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Aim: Perform a cost–effectiveness analysis of addition of subcutaneous semaglutide versus empagliflozin to usual treatment for patients with Type 2 diabetes and cardiovascular disease in US setting. Materials & methods: A Markov decision model estimated the impact of each strategy using cardiovascular complication rates based on EMPA-REG and SUSTAIN-6 trials. Modeled cohorts were followed for 3 years at 1-month intervals beginning at age 66. Results: Compared with empagliflozin, semaglutide resulted in cost of US$19,964 per quality-adjusted life-year gained. In one-way sensitivity analysis, only semaglutide cost >US$36.25/day (base case US$18.04) resulted in empagliflozin being preferred at a willingness-to-pay threshold of US$50,000/quality-adjusted life-year gained. Conclusion: For patients with Type 2 diabetes and cardiovascular disease, semaglutide is likely more cost-effective than empagliflozin added to usual treatment.

Background: Efforts to reduce type 2 diabetes morbidity and mortality focus on reducing microvascular and macrovascular complications. Development of GLP-1 receptor agonists and SGLT2 inhibitors has furthered progress toward this goal. As these medication classes have distinct effects on complication risk, the optimal approach is not clear. Methods: We evaluated the cost-effectiveness of 2 strategies to intensify treatment of patients with type 2 diabetes and cardiovascular disease: addition of 1 mg subcutaneous semaglutide weekly or 25 mg oral empagliflozin daily to usual diabetes treatment. A Markov decision model estimated the impact of each strategy; complications included nonfatal myocardial infarction, hospitalization for congestive heart failure, nonfatal stroke, new or worsening nephropathy, and death. The empagliflozin strategy also included possible genital mycotic infection. Complication rates were based on EMPA-REG and SUSTAIN-6 trials. Modeled cohorts began at age 66 and were followed for 3 years at 1 month intervals. Analyses took a healthcare perspective, discounting 3%/year. For the base case, all patients entered the model with no complications. Results: Compared to empagliflozin, semaglutide gained 0.053 quality-adjusted life year (QALY) at a cost of $1,006, or $18,897 per QALY gained. In one-way sensitivity analysis, only a semaglutide cost >$38/day (base case $18.04) resulted in empagliflozin being preferred at a willingness-to-pay threshold of $50,000/QALY. In probabilistic sensitivity analysis, semaglutide was preferred in 55% of model iterations at a $50,000/QALY threshold and in 57% at $100,000/QALY. When patients entered the model in complication states based on trial cohorts, semaglutide remained the preferred strategy at $23,518 per QALY gained. Conclusion: For patients with type 2 diabetes mellitus with cardiovascular disease, semaglutide is likely more cost-effective than empagliflozin as an addition to usual treatment. Disclosure M. Zupa: None. R. Codario: None. K. J. Smith: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK007052-45)

Metformin is the most prescribed oral medication for type 2 diabetes in the US due to its low cost, efficacy in reducing insulin resistance, and overall safety profile. However, literature shows that metformin can cause a rare but serious side effect of lactic acidosis (LA) with an incidence of 0.03-0.06 per 1000 patients. Persons requiring continuous oxygen therapy (COT) may be at risk for LA associated with hypoxia and decreased tissue perfusion, but the risk of metformin associated lactic acidosis (MALA) in persons requiring COT is unclear. Due to lack of evidence, some clinicians may empirically discontinue metformin in patients on COT, compromising glycemic stability. The objective of this drug utilization evaluation was to determine the frequency of metformin use and incidence of MALA in patients receiving COT. A retrospective review was conducted at a large regional Veterans Affairs Medical Center for patients with active prescriptions of metformin and supplemental oxygen therapy from 4/2017-4/2020. Of 578 unique patients identified, manual medical-record review was conducted for 6 patients who had serum lactate levels >4 mmol/L while using concomitant metformin and COT. All were white males with mean: age of 71, pH of 7.35, and eGFR of 56. No cases of LA or DKA were identified. In all cases, elevated lactate levels were attributed to advanced medical conditions including: COPD, sepsis, CHF, CKD, and liver disease. None had serum metformin levels drawn. In conclusion, the association of elevated serum lactate among persons using concomitant metformin and COT was low and occurred in persons with advanced medical conditions. It could not be determined if metformin use was a contributing factor without metformin levels. These findings confirm the importance of clinical judgement when prescribing and continuing metformin for persons with advanced underlying medical conditions. Further study with serum metformin levels may help to better characterize the risk of MALA for persons on COT. Disclosure S. J. Lutz-mccain: None. B. E. Desanzo: None. B. Herk: None. M. Mclinden: None. M. M. Dinardo: None. R. Codario: None.

Objective: To determine the efficacy and safety of a diabetic ketoacidosis (DKA)-Power Plan (PP) for guiding intravenous (IV) insulin infusions prior to anion gap (AG) closure and administering subcutaneous (SC) insulin ≥1 hour before discontinuing IV insulin. Methods: Retrospective chart review of patients with DKA before (pre-PP) (n = 60) and following (post-PP) (n = 60) implementation of a DKA-PP. Groups were compared for percentage of patients for whom IV insulin therapy was continued until AG closure, the percentage of patients receiving SC insulin ≥1 hour before discontinuation of IV insulin, and percentage of patients with rebound DKA during the index hospitalization. Results: Admission plasma glucose (514 mg/dL vs. 500 mg/dL; P = .36) and venous pH (7.2 vs. 7.2; P = .57) were similar in pre- and post-PP groups. Inappropriate discontinuation of IV insulin occurred less frequently in post-PP patients (28% vs. 7%; P = .007), with a lower frequency of rebound DKA (40% vs. 8%; P = .001) following acute management. More post-PP patients received SC insulin ≥1 hour before discontinuation of IV insulin (65% vs. 78%; P = .05). Conclusion: Implementation of a DKA-PP was associated with appropriate discontinuation of IV insulin in more patients, more frequent administration of SC insulin ≥1 hour prior to discontinuation of IV insulin, and fewer episodes of rebound DKA. Abbreviations: ADA = American Diabetes Association; AG = anion gap; BG = blood glucose; DKA = diabetic ketoacidosis; DKA-PP = DKA-Power Plan; ICU = intensive care unit; IQR = interquartile range; IV = intravenous; IVF = IV fluid; LOS = length of stay; SC = subcutaneous

Diabetic patients are at high risk for cardiovascular mortality, the greatest cause being atherosclerotic vascular disease and its subsequent sequelae. Diabetic patients have greater risk of permanent brain damage with carotid emboli, threefold greater mortality from stroke, poor prognosis for survival, and a two to fourfold greater risk of cardiovascular disease. In the Framingham Heart study, men with type-2 diabetes are twice as likely to develop heart failure compared to non-diabetics and women are five times more likely. The management and control of cardiovascular disease may be the most challenging and elusive task since cardiovascular damage may already be present even before the disease is diagnosed.

This autoimmune disease is the result of genetic environmental triggers. These patients demonstrate CD8 cell infiltration of the islet cells that are likely involved with subsequent beta cell destruction. A long prodrome is usually present from genetic pre-disposition to onset of disease. These patients may demonstrate various antibodies to islet antigens including insulin, glutamic acid decarboxylase (GAD), and tyrosine phosphatase 1A-2. Hence, a combination of markers rather than a single test should be used for predictive and diagnostic testing to enhance sensitivity without losing specificity.

The description of the incretin effect was first described in 1964 by Elwick when he observed a greater insulin secretory response if glucose was administered orally compared to intravenously despite similar elevations in plasma glucose. This incretin effect is attributed to the release of peptide hormones from the K and L cells in the intestines in the response to eating, so that approximately 60% of the insulin subsequently secreted is related directly to the effect of incretins [1]. Glucagon like peptide-1 (GLP-1) is secreted by the L cells, suppresses postprandial glucagon secretion, reduces appetite and stimulates insulin secretion in a dose dependent manner.

The clustering of abnormal laboratory test data and body measurements, listed in 1, encompassing parameters that should be measured on a regular basis in physician offices, collectively referred to as “The Metabolic Syndrome” represents an important risk stratification determination with its awareness and applicability to primary care increasing worldwide. A recent review found that greater than 66% of physicians consider this syndrome in the diagnosis, treatment, and management of their patients. These physicians felt that greater than 20% of their patients had metabolic syndrome with over 94% of physicians expecting patients diagnosed with metabolic syndrome to increase within the near future [1].

Clearly oral agents are more popular with patients in the battle for glycemic control. Significant recent advances in oral agents have provided several interesting and synergistic medications to make glycemic control more attainable. These newer agents, by addressing the various causes of hyperglycemia in the type-2 diabetic state can be used synergistically with enhanced glycemic control.

The worldwide prevalence of hypertension is expected to increase from approximately 1 billion individuals in 2000 to over 1.5 billion in 2025 and is currently the most frequent medical diagnosis in the USA [1]. Not only is hypertension a powerful risk factor for cardiovascular disease, doubling the risk of mortality from coronary heart disease and stroke for every 20 mmHg increase in systolic blood pressure and 10 mmHg increase in diastolic pressure, but also is closely linked to the risk of developing type-2 diabetes.

Major depressive disorders and depressive symptoms not only occur frequently with diabetes, but in many patients, mental health symptoms and even depression go unrecognized or incorrectly diagnosed [1]. Even among those that undergo successful treatment, close to 80% will experience relapsing symptoms within 5 years. Diabetic patients at higher risk for depression include those of female gender, poor social support system, lower education, low socioeconomic status, and unmarried status. Clinical research has revealed that having type-2 diabetes increases the risk of depression and depression is an independent risk and predictive factor for the quantity and severity of type-2 diabetes complications. Depression early in life also increases the risk for unhealthy lifestyle, obesity, sedentary existence, and addictive habits – especially smoking. In addition, patients with depression and type-2 diabetes are far more likely to be non-compliant with medications, glucose self monitoring, and therapeutic life style changes [1].

Appropriate treatment of type-2 diabetes is dependent upon the knowledge of the pathophysiology of the disease, the mechanisms underlying hyperglycemia, and the efficacy of various oral agents and insulins to improve fasting or postprandial hyperglycemia.

The current epidemic of obesity and the increase in type II diabetes have had a profound effect on health care in women in the United States. Alarmingly, there has been a 70% increase in type II diabetes among women between the age groups of 30 and 39 from 1990 to 1998. It is estimated that nearly 2 million reproductive age women in the United States have type II diabetes with about 30% of these cases as yet undiagnosed (1).