunter: None. B. Bindon: None. S. Jumani: None. S.D. Bolen: None. N.M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. E. Huang: None. L.H. Philipson: None. N. Laiteerapong: None. Funding American Diabetes Association (1-18-JDF-037 to N.L.); National Institutes of Health (P30DK092949)

Objectives: Falls represent a significant cause of morbidity and mortality in older adults, and are more common among those living alone. We aimed to determine if there is an association between loneliness and falls. Methods: Participants were surveyed in three waves separated by 5 years. We used the three-item UCLA Loneliness Scale to measure loneliness. Results: Data from 2337 respondents, with both loneliness and fall data in at least two consecutive waves, were included. Over three waves, 51% respondents reported a fall and 23% reported ≥ two falls. In multivariate analysis, the odds of having ≥ one fall 5 years later increased by a factor of 1.11 per one point increase on the loneliness scale (OR = 1.11, 95% CI 1.04, 1.19; p

In the United States, one out of every four adults over the age of 65 has diabetes and one half of all adults in this age group are prediabetic, placing them at high risk for developing the disease. Beyond the United States, many other countries are also facing aging populations and high obesity rates that contribute to a staggering global diabetes epidemic. The care of the older patient with diabetes is frequently challenging, due to the accumulation of diabetic complications, extensive comorbidities, and functional impairments. Compounding this challenge is the lack of directly available evidence to guide management and care in this population. Though the global community shares in the epidemiologic burden of diabetes, there are large disparities across health systems and nations in the allocation of resources to the prevention, diagnosis, and treatment of the disease. Yet there is a consistency across many countries in the sub-optimal glycemic control and health outcomes for a majority of diabetics. This article reviews the context in which health systems provide diabetes care for the elderly and provides a framework for policy makers to support comprehensive diabetes care in the older adult. Nearly half of global diabetes expenditures occur in the United States, where only 6% of the world's diabetics reside. This article focuses on how to improve diabetes care in the United States, given its disproportionate contribution to global diabetes expenditures. Many of the recommendations presented, however, may be adapted and applied to other health systems.

Immunosuppression during the post-transplantation period has led to dramatic outcome improvements in PLTR patients. There have been reports describing the development of food allergies and an increased predilection for development of EGI in PLTR. We aimed to identify the clinical, endoscopic and histologic features of EGI in PLTR patients. In this retrospective case series we analyzed medical record of all PLTR who underwent EGD and/or colonoscopy at our institution from 2000 to 2006. From 2000 to 2006, 32 PLTR patients underwent endoscopic evaluation. Seventeen (53%) of 32 patients were diagnosed with EGI. Endoscopic abnormalities were seen in the esophagus, stomach, and small intestine in 11 (65%), 11 (65%), and four (24%) patients, respectively. Eosinophilic inflammation was seen in the esophagus, stomach, and small intestine in 13 (76%), 10 (59%), and five (29%) patients, respectively. Nine of 17 patients underwent colonoscopy and endoscopic abnormalities were seen in four (44%) patients. Five patients (56%) had eosinophilic inflammation. In conclusion, we have characterized the clinical, endoscopic, and histologic features of EGI. Histologic and endoscopic examination reveals that, when present, EGI is often found at multiple segments along the gastrointestinal tract.

Osteoporosis is a highly prevalent condition, resulting in significant morbidity and mortality. Nevertheless, it is frequently untreated. Vertebral fractures often do not come to clinical attention, yet, their presence is diagnostic of osteoporosis, helps to predict the risk of future fractures, and may alter the choice of pharmacotherapy. The addition of lateral spine imaging technology to the densitometer, for vertebral fracture assessment (VFA), represented a major advancement in the ability to diagnose vertebral fractures and osteoporosis. VFA is an under-utilized and highly effective imaging tool to enhance osteoporosis detection and fracture prevention. Several factors make VFA an ideal technology to evaluate for vertebral fractures. These include: the ability to obtain the image at the same time the bone density is done, with significantly lower radiation exposure than with spine radiography, and at a lower cost. This review provides an overview of the clinical significance of identifying vertebral fractures, the origins of the VFA, its clinical indications, a review of the methods used to diagnose vertebral fracture, an overview on interpreting the VFA, and the strengths and limitations of this technique.

Diabetes mellitus, thyroid disorders, and osteoporosis are endocrine conditions affecting a significant proportion of women presenting to the obstetrician-gynecologist. Obstetrician-gynecologists are often the first health-care providers that young women see in adulthood, and thus, have a critical opportunity to identify women at risk for gestational and overt diabetes and manage the condition in those who have developed it. The obstetrician-gynecologist should be aware of the appropriate therapeutic options and treatment goals (eg, hemoglobin A1c) for women with diabetes. Thyroid disorders often present with menstrual irregularities or infertility, can affect pregnancy outcomes, and contribute to cardiovascular and bone disorders as women age. Finally, osteoporosis and low bone mineral density affect a substantial proportion of older women and some younger women with risk factors for secondary osteoporosis. The morbidity and mortality of osteoporotic fractures is substantial. There are many lifestyle interventions and therapeutic options available for these conditions, and the gynecologist plays a key role in optimizing risk factor assessment, screening, and providing treatment when appropriate.

With an increasingly older and overweight global population, the public health burden of diabetes mellitus and cardiovascular disease is rapidly growing. Throughout the developed world, primary care providers play the leading role in managing diabetes and its complications. Evidence shows that there is substantial room for improvement in primary, secondary, and tertiary diabetes prevention, and that improving diabetes care requires redesign of health-care delivery systems. These systems should be designed with an actively engaged patient at the center of a proactive, multi-disciplinary, coordinated care team. The Chronic Care Model and Patient-Centered Medical Home are two models which have been used to provide this kind of care. Locally and internationally, policies are needed to: (1) improve access to and training of primary care and diabetes specialists; (2) improve access to self-management education, diabetes supplies, and medications; (3) provide appropriate reimbursement for care coordination and population-based disease management (i.e., electronic health records and diabetes registries); and (4) promote individualized programs to address unique individual determinants of health such as age, race/ethnicity, socioeconomic status, co-morbid medical conditions, and mental illnesses. Primary care providers, through such system-wide reform, will continue to be the champions of their patients’ health and work to ease the burden of the diabetes epidemic.

Although dying is an inevitable part of the life cycle, there has been extensive political debate over end-of-life care. Participating in end-of-life care conversations can be emotionally challenging for everyone involved. Messages about serious or terminal illnesses can be very hard for patients and their families to hear, and physicians frequently struggle with the burden of delivering these messages. Still, evidence shows that conversations about end-of-life care options between physicians and patients can improve the quality of life of dying patients and help to relieve the emotional burden on surviving loved ones. Legislation to support these discussions by consistently reimbursing physicians for their time spent performing this service has been blocked on multiple occasions. More research on how to improve end-of-life care will enable health care providers to optimize treatment of their patients. Overcoming political divides to support end-of-life care conversations is needed to promote care that is consistent with patients' values and needs and is a key step in encouraging better quality of life for dying patients.