Polygenic subtype identified in ACCORD trial displays a favorable type 2 diabetes phenotype in the UKBiobank population.

INTRODUCTION: We previously identified a genetic subtype (C4) of type 2 diabetes (T2D), benefitting from intensive glycemia treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Here, we characterized the population of patients that met the C4 criteria in the UKBiobank cohort. RESEARCH DESIGN AND METHODS: Using our polygenic score (PS), we identified C4 individuals in the UKBiobank and tested C4 status with risk of developing T2D, cardiovascular disease (CVD) outcomes, and differences in T2D medications. RESULTS: C4 individuals were less likely to develop T2D, were slightly older at T2D diagnosis, had lower HbA1c values, and were less likely to be prescribed T2D medications (P < .05). Genetic variants in MAS1 and IGF2R, major components of the C4 PS, were associated with fewer overall T2D prescriptions. CONCLUSION: We have confirmed C4 individuals are a lower risk subpopulation of patients with T2D.

Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison.

AIMS: To compare the efficacy and safety of tirzepatide 5, 10 and 15 mg with subcutaneous semaglutide 0.5 mg as second-line treatment for adults with type 2 diabetes mellitus, after metformin monotherapy, using adjusted indirect treatment comparisons (aITCs). METHODS: The aITCs were performed using the Bucher method to compare the relative efficacy and safety of tirzepatide 5, 10 and 15 mg versus semaglutide 0.5 mg via a common comparator (subcutaneous semaglutide 1.0 mg) based on trial results from SURPASS-2 (NCT03987919) and SUSTAIN7 (NCT02648204). RESULTS: All tirzepatide doses showed statistically significantly greater reductions in glycated haemoglobin, body weight and body mass index from baseline to week 40, with a comparable adverse event (AE) profile and no statistically significant differences in the odds of gastrointestinal AEs versus semaglutide 0.5 mg. Furthermore, all tirzepatide doses showed greater odds of patients achieving HbA1c targets of ≤ 6.5 % (≤48 mmol/mol) and < 7.0 % (<53 mmol/mol) and weight loss targets of ≥ 5 % and ≥ 10 %, versus semaglutide 0.5 mg. CONCLUSIONS: In these aITCs, glycated haemoglobin and weight reductions were significantly greater for all tirzepatide doses versus semaglutide 0.5 mg with a comparable AE profile. These findings provide comparative effectiveness insights in the absence of a head-to-head clinical trial.

An Obesity-Centric Approach with and Without Anti-Obesity Medications Compared to the Usual-Care Approach to Management of Patients with Obesity and Type 2 Diabetes in an Employer Setting: A Pragmatic Randomized Controlled Trial (EMPOWER-T2D).

INTRODUCTION: This study aimed to compare weight loss and glycated hemoglobin (HbA1c)-reduction effects of two obesity-centric, weight-loss management approaches (with or without anti-obesity medication) versus usual glucose-centric care in patients with obesity and type 2 diabetes. METHODS: Single-center, randomized, open-label, 3-armed, parallel-group, pragmatic, noninferiority trial, July 2020 to August 2022. Adults enrolled in the Cleveland Clinic Employee Health Plan (body mass index [BMI] ≥ 30 kg/m2, type 2 diabetes diagnosis, HbA1c > 7.5%) were randomized to usual glucose-centric management ("Usual-Care" group) or one of two obesity-centric management strategies: participation in a weight management program plus anti-obesity medication ("WMP + AOM" group), or WMP participation without anti-obesity medication ("WMP-Only" group). Primary endpoints were changes in weight and HbA1c, baseline to month 12. RESULTS: Due to enrollment and retention challenges, largely related to COVID-19, only 74/300 planned participants were randomized and the study was terminated early. Participants were predominantly female (59%), median (interquartile range [IQR]) age 53.5 (47, 60) years, 68% white, with baseline median (IQR) BMI and HbA1c of 37.4 (34.2, 42.7) kg/m2 and 8.8% (7.9%, 10.4%), respectively. At month 12, mean (90% confidence interval [CI]) percentage weight change in the Usual-Care, WMP-Only, and WMP + AOM groups was - 4.5% (- 6.5%, - 2.5%), - 6.7% (- 8.7%, - 4.7%), and - 8.7% (- 10.7%, - 6.8%), respectively; mean (90% CI) HbA1c change was - 1.7% (- 2.1%, - 1.2%), - 2.2% (- 2.7%, - 1.8%), and - 2.2% (- 2.6%, - 1.7%), respectively. WMP + AOM was superior to Usual-Care for weight change (P = 0.02); both WMP + AOM and WMP-Only were noninferior (P ≤ 0.01) to Usual-Care for change in HbA1c. CONCLUSIONS: Including anti-obesity medication was associated with superior weight loss with noninferior HbA1c reductions, warranting further evaluation in larger study populations of obesity-focused approaches to type 2 diabetes management. Graphical abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov NCT03799198.

An interpretable predictive deep learning platform for pediatric metabolic diseases.

OBJECTIVES: Metabolic disease in children is increasing worldwide and predisposes a wide array of chronic comorbid conditions with severe impacts on quality of life. Tools for early detection are needed to promptly intervene to prevent or slow the development of these long-term complications. MATERIALS AND METHODS: No clinically available tools are currently in widespread use that can predict the onset of metabolic diseases in pediatric patients. Here, we use interpretable deep learning, leveraging longitudinal clinical measurements, demographical data, and diagnosis codes from electronic health record data from a large integrated health system to predict the onset of prediabetes, type 2 diabetes (T2D), and metabolic syndrome in pediatric cohorts. RESULTS: The cohort included 49 517 children with overweight or obesity aged 2-18 (54.9% male, 73% Caucasian), with a median follow-up time of 7.5 years and mean body mass index (BMI) percentile of 88.6%. Our model demonstrated area under receiver operating characteristic curve (AUC) accuracies up to 0.87, 0.79, and 0.79 for predicting T2D, metabolic syndrome, and prediabetes, respectively. Whereas most risk calculators use only recently available data, incorporating longitudinal data improved AUCs by 13.04%, 11.48%, and 11.67% for T2D, syndrome, and prediabetes, respectively, versus models using the most recent BMI (P < 2.2 × 10-16). DISCUSSION: Despite most risk calculators using only the most recent data, incorporating longitudinal data improved the model accuracies because utilizing trajectories provides a more comprehensive characterization of the patient's health history. Our interpretable model indicated that BMI trajectories were consistently identified as one of the most influential features for prediction, highlighting the advantages of incorporating longitudinal data when available.

Endocrinology/Primary Care Pharmacy Collaboration vs Endocrinology Care Alone in Patients With Type 2 Diabetes and A1c >9.

Background: Type 2 diabetes (T2D) requires close collaboration between patients and their care management team, often including endocrinology. Primary care pharmacist impact on diabetes management in collaboration with endocrinology is not well established. Objective: To assess if pharmacy and endocrinology collaboration results in a greater A1c reduction in patients with T2D vs endocrinology alone. Methods: This retrospective, observational cohort study was conducted in adult outpatients with T2D and baseline A1c >9% who saw endocrinology within 1 year preceding the study period (January 1, 2021 to January 1, 2022). Patients were included if they had a follow-up A1c 6 months (±90 days) from index date and completed at least 1 endocrinology visit during the study period. Patients managed by endocrinology/primary care pharmacist collaboration (Endo/PharmD) were compared with those who received endocrinology care alone (Endo). Primary outcome was change in A1c from baseline to 6 months. Secondary outcomes included total number of completed visits and percentage of patients achieving A1c <6.5%, <7%, <8%, and <9% between groups at 6 months. Results: A total of 418 patients were included (22 Endo/PharmD, 396 Endo). The change in follow-up A1c was not significantly different between groups, -0.481% (standard error [SE] = 0.396); P = 0.6179. Endo/PharmD patients had significantly more provider visits during the study period (5.3 ± 2.3 vs 2.3 ± 1.2; P < 0.001). No significant difference was observed in odds of A1c goal attainment between groups at 6 months. Conclusion and Relevance: Endocrinology/primary care pharmacist collaboration occurred infrequently but was associated with a trend toward greater A1c reduction in patients with T2D and A1c >9%.

Therapeutic Inertia in the Management of Type 2 Diabetes: A Narrative Review.

Adequate glycemic control is key to prevent morbi-mortality from type 2 diabetes (T2D). Despite the increasing availability of novel, effective, and safe medications for the treatment of T2D, and periodically updated guidelines on its management, the overall rate of glycemic goal attainment remains low (around 50%) and has not improved in the past decade. Therapeutic inertia (TI), defined as the failure to advance or de-intensify medical therapy when appropriate to do so, has been identified as a central contributor to the lack of progress in the rates of HbA1c goal attainment. The time to treatment intensification in patients not meeting glycemic goals has been estimated to be between 1 and 7 years from the time HbA1c exceeded 7%, and often, even when an intervention is carried out, it proves insufficient to achieve glycemic goals, which led to the concept of intensification inertia. Therefore, finding strategies to overcome all forms of TI in the management of T2D is a fundamental initiative, likely to have an enormous impact in health outcomes for people with T2D. There are several factors that have been described in the literature leading to TI, including clinician-related, patient-related, and healthcare system-related factors, which are discussed in this review. Likewise, several interventions addressing TI had been tested, most of them proving limited efficacy. Within the most effective interventions, there appear to be two common factors. First, they involve a team-based effort, including nurses, pharmacists, and diabetes educators. Second, they were built upon a framework based on results of qualitative studies conducted in the same context where they were later implemented, as will be discussed in this article. Given the complex nature of TI, it is crucial to use a research method that allows for an in-depth understanding of the phenomenon. Most of the literature on TI is focused on quantitatively describing its consequences; unfortunately, however, not many study groups have undertaken qualitative studies to deeply investigate the drivers of TI in their diverse contexts. This is particularly true in the United States, where there is an abundance of publications exploring the effects of different strategies to overcome TI in type 2 diabetes, but a severe shortage of qualitative studies aiming to truly understand the phenomenon.

The evolution of type 2 diabetes management: glycemic control and beyond with SGLT-2 inhibitors and GLP-1 receptor agonists.

Diabetes mellitus (DM) is one of the most prevalent diseases encountered by the primary care physician on a daily basis. Complications associated with DM can include nephropathy, neuropathy, and retinopathy ("microvascular complications"), along with cardiovascular disease (CVD), which can include myocardial infarction (MI) and strokes ("macrovascular complications"). In the 1990s, landmark clinical trials demonstrated that intensive glycemic control can reduce the risk of developing microvascular complications, but reduction in macrovascular complications with intensive glycemic control was not clearly demonstrated. At this point, intensive glycemic control became the standard of care (SOC). In the 2000s, additional trials evaluating the effect of intensive glycemic control in patients with type 2 diabetes mellitus (T2D) and established CVD, or risk factors for CVD, subsequently failed to identify a macrovascular benefit from intensive glycemic control, and one of the trials was terminated early because of an increase in the risk of mortality observed among patients assigned to receive intensive glycemic control. These results led to less strict glycemic targets being recommended in older patients, particularly those with established CVD. In 2007, everything changed after a report surfaced suggesting that rosiglitazone was associated with a significant increase in the risk of MI, as well as an increase in the risk of cardiovascular death that was of borderline significance. As a result, in 2008, the FDA mandated that all new diabetes medications must exclude an unacceptable level of risk for atherosclerotic cardiovascular disease (ASCVD) prior to drug approval, and thus undergo additional cardiovascular safety trials. Accordingly, through these trials, some of the newer agents, particularly sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), were demonstrated to reduce the risk of major adverse cardiovascular events (MACEs), independent of their effect on glycemic control. These findings subsequently led to further trials to evaluate the effects of some of these therapies on the risk of chronic kidney disease (CKD) progression, as well as adverse heart failure-related outcomes. SGLT-2 inhibitors have been demonstrated to reduce the risk of CKD progression, as well as a reduction in the risk of cardiovascular death or hospitalization secondary to heart failure in patients with both reduced ejection and preserved ejection fractions. A trial evaluating the effects of GLP-1RA on CKD outcomes is ongoing. The aim of this narrative review article, compiled by identifying relevant studies via the utilization of PubMed, is to provide a broad overview over the various clinical trials and analyses that have led to current diabetes management guidelines, and ultimately, help guide primary care physicians in selecting therapies that will not only improve glycemic control and reduce the risk of microvascular complications, but also reduce the risk of macrovascular disease in their patients with T2D.

Erratum: Addressing Therapeutic Inertia: Development and Implementation of an Electronic Health Record-Based Diabetes Intensification Tool. Diabetes Spectrum 2023;36:161-170 (https://doi.org/10.2337/ds22-0031).

[This corrects the article DOI: 10.2337/ds22-0031.].

Initiation of iGlarLixi Versus Basal-Bolus Insulin in Adults With Type 2 Diabetes Advancing From Basal Insulin Therapy: The SoliComplex Real-World Study.

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 <0.001). Adherence was numerically higher for iGlarLixi, and hypoglycemia events, HCRU, and costs were numerically lower for iGlarLixi. A1C reduction from baseline was slightly greater for basal-bolus insulin. Results for both subgroups (≥65 years of age and baseline A1C ≥9%) were similar to those of the overall population. 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.

The impact of obesity on cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes treated with finerenone: Post hoc analysis of the FIDELITY study.

AIM: To assess the effect of finerenone on the risk of cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes, with and without obesity. MATERIALS AND METHODS: A post hoc analysis of the prespecified pooled FIDELITY dataset assessed the association between waist circumference (WC), composite cardiovascular and kidney outcomes, and the effects of finerenone. Participants were stratified by WC risk groups (representing visceral obesity) as low-risk or high-very high-risk (H-/VH-risk). RESULTS: Of 12 986 patients analysed, 90.8% occupied the H-/VH-risk WC group. Incidence of the composite cardiovascular outcome was similar between finerenone and placebo in the low-risk WC group (hazard ratio [HR] 1.03; 95% confidence interval [CI], 0.72-1.47); finerenone reduced the risk in the H-/VH-risk WC group (HR 0.85; 95% CI, 0.77-0.93). For the kidney outcome, the risk was similar in the low-risk WC group (HR 0.98; 95% CI, 0.66-1.46) and reduced within the H-/VH-risk WC group (HR 0.75; 95% CI, 0.65-0.87) with finerenone versus placebo. There was no significant heterogeneity between the low-risk and H-/VH-risk WC groups for cardiovascular and kidney composite outcomes (P interaction = .26 and .34, respectively). The apparent greater benefit of finerenone on cardiorenal outcomes but lack of significant heterogeneity observed in H-/VH-risk WC patients may be because of the small size of the low-risk group. Adverse events were consistent across WC groups. CONCLUSION: In FIDELITY, benefits of finerenone in lowering the risk of cardiovascular and kidney outcomes were not significantly modified by patient obesity.

Association of Metformin, Dipeptidyl Dipeptidase-4 Inhibitors, and Insulin with Coronavirus Disease 2019-Related Hospital Outcomes in Patients with Type 2 Diabetes.

OBJECTIVE: The effects of diabetes medications on COVID-19 hospitalization outcomes have not been consistent. We sought to determine the effect of metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), and insulin on admission to the intensive care unit (ICU), need for assisted ventilation, development of renal insufficiency, and mortality in patients admitted with COVID-19 infection after controlling for clinical variables and other relevant diabetes-related medications in patients with type 2 diabetes mellitus (DM). METHODS: This was a retrospective study of patients hospitalized with COVID-19 from a single hospital system. Univariate and multivariate analyses were performed that included demographic data, glycated hemoglobin, kidney function, smoking status, insurance, Charlson comorbidity index, number of diabetes medications, and use of angiotensin-converting enzyme inhibitors and statin prior to admission and glucocorticoids during admission. RESULTS: A total of 529 patients with type 2 DM were included in our final analysis. Neither metformin nor DPP4i prescription was associated with ICU admission, need for assisted ventilation, or mortality. Insulin prescription was associated with increased ICU admission but not with need for assisted ventilation or mortality. There was no association of any of these medications with development of renal insufficiency. CONCLUSIONS: In this population, limited to type 2 DM and controlled for multiple variables that have not been consistently studied (such as a measure of general health, glycated hemoglobin, and insurance status), insulin prescription was associated with increased ICU admission. Metformin and DPP4i prescriptions did not have an association with the outcomes.

Addressing Therapeutic Inertia: Development and Implementation of an Electronic Health Record-Based Diabetes Intensification Tool.

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 (<8%) were not significantly improved between IMP and non-IMP sites at 6 months (range 42.9-46.5%) or 12 months (range 46.5-53.1%). In phase 3, fewer patients at IMP sites versus non-IMP sites achieved the goal at 12 months (46.7 vs. 52.3%, P = 0.02). In phases 1-3, mean changes in A1C from baseline to 6 and 12 months (range -0.88 to -1.08%) were not significantly different between IMP and non-IMP sites. 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.

Surgical Management of Giant Prolactinomas: A Descriptive Study.

Introduction: Giant prolactinoma (GP) is a rare pituitary lactotropic cell tumor larger than 4 cm in its widest dimension, and is less likely than a smaller prolactinoma to achieve prolactin normalization on dopamine agonist (DA) monotherapy. There is a paucity of data on the circumstances and outcomes of second-line management of GP with surgery. Herein, our institution's experience with the surgical management of GPs is described. Methods: A single-center retrospective analysis was conducted of patients who underwent surgery for giant prolactinoma from 2003 to 2018. A chart review was conducted for demographic data, clinical features, laboratory and radiographic findings, operative and pathology reports, perioperative management, and clinical outcomes in follow-up. Descriptive statistics were used. Results: Of 79 prolactinoma cases, 8 patients had GP with a median age of 38 years (range 20-53), 75% (6/8) were male, with a median largest tumor dimension of 6 cm (range 4.6-7.7), and a median prolactin level of 2,500 µg/L (range 100->13,000). Six patients had transsphenoidal surgery for dopamine agonist (DA) resistance or intolerance. Two patients had a craniotomy for a missed diagnosis; one was due to the hook effect. No tumor resections were complete by either surgical approach; all had persistent hyperprolactinemia requiring postoperative DA therapy, and two patients had an additional craniotomy procedure for further tumor debulking. There was no recovery of pituitary axes and postoperative deficits were common. Remission as defined by prolactin normalization occurred in 63% (5/8) at a median time of 36 months (range 14-63 months) on DA therapy after surgery with a follow-up of 3-13 years. Conclusions: GPs infrequently require surgical resection, which is generally incomplete and requires adjuvant therapy. Given the rarity of surgery for GPs, multi-institutional or registry studies would yield clearer guidance on optimal management.

Design and rationale of FINE-REAL: A prospective study of finerenone in clinical practice.

AIMS: Contemporary 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. METHODS: FINE-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. RESULTS: The 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. CONCLUSIONS: FINE-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.

Time to Reach Glycaemic and Body Weight Loss Thresholds with Tirzepatide in Patients with Type 2 Diabetes: A Pre-planned Exploratory Analysis of SURPASS-2 and SURPASS-3.

INTRODUCTION: Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, provides clinically meaningful improvements in glycaemic control and body weight loss in people with type 2 diabetes. The early efficacy profile of tirzepatide after treatment initiation is of interest. In this exploratory pre-planned analysis, we evaluated the time to achieve glycaemic control and body weight loss thresholds with tirzepatide. METHODS: In two randomised studies, we compared time to achieve HbA1c (< 7.0% and ≤ 6.5%) and weight loss (≥ 5%, SURPASS-2 only) thresholds among people treated with tirzepatide (5, 10, and 15 mg), semaglutide 1 mg in SURPASS-2, and titrated insulin degludec in SURPASS-3. Longitudinal logistic regression models were used to explore the proportion of participants achieving HbA1c and body weight loss thresholds at 4, 12, and 24 weeks. The time to achieve these thresholds was analysed and compared between groups using the Cox proportional-hazards model. RESULTS: Overall, greater proportions of participants achieved the HbA1c and body weight loss thresholds at 4, 12, and 24 weeks with tirzepatide compared with semaglutide 1 mg and insulin degludec. The median time to achieve HbA1c < 7.0% (8.1 weeks with each tirzepatide dose, 12.0 weeks with semaglutide 1 mg, and 12.1 weeks with insulin degludec) and ≤ 6.5% (12.1, 15.7, and 24.1 weeks, respectively) was faster with tirzepatide than semaglutide 1 mg and insulin degludec. In SURPASS-2, the median time to first achieve a body weight loss of ≥ 5% was faster with tirzepatide 5 mg (16.0 weeks) and 10 and 15 mg (12.4 weeks) than with semaglutide 1 mg (24.0 weeks). CONCLUSION: Analyses of data from SURPASS-2 and -3 revealed that tirzepatide treatment enabled more people with type 2 diabetes to achieve glycaemic thresholds and these were achieved faster than with semaglutide 1 mg or insulin degludec. Tirzepatide-treated participants also achieved a body weight loss of ≥ 5% significantly faster with tirzepatide than with semaglutide 1 mg. TRIAL REGISTRATION NUMBERS: NCT03987919; NCT03882970.

Unmet needs and opportunities for optimal management of patients with type 2 diabetes and chronic kidney disease.

This brief report utilizes EHR data from a large US health system to summarize unmet needs in patients with type 2 diabetes and chronic kidney disease and identifies areas of opportunity to optimize management within this patient population from treatment, screening and monitoring, and health care resource use perspectives.

iGlarLixi versus premixed insulin initiation in adults with type 2 diabetes advancing from basal insulin therapy: The SoliComplex real-world study.

AIM: To compare outcomes in adults with type 2 diabetes (T2D) suboptimally controlled with basal insulin who initiated treatment with iGlarLixi or premixed insulin. METHODS: This retrospective real-world analysis was conducted using data from adults (age ≥ 18 years) with T2D in the US Optum Clinformatics database who had previously received basal insulin and newly initiated iGlarLixi or premixed insulin. Cohorts were propensity-score matched on baseline characteristics using a greedy nearest neighbour-matching algorithm, and outcomes were assessed at 12 months. Subgroup analyses were performed for those aged 65 years or older and those with a baseline HbA1c of 9% or higher. The primary endpoint was treatment persistence in the overall population. Secondary endpoints were treatment adherence, healthcare resource utilization (HRU), costs, hypoglycaemia events and change in HbA1c from baseline. RESULTS: Each cohort comprised 834 participants. In the overall population, treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus premixed insulin: 42.5% versus 39.1%; hazard ratio 0.88; 95% confidence interval 0.778-0.998; P = .0465. Adherence and HbA1c reduction were similar between groups, whereas hypoglycaemia events, HRU and costs were numerically lower for iGlarLixi. Outcomes in both the age 65 years or older subgroup and in those with an HbA1c of 9% or higher were consistent with those for the overall population. CONCLUSIONS: In this observational study in people with T2D suboptimally controlled on basal insulin, once-daily iGlarLixi was an effective treatment alternative to premixed insulin with significantly higher treatment persistence, similar adherence and HbA1c reduction, and numerically lower hypoglycaemia events, HRU and costs, regardless of age or baseline HbA1c.

Impacts of COVID-19 on Glycemia and Risk of Diabetic Ketoacidosis.

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.