Early-Onset Type 2 Diabetes and Tirzepatide Treatment: A Post Hoc Analysis From the SURPASS Clinical Trial Program.

OBJECTIVE: We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide's effects on glycemic control, body weight (BW), and cardiometabolic markers. RESEARCH DESIGN AND METHODS: This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1] and A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. RESULTS: At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P < 0.001) higher glycemic levels (8.5% vs. 8.2%, P < 0.001), higher BW (97 vs. 93 kg, P < 0.001) and BMI (35 vs. 34 kg/m2, P < 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (-2.6% vs. -2.4%), BW (-14 vs. -13 kg), WC (-10 vs. -10 cm), triglycerides (-26% vs. -24%), HDL (7% vs. 7%), and systolic BP (-6 vs. -7 mmHg) were observed in both subgroups with tirzepatide. CONCLUSIONS: Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D.

An Economic Evaluation of the Relationship Between Glycemic Control and Total Healthcare Costs for Adults with Type 2 Diabetes: Retrospective Cohort Study.

INTRODUCTION: Glycemic control is associated with better outcomes among individuals with type 2 diabetes (T2D). This research examines total US all-cause medical costs for adults with T2D with recommended glycemic control (HbA1c < 7%) compared to poor glycemic control (HbA1c ≥ 7%). METHODS: The study used administrative claims data linked to HbA1c laboratory test results from January 1, 2015 through June 30, 2021 to identify adults with T2D with a recorded HbA1c test. Patients with recommended glycemic control at index date were propensity score matched to patients with poor glycemic control. General linear models and two-part models were used to compare all-cause outpatient, drug, acute care and total costs for 1 year post index date. RESULTS: The study included 59,830 propensity-matched individuals. Results indicate that recommended glycemic control, compared to poor glycemic control, was associated with statistically significantly lower all-cause acute care ($23,868 ± $21,776 vs. $24,352 ± $22,223), drug ($10,277 ± $14,671 vs. $10,540 ± $14,928), and total medical costs ($41,381 ± $42,757 vs. $42,054 ± $43,422) but significantly higher outpatient costs ($7290 ± $12,028 vs. $7026 ± $11,587) (all p < 0.0001). Sensitivity analyses examined results based upon alternative HbA1c thresholds of ≤ 6.5% and < 8%. Results were generally robust to alternative HbA1c thresholds, with higher HbA1c thresholds associated with higher all-cause total costs as well as increased savings for having HbA1c below threshold. CONCLUSIONS: Glycemic control was associated with significantly lower all-cause total, drug, and acute care medical costs. Given the high prevalence of T2D in the USA, our results suggest potential economic benefits associated with glycemic control for healthcare providers.

Impact of Weight Change on Glycemic Control and Metabolic Parameters in T2D: A Retrospective US Study Based on Real-World Data.

INTRODUCTION: Weight loss has been identified as a key strategy for improving glycemic and metabolic outcomes in people with type 2 diabetes (T2D). However, the long-term, real-world impact of weight loss on these outcomes remains unclear. This study aimed to investigate (1) the association between weight loss and glycemic control, (2) association between weight loss and metabolic parameters, and (3) predictors of weight loss and how weight change trajectory varies based on index body mass index (BMI). METHODS: A retrospective, longitudinal cohort study using the linked IQVIA Ambulatory electronic medical records and PharMetrics® Plus databases was performed from January 1, 2010 through December 31, 2019 in adults with T2D. Participants were categorized into 1-year and 5-year follow-up cohorts based on their observed weight change over time. Longitudinal values for vital signs and laboratory parameters, including BMI, weight, glycated hemoglobin (HbA1c), and metabolic parameters (liver enzymes and cholesterol), were reported at index date and every 6 months post index date. Multivariable logistic regression analysis was used to evaluate the factors associated with weight loss. RESULTS: Of 1,493,964 people evaluated, 1,061,354 (71%) and 308,320 (20.6%) were classified into the 1-year and 5-year follow-up cohorts. Average HbA1c reductions of 1.2% and 0.5% were observed among people who lost ≥ 15% of index weight in the 1-year and 5-year follow-up cohorts, respectively. Higher weight loss percentages were associated with numerically greater improvements in metabolic parameters. The presence of bariatric surgery and higher index BMIs were identified as the strongest predictors of ≥ 15% and ≥ 10% weight loss in both follow-up cohorts. CONCLUSION: Results from this study suggest that modest and sustained weight loss can lead to clinically meaningful improvements in glycemic and metabolic parameters among people with T2D. These findings highlight the importance of weight management in managing T2D and preventing its associated complications.

Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide.

INTRODUCTION: Limited data are available on the relationship between quality of life (QoL) change and significant degrees of reduction in glycated haemoglobin (HbA1c) and/or weight loss in people with type 2 diabetes (T2D). We explored the associations between HbA1c targets and/or weight loss achieved and patient-reported outcomes (PROs) in adults with T2D treated with tirzepatide, a first-in-class once weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, using pooled data from SURPASS-1 to -5 Phase 3 clinical trials. METHODS: PROs were assessed using five instruments at baseline and endpoint (Week 40 in SURPASS-1, -2 and -5; Week 52 in SURPASS-3 and -4): Impact of Weight on Quality of Life-Lite Clinical Trials Version; Impact of Weight on Self-Perception (IW-SP) questionnaire; Ability to Perform Physical Activities of Daily Living (APPADL); Diabetes Treatment Satisfaction Questionnaire change; and EQ-5D-5L. All PROs were assessed in participants receiving pooled doses of tirzepatide (5, 10 or 15 mg) and achieving HbA1c targets of < 5.7%, ≥ 5.7-≤ 6.5% and > 6.5% or achieving ≥ 0-< 5%, ≥ 5-< 10%, ≥ 10-< 15% and ≥ 15% weight loss from baseline at endpoint. The APPADL, IW-SP and EQ visual analogue scores were evaluated in participants achieving each combination of HbA1c target and weight loss. RESULTS: Achievement of lower HbA1c targets or higher body weight percentage losses were each associated with greater improvements in QoL than achievement of higher HbA1c targets or lower body weight percentage losses, respectively. Achievement of lower HbA1c targets in combination with greater weight loss was generally associated with the best QoL ratings. CONCLUSIONS: Our findings demonstrate that HbA1c targets and significant percentage body weight reduction thresholds need to be achieved for people with T2D to help substantially increase their overall health-related QoL. Tirzepatide treatment may allow a high proportion of people with T2D to achieve these targets, enabling improved QoL. CLINICAL TRIAL REGISTRATION: SURPASS-1: NCT03954834; SURPASS-2: NCT03987919; SURPASS-3: NCT03882970; SURPASS-4: NCT03730662; SURPASS-5: NCT04039503.

Limited data exist about the relationship between quality of life (QoL) and changes in clinical measures, for example management of blood sugar levels and weight, in people with type 2 diabetes. We explored the associations between glucose and weight loss targets achieved and QoL outcomes reported by adults treated with tirzepatide, the first glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for the treatment of people with type 2 diabetes, using data from SURPASS-1 to -5 Phase 3 clinical trials.Five questionnaires, developed to evaluate patients' health-related QoL, were completed by patients at the beginning and end of the clinical trials, which was after 40 weeks for SURPASS-1, -2 and -5 and after 52 weeks for SURPASS-3 and -4, or when the person left the trial if this was before the official end. These questionnaires were: EQ-5D-5L (SURPASS-1 to -5); Impact of Weight on Self-Perception questionnaire (SURPASS-1 to -5); Ability to Perform Physical Activities of Daily Living (SURPASS-1 to -5); Diabetes Treatment Satisfaction Questionnaire change (SURPASS-2 to -5); and Impact of Weight on Quality of Life­Lite Clinical Trials Version (SURPASS-2 only).Overall, achievement of lower glucose targets or higher percentage of body weight losses were each associated with greater improvements in QoL. Achievement of lower glucose targets in combination with greater weight loss was generally associated with the highest health-related QoL ratings.Tirzepatide treatment may allow a high proportion of people with type 2 diabetes to achieve lower glucose levels and higher weight loss, enabling improved health-related QoL.

Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme.

INTRODUCTION: Tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, is approved for glycaemic control for people with type 2 diabetes (T2D). The SURPASS-1 to -5 clinical trials assessed the efficacy of once weekly tirzepatide (5, 10 and 15 mg) versus placebo or active comparators (semaglutide 1 mg, insulin degludec and insulin glargine) in T2D. We evaluated patient-reported outcomes (PROs) that measured overall quality of life (QoL), treatment satisfaction and weight-related attributes across the five SURPASS studies. METHODS: PRO instruments utilised at baseline and primary timepoint (40 weeks for SURPASS-1, -2 and -5; 52 weeks for SURPASS-3 and -4) or early termination visit were EQ-5D-5L (SURPASS-1 to -5); Impact of Weight on Self-Perceptions (SURPASS-1 to -5); Ability to Perform Physical Activities of Daily Living (SURPASS-1 to -5); Diabetes Treatment Satisfaction Questionnaire (SURPASS-2 to -5); and Impact of Weight on Quality of Life-Lite Clinical Trials Version (SURPASS-2 only). RESULTS: Across all five studies at week 40/52, tirzepatide improved patients' QoL measured by general health and weight-related PROs over the comparator. Generally, higher doses of tirzepatide resulted in greater increases in PRO scores. CONCLUSION: Overall, tirzepatide produced significant health and weight-related QoL improvements versus comparators in the five SURPASS studies. CLINICAL TRIAL REGISTRATION: SURPASS-1: NCT03954834; SURPASS-2: NCT03987919; SURPASS-3: NCT03882970; SURPASS-4: NCT03730662; SURPASS-5: NCT04039503.

Tirzepatide is the first glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist approved for the treatment of people with type 2 diabetes. The SURPASS-1 to -5 clinical trials evaluated the efficacy and safety of tirzepatide (5, 10 and 15 mg) compared with placebo or active comparators (including semaglutide 1 mg and basal insulins) in people with type 2 diabetes. We evaluated other outcomes reported by patients that measured overall quality of life, treatment satisfaction and weight-related attributes across the five SURPASS studies.Five validated questionnaires were completed by patients at the beginning and end of the clinical trials, which was after 40 weeks for SURPASS-1, -2 and -5 and after 52 weeks for SURPASS-3 and -4, or when the person left the trial if this was before the official end. These questionnaires were EQ-5D-5L (SURPASS-1 to -5); Impact of Weight on Self-Perceptions (SURPASS-1 to -5); Ability to Perform Physical Activities of Daily Living (SURPASS-1 to -5); Diabetes Treatment Satisfaction Questionnaire (SURPASS-2 to -5); and Impact of Weight on Quality of Life-Lite Clinical Trials Version (SURPASS-2 only).Across all five studies, treatment with tirzepatide resulted in greater improvements in people's quality of life at the end of the study compared with placebo or treatment with the comparators. Generally, higher doses of tirzepatide resulted in greater increases in questionnaire scores than lower doses of tirzepatide.Overall, tirzepatide 5, 10 or 15 mg treatment resulted in significant health- and weight-related quality of life improvements versus comparators in the five SURPASS studies.

Tirzepatide as Monotherapy Improved Markers of Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes (SURPASS-1).

Context: Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for treatment of type 2 diabetes (T2D). SURPASS-1, a phase 3 trial of tirzepatide monotherapy in people with early T2D, enables evaluating effects of tirzepatide on pancreatic beta-cell function and insulin sensitivity (IS) without other background antihyperglycemic medications. Objective: Explore changes in biomarkers of beta-cell function and IS with tirzepatide monotherapy. Design: Post hoc analyses of fasting biomarkers with analysis of variance and mixed model repeated measures. Setting: Forty-seven sites in 4 countries. Patients: Four hundred seventy-eight T2D participants. Intervention: Tirzepatide (5, 10, 15 mg), placebo. Main Outcome Measures: Analyze biomarkers of beta-cell function and IS at 40 weeks. Results: At 40 weeks, markers of beta-cell function improved with tirzepatide monotherapy vs placebo with reductions from baseline in fasting proinsulin levels (49-55% vs -0.6%) and in intact proinsulin/C-peptide ratios (47-49% vs -0.1%) (P < .001, all doses vs placebo). Increases from baseline in homeostatic model assessment for beta-cell function (computed with C-peptide) (77-92% vs -1.4%) and decreases in glucose-adjusted glucagon levels (37-44% vs +4.8%) were observed with tirzepatide vs placebo (P < .001, all doses vs placebo). IS improved as indicated by reductions from baseline in homeostatic model assessment for insulin resistance (9-23% vs +14.7%) and fasting insulin levels (2-12% vs +15%), and increases in total adiponectin (16-23% vs -0.2%) and insulin-like growth factor binding protein 2 (38-70% vs +4.1%) with tirzepatide vs placebo at 40 weeks (P ≤ .031, all doses vs placebo, except for fasting insulin levels with tirzepatide 10 mg). Conclusions: As monotherapy for early T2D, tirzepatide achieved significant improvements in biomarkers of both pancreatic beta-cell function and IS.

Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme.

AIM: To assess the relationship between HbA1c and body weight reductions with tirzepatide treatment (5, 10 or 15 mg). MATERIALS AND METHODS: HbA1c and body weight data at 40 weeks (SURPASS-1, -2 and -5) and 52 weeks (SURPASS-3 and -4) were analysed by trial. RESULTS: Across the SURPASS clinical trials, HbA1c reductions from baseline were observed in 96%-99%, 98%-99% and 94%-99% of participants treated with tirzepatide 5, 10 and 15 mg, respectively. Moreover, 87%-94%, 88%-95% and 88%-97% of participants, respectively, experienced weight loss associated with HbA1c reductions. Statistically significant associations (correlation coefficients ranging from 0.1438 to 0.3130 across studies; P ≤ .038) between HbA1c and body weight changes were observed with tirzepatide in SURPASS-2, -3, -4 (all doses) and -5 (tirzepatide 5 mg only). CONCLUSIONS: In this post hoc analysis, consistent reductions in both HbA1c and body weight were observed in most participants treated with tirzepatide at doses of 5, 10 or 15 mg. A statistically significant but modest association between HbA1c and body weight change was observed in SURPASS-2, SURPASS-3 and SURPASS-4, suggesting that both weight-independent and weight-dependent mechanisms are responsible for the tirzepatide-induced improvement in glycaemic control.

The Association Between Obesity and the 5-Year Prevalence of Morbidity and Mortality Among Adults with Type 2 Diabetes.

INTRODUCTION: This retrospective claims database study examined the prevalence of mortality and morbidity among adults with type 2 diabetes (T2D) and obesity. METHODS: The study used deidentified data from 2007 to 2021 from the Optum® Market Clarity Dataset. A cohort of adults with T2D and obesity were identified, and age- and sex-adjusted prevalence rates were calculated for mortality, a composite cardiovascular outcome (CCO), a composite microvascular outcome (CMO), and other complications. Results were examined overall and by obesity class (class 1, class 2, and class 3). RESULTS: For the 15,970 adults included in the study, the prevalence of CCO and CMO after 5 years was 15.3% and 60.7%, respectively. The 5-year prevalence of mortality was 10.9%. There were statistically significant differences in prevalence rates by obesity class, with obesity class 3 associated with higher rates of morbidity and mortality compared to obesity classes 1 or 2. Specifically, after 5 years, the prevalence of mortality was 9.4%, 10.3% and 13.6% for obese classes 1, 2 and 3, respectively (P < 0.05 between class 3 and class 2 or 1). Similarly, For obesity classes 1, 2 and 3, the 5-year prevalence of CCO was 13.0%, 14.5% and 18.4% and the rates for CMO were 58.0%, 57.9% and 64.8%, respectively (both P < 0.05 between class 3 and class 2 or 1). Regarding other complications, differences in the prevalence of atherosclerotic cardiovascular disease (ASCVD) and obstructive sleep apnea (OSA) were statistically significantly higher with increasing obesity class. CONCLUSIONS: The results indicate that for a cohort of adults with T2D and obesity, obesity class 3 is associated with significantly higher mortality and morbidity, including CCO, CMO, ASCVD and OSA. These findings suggest that treatment which reduces obesity among individuals with T2D may have significant health benefits, although additional studies are needed to confirm the results.

Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies.

AIM: To assess composite endpoints combining glycaemic control (HbA1c < 7.0%, ≤ 6.5% or < 5.7%) with weight loss (≥ 5%, ≥ 10% or ≥ 15%) and without hypoglycaemia with tirzepatide in type 2 diabetes (T2D). MATERIALS AND METHODS: Data from the phase 3 SURPASS programme were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10 and 15 mg), placebo (SURPASS-1,5), semaglutide 1 mg (SURPASS-2) or titrated basal insulin (SURPASS-3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52. RESULTS: The proportions of participants achieving an HbA1c value of less than 7.0% with 5% or more weight loss and without hypoglycaemia ranged from 43% to 82% with tirzepatide across the SURPASS-1 to -5 trials versus 4%-5% with placebo, 51% with semaglutide 1 mg and 5% with basal insulin (P < .001 vs. all comparators). The proportions of participants achieving an HbA1c value of less than 7.0% with 10% or more, or 15% or more weight loss and without hypoglycaemia were significantly higher with all tirzepatide doses versus comparators across trials (P < .001 or P < .05). Similar results were observed for all other combinations of endpoints with an HbA1c value of 6.5% or less, or less than 5.7%, with more tirzepatide-treated participants achieving these endpoints versus those in the comparator groups, including semaglutide. CONCLUSIONS: Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycaemic targets with various degrees of weight loss and without hypoglycaemia, than those in the comparator groups.

The Benefits of Safely Achieving Near Normoglycemia from the Perspective of People with Type 2 Diabetes: A Quantitative Survey Study.

Purpose: To understand the perspectives of people with type 2 diabetes (T2D) on safely reaching near normoglycemia, defined as a glycated hemoglobin A1c (HbA1c) value of <6%. HbA1c indicates the average blood sugar level over the past few months. Patients and Methods: This cross-sectional online quantitative survey of people with T2D asked about the current impacts of T2D, the anticipated benefits of safely achieving near normoglycemia among participants with a current HbA1c ≥6%, or the actual benefits of safely achieving near normoglycemia among participants who had an HbA1c <6%. Participants reported on specific areas of psychological/emotional impact of T2D and the psychological/emotional benefits of achieving near normoglycemia. Results: Participants (N = 1000; United States = 500 and United Kingdom = 500) were 53.1% male and had a mean age of 62.9 years (SD = 13.3). The majority reported that the current HbA1c ≥6% (81.2%) and 49.2% had been diagnosed more than 10 years ago. The vast majority of participants (>90%) indicated that achieving near normoglycemia was meaningful, with 95% of the participants indicating that achieving near normoglycemia would be of somewhat or extreme importance to them. In total, 93.8% of participants with a current HbA1c ≥6% and 80.3% of those with a current HbA1c <6% anticipated/reported having experienced improvements as a result of achieving near normoglycemia. Among those who experienced or anticipated positive psychological/emotional impacts (n = 247), the most commonly reported impacts included less worry about future diabetes-related complications (79.8%), feeling in control over one's life (72.9%), and overall health-related quality of life (59.9%). Conclusion: Achieving near normoglycemia is both meaningful and important to the majority of people with T2D, including both those who have and those who have not experienced reaching near normoglycemia. A wide range of specific impacts, including psychological/emotional concepts, are experienced by people with T2D, many of which may be improved through achieving near normoglycemia.

The Association Between Sustained HbA1c Control and Long-Term Complications Among Individuals with Type 2 Diabetes: A Retrospective Study.

INTRODUCTION: The prevalence of type 2 diabetes (T2D) represents a rising burden in the US and worldwide, with the condition shown to be associated with relatively large human and economic costs. Part of the reason for such high costs associated with T2D is that the condition is often accompanied by additional health-related complications. The goal of this research is to examine the association between glycemic control and diabetes-related complications for individuals with T2D. METHODS: The Optum Clinformatics® Data Mart (CDM) database from 2007 to 2020 was used to identify adults with T2D. Individuals were classified as having sustained glycemic control (all hemoglobin A1c [HbA1c] < 7%) or poor glycemic control (all HbA1c ≥ 7%) over the 5-year post-period, and diabetes-related complications were identified based upon the Diabetes Complications Severity Index. Multivariable analyses examined the association between sustained glycemic control and diagnosis of a diabetes-related complication in the post-period. RESULTS: Maintaining HbA1c < 7% over the 5-year post-period, compared to maintaining HbA1c ≥ 7%, was associated with reduced odds of the diabetes-related complications of cardiovascular disease (odds ratio [OR] = 0.76, 95% confidence interval [CI] 0.61-0.94), metabolic disease (OR = 0.37, 95% CI 0.22-0.600), neuropathy (OR = 0.62, 95% CI 0.45-0.84), nephropathy (OR = 0.81, 95% CI 0.69-0.94), and peripheral vascular disease (OR = 0.52, 95% CI 0.33-0.83). There was no statistically significant association between sustained glycemic control and cerebrovascular disease. CONCLUSIONS: Sustained glycemic control was found to be associated with significant reductions in the odds of being diagnosed with diabetes-related complications over a 5-year post-period.

The Association Between HbA1c and 1-Year Diabetes-Related Medical Costs: A Retrospective Claims Database Analysis.

INTRODUCTION: The American Diabetes Association (ADA) has identified a target hemoglobin A1c (HbA1c) < 7% as appropriate for most adults with type 2 diabetes (T2D). This research examines US diabetes-related healthcare costs for adults with T2D for individuals with glycemic control (HbA1c < 7%) compared to poor glycemic control (HbA1c ≥ 7%). METHODS: The Optum Clinformatics® Data Mart database from 2016 to 2020 was used to identify a cohort of adults with T2D who had a recorded HbA1c test (with first such date identified as the index date) and continuous insurance from 1 year prior through 1 year post index date. Patients with glycemic control were propensity matched to patients with poor glycemic control. Generalized linear models and two-part models examined diabetes-related outpatient, drug, acute care, and total costs over the 1-year post-period. RESULTS: There were 34,538 propensity matched individuals included in the study. Results indicate that glycemic control (HbA1c < 7%), compared to poor glycemic control (HbA1c ≥ 7%) ,was associated with statistically significantly lower annual diabetes-related acute ($5671 ± $4216 vs $6138 ± $4211), outpatient ($6051 ± $4216 vs $7259 ± $7771), drug ($3739 ± $4581 vs $4288 ± $4788), and total costs care ($13,704 ± $10,635 vs $16,460 ± $10,885) (all P < 0.0001). Sensitivity analyses also examined results based upon alternative HbA1c thresholds which were chosen on the basis of expert guidelines and prior clinical trial thresholds (< 6%, ≤ 6.5%, < 8%, and ≤ 9%). In all cases, being below threshold was associated with statistically significantly lower diabetes-related total costs and component costs. Results also illustrate that, in general, higher HbA1c thresholds are associated with higher diabetes-related costs. CONCLUSION: Glycemic control was found to be associated with significantly lower annual diabetes-related component and total costs. Results suggest economic benefits associated with having HbA1c at or below target.

Weight Change and the Association with Adherence and Persistence to Diabetes Therapy: A Narrative Review.

PURPOSE: Type 2 diabetes (T2D) medication adherence is poor and is impacted by individual drug characteristics. Treatment-associated weight change can affect medication-taking behavior. This review aimed to explore weight change on T2D therapy and consider its impact on adherence and discontinuation. METHODS: Searches were conducted in MEDLINE and EMBASE (2005 to September 2020), and among recent congress abstract books for studies providing data on medication adherence or discontinuation and weight change in people with T2D (PwD). RESULTS: Nine studies meeting the inclusion criteria were identified from 9188 bibliographic records. All three studies exploring weight change and discontinuation reported weight loss to be associated with higher persistence. Seven studies of varying design explored weight change and adherence. Four reported absolute weight change (kg) and adherence: one pooled data from different diabetes medications and demonstrated that self-reported adherence was significantly associated with weight loss; however, three studies found that weight change in adherent PwD was in the direction of the known weight profile (loss/gain) of the evaluated drug. Categorical weight loss (≥3%) and adherence were reported in two studies: one reported that numerically more adherent versus non-adherent PwD lost ≥3% weight regardless of the drug's weight profile, the other showed that early weight loss with a glucagon-like peptide-1 agonist was significantly associated with better adherence. One study reported adherence by categorical weight change; as weight loss increased, adherence scores improved, regardless of drug type. CONCLUSION: Findings suggest that discontinuation rates may be lower in PwD who lose as compared to those who gain weight on T2D treatment. The evidence base on adherence and weight change is more challenging to interpret due to the range of study designs. Given the importance of weight control in T2D, further research exploring the individual's treatment, weight journey, and behaviors over time should be undertaken.

Obesity and glycemic control among people with type 2 diabetes in the United States: A retrospective cohort study using insurance claims data.

AIMS: To examine body mass index (BMI) and HbA1c for individuals with type 2 diabetes (T2D) in the United States. METHODS: The retrospective study utilized data from IBM® MarketScan® Explorys® Claims-EMR Data for the years 2012-2019. Individuals with T2D and a recorded HbA1c laboratory result and BMI were included. The relationship between BMI and HbA1c was assessed descriptively and logistic regressions examined the relationship between benchmark BMI and the probability of having HbA1c above targets of 7% or 8% in the 1year post-period. RESULTS: In our sample of 44,723 patients, results indicated that compared to individuals of normal weight, those classified as obese class I or obese class II were 24% more likely to have a last HbA1c≥7% (Odds Ratio [OR]=1.24; 95% Confidence Interval [CI] 1.14-1.35 for both obese class I and obese class II), while those classified as obese class III were 16% more likely (OR=1.16; 95% CI 1.06-1.27). Results were similar when using a HbA1c threshold of 8%. CONCLUSIONS: Given the importance of glycemic control for people with T2D, these results suggest that treatments which reduce rates of obesity may help to improve health outcomes.

Trends in HbA1c and Body Mass Index Among Individuals with Type 2 Diabetes: Evidence from a US Database 2012-2019.

INTRODUCTION: Given the high rates of obesity and poor glycemic control among individuals with type 2 diabetes (T2D), this study examines current trends in HbA1c and body mass index (BMI) as well as the association between HbA1c and BMI among adults with T2D. METHODS: Data from the IBM® MarketScan® Explorys® Claims-EMR Data were used to construct eight annual cohorts for the years 2012-2019. Each annual cohort included adults identified with T2D who had at least one recorded HbA1c laboratory result and BMI value in the year of interest. Given these cohorts, trends in HbA1c and BMI were described over time using generalized estimating equation (GEE) tests. RESULTS: Results indicate that, over the study period from 2012-2019, average BMI increased significantly and there was a decrease in the percentage of adults with T2D who achieved glycemic control. In addition, for all years, higher BMI classification was associated with higher HbA1c values. When examining results for patients in different age groups, the findings were generally consistent with the overall population. In each age group, but most notably the age 18-44 group, the mean BMI increased over time and higher BMI was associated with higher HbA1c. CONCLUSION: Given the increase in BMI and decreasing percentage of individuals achieving glycemic control among adults with T2D found over the study period, therapies which decrease BMI as well as HbA1c can potentially have a significant impact on the management of T2D. The growing proportion of the younger age group with higher mean BMI may remain a key subgroup of interest.

Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.

BACKGROUND: Despite advancements in care, many people with type 2 diabetes do not meet treatment goals; thus, development of new therapies is needed. We aimed to assess efficacy, safety, and tolerability of novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide monotherapy versus placebo in people with type 2 diabetes inadequately controlled by diet and exercise alone. METHODS: We did a 40-week, double-blind, randomised, placebo-controlled, phase 3 trial (SURPASS-1), at 52 medical research centres and hospitals in India, Japan, Mexico, and the USA. Adult participants (≥18 years) were included if they had type 2 diabetes inadequately controlled by diet and exercise alone and if they were naive to injectable diabetes therapy. Participants were randomly assigned (1:1:1:1) via computer-generated random sequence to once a week tirzepatide (5, 10, or 15 mg), or placebo. All participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) from baseline at 40 weeks. This study is registered with ClinicalTrials.gov, NCT03954834. FINDINGS: From June 3, 2019, to Oct 28, 2020, of 705 individuals assessed for eligibility, 478 (mean baseline HbA1c 7·9% [63 mmol/mol], age 54·1 years [SD 11·9], 231 [48%] women, diabetes duration 4·7 years, and body-mass index 31·9 kg/m2) were randomly assigned to tirzepatide 5 mg (n=121 [25%]), tirzepatide 10 mg (n=121 [25%]), tirzepatide 15 mg (n=121 [25%]), or placebo (n=115 [24%]). 66 (14%) participants discontinued the study drug and 50 (10%) discontinued the study prematurely. At 40 weeks, all tirzepatide doses were superior to placebo for changes from baseline in HbA1c, fasting serum glucose, bodyweight, and HbA1c targets of less than 7·0% (<53 mmol/mol) and less than 5·7% (<39 mmol/mol). Mean HbA1c decreased from baseline by 1·87% (20 mmol/mol) with tirzepatide 5 mg, 1·89% (21 mmol/mol) with tirzepatide 10 mg, and 2·07% (23 mmol/mol) with tirzepatide 15 mg versus +0·04% with placebo (+0·4 mmol/mol), resulting in estimated treatment differences versus placebo of -1·91% (-21 mmol/mol) with tirzepatide 5 mg, -1·93% (-21 mmol/mol) with tirzepatide 10 mg, and -2·11% (-23 mmol/mol) with tirzepatide 15 mg (all p<0·0001). More participants on tirzepatide than on placebo met HbA1c targets of less than 7·0% (<53 mmol/mol; 87-92% vs 20%) and 6·5% or less (≤48 mmol/mol; 81-86% vs 10%) and 31-52% of patients on tirzepatide versus 1% on placebo reached an HbA1c of less than 5·7% (<39 mmol/mol). Tirzepatide induced a dose-dependent bodyweight loss ranging from 7·0 to 9·5 kg. The most frequent adverse events with tirzepatide were mild to moderate and transient gastrointestinal events, including nausea (12-18% vs 6%), diarrhoea (12-14% vs 8%), and vomiting (2-6% vs 2%). No clinically significant (<54 mg/dL [<3 mmol/L]) or severe hypoglycaemia were reported with tirzepatide. One death occurred in the placebo group. INTERPRETATION: Tirzepatide showed robust improvements in glycaemic control and bodyweight, without increased risk of hypoglycaemia. The safety profile was consistent with GLP-1 receptor agonists, indicating a potential monotherapy use of tirzepatide for type 2 diabetes treatment. FUNDING: Eli Lilly and Company.

The Burden of Type 2 Diabetes and the Value of Achieving Near Normoglycemia from the Patient Perspective.

INTRODUCTION: Type 2 diabetes (T2D) is extremely burdensome to people with T2D and associated with impaired health-related quality of life. This study explores the impact of T2D and potentially relevant outcomes for new therapies using a unique approach to in-depth qualitative interviews where people with T2D are asked to think about their future with T2D. METHODS: A cross-sectional qualitative interview study among people with T2D from the USA and UK. Interviews explored their treatment journey, perceptions of their future with T2D, and the value of achieving normoglycemia (explored through presentation of two vignettes with hypothetical medications that reduced hemoglobin A1c [HbA1c] levels < 7% and < 5.7%). RESULTS: Patients with T2D (N = 50; US n = 25; UK n = 25) were 66.0% male, had a mean body mass index (BMI) of 30.8 ± 6.3 kg/m2, and had a mean of 13.0 ± 10.0 years since diagnosis. Current diabetes treatments included diet and exercise only (8.0%), oral medications only (62.0%), oral plus injections (24.0%), and insulin only (6.0%). Despite being treated, participants reported over 25 different unmet needs related to their T2D across a broad range of domains. The most common concerns were diet, diabetes-related complications, weight changes, and psychological and emotional issues. A large majority of participants indicated that achieving lower HbA1c values would change their life. When reflecting on the value of improved glycemic control, patients primarily anticipated physical improvements and improved psychological well-being. When presented with two hypothetical treatments, about 70% of participants preferred the < 5.7% treatment option over the < 7% HbA1c treatment option. CONCLUSIONS: People with T2D have a high disease burden, a broad range of unmet needs, and extremely varied experiences and expectations on the impacts of T2D on their lives and future. Many patients indicated that achieving near normoglycemia would substantially change their lives primarily in terms of their physical and emotional health.

Decision-Making and Relationship Competence When Reporting Suspected Physical Abuse and Child Neglect: An Objective Structured Clinical Evaluation.

Mandatory reporting of suspected child abuse and neglect highlights the challenges between the ethical and legal obligations of social workers and the need to maintain the therapeutic relationship with the client. The ability to bridge this tension is paramount to ensure continued psychosocial treatment and the well-being of children. This paper discusses a study to determine the decision-making factors of social work students and practitioners when facing a suspicion of child abuse and neglect, how they justify their decision to report or not report to child protection services, and the current and future relationship repair strategies used with simulated clients during an objective structured clinical evaluation (OSCE). Nineteen BSW, MSW, and experienced practitioners (N = 19) underwent an OSCE with one of two child maltreatment vignettes, physical abuse or neglect. Fisher's exact test was used to examine participants' historical and current reporting behaviors. Independent samples T-tests, Cohen's D, and qualitative content analysis was used to examine participants' decision making and relationship repair strategies when faced with suspected child abuse and neglect. Results showed that six participants discussed the duty to report during the OSCE while 13 participants did not. Participants' who discussed and did not discuss the duty to report during the OSCE articulated clear reasons for their decision and identified relationship repair strategies in working with the client. A sub-group of participants who identified the child maltreatment but did not discuss the duty to report, provided more tentative and complex reasons for their inaction and next steps in working with the client. All participants demonstrated a degree of competence and critical reflection in the OSCE, with integration for future learning. These findings are discussed and implications for future practice are offered.

Treatment and prevention of severe hypoglycaemia in people with diabetes: Current and new formulations of glucagon.

Some therapies for diabetes increase the risk of hypoglycaemia, in particular all insulins and insulin secretagogues, including the glinides and sulfonylureas. Hypoglycaemia remains a major limiting factor to successful glycaemic management, despite the availability of prevention options such as insulin analogues, continuous glucose monitoring, insulin pumps, and dogs that have been trained to detect hypoglycaemia. Non-severe (self-treated) and severe (requiring assistance for recovery) hypoglycaemia rates are higher in people with type 1 diabetes, but those with insulin-treated type 2 diabetes are also at risk. Education and regular review are essential between people with diabetes and their caregivers and healthcare professionals about symptoms, prevention and treatment. Awareness of the potential dangers of hypoglycaemia is fundamental to the optimal management of diabetes. When therapy is intensified to achieve glycaemic targets, it is important that people at risk of severe hypoglycaemia, and particularly their caregivers, have ready access to effective treatment for hypoglycaemia emergencies. The current and potential formulations of glucagon available for treatment of severe hypoglycaemia are reviewed.