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This study aimed to demonstrate noninferiority using telehealth in treating obesity with phentermine in patients with BMI ≥ 27 kg/msup2/supwith comorbidities or BMI ≥ 30 compared with the standard in-person approach over a 90-day period.A 12-week, randomized, prospective, single-center, open label trial compared the use of virtual visits versus in-person visits for the treatment of obesity using phentermine. The primary end point was percentage mean change in body weight from baseline to 12 weeks. A noninferiority approach assuming a 3% noninferiority region was used to assess effect size differences.The weight loss in the virtual visit arm was noninferior to the in-person arm at all time points. At 12 weeks, the mean change in weight was -6.5% among the virtual group and -7.7% among the in-person group. In addition, 65% of virtual patients and 71% of in-person patients demonstrated a weight reduction of at least 5%. There was no difference in medication tolerance, adherence, and compliance.These results indicate that the virtual obesity pharmacotherapy visits in adults aged 18 to 65 years prescribed phentermine are effective and noninferior in achieving meaningful weight loss after 12 weeks. Future clinical trials are needed to better assess the effectiveness of televisits for obesity pharmacotherapy.

Objective To assess whether an electronic health record (EHR)-based diabetes intensification tool can improve the rate of A1C goal attainment among patients with type 2 diabetes and an A1C ≥8%. Methods An EHR-based tool was developed and sequentially implemented in a large, integrated health system using a four-phase, stepped-wedge design (single pilot site [phase 1] and then three practice site clusters [phases 2–4]; 3 months/phase), with full implementation during phase 4. A1C outcomes, tool usage, and treatment intensification metrics were compared retrospectively at implementation (IMP) sites versus nonimplementation (non-IMP) sites with sites matched on patient population characteristics using overlap propensity score weighting. Results Overall, tool utilization was low among patient encounters at IMP sites (1,122 of 11,549 [9.7%]). During phases 1–3, the proportions of patients achieving the A1C goal ( Conclusion Utilization of a diabetes intensification tool was low and did not influence rates of A1C goal attainment or time to treatment intensification. The low level of tool adoption is itself an important finding highlighting the problem of therapeutic inertia in clinical practice. Testing additional strategies to better incorporate, increase acceptance of, and improve proficiency with EHR-based intensification tools is warranted.

Bariatric and metabolic surgery is an effective treatment for patients with severe obesity and obesity-related diseases. In patients with type 2 diabetes, it provides marked improvement in glycemic control and even remission of diabetes. In patients with type 1 diabetes, bariatric surgery may offer improvement in insulin sensitivity and other cardiometabolic risk factors, as well as amelioration of the mechanical complications of obesity. Because of these positive outcomes, there are increasing numbers of patients with diabetes who undergo bariatric surgical procedures each year. Prior to surgery, efforts should be made to optimize glycemic control. However, there is no need to delay or withhold bariatric surgery until a specific glycosylated hemoglobin target is reached. Instead, treatment should focus on avoidance of early postoperative hyperglycemia. In general, oral glucose-lowering medications and noninsulin injectables are not favored to control hyperglycemia in the inpatient setting. Hyperglycemia in the hospital is managed with insulin, aiming for perioperative blood glucose concentrations between 80 and 180 mg/dL. Following surgery, substantial changes of the antidiabetic medication regimens are common. Patients should have a clear understanding of the modifications made to their treatment and should be followed closely thereafter. In this review article, we describe practical recommendations for the perioperative management of diabetes in patients with type 2 or type 1 diabetes undergoing bariatric surgery. Specific recommendations are delineated based on the different treatments that are currently available for glycemic control, including oral glucose-lowering medications, noninsulin injectables, and a variety of insulin regimens.

To conduct an adjusted indirect treatment comparison (aITC) of the efficacy of tirzepatide 5/10/15 mg versus semaglutide 2 mg in patients with type 2 diabetes.The primary analysis was a Bucher aITC of the change from baseline at week 40 in HbA1c (%) and body weight (kg). Aggregate data from the SURPASS-2 study that met the HbA1c inclusion criterion of the SUSTAIN FORTE study and from SUSTAIN FORTE metformin-only treated patients were used for primary analysis.The SURPASS-2 refined population comprised 238/245/240 and 240 participants for tirzepatide 5/10/15 mg and semaglutide 1 mg, respectively. The SUSTAIN FORTE metformin-only population comprised 222 and 227 participants for semaglutide 1 and 2 mg, respectively. In this aITC, tirzepatide 10 and 15 mg significantly reduced HbA1c versus semaglutide 2 mg with an estimated treatment difference (ETD) of -0.36% (95% confidence interval [CI] -0.63, -0.09) and -0.4% (95% CI -0.67, -0.13), respectively. Tirzepatide 10 and 15 mg significantly reduced body weight versus semaglutide 2 mg with an ETD of -3.15 kg (95% CI -4.84, -1.46) and -5.15 kg (95% CI -6.85, -3.45), respectively. There were no significant differences between tirzepatide 5 mg and semaglutide 2 mg on change from baseline in HbA1c and body weight.In this aITC, HbA1c and weight reductions were significantly greater for tirzepatide 10 and 15 mg versus semaglutide 2 mg and were similar for tirzepatide 5 mg versus semaglutide 2 mg. These findings provide comparative effectiveness insights in the absence of a head-to-head clinical trial.

AimsContemporary patterns of care of patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) and the adoption of finerenone are not known. The FINE-REAL study (NCT05348733) is a prospective observational study in patients with CKD and T2D to provide insights into the use of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in clinical practice.MethodsFINE-REAL is an international, prospective, multicenter, single-arm study enrolling approximately 5500 adults with CKD and T2D in an estimated 200 sites across 22 countries. The study is anticipated to be ongoing until 2027.ResultsThe primary objective is to describe treatment patterns in patients with CKD and T2D treated with finerenone in routine clinical practice. Secondary objectives include assessment of safety with finerenone. Other endpoints include characterization of healthcare resource utilization and occurrence of newly diagnosed diabetic retinopathy or its progression from baseline in patients with existing disease. A biobank is being organized for future explorative analyses with inclusion of participants from the United States.ConclusionsFINE-REAL is the first prospective observational study with a nonsteroidal MRA in a population with CKD and T2D and is expected to provide meaningful insights into the treatment of CKD associated with T2D. FINE-REAL will inform decision-making with respect to initiation of finerenone in patients with CKD and T2D.

BACKGROUND When type 2 diabetes is suboptimally controlled with basal insulin, prandial insulin injections are commonly added (i.e., a basal-bolus insulin regimen), which can increase treatment burden and hypoglycemia risk. The once-daily injectable iGlarLixi is an alternative treatment. METHODS This retrospective analysis of the U.S. Optum Clinformatics database compared outcomes in adults (≥18 years of age) with type 2 diabetes who previously received basal insulin and were newly initiated on iGlarLixi or basal-bolus insulin therapy. Cohorts were propensity score–matched in a 1:1 ratio on baseline characteristics, and imbalances were adjusted in multivariate analyses. Subgroup analyses were performed for people ≥65 years of age and those with a baseline A1C ≥9%. The primary end point was persistence with therapy at 12 months in the overall population. Secondary end points were treatment adherence, health care resource utilization (HCRU), costs, any hypoglycemia, and A1C change at 12 months. RESULTS Cohorts each comprised 1,070 participants. Treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus basal-bolus insulin therapy (43.7 vs. 22.3%, hazard ratio 0.51, 95% CI 0.46–0.57, adjusted P CONCLUSION In this observational study, initiation of once-daily iGlarLixi versus basal-bolus insulin was associated with higher persistence, lower hypoglycemia, and similar A1C reduction without increasing HCRU or costs regardless of age or A1C. iGlarLixi could be an alternative to basal-bolus insulin, particularly for older adults with type 2 diabetes who require treatment simplification with lower hypoglycemia risk.

Aims Little is known about the impact of weight loss on developing comorbidities in patients with obesity in real-world settings. Understanding health benefits and associated comorbidities with weight loss are critical to addressing the global obesity health epidemic. This study aimed to determine health outcomes associated with weight loss in individuals with obesity, and to better understand the relationship between disease burden (i.e., prior comorbidities, healthcare utilization) and weight loss in individuals with obesity. Electronic health records (EHRs) represent an important resource to investigate these impacts. Materials and methods We conducted a case-control study using deidentified EHR-derived information from 204,921 patients seen at the Cleveland Clinic between 2000-2018. Patients were ≥20 years of age with BMI ≥30 kg/m2 and ≥7 weight measurements, over ≥3 years. Thirty outcomes were investigated, including chronic and acute diseases, as well as psychological and metabolic disorders. Weight change was investigated three, five, and ten years prior to an event. Results Weight loss was associated with reduced incidence of many outcomes (e.g., type 2 diabetes, non-alcoholic steatohepatitis/non-alcoholic fatty liver disease, obstructive sleep apnea, hypertension) (P 10% was associated with increased incidence of certain outcomes including stroke and substance abuse. However, many outcomes that increased with weight loss were attenuated by disease burden adjustments. Conclusions This study provides the most comprehensive real-world evaluation of health impacts of weight change to date. After comorbidity burden and healthcare utilization adjustments, weight loss was associated with an overall reduction in risk of many adverse outcomes. This article is protected by copyright. All rights reserved.

Objective. To assess whether an electronic health record (EHR) based diabetes intensification tool can improve the rate of A1C goal attainment among patients with type 2 diabetes and an A1C ≥8%. Methods. An EHR-based tool was developed and sequentially implemented in a large, integrated health system using a four-phase, stepped-wedge design (single pilot site [phase 1] and then three practice site clusters [phases 2–4]; 3 months/phase), with full implementation during phase 4. A1C outcomes, tool usage, and treatment intensification metrics were compared retrospectively at implementation (IMP) sites versus nonimplementation (non-IMP) sites with sites matched on patient population characteristics using overlap propensity score weighting. Results. Overall, tool utilization was low among patient encounters at IMP sites (1,122 of 11,549 [9.7%]). During phases 1–3, the proportions of patients achieving the A1C goal (P = 0.02). Implementation was not associated with mean A1C improvement from baseline (range −0.88 to −1.08%, IMP sites vs. non-IMP sites P ≥0.093). Times to intensification were similar between IMP and non-IMP sites. Conclusion. Utilization of a diabetes intensification tool was low and did not influence rates of A1C goal attainment or time to treatment intensification. The low level of tool adoption is itself an important finding highlighting the problem of therapeutic inertia in clinical practice. Testing additional strategies to better incorporate, increase acceptance of, and improve proficiency with EHR-based intensification tools is warranted.

Reports indicate that coronavirus disease 2019 (COVID-19) may impact pancreatic function and increase type 2 diabetes (T2D) risk, although real-world COVID-19 impacts on HbA1c and T2D are unknown. We tested whether COVID-19 increased HbA1c, risk of T2D, or diabetic ketoacidosis (DKA). We compared pre– and post–COVID-19 HbA1c and T2D risk in a large real-world clinical cohort of 8,755 COVID-19(+) patients and 11,998 COVID-19(−) matched control subjects. We investigated whether DKA risk was modified in COVID-19(+) patients with type 1 diabetes (T1D) (N = 701) or T2D (N = 21,830), or by race and sex. We observed a statistically significant, albeit clinically insignificant, HbA1c increase post–COVID-19 (all patients ΔHbA1c = 0.06%; with T2D ΔHbA1c = 0.1%) and no increase among COVID-19(−) patients. COVID-19(+) patients were 40% more likely to be diagnosed with T2D compared with COVID-19(−) patients and 28% more likely for the same HbA1c change as COVID-19(−) patients, indicating that COVID-19–attributed T2D risk may be due to increased recognition during COVID-19 management. DKA in COVID-19(+) patients with T1D was not increased. COVID-19(+) Black patients with T2D displayed disproportionately increased DKA risk (hazard ratio 2.46 [95% CI 1.48–6.09], P = 0.004) compared with White patients, suggesting a need for further clinical awareness and investigation.

Introduction Randomized clinical trials identified a small increased risk of acute pancreatitis in patients using glucagon-like peptide-1 receptor agonist (GLP1- RA) therapy. As a result, GLP-1RA therapy is generally avoided in patients with a history of acute pancreatitis. The aim of this report was to evaluate the real-world experience of GLP-1RA therapy in patients with a history of acute pancreatitis. Methods A retrospective chart review was conducted (2010-2019) using the enterprise-wide electronic health record (EHR) system. Patients with a history of acute pancreatitis and a subsequent encounter diagnosis of acute pancreatitis (ICD-9/ ICD-10 codes), after exposure to GLP-1R, were identified. Exposure to GLP-1RA was defined as a documented prescription for GLP-1RA in the EHR. Patients were followed until the date of recurrent acute pancreatitis (RAP) or censoring. Categorical and continuous variables were summarized using N (%) and mean (SD), respectively. Results A total of 161 patients were identified, 50.9% were female, 56.6% Caucasian, with mean age (years) 54 (±13) and mean BMI 35 kg/m2 (±8). Type 2 diabetes, hypertension, and obesity were present in 92.5% (N=149), 86.3% (N=139), and 73.9% (N=119), respectively. The mean duration of follow-up for all patients was 28.2 months (±24.6). The etiologies of the first documented episode of pancreatitis prior to GLP-1RA exposure were gall stones (N=49, 30.4%), alcoholism (N=21, 13%), hypertriglyceridemia (N=9, 5.6%), medication-induced N=5 (3.1%), and the remaining cases (N=77, 47.8%) were classified as idiopathic. Among these 161 patients, N=16 (9.9%) had a second episode of pancreatitis after GLP1-RA exposure. The mean duration of exposure to GLP-1RA prior to RAP was 10.8 months (±7.2). RAP was attributed to GLP 1-RA exposure N=6 (37.5%), alcohol intake N=2 (12.5%), hypertriglyceridemia N=3 (18.8%), oral hypoglycemic agent N=1 (6.2%), ampulla stenosis N=1 (6.2%), and the remaining N=3 (18.8%) were considered idiopathic. Conclusions Among 161 patients with a history of acute pancreatitis exposed to GLP-1RA, a total of 16 (9.9%) cases of RAP were identified, but only N=6 (4%) of these were determined attributable to GLP-1RA exposure. The overall rate of RAP among our cohort of GLP-1RA exposed patients (9.9%) is similar to the overall rate of RAP reported in the literature (12.7%), regardless of the underlying etiology or drug exposure.1 Acute pancreatitis related to drug exposure is a diagnosis of exclusion; thus, it is certainly possible that some of the cases in our report considered idiopathic were actually related to GLP-1RA exposure. While caution needs to be exercised, our data would support the use of GLP-1RA in patients with a history of acute pancreatitis, on an individualized basis, where the benefits are considered to outweigh the risks. References 1) Mallick et al. Differences between the outcome of recurrent acute pancreatitis and acute pancreatitis. JGH Open. 2018 Jun 6;2(4): 134-138. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:30 p.m. - 12:35 p.m.

Introduction There is controversy surrounding the value of bilateral inferior petrosal sinus sampling (BIPSS) for tumor lateralization in Cushing's disease (CD). We compare lateralization results between BIPSS and pituitary imaging against gold-standard surgical localization. Methods A retrospective chart review was conducted in patients with pathology-confirmed CD, visible tumor on MRI (with and without contrast), and who underwent BIPSS at our institution between 2003-2020. An inferior petrosal sinus to peripheral (IPS/P) prolactin ratio >1.8 was used to confirm appropriate IPS sampling. An inter-sinus ACTH gradient ratio greater than 1.4, adjusted for prolactin where available, was used to determine lateralization. In each case, the neurosurgeon performed a full pituitary gland exploration to avoid missing any tumors despite visible tumor on MRI. Descriptive statistics were used. Results Of 32 patients with CD, visible tumor on MRI, and BIPSS testing, 27 (84%) patients had technically successful bilateral IPSS catheterization and are the subjects of this study. All 27 of these patients had IPS/P ACTH ratio greater than 2 at baseline or 3 after CRH stimulation, consistent with CD, and all 27 lateralized. The median age at diagnosis was 42 years (range 21-69 years) and 85% were female (N=23). The median tumor size on MRI was 5 mm (range 3-8 mm). In 22/27 (81%) patients, the result of the IPSS lateralization was concordant with MRI findings. When MRI and BIPSS lateralization agreed, 21/22 (95%) were confirmed by surgical pathology. Of the 5 cases where MRI and BIPSS disagreed on laterality, the operative report was consistent with MRI lateralization in 3/5 cases, and bilateral disease in the remaining 2 cases. There were no cases where BIPSS lateralization was correct when MRI lateralization was incorrect. Overall, MRI correctly lateralized 26/27 cases (96%), whereas BIPSS correctly lateralized 23/27 (85%). In the subset of 13 patients with tumors measuring Conclusion When a tumor is visible on MRI, regardless of its size (≥ 3mm), BIPSS does not add to the accuracy of determining tumor lateralization. BIPSS may best be reserved for situations where the diagnosis of CD is in question. Further studies are required to determine the value of BIPSS in lateralizing the source of CD in patients without visible tumor. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Context The 2012 Endocrine Society Clinical Practice Guidelines recommend that men aged 50 years or older with a diagnosis of hypogonadism undergo bone mineral density (BMD) testing. Objective The objective of this study was to determine the frequency at which men aged 50 years or older with a diagnosis of hypogonadism undergo BMD testing, and if found to have low BMD, are subsequently treated with an osteoporosis medication. Methods A retrospective chart review was conducted at a large academic medical center. Inclusion requirements were an International Classification of Diseases (ICD)-9 or -10 code for hypogonadism at any time between July 1, 2012 and September 30, 2020. Patients were followed until the date of BMD assessment or censoring (September 30, 2021). BMD results and treatment with osteoporosis medication were recorded. Results A total of 10 169 men with hypogonadism were identified, of whom the mean age was 63.4 (± 9.2), 86.3% White, mean body mass index 31.3 with prevalence of chronic kidney disease, type 2 diabetes, and hypertension of 20.6%, 36.9%, and 68.2%, respectively. The percentage that underwent BMD testing was 7.2%, of which 352 (48.4%) and 87 (12.0%) had osteopenia and osteoporosis, respectively. Among the 87 patients with osteoporosis, 57.5% were treated with an osteoporosis medication. Conclusion Only 7.2% of hypogonadal men underwent BMD testing, and among them, 12.0% were found to have osteoporosis. Among those with osteoporosis, 57.5% underwent treatment with osteoporosis medication. Further studies are needed to determine why so few men with hypogonadism undergo BMD assessment and what systems can be put in place to overcome this clinical conundrum.

Aim: Premixed insulin (premix) , conventionally administered twice daily, is often used in the US to treat T2D that is suboptimally controlled with BI, particularly for people with consistent eating patterns who require affordable treatment. This analysis evaluated use of once daily iGlarLixi vs. premix on T2D outcomes. Method: This retrospective analysis of the US Optum Clinformatics database compared outcomes in adults (≥18 y) with T2D who previously received BI and newly initiated iGlarLixi or premix. Persistence (primary endpoint) , adherence, healthcare resource utilization (HRU) , costs, any hypoglycemia, and HbA1c change were assessed at 12 months. Results: After propensity score matching, cohorts (n=834 each) were well balanced with respect to age, HbA1c, use of oral agents, BI, and HRU. The primary endpoint was met with persistence being statistically significantly higher for iGlarLixi vs. premix at 12 months. Adherence and HbA1c reduction were similar between groups, whereas hypoglycemia rates, HRU, and costs were numerically lower for iGlarLixi (Table) . Conclusion: In this observational study, once daily iGlarLixi was an effective post-BI treatment with higher treatment persistence than premixed insulin, with similar adherence and HbA1c reduction, and numerically lower hypoglycemia rates, HRU, and costs. Disclosure R.Lajara: None. C.Heller: Consultant; Sanofi, Employee; Aetion. K.M.Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. E.Lew: Employee; Sanofi. X.Li: Employee; Eisai Co., Ltd., Sanofi. T.A.Dex: Employee; Sanofi, Stock/Shareholder; Pfizer Inc., Teva Pharmaceutical Industries Ltd., Viatris Inc. R.Kilpatrick: Speaker's Bureau; Abbott Diabetes, Amgen Inc., Novo Nordisk, Sanofi. Funding Sanofi

Aim: When T2D is suboptimally controlled with BI, 1-3 daily injections of prandial insulin are commonly added (BB regimen) . Once daily iGlarLixi is an alternative treatment. This analysis evaluated the use of iGlarLixi vs. BB on T2D outcomes. Methods: This retrospective analysis of the US Optum Clinformatics database compared outcomes in adults (≥18 y) with T2D who previously received BI and newly initiated iGlarLixi or BB between Jan 1, 2017, and Jun 30, 2020. Persistence (primary endpoint) , adherence, healthcare resource utilization (HRU) , costs, any hypoglycemia, and HbA1c change were assessed at 12 months. Results: Propensity score matching generated cohorts (n=1070 each) that were well balanced with similar mean ± SD age (iGlarLixi: 63.9 ± 11.0 y; BB: 64.5 ± 11.3 y) , HbA1c (iGlarLixi: 9.2 ± 1.7%; BB: 9.2 ± 1.8%) , oral agent use, BI use, and HRU. The primary endpoint was met with treatment persistence being statistically significantly higher for iGlarLixi vs. BB at 12 months. Adherence was numerically higher for iGlarLixi, and hypoglycemia rates, HRU and costs, numerically lower. HbA1c reduction was similar between groups (Table) . Conclusions: In this observational study, initiation of once daily iGlarLixi vs. BB insulin was associated with higher persistence and similar HbA1c reduction without increasing HRU or costs. Disclosure K.M. Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. C. Heller: Consultant; Sanofi. Employee; Aetion. R. Lajara: None. E. Lew: Employee; Sanofi. X. Li: Employee; Eisai Co., Ltd., Sanofi. T.A. Dex: Employee; Sanofi. Stock/Shareholder; Pfizer Inc., Teva Pharmaceutical Industries Ltd., Viatris Inc. R. Kilpatrick: Speaker's Bureau; Abbott Diabetes, Amgen Inc., Novo Nordisk, Sanofi. Funding Sanofi

Tirzepatide (TZP) is a novel dual GIP/GLP-1 receptor agonist in development for treatment of type 2 diabetes (T2D) . TZP 5 mg, mg, and 15 mg demonstrated superiority versus semaglutide 1 mg (SEMA) and titrated insulin degludec (iDeg) in HbA1c change from baseline and proportion of patients reaching HbA1c Disclosure K.M. Pantalone: Consultant; AstraZeneca, Bayer AG, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. Research Support; Bayer AG, Merck & Co., Inc., Novo Nordisk. Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. A. Viljoen: Advisory Panel; Eli Lilly and Company, Mundipharma. Consultant; Amgen Inc., Daiichi Sankyo. Research Support; Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk A/S, Sanofi. R.J. Galindo: Advisory Panel; Sanofi, WW International, Inc. Research Support; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk. X. Cui: Employee; Eli Lilly and Company. R. Huh: None. L. Fernandez Lando: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Patel: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

Objective To compare glycemic efficacy of Technosphere insulin (TI) versus that of insulin aspart (IA), each added to basal insulin, in type 2 diabetes. Methods This randomized, 24-week trial included subjects aged from 18 to 80 years who were treated with subcutaneous insulin for 3 months and had glycated hemoglobin (HbA1C) levels of 7.0% to 11.5%. After receiving stabilized insulin glargine doses during a 4-week lead in, the subjects were randomized to TI or IA. The primary end point was an HbA1C change from baseline, with the differences analyzed by equivalence analyses. Results In the overall cohort (N = 309; males, 23.3%), mean (SD) age was 58.5 (8.4) years, body mass index was 30.8 (4.7) kg/m2, weight was 82.2 (13.6) kg, and duration of diabetes was 12.2 (7.1) years. An intention-to-treat cohort had 150 subjects randomized to TI (mean [SD] HbA1C: 8.9% [1.1%]) and 154 randomized to IA (mean [SD] HbA1C: 9.0% [1.3%]). At 24 weeks, mean (SD) HbA1C value declined to 7.9% (1.3%) and 7.7% (1.1%) in the TI and IA cohorts, respectively. A treatment difference of 0.26% was not statistically significant, but the predefined equivalency margin was not met. Subjects receiving TI lost 0.78 kg compared to baseline; subjects receiving IA gained 0.23 kg (P =.0007). The incidence of mild/moderate hypoglycemia was lower for the TI cohort, though not statistically significant. Conclusion Both TI and IA resulted in significant and clinically meaningful HbA1C reductions. TI also resulted in significant and clinically meaningful weight reductions. These data support the use of inhaled insulin as a treatment option for individuals with type 2 diabetes.

Maturity-onset diabetes of the young, or MODY-monogenic diabetes, is a not-so-rare collection of inherited disorders of non-autoimmune diabetes mellitus that remains insufficiently diagnosed despite increasing awareness. These cases are important to efficiently and accurately diagnose, given the clinical implications of syndromic features, cost-effective treatment regimen, and the potential impact on multiple family members. Proper recognition of the clinical manifestations, family history, and cost-effective lab and genetic testing provide the diagnosis. All patients must undergo a thorough history, physical examination, multigenerational family history, lab evaluation (glycated hemoglobin A1c [HbA1c], glutamic acid decarboxylase antibodies [GADA], islet antigen 2 antibodies [IA-2A], and zinc transporter 8 [ZnT8] antibodies). The presence of clinical features with 3 (or more) negative antibodies may be indicative of MODY-monogenic diabetes, and is followed by genetic testing. Molecular genetic testing should be performed before attempting specific treatments in most cases. Additional testing that is helpful in determining the risk of MODY-monogenic diabetes is the MODY clinical risk calculator (>25% post-test probability in patients not treated with insulin within 6 months of diagnosis should trigger genetic testing) and 2-hour postprandial (after largest meal of day) urinary C-peptide to creatinine ratio (with a ≥0.2 nmol/mmol to distinguish HNF1A- or 4A-MODY from type 1 diabetes). Treatment, as well as monitoring for microvascular and macrovascular complications, is determined by the specific variant that is identified. In addition to the diagnostic approach, this article will highlight recent therapeutic advancements when patients no longer respond to first-line therapy (historically sulfonylurea treatment in many variants). LEARNING OBJECTIVES: Upon completion of this educational activity, participants should be able to: Identify risk factors and learn when to suspect MODY-monogenic diabetes. Obtain appropriate diagnostic testing and evaluation prior to treatment. Determine appropriate monitoring and treatment for microvascular and macrovascular comorbidities. Recognize the recommended approach to treatment and monitoring that was performed in a patient with MODY-monogenic diabetes. TARGET AUDIENCE: This continuing medical education activity should be of substantial interest to endocrinologists and all health care professionals who care for people with diabetes mellitus.

Despite treatment advances leading to improved outcomes over the past 2 decades, cardiovascular (CV) disease (CVD) remains the leading cause of morbidity and mortality in people with diabetes. People with type 2 diabetes (T2D) have a 2‐ to 4‐fold increased risk of CVD and CV death. Individuals with T2D have not seen the same improvements in CV morbidity and mortality as those without T2D. Given this, it is important to understand the CV impact of drugs used to treat T2D. In patients with T2D, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have shown a reduction in HbA1c and body weight regardless of their differences in chemical structure and pharmacokinetic variables. Glycaemic efficacy, accompanied by the potential for weight reduction and a low risk of hypoglycaemia, has moved GLP‐1 RAs to the first treatment of choice following metformin monotherapy in the latest American Diabetes Association treatment guidelines. Additionally, all GLP‐1 RAs have shown CV safety and several have proven CV benefit. GLP‐1 RAs have been evaluated in cardiovascular outcomes trials (CVOTs) of varying sizes, designs and patient populations with differing reported effects on CV outcomes. The purpose of this article is to review the completed GLP‐1 RA CVOTs with special attention to how their design, size, patient populations and conduct may influence the interpretation of results.

OBJECTIVE To assess patient characteristics and treatment factors associated with uncontrolled type 2 diabetes (T2D) and the probability of hemoglobin A1c (A1C) goal attainment. RESEARCH DESIGN AND METHODS This was a retrospective cohort study using the electronic health record at Cleveland Clinic. Patients with uncontrolled T2D (A1C >9%) were identified on the index date of 31 December 2016 (n = 6,973) and grouped by attainment (n = 1,653 [23.7%]) or nonattainment (n = 5,320 [76.3%]) of A1C RESULTS For the entire population, median age at index date was 57.7 years (53.3% male), and the majority were white (67.2%). Median A1C was 10.2%. Obesity (50.6%), cardiovascular disease (46.9%), and psychiatric disease (61.1%) were the most common comorbidities. Metformin (62.7%) and sulfonylureas (38.7%) were the most common antidiabetes medications. Only 1,653 (23.7%) patients achieved an A1C CONCLUSIONS A minority of patients with an A1C >9% achieved an A1C

OBJECTIVE To determine if natural language processing (NLP) improves detection of nonsevere hypoglycemia (NSH) in patients with type 2 diabetes and no NSH documentation by diagnosis codes and to measure if NLP detection improves the prediction of future severe hypoglycemia (SH). RESEARCH DESIGN AND METHODS From 2005 to 2017, we identified NSH events by diagnosis codes and NLP. We then built an SH prediction model. RESULTS There were 204,517 patients with type 2 diabetes and no diagnosis codes for NSH. Evidence of NSH was found in 7,035 (3.4%) of patients using NLP. We reviewed 1,200 of the NLP-detected NSH notes and confirmed 93% to have NSH. The SH prediction model (C-statistic 0.806) showed increased risk with NSH (hazard ratio 4.44; P < 0.001). However, the model with NLP did not improve SH prediction compared with diagnosis code–only NSH. CONCLUSIONS Detection of NSH improved with NLP in patients with type 2 diabetes without improving SH prediction.

Summary Objective In shared medical appointments (SMAs), multiple patients with a similar clinical diagnosis are seen by a multidisciplinary team for interactive group sessions. Very few studies have specifically studied SMAs and weight loss in patients with obesity. This study compared weight loss outcomes and anti‐obesity medication (AOM) access between patients with obesity managed through (SMAs) versus individual appointments. Methods Retrospective study of adults seen for obesity between September 2014 and February 2017 at Cleveland Clinic Institute of Endocrinology and Metabolism. Percent weight loss from baseline was compared between two propensity score‐matched populations: patients who attended ≥1 SMA and patients managed with individual medical appointments. Results From all eligible patients identified (n=310 SMA, n=1,993 non‐SMA), 301 matched pairs were evaluated for weight loss. The SMA group (n=301) lost a mean of 4.2%, 5.2% and 3.8% of baseline weight over 6, 12 and 24 months; the non‐SMA group (n=301) lost significantly less weight (1.5%, 1.8% and 1.6%, respectively) (paired t‐test, P

Type 2 diabetes (T2D) has a strong association with atrial fibrillation (AF) which increases risk of thromboembolic events, heart failure, and frequent hospitalizations. Metformin is the first-line medication for T2D with proposed anti-inflammatory, pro-metabolic, and cardio-protective benefits. Our objective was to investigate if initial therapy with metformin is associated with reduced incidence of AF in comparison to other non-insulin anti-hyperglycemic agents in patients with newly diagnosed T2D.This retrospective cohort analysis included adults with a new diagnosis of T2D who were started on monotherapy (except insulin) between 2007 and 2017, without prior anti-hyperglycemic agent use, history of arrhythmias, or estimated GFR (eGFR) ≤ 30 ml/min. A multivariate analysis was performed using a fine-gray regression competing risk analysis to control for confounding variables after which pooled hazard ratios and 95 % confidence intervals were reported. Patients were followed until the end of study date, development of AF, addition of more anti-hyperglycemic agents, or death, whichever occurred first.Among 4584 metformin initiators compared to 1080 non-metformin monotherapy initiators, 10-year cumulative incidence of AF in metformin group was 5.2 % as compared to 8.1 % with other agents which was not statistically significant. Competing risk analysis did not demonstrate reduced rates of AF with metformin use (HR 0.92, 95 % CI 0.69 to 1.21; P = 0.55). Increased age and the presence of congestive heart failure were associated with significantly higher risk of AF in both groups (HR: 1.29, 95 % CI: 1.21 to 1.37; P ≤ 0.001; HR: 2.73, 95 % CI: 1.62 to 4.61; P ≤ 0.001, respectively).Initiation of metformin as a first line monotherapy for T2D, when compared to other non-insulin monotherapies, was not associated with decreased risk of developing AF in this retrospective observational study.

Aims To evaluate HbA1c and body weight changes when semaglutide 0.5 mg or 1.0 mg once weekly (QW) is switched to dulaglutide 3.0 mg or 4.5 mg QW via exposure-response modelling. Materials and methods HbA1c and body weight time-course models were developed and validated with data from SUSTAIN 1 to 10 trials for semaglutide and AWARD-11 trial for dulaglutide. Simulations were conducted for HbA1c and body weight over 52 weeks. In the initial 26 weeks, semaglutide was initiated at 0.25 mg and titrated to 0.5 or 1.0 mg QW via 4-weekly stepwise titration, followed by 26 weeks of dulaglutide initiated at 0.75 or 1.5 mg QW and escalated to 3.0 or 4.5 mg QW via 4-weekly stepwise titration. Results At 26 weeks, model-predicted mean changes from baseline in HbA1c and weight for semaglutide 0.5 mg were up to -1.55% and -3.44 kg, respectively. After switching to dulaglutide 3.0 mg, further reductions were 0.19% and 1.40 kg, respectively, at 52 weeks. Predicted mean HbA1c and weight changes for semaglutide 1.0 mg at 26 weeks were -1.84% and -4.96 kg, respectively; after switching to dulaglutide 4.5 mg, HbA1c was maintained with additional weight reduction of up to 0.57 kg at 52 weeks. Glycemic control was preserved switching from semaglutide 1.0 mg to dulaglutide 3.0 mg. Conclusions Switching from semaglutide 0.5 mg to dulaglutide 3.0 or 4.5 mg with dose escalation potentially yields additional HbA1c and weight reductions; switching from semaglutide 1.0 mg to dulaglutide 4.5 mg may enhance weight loss. This article is protected by copyright. All rights reserved.

The jury is still out on whether a low-carbohydrate, ketosis-inducing diet is an effective and safe adjunctive therapy to insulin in type 1 diabetes. The limited published literature reports an association with weight loss and improved glycemic control and may, over the long-term, lead to reduced macrovascular and microvascular harm. However, the attendant increased risk of dyslipidemia, diabetic ketoacidosis, and hypoglycemia warrant caution, close monitoring of patients who embark on the diet, and further research.