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To examine the mediating role of adiposity on the associations of diet quality with longitudinal changes in insulin sensitivity and beta-cell function.Adults at-risk for type 2 diabetes (T2D) in the PROMISE cohort had 4 assessments over 9 years (n = 442). Alternate Healthy Eating Index (AHEI) scores were used to assess diet quality. Generalized Estimating Equations (GEE) evaluated the associations between the AHEI and longitudinal changes in insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI/HOMA-IR and ISSI-2). The proportion of the mediating effect of waist circumference changes was estimated using the difference method. In the primary longitudinal analysis, AHEI was positively associated with insulin sensitivity and beta-cell function over time (% difference per standard deviation increase of AHEI for HOMA2-%S (β = 11.0, 95%CI 5.43-17.0), ISI (β = 10.4, 95%CI 4.35-16.8), IGI/HOMA-IR (β = 7.12, 95%CI 0.98-13.6) and ISSI-2 (β = 4.38, 95%CI 1.05-7.80), all p 0.05). There was no significant association between AHEI and dysglycemia incidence (OR = 0.95, 95%CI 0.77-1.17). Adjustments for longitudinal changes in waist circumference substantially attenuated all associations of AHEI with insulin sensitivity and beta-cell function. Mediation analysis indicated that waist circumference mediated 73%, 70%, 83% and 81% of the association between AHEI and HOMA2-%S, ISI, IGI/HOMA-IR, and ISSI-2, respectively (all p 0.01).In a Canadian population at-risk for T2D, AHEI score was positively associated with changes in insulin sensitivity and beta-cell function. These associations were substantially mediated by waist circumference, suggesting that changes in adiposity may represent an important pathway linking diet quality with risk phenotypes for T2D.

OBJECTIVE To determine the association of adipose tissue insulin resistance with longitudinal changes in biomarkers of adipose tissue function, circulating lipids, and dysglycemia. RESEARCH DESIGN AND METHODS Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort had up to four assessments over 9 years (n = 468). Adipose tissue insulin resistance was determined using a novel validated index, Adipo-IR, calculated as the product of fasting insulin and nonesterified fatty acids measured at baseline. Fasting serum was used to measure biomarkers of adipose tissue function (adiponectin and soluble CD163 [sCD163]), circulating lipids (total cholesterol, HDL, LDL, triglyceride [TG]), and systemic inflammation (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes at follow-up. Generalized estimating equation (GEE) models were used to assess the relationship of Adipo-IR with longitudinal outcomes. RESULTS GEE analyses showed that elevated Adipo-IR was longitudinally associated with adipose tissue dysfunction (adiponectin −4.20% [95% CI −6.40 to −1.95]; sCD163 4.36% [1.73–7.06], HDL −3.87% [−5.15 to −2.57], TG 9.26% [5.01–13.69]). Adipo-IR was associated with increased risk of incident dysglycemia (odds ratio 1.59 [95% CI 1.09–2.31] per SD increase). Associations remained significant after adjustment for waist circumference and surrogate indices for insulin resistance. There were no significant longitudinal associations of Adipo-IR with IL-6, TNF-α, total cholesterol, or LDL. CONCLUSIONS Our findings demonstrate that adipose tissue insulin resistance is prospectively associated with adipose tissue function, HDL, TG, and incident dysglycemia.

Objective Hypoglycemia can cause psychological distress in people with diabetes; however, less is understood about the emotional impact of hypoglycemia on their health care providers (HCPs). This article focuses on the experiences and emotions of HCPs caring for patients with diabetes. Methods This was a descriptive qualitative study from the InHypo-DM research program. Purposive sampling was used to recruit 20 HCPs from a variety of professions for 30- to 45-minute semi-structured interviews. An iterative analysis was conducted to identify the overarching themes. Results Three overarching themes encompassed the responses of participants when their patients experienced hypoglycemia. The first was a sense of professional responsibility, as participants felt they must have failed or inadequately fulfilled their professional duties. The second was a more personal range of emotions such as sadness and guilt. The final theme was how these emotions created a “call to action,” prompting participants to identify potential strategies to prevent future hypoglycemic events. Conclusion This qualitative study highlights the emotional impact of patients’ hypoglycemia on HCPs. Although it may have been expected that HCPs have a strong sense of professional responsibility, it was unexpected that these responses often became personal emotions. To ameliorate the negative impact of these responses on patient care, HCPs should engage in activities that enable them to anticipate and manage their own emotional responses. In addition, strategies to optimize hypoglycemia detection and prevention should be promoted.

Introduction The aim of the study was to examine glycaemic control and safety of insulin degludec (degludec) in patients with either type 1 diabetes (T1D) or type 2 diabetes (T2D) under routine care settings in Canada. Methods Data were extracted from medical records of adults with T1D or T2D who switched to degludec (± prandial insulin) from another basal insulin (± prandial insulin) ≥ 6 months prior to data collection. The primary endpoint was change in glycated haemoglobin (HbA1c) at 6 ± 3 months after degludec initiation. Secondary endpoints included change in hypoglycaemia rate in the 6 months before versus the 6 months after switching, and change in mean total daily insulin dose. Results Of 667 patients assessed for eligibility, 626 were included. After 6 ± 3 months, HbA1c decreased from baseline in patients with T1D (− 0.3% [− 0.42, − 0.14]95% CI; p

Background: First Nations (FN) peoples in Canada face spiraling rates of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Data on the extent of CVD risk-factor management in FN peoples with T2DM in Canada are scarce. Methods: A T2DM registry with data from 7 FN communities in Canada was utilized to identify individuals eligible for primary and secondary CVD prevention. Proportions of individuals meeting clinical practice guideline–specified targets (hemoglobin A1c ≤7.0%; blood pressure ≤130/80 mm Hg; low-density lipoprotein ≤2 mmol/L) were calculated. Prescription of recommended cardioprotective medications (antithrombotic medication, lipid-lowering agents, renin-angiotensin-aldosterone system inhibitors, and beta-blockers) among those with CVD was assessed. χ2 tests were employed to evaluate differences between CVD prevention groups and sexes. Results: Of the 2098 individuals in the registry, 18% had documented CVD (female: male = 1.12). Overall

Objective To examine diabetes remission following a short-term intensive metabolic intervention combining lifestyle and glucose-lowering approaches. Methods We conducted an open-label, randomized controlled trial in 154 patients with type 2 diabetes up to 8 years in duration on 0 to 2 glucose-lowering medications. Participants were randomized to (a) a 12-week intensive intervention comprising lifestyle approaches and treatment with insulin glargine, metformin, and dapagliflozin or (b) standard diabetes care. At 12 weeks, diabetes medications were discontinued in participants with hemoglobin A1c (HbA1C) Results The primary outcome was achieved in 19 (24.7%) intervention group participants and 13 (16.9%) control group participants at 24 weeks (relative risk [RR] 1.5; 95% confidence interval [CI], 0.8-2.7). The relative risks of remission at 36, 48, and 64 weeks were 2.4 (95% CI, 1.2-5.0), 2.1 (95% CI, 1.0-4.4), and 1.8 (95% CI, 0.7-4.7), respectively. In an exploratory analysis, the intervention reduced the hazard of diabetes relapse with overt hyperglycemia by 43% (hazard ratio 0.57; 95% CI, 0.39-0.81). Conclusions Our primary outcome of diabetes remission at 24 weeks was not statistically significantly different. However, our overall results suggest that some patients with early type 2 diabetes are able to achieve sustained diabetes remission following a short-term intensive intervention. Further studies are needed to optimize the combined therapeutic approach used.

Primary care providers are well-positioned to help patients with type 2 diabetes achieve glycemic control while reducing their risks of serious complications such as atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease. Recent outcomes trials of glucagon-like peptide 1 receptor agonists and sodium– glucose cotransporter 2 inhibitors have revealed that these agents offer cardiorenal benefits beyond their glucose-lowering effects. The American Diabetes Association and the European Association for the Study of Diabetes now recommend a person-centered approach to type 2 diabetes treatment through which a patient’s multimorbidities, preferences, characteristics, and barriers are considered alongside A1C in individualizing the diabetes management plan. Here, we review the evidence supporting this guidance and describe how to implement the new holistic approach. Research has demonstrated the potential for offering a continuum of benefit from primary through tertiary prevention of microvascular and macrovascular disease while also achieving glycemic targets. The new outcomes-based guidelines provide a roadmap for integrating this newfound knowledge into clinical practice.

Main objectiveTo determine how and to what extent COVID-19 has affected real-world, self-reported glycaemic management in Americans with type 1 or type 2 diabetes taking insulin and/or secretagogues, with or without infection.DesignA cross-sectional substudy using data from the Investigating Novel Predictions of Hypoglycemia Occurrence using Real-world Models panel survey.SettingUSA.ParticipantsAmericans 18–90 years old with type 1 or 2 diabetes taking insulin and/or secretagogues were conveniently sampled from a probability-based internet panel.Primary outcome measureA structured, COVID-19-specific questionnaire was administered to assess the impact of the pandemic (irrespective of infection) on socioeconomic, behavioural/clinical and psychosocial aspects of glycaemic management.ResultsData from 667 respondents (type 1 diabetes: 18%; type 2 diabetes: 82%) were analysed. Almost 25% reported A1c values ≥8.1%. Rates of severe and non-severe hypoglycaemia were 0.68 (95% CI 0.5 to 0.96) and 2.75 (95% CI 2.4 to 3.1) events per person-month, respectively. Ten respondents reported a confirmed or probable COVID-19 diagnosis. Because of the pandemic, 24% of respondents experienced difficulties affording housing; 28% struggled to maintain sufficient food to avoid hypoglycaemia; and 19% and 17% reported challenges accessing diabetes therapies and testing strips, respectively. Over one-quarter reported issues retrieving antihyperglycaemics from the pharmacy and over one-third reported challenges consulting with diabetes providers. The pandemic contributed to therapeutic non-adherence (14%), drug rationing (17%) and reduced monitoring (16%). Many struggled to keep track, and in control, of hypoglycaemia (12%–15%) and lacked social support to help manage their risk (19%). Nearly half reported decreased physical activity. Few statistically significant differences were observed by diabetes type.ConclusionsCOVID-19 was found to cause substantial self-reported deficiencies in glycaemic management. Study results signal the need for decisive action to restabilise routine diabetes care in the USA.Trial registration numberNCT04219514.

Therapeutic inertia is a prevalent problem in people with type 2 diabetes in primary care and affects clinical outcomes. It arises from a complex interplay of patient-, clinician-, and health system–related factors. Ultimately, clinical practice guidelines have not made an impact on improving glycemic targets over the past decade. A more proactive approach, including focusing on optimal combination agents for early glycemic durability, may reduce therapeutic inertia and improve clinical outcomes.

Achieving target glycaemic control is essential in people with diabetes to minimize the risk of long‐term complications, and many people with type 2 diabetes will ultimately require basal insulin (BI) therapy to achieve their individualized glycaemic targets. Usually, the first 12 weeks following initiation of BI therapy represents the period when the greatest dose increases and glycaemic reductions occur. Effective glycaemic control combined with minimizing the risk of hypoglycaemia is important to enable the achievement of glycaemic control in the longer term. However, substantial therapeutic inertia exists in clinical practice, both in initiation and up‐titration of BI, owing to patient‐, physician‐ and healthcare system‐related barriers, including fear of hypoglycaemia and the perception of a burdensome regimen. The more prolonged duration of action, reduced glycaemic variability and lower risk of hypoglycaemia seen with second‐generation versus first‐generation BI analogues may help alleviate patients’ and physicians’ concerns and facilitate titration. In turn, optimal BI titration and subsequent metabolic benefits may help improve therapy adherence and self‐management. This review details the clinical implications of prompt titration of BI to achieve early glycaemic control, and the importance of minimizing hypoglycaemia risk within the initial titration period. Facilitation of patients’ self‐management of BI is also addressed.

Aim To further investigate glycaemic control and hypoglycaemia in BRIGHT, focusing on the titration period. Materials and Methods BRIGHT was a multicentre, open‐label, randomized, active‐controlled, two‐arm, parallel‐group, 24‐week study in insulin‐naïve patients with uncontrolled type 2 diabetes initiated on glargine 300 U/mL (Gla‐300) (N = 466) or degludec (IDeg‐100) (N = 463). Predefined efficacy and safety outcomes were investigated during the initial 12‐week titration period. In addition, patients’ characteristics and clinical outcomes were assessed descriptively, stratified by confirmed (≤3.9 mmol/L) hypoglycaemia incidence during the initial titration period. Results At week 12, HbA1c was comparable between Gla‐300 (7.32%) and IDeg‐100 (7.23%), with similar least squares (LS) mean reductions from baseline (−1.37% and − 1.39%, respectively; LS mean difference of 0.02; 95% confidence interval: −0.08 to 0.12). Patients who experienced hypoglycaemia during the initial titration period had numerically greater HbA1c reductions by week 12 than patients who did not (−1.46% vs. −1.28%), and higher incidence of anytime (24 hours; 73.3% vs. 35.7%) and nocturnal (00:00–06:00 hours; 30.0% vs. 11.9%) hypoglycaemia between weeks 13–24. Conclusions The use of Gla‐300 resulted in similar glycaemic control as IDeg‐100 during the initial 12‐week titration period of the BRIGHT study, when less anytime (24 hours) hypoglycaemia with Gla‐300 versus IDeg‐100 has been reported. Experiencing hypoglycaemia shortly after initiating Gla‐300 or IDeg‐100 may be associated with hypoglycaemia incidence in the longer term, potentially impacting glycaemic management.

Summary: Background: Historical, colonial, and racist policies continue to influence the health of Indigenous people, and they continue to have higher rates of chronic diseases and reduced life expectancy compared with non-Indigenous people. We determined factors accounting for variations in cardiovascular risk factors among First Nations communities in Canada. Methods: Men and women (n=1302) aged 18 years or older from eight First Nations communities participated in a population-based study. Questionnaires, physical measures, blood samples, MRI of preclinical vascular disease, and community audits were collected. In this cross-sectional analysis, the main outcome was the INTERHEART risk score, a measure of cardiovascular risk factor burden. A multivariable model was developed to explain the variations in INTERHEART risk score among communities. The secondary outcome was MRI-detected carotid wall volume, a measure of subclinical atherosclerosis. Findings: The mean INTERHEART risk score of all communities was 17·2 (SE 0·2), and more than 85% of individuals had a risk score in the moderate to high risk range. Subclinical atherosclerosis increased significantly across risk score categories (p

Context Chronic inflammation arising from adipose tissue macrophage (ATM) activation may be central in type 2 diabetes etiology. Our objective was to assess the longitudinal associations of soluble CD163 (sCD163), a novel biomarker of ATM activation, with insulin sensitivity, β-cell function, and dysglycemia in high-risk subjects. Methods Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 408). Levels of sCD163 were measured using fasting serum. Insulin sensitivity was assessed by HOMA2-%S and the Matsuda index (ISI). β-cell function was determined by insulinogenic index (IGI) over HOMA-IR and insulin secretion-sensitivity index-2 (ISSI-2). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Generalized estimating equations (GEE) evaluated longitudinal associations of sCD163 with insulin sensitivity, β-cell function, and incident dysglycemia adjusting for demographic and lifestyle covariates. Areas under receiver-operating-characteristic curve (AROC) tested whether sCD163 improved dysglycemia prediction in a clinical model. Results Longitudinal analyses showed significant inverse associations between sCD163 and insulin sensitivity (% difference per standard deviation increase of sCD163 for HOMA2-%S (β = −7.01; 95% CI, −12.26 to −1.44) and ISI (β = −7.60; 95% CI, −11.09 to −3.97) and β-cell function (ISSI-2 (β = −4.67; 95 %CI, −8.59 to −0.58) and IGI/HOMA-IR (β = −8.75; 95% CI, −15.42 to −1.56)). Increased sCD163 was associated with greater risk for incident dysglycemia (odds ratio = 1.04; 95% CI, 1.02-1.06; P < 0.001). Adding sCD163 data to a model with clinical variables improved prediction of incident dysglycemia (AROC=0.6731 vs 0.638; P < 0.05). Conclusions sCD163 was longitudinally associated with core disorders that precede the onset of type 2 diabetes.

Hypoglycemia is one of the most common adverse events for people living with type 1 or type 2 diabetes. To gain a deeper understanding of patients’ emotions regarding hypoglycemia, we conducted a descriptive qualitative study. Purposive sampling was used to recruit participants for a 30- to 45-minute semi-structured interview. The 16 participants included both women and men with either type 1 or type 2 diabetes, with a mean age of 53 years and mean time since diagnosis of 21 years. All participants had experienced more than one hypoglycemia event in the past year, ranging from nonsevere to severe. Data collection and analysis occurred in an iterative manner. Individual and team analyses of interviews were conducted to identify overarching themes and sub-themes. Thematic analysis revealed the unique interconnection among the emotions experienced by participants, including fear, anxiety, frustration, confidence, and hope. Time, experience, and reflection helped to build participants’ confidence in their ability to manage a hypoglycemia event. Patients’ emotions regarding hypoglycemia provide valuable insights into life with diabetes. Although hypoglycemia continues to evoke feelings of fear and anxiety, the role of hope may temper these emotions. Understanding the complex interplay of emotions concerning hypoglycemia can guide health care providers in improving clinical practice and promoting patient-centered interventions. Ultimately, health care providers can build patients’ hypoglycemia-related confidence by using a strengths-based approach.

OBJECTIVE To investigate the efficacy, safety, and tolerability of oral semaglutide added to insulin with or without metformin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes uncontrolled on insulin with or without metformin were randomized to oral semaglutide 3 mg (N = 184), 7 mg (N = 182), or 14 mg (N = 181) or to placebo (N = 184) in a 52-week, double-blind trial. End points were change from baseline to week 26 in HbA1c (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients. RESULTS Oral semaglutide was superior to placebo in reducing HbA1c (estimated treatment difference [ETD] –0.5% [95% CI –0.7, –0.3], –0.9% [–1.1, –0.7], and –1.2% [–1.4, –1.0] for 3, 7, and 14 mg, respectively; P < 0.001) and body weight (ETD −0.9 kg [95% CI −1.8, −0.0], −2.0 kg [−3.0, −1.0], and −3.3 kg [−4.2, −2.3]; P = 0.0392 for 3 mg, P ≤ 0.0001 for 7 and 14 mg) at week 26 (treatment policy estimand). Significantly greater dose-dependent HbA1c and body weight reductions versus placebo were achieved with oral semaglutide at weeks 26 and 52 (both estimands). The most frequent adverse event with oral semaglutide was nausea (11.4–23.2% of patients vs. 7.1% with placebo; mostly mild to moderate). CONCLUSIONS Oral semaglutide was superior to placebo in reducing HbA1c and body weight when added to insulin with or without metformin in patients with type 2 diabetes. The safety profile was consistent with other glucagon-like peptide 1 receptor agonists.

Hypoglycaemia is a common side‐effect of diabetes therapies, particularly insulin, and imposes a substantial burden on individuals and healthcare systems. Consequently, regulatory approval of newer basal insulin (BI) therapies has relied on demonstration of a balance between achievement of good glycaemic control and less hypoglycaemia. Randomized controlled trials (RCTs) are the gold standard for assessing efficacy and safety, including hypoglycaemia risk, of BIs and are invaluable for obtaining regulatory approval. However, their highly selected patient populations and their conditions lead to results that may not be representative of real‐life situations. Real‐world evidence (RWE) studies are more representative of clinical practice, but they also have limitations. As such, data both from RCTs and RWE studies provide a fuller picture of the hypoglycaemia risk with BI therapies. However, substantial differences exist in the way hypoglycaemia is reported across these studies, which confounds comparisons of hypoglycaemia frequency among different BIs. This problem is ongoing and persists in recent trials of second‐generation BI analogues. Although they provide a lower risk of hypoglycaemia when compared with earlier BIs, they do not eliminate it. This review describes differences in the way hypoglycaemia is reported across RCTs and RWE studies of second‐generation BI analogues and examines potential reasons for these differences. For studies of BIs, there is a need to standardize aspects of design, analysis and methods of reporting to better enable interpretation of the efficacy and safety of such insulins among studies; such aspects include length of follow‐up, glycaemic targets, hypoglycaemia definitions and time intervals for determining nocturnal events.

Background: Individual and societal determinants can affect the need and propensity for healthcare utilization (HCU) following diabetes-related severe hypoglycemia (SH). This is the first US study to explore the real-world risk factors of HCU- versus non HCU-based SH. Methods: Data were collected online from a generalized cohort of Americans (≥18 years old) with type 1 or type 2 diabetes (T1D, T2D) on insulin and/or secretagogues. Multivariable logistic regression using backward selection was performed to identify the socio-demographic/clinical risk factors of past-year HCU- versus non HCU-based SH (daytime/nocturnal SH resulting in hospital or paramedical services). Results: Results are based on 642 (T1D: 22.7%; female: 46.3%) of 1694 baseline respondents who experienced ≥1 SH events (past year). People with T1D were 40.9 (SD:12.5) years old, while those with T2D were 45.4 (SD: 13.3) years old. Among T2D respondents, 42.5% were on insulin and secretagogues, 31.1% were on insulin alone, and 26.4% on secretagogues alone. Almost half (44.6%) of participants (T1D: 29.9%; T2D: 49.0%) reported ≥1 HCU-based SH events (past year). In the final backward logistic model, the odds of past-year HCU-based SH decreased significantly with female sex, increasing age, decreasing income, and suburban or rural (versus urban) living. Diabetes type did not have an independent effect. However, for individuals on combination insulin-secretagogue therapy, the adjusted odds of HCU-based SH were 2- and 3-times that of those on insulin alone and secretagogues alone, respectively. High A1C (versus Conclusion: Our study reveals several factors that can promote or reduce the odds of HCU-based SH. Therapeutic optimizations to mitigate non-essential HCU should prioritize patients on combination insulin-secretagogue therapy and those with poor glycemic control. Disclosure A. Ratzki-leewing: Consultant; Self; Eli Lilly and Company, Novo Nordisk, Other Relationship; Self; Sanofi. J. E. Black: None. B. L. Ryan: None. G. Zou: None. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Funding Sanofi Global

Background: Diabetes remission due to non-surgical approaches has not been well studied. We investigated induction of diabetes remission following a short-term treatment with insulin glargine, lixisenatide and metformin and changes in exercise and dietary behaviours. Methods: We randomized 160 individuals with type 2 diabetes to (i) 12-week intensive treatment with insulin glargine, lixisenatide, metformin and lifestyle approaches or (ii) standard glycemic management. At 12 weeks, diabetes medications were stopped in patients with HbA1C Results: The intervention significantly reduced the hazard of diabetes relapse (HR 0.57, 95% CI 0.40-0.81; p=0.002). The proportion of participants with diabetes remission was significantly higher in the intervention group compared to the control group at 24 weeks (38% vs. 20%; relative risk RR 1.92 (1.14-3.24)) and at 36 weeks (32% vs. 17%; RR 1.83 (1.03-3.26)), but not at 48 and 64 weeks (RR 1.88 (1.00-3.53) and 2.05 (0.98-4.29), respectively). Conclusion: Short-term intensive treatment targeting normoglycemia and weight loss with insulin glargine, lixisenatide, metformin and lifestyle changes can induce sustained remission of type 2 diabetes. Disclosure N. Mcinnes: Other Relationship; Self; Merck & Co., Inc., Novo Nordisk, Sanofi. J. Yale: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Self; Bayer Inc., Speaker’s Bureau; Self; Dexcom, Inc., Medtronic, Merck & Co., Inc., Omnipod. F. Sultan: Employee; Self; Abbott Diabetes. A. C. Smith: None. R. E. Otto: None. D. Sherifali: None. Y. Liu: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Remit-iglarlixi collaborative group: n/a. S. Hall: None. H. A. Lochnan: Research Support; Self; Novo Nordisk Inc., Sanofi. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Z. Punthakee: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Self; AstraZeneca, Lexicon Pharmaceuticals, Inc., Novo Nordisk. R. J. Sigal: Advisory Panel; Self; Novo Nordisk, Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk. I. Hramiak: Advisory Panel; Self; AstraZeneca, Bayer Inc., BI-Lilly Joint Venture (Boehringer Ingelheim and Eli Lilly), Dexcom, Inc., Insulet Corporation, Medtronic, Research Support; Self; Eli Lilly and Company, Novo Nordisk, Sanofi. M. Azharuddin: Consultant; Self; Novo Nordisk Canada Inc. J. F. Liutkus: Advisory Panel; Self; Novo Nordisk Canada Inc., Research Support; Self; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., IQVIA, Kowa Research Institute, Inc., Novo Nordisk Canada Inc., Sanofi, Speaker’s Bureau; Self; Novo Nordisk Canada Inc., Stock/Shareholder; Self; Bayer Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Spouse/Partner; Bayer Inc., Eisai Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Pfizer Inc. Funding Sanofi

The combination of basal insulin with a GLP-1 RA may be helpful for people with T2DM to achieve and maintain HbA1c targets compared with each used individually. This randomized, 26-week, multicenter Phase 3 study (NCT03767543) in people with T2DM included participants with HbA1c ≥7.5% and ≤10.5%, and on basal insulin for ≥6 months (dose of ≤40 units/day). In addition to background oral glucose lowering medications, all participants received once-daily iGlarLixi, a fixed-ratio combination given within 1 hour prior to their first meal of the day, and were randomized 1:1 with instructions to titrate daily using a 1 unit per day algorithm or the traditional once-weekly titration (2 or 4 units per week) with target FPG of 4.4 to 5.6 mmol/L (79.2 to 100.8 mg/dL). Daily titration of iGlarLixi was superior to a weekly titration for the primary endpoint of change from baseline in HbA1c at week 26. The proportion of participants experiencing ≥1 gastrointestinal event(s) (27.9% daily vs. 27.8% weekly titration) and incidence of hypoglycemic events (84% daily vs. 81% weekly titration) were similar between the two arms. In this randomized trial, a daily titration algorithm for iGlarLixi was demonstrated as a safe alternative to the traditional weekly titration, while allowing patients to reach their maintenance dose earlier. Disclosure I. Hramiak: Advisory Panel; Self; AstraZeneca, Bayer Inc., BI-Lilly Joint Venture (Boehringer Ingelheim and Eli Lilly), Dexcom, Inc., Insulet Corporation, Medtronic, Research Support; Self; Eli Lilly and Company, Novo Nordisk, Sanofi. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. L. A. Leiter: Advisory Panel; Self; Abbott Diabetes, Amgen Inc., AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Self; Applied Therapeutics, Research Support; Self; Amgen Inc., AstraZeneca, Esperion, Kowa Company, Ltd., Lexicon Pharmaceuticals, Inc., Medicines Company, Novartis Pharmaceuticals Corporation, Speaker’s Bureau; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. J. Yale: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Self; Bayer Inc., Speaker’s Bureau; Self; Dexcom, Inc., Medtronic, Merck & Co., Inc., Omnipod. H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. J. A. Stewart: Employee; Self; Sanofi. M. Toutounji: Employee; Self; Sanofi. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Funding Sanofi Canada

This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and beta-cell dysfunction. Sixteen studies (seven cross-sectional, two case-control, one nested case-control, three prospective cohort, and three experimental) were identified. Most studies demonstrated that elevated sCD163 concentrations were associated with increased insulin resistance. Cross-sectional, case-control, and nested case-control studies showed higher sCD163 in subjects with T2DM compared with healthy individuals. An 18-year follow-up prospective cohort study showed that elevated baseline sCD163 was a strong predictor of T2DM incidence. Prospective cohort studies demonstrated that baseline measures and longitudinal changes in sCD163 were positively associated with insulin resistance; however, associations with beta-cell function were inconsistent. Two experimental studies evaluated the relationship of sCD163 with T2DM and HOMA-IR after weight-reducing interventions. After very low-calorie diet treatments, sCD163 concentration declined significantly in patients with T2DM but was not associated with insulin resistance. Bariatric surgery did not significantly impact sCD163 levels. In a double-blind randomized controlled trial, resveratrol supplementation significantly reduced circulating sCD163 in T2DM patients. Current studies demonstrate the potential utility of sCD163 as an early biomarker of T2DM risk and highlight a potential mechanism linking obesity with T2DM onset.

Objectives Hypoglycemia is a common adverse event for people with type 1 and type 2 diabetes mellitus. In this article, we explore the specific roles that individuals assume to prevent or treat hypoglycemia. Methods A descriptive qualitative study from the UnderstandINg the impact of HYPOglycemia on Diabetes Management Study (InHypo-DM) research program. A purposive sample of people with type 1 and type 2 diabetes were recruited for semistructured interviews. There were 16 participants (women and men), who were, on average, 53 years old. Average time since diagnosis was 15 (type 1) and 21 (type 2) years; all patients had at least 1 hypoglycemic event in the past year. Individual and team analysis of interviews were conducted to identify overarching themes. Results Participants articulated 4 roles in preventing or treating hypoglycemia. The first role was being a manager by assuming ownership and accountability for their own glycemic control. The second role, being a technician, used both subjective and objective information and employed specific strategies to respond to hypoglycemic events. The third role, educator, extended beyond self-management to increase others’ awareness of hypoglycemia. The fourth role, advocate, involved championing one’s own needs during a hypoglycemic event. These 4 roles were, in turn, influenced by the contexts of work, social settings, exercise and travel. Conclusions These findings demonstrate that strategies that individuals use to avoid or reduce the severity of a hypoglycemic event extend beyond merely making impromptu decisions during events. Instead, these 4 roles of manager, technician, educator and advocate, embedded in specific contexts, enhanced their mastery in managing hypoglycemia in daily life.

An exploratory subgroup analysis of the 52-week, double-blind PIONEER 8 trial (NCT03021187) evaluated the effect of background insulin regimen (basal, premixed, or basal-bolus) with or without metformin on the efficacy and safety of oral semaglutide (sema). Patients (pts) (N=731) with type 2 diabetes and treated with insulin were randomized to once-daily oral sema (3, 7, or 14 mg) or placebo (pbo). Endpoints included change from baseline in HbA1c, body weight (BW), and total daily insulin dose at week 52. Baseline age and HbA1c were similar across insulin regimen subgroups whereas BW was greater and diabetes duration was longer in pts on basal-bolus vs. basal and premix subgroups. There were greater dose-dependent HbA1c and BW reductions with oral sema vs. pbo; these were generally similar across all insulin subgroups (Table). Total daily insulin dose at week 52 was decreased for pts on basal (oral sema 7 and 14 mg), premix (oral sema 14 mg), and basal-bolus (oral sema 3, 7, and 14 mg), mainly driven by the bolus component for pts on basal-bolus (Table). Most hypoglycemic episodes were in pts on basal-bolus insulin. Fewer pts had hypoglycemia with oral sema vs. pbo except in the basal-bolus subgroup (Table). In conclusion, oral sema reduced HbA1c and BW in a dose-dependent manner, and reduced insulin dose regardless of background insulin regimen, with a safety profile similar to other glucagon-like peptide-1 receptor agonists. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. E. Christiansen: None. S.B. Harris: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Canadian Institutes of Health Research, Eli Lilly and Company, Health Canada/First Nations and Inuit Health Branch, Janssen Pharmaceuticals, Inc., JDRF, Lawson Foundation, Novo Nordisk Inc., Sanofi. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Sanofi. K. Pedersen: Employee; Self; Novo Nordisk A/S. M. Tarp-Johansen: Employee; Self; Novo Nordisk A/S. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. Funding Novo Nordisk A/S

BI analogs can help optimize glycemic control in people with T2D, but the patients’ satisfaction is key for acceptance and treatment adherence. ACHIEVE, REACH, and REGAIN were open-label real-world studies comparing Gla-300 with standard of care BI (ACHIEVE: insulin glargine 100 U/mL [Gla-100] or insulin detemir [IDet]; REACH and REGAIN: Gla-100, IDet, insulin degludec [IDeg] or neutral protamine Hagedorn). EDITION 1-3 and BRIGHT were open-label RCTs comparing Gla-300 with Gla-100 and IDeg, respectively. All studies were in people with uncontrolled T2D and used the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs; Table). In RCTs and real-world studies, initiating BI in insulin-naïve participants was associated with improved treatment satisfaction after 6 months (ACHIEVE, 12 months) and a reduction in the perceived frequency of hyperglycemia. Perceived hypoglycemia increased slightly from low baseline values. Similar findings were found in patients switching BI, with improved patient satisfaction and reduced perceived frequency of hyperglycemia after 6 months of treatment, and no change in perceived hypoglycemia. Initiating or switching BI in people with uncontrolled T2D can improve patient satisfaction, irrespective of baseline diabetes treatment. Disclosure S.B. Harris: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Canadian Institutes of Health Research, Eli Lilly and Company, Health Canada/First Nations and Inuit Health Branch, Janssen Pharmaceuticals, Inc., JDRF, Lawson Foundation, Novo Nordisk Inc., Sanofi. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Sanofi. F.J. Snoek: Advisory Panel; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Research Support; Self; Sanofi. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Applied Therapeutics, Sanofi US. F. Lauand: Employee; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A. Roborel de Climens: Employee; Self; Sanofi. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Funding Sanofi

Minimizing hypoglycemia is a key clinical goal for healthcare providers (HCPs) in the care of patients with T1DM and T2DM as the associated morbidity and mortality of hypoglycemia is well understood. Yet, there is a paucity of literature regarding the impact of reported hypoglycemia on HCPs. Using qualitative data from the InHypo-DM Study, Canada’s largest mixed methods study of hypoglycemia to date, we explored the emotional impact of patients’ hypoglycemia on HCPs. Our research team conducted semi-structured interviews lasting 30-45 minutes. Interviews were transcribed verbatim. An iterative and interpretative process was used during both individual and team analysis to identify the main themes. A purposive sample of twenty HCPs was interviewed including endocrinologists (4), family physicians (4), nurse practitioners (3), and diabetes educators (9). Three themes emerged in the analysis: (1) a sense of professional responsibility with the subsequent feeling that the HCP must have failed or inadequately fulfilled their professional duties; (2) a mix of personal emotions including sadness, “feeling bad,” guilt and distress; and (3) the desire to act on these emotions through a “call to action” expressed as a strong desire to identify potential causes of patients’ hypoglycemia and ways in which to help prevent future events. This qualitative study highlights the emotional impact on HCPs as they care for patients at risk of hypoglycemia. While it may have been expected that HCPs have a strong sense of professional responsibility, it was unexpected to discover that these responses often became personal emotions. Clinical strategies that support HCPs in their efforts to optimize hypoglycemia detection and prevention should be promoted. Such strategies could help facilitate not only reductions in hypoglycemia among patients, but also lessen the emotional burden experienced by diabetes care providers over the span of their careers. Disclosure S.M. Reichert: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Novo Nordisk Inc., Sanofi, Servier. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Canadian Institutes of Health Research. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc., Sanofi. J.B. Brown: None. Y. Valliere: None. C. McLachlan: None. S. Webster-Bogaert: None. A. Ratzki-Leewing: Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; Sanofi. B.L. Ryan: None. N.H. Au: None. S.B. Harris: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Canadian Institutes of Health Research, Eli Lilly and Company, Health Canada/First Nations and Inuit Health Branch, Janssen Pharmaceuticals, Inc., JDRF, Lawson Foundation, Novo Nordisk Inc., Sanofi. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Funding Sanofi Canada

The aim of this study was to estimate the real-world incidence of self-reported non-severe hypoglycemia (NSH) and its related sociodemographic and clinical risk factors in a general population of Canadian adults with type 2 diabetes mellitus (T2DM) taking insulin and/or secretagogues.Data for this study were obtained from the InHypo-DM Study. Self-reported data on the frequency of NSH (past 30 days) as well as sociodemographic and clinical characteristics were collected through an online questionnaire. Risk factors for any, daytime and nocturnal NSH were identified using multivariable negative binomial regression with backward selection.Among 432 adults with T2DM (43.8% female, mean age of 53.1 years), 53.9% (95% confidence interval [CI], 49.2% to 58.6%) reported ≥1 event of any (i.e. daytime or nocturnal) NSH in the past 30 days. The 30-day incidence rate of any NSH was 2.3 events per 30 person-days (95% CI, 2.1 to 2.4). Risk factors associated with the increased rate of any NSH were younger age, lower annual household income, being employed, longer duration of diabetes, higher glycated hemoglobin and presence of comorbidity. Risk factors were generally similar for daytime NSH (except for the exclusion of diabetes duration and addition of diabetes medication type) and nocturnal NSH (except for the exclusion of being employed).This is the largest Canadian investigation to estimate the real-world frequency and distribution of self-reported NSH in T2DM. Events were alarmingly frequent and recurrent. Numerous sociodemographic and clinical risk factors were elucidated. These results highlight the importance of identifying high-risk individuals to minimize future occurrences of hypoglycemia.

Introduction The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. Methods Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI ( 58– 7.5– 30 kg/m2 subgroup. Conclusions In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m2) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation. Trial Registration ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3). Funding Novo Nordisk A/S, Søborg, Denmark. Electronic supplementary material The online version of this article (10.1007/s13300-018-0553-7) contains supplementary material, which is available to authorized users.

INTRODUCTION A significant body of research exists on the impact of the social determinants of health (SDoHs) on diabetes care and general health outcomes. However, less is known about health care practitioners' (HCPs') perspectives and experiences regarding the impact of the SDoHs on their patients with Type I and Type 2 diabetes mellitus and how this affects the prevention and treatment of hypoglycemia. METHOD A descriptive qualitative study, derived from the InHypo-DM (Canada) research program. A purposive sampling technique was used to recruit participants residing in southwestern Ontario, Canada, for a 30- to 45-min semistructured interview. Individual and team analysis of interviews was conducted to identify overarching and subthemes. Twenty HCP participants, including endocrinologists, family physicians, and allied health care practitioners, were recruited. Seven were Certified Diabetes Educators. RESULTS Participants articulated 2 overarching components of the SDoHs: patients' socioeconomic issues and psychosocial issues. They highlighted two socioeconomic issues: occupation type and poverty. Participants also emphasized 3 areas pertaining to patients' psychosocial issues: stage in the life cycle (e.g., elderly), social isolation, and mental health. DISCUSSION This study emphasizes the need for conducting detailed and comprehensive social histories during clinical diabetes assessments, as well as the necessity of adequate clinical time and resources for HCPs and patients to address these issues in the context of hypoglycemia management. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

OBJECTIVE SENIOR compared the efficacy and safety of insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in older people (≥65 years old) with type 2 diabetes. RESEARCH DESIGN AND METHODS SENIOR was an open-label, two-arm, parallel-group, multicenter phase 3b trial designed to enroll ∼20% of participants aged ≥75 years. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to a fasting self-monitored plasma glucose of 5.0–7.2 mmol/L (90–130 mg/dL). RESULTS In total, 1,014 participants were randomized (mean age: 71 years). Comparable reductions in HbA1c were observed from baseline to week 26 for Gla-300 (−0.89%) and Gla-100 (−0.91%) in the overall population (least squares mean difference: 0.02% [95% CI −0.092 to 0.129]) and for participants aged ≥75 years (−0.11% [−0.330 to 0.106]). Incidence and rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia events were low and similar between both treatment groups, with lower rates of documented symptomatic hypoglycemia with Gla-300. The lower risk of hypoglycemia with Gla-300 versus Gla-100 was more apparent in the subgroup aged ≥75 years versus the overall population. Significantly lower annualized rates of documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) hypoglycemia were observed (Gla-300: 1.12; Gla-100: 2.71; rate ratio: 0.45 [95% CI 0.25–0.83]). CONCLUSIONS Efficacy and safety of Gla-300 was demonstrated in older people (≥65 years of age) with type 2 diabetes, with comparable reductions in HbA1c and similarly low or lower risk of documented symptomatic hypoglycemia versus Gla-100. A significant benefit in hypoglycemia reduction was seen in participants aged ≥75 years.

It is currently estimated that 11 million Canadians are living with diabetes or prediabetes. Although hyperglycemia is associated with serious complications, it is well established that improved glycemic control reduces the risk of microvascular complications and can also reduce cardiovascular (CV) complications over the long term. The UKPDS and ADVANCE landmark trials have resulted in diabetes guidelines recommending an A1C target of ≤ 7.0% for most patients or a target of ≤ 6.5% to further reduce the risk of nephropathy and retinopathy in those with type 2 diabetes (T2D), if it can be achieved safely. However, half of the people with T2D in Canada are not achieving these glycemic targets, despite advances in diabetes pharmacological management. There are many contributing factors to account for this poor outcome; however, one of the major factors is the delay in treatment advancement, particularly a resistance to insulin initiation and intensification. To simplify the process of initiating and titrating insulin in T2D patients, a group of Canadian experts reviewed the evidence and best clinical practices with the goal of providing guidance and practical recommendations to the diabetes healthcare community at large. This expert panel included general practitioners (GPs), nurses, nurse practitioners, endocrinologists, dieticians, pharmacists, and a psychologist. This article summarizes the panel recommendations.

Our objective was to examine risk factor modification targets and treatment in relation to duration of diabetes.The Diabetes Mellitus Status in Canada (DM-SCAN) study collected data on 5109 patients with type 2 diabetes mellitus (T2DM) in 2012 in primary care. We compared the prevalence of vascular complications, treatment targets, and interventions between patients with diagnosed diabetes duration ≤10 and 10 years.Physicians more frequently assigned HbA1c (glycated hemoglobin) targets of 7.1-8.5% (54-69 mmol/mol) to patients with longer duration of diabetes (n = 1647) (19.8% vs 9.5%, p 0.001). Patients with longer duration of diabetes were less likely to achieve HbA1c targets of ≤7.0% (53 mmol/mol) (39% vs. 55%, p 0.001), had similar likelihood of achieving blood pressure targets of ≤130/80 mmHg (38% vs. 36%, p = 0.26) and were more likely to achieve LDL-C targets of ≤2.0 mmol/L (≤77.3 mg/dL) (63% vs. 53%, p 0.001) compared to patients with shorter duration of diabetes (n = 3462). Achievement of all three targets between both groups were similar (13% vs. 13%, p = 0.82). Overall, patients with longer duration of diabetes were more likely to be prescribed anti-hyperglycemic, anti-hypertensive, lipid-lowering medications and referred for diabetes education.Only 13% of patients achieved glycemic, blood pressure, and LDL-C targets irrespective of duration of diabetes. Despite being managed with more medications, patients with longer duration of diabetes were less likely to achieve glycemic targets. More focus is needed on developing methods to bridge best care and real-world practice.

Objective It was uncertain whether an algorithm that involves increasing insulin dosages by 1 unit/day may cause more hypoglycemia with the longer-acting insulin glargine 300 units/mL (GLA-300). The objective of this study was to compare safety and efficacy of 2 titration algorithms, INSIGHT and EDITION, for GLA-300 in people with uncontrolled type 2 diabetes mellitus, mainly in a primary care setting. Methods This was a 12-week, open-label, randomized, multicentre pilot study. Participants were randomly assigned to 1 of 2 algorithms: they either increased their dosage by 1 unit/day (INSIGHT, n=108) or the dose was adjusted by the investigator at least once weekly, but no more often than every 3 days (EDITION, n=104). The target fasting self-monitored blood glucose was in the range of 4.4 to 5.6 mmol/L. Results The percentages of participants reaching the primary endpoint of fasting self-monitored blood glucose ≤5.6 mmol/L without nocturnal hypoglycemia were 19.4% (INSIGHT) and 18.3% (EDITION). At week 12, 26.9% (INSIGHT) and 28.8% (EDITION) of participants achieved a glycated hemoglobin value of ≤7%. No differences in the incidence of hypoglycemia of any category were noted between algorithms. Participants in both arms of the study were much more satisfied with their new treatment as assessed by the Diabetes Treatment Satisfaction Questionnaire. Most health-care professionals (86%) preferred the INSIGHT over the EDITION algorithm. The frequency of adverse events was similar between algorithms. Conclusions A patient-driven titration algorithm of 1 unit/day with GLA-300 is effective and comparable to the previously tested EDITION algorithm and is preferred by health-care professionals.

Primary care physicians are uniquely placed to offer holistic, patient-centred care to patients with T2DM. While the recent FDA-mandated cardiovascular outcome trials offer a wealth of data to inform treatment discussions, they have also contributed to increasing complexity in treatment decisions, and in the guidelines that seek to assist in making these decisions. To assist physicians in avoiding treatment inertia, Primary Care Diabetes Europe has formulated a position statement that summarises our current understanding of the available T2DM treatment options in various patient populations. New data from recent outcomes trials is contextualised and summarised for the primary care physician. This consensus paper also proposes a unique and simple tool to stratify patients into 'very high' and 'high' cardiovascular risk categories and outlines treatment recommendations for patients with atherosclerotic cardiovascular disease, heart failure and chronic kidney disease. Special consideration is given to elderly/frail patients and those with obesity. A visual patient assessment tool is provided, and a comprehensive set of prescribing tips is presented for all available classes of glucose-lowering therapies. This position statement will complement the already available, often specialist-focused, T2DM treatment guidelines and provide greater direction in how the wealth of outcome trial data can be applied to everyday practice.

Type 2 diabetes and its associated comorbidities are growing more prevalent, and the complexity of optimising glycaemic control is increasing, especially on the frontlines of patient care. In many countries, most patients with type 2 diabetes are managed in a primary care setting. However, primary healthcare professionals face the challenge of the growing plethora of available treatment options for managing hyperglycaemia, leading to difficultly in making treatment decisions and contributing to therapeutic inertia. This position statement offers a simple and patient-centred clinical decision-making model with practical treatment recommendations that can be widely implemented by primary care clinicians worldwide through shared-decision conversations with their patients. It highlights the importance of managing cardiovascular disease and elevated cardiovascular risk in people with type 2 diabetes and aims to provide innovative risk stratification and treatment strategies that connect patients with the most effective care.

Therapeutic inertia is a substantial obstacle to the initiation of insulin therapy in people with uncontrolled type 2 diabetes (T2D). This effect has in part been perpetuated by concerns over the impact of a burdensome regimen and the increased risk of hypoglycemia and body weight gain often associated with insulin use. An effective, yet simple, less burdensome regimen with a lower risk of body weight gain and hypoglycemia compared with an insulin-only regimen, may help to address these concerns more effectively. We review the available clinical and real-world data on IDegLira, a once-daily, injectable, fixed-ratio combination of insulin degludec (degludec) and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, in people with T2D. Evidence from the comprehensive DUAL clinical trial program suggests an advantage of IDegLira over traditional insulin therapies in a number of clinical outcomes, including maintenance of glycemic control, achievement of glycemic targets, reducing the risk of hypoglycemia, and body weight loss. These findings were demonstrated in participants with T2D irrespective of prior GLP-1RA and insulin use. Furthermore, the individual components of IDegLira have confirmed safety (degludec) or significant benefit in terms of improvement of cardiovascular risk (liraglutide). As an injectable therapy that is simple to titrate, IDegLira has the potential to optimize the ability to achieve relevant glycemic targets, and offers a suitable treatment option for people with T2D requiring insulin therapy who are at risk of hypoglycemia or weight gain.

TransFORmation of IndiGEnous PrimAry HEAlthcare Delivery (FORGE AHEAD) partnered with local clinical and community teams in 11 First Nations (FN) communities across Canada to develop quality improvement (QI) initiatives aimed at improving T2DM.Pre-post mixed-methods case study design was used. The 18-month intervention included community and clinical readiness, development of a community diabetes registry and clinical system, and QI activities. Participants consisted of community members, 18 yrs and older, with diabetes. Changes in clinical outcomes and clinical practice guideline (CPG) recommendations were assessed pre and post intervention using multilevel regression (patients nested within communities) adjusted forindividual andcommunity baseline characteristics.No significant change in HbA1c orsBP, but a small reduction indBP(-0.75 mmHg, p 0.05) and LDL (-0.09 mmol/L, p 0.05) was observed in 2008 adults with T2DM (mean age: 60·5 (SD:14·6) years; female: 57·2%). Individuals not at CPG targets at baseline had significant reductions in: %HbA1c (N = 616): -0.40 (95%CI:-0·55,-0·24),sBP (N = 561): -7·67 mmHg (95%CI:-9·23, -5·72),dBP (N = 291): -7·46 mmHg (95%CI:-8·69, -6·26), LDL (N = 450): -0·37mmo/l (95%CI:-0·44, -0·29).Annual HbA1c (OR: 1·95; 95%CI:1·66, 2·29), BP (OR: 1·78; 95%CI:1·52, 2·09), LDL (OR: 1·27; 95%CI:1·10, 1·47) and CKD screening (OR: 6·37; 95%CI:5·16, 7·92)increased but retinopathy screening decreased (OR: 0·68; 95%CI:0·57, 0·82). No significant change in foot exams (OR: 0·97; 95%CI:0·76, 1·23) or BMI recordings (OR: 0·96; 95%CI:0·82, 1·12) was seen. Overall, individualsweremorelikely to receive ≥75% of CPG recommended services compared to baseline (OR: 1·51; 95%CI:1·27, 1·80).FORGE AHEAD is the first Canadian study to demonstrate that a FN community-led QI intervention can lead to diabetes improvements.

ObjectiveTo evaluate multiple determinants of the longitudinal change in insulin clearance (IC) in subjects at high risk for type 2 diabetes (T2D).Research design and methodsAdults (n=492) at risk for T2D in the Prospective Metabolism and Islet Cell Evaluation cohort, a longitudinal observational cohort, had four visits over 9 years. Values from oral glucose tolerance tests collected at each assessment were used to calculate the ratios of both fasting C peptide-to-insulin (ICFASTING) and areas under the curve of C peptide-to-insulin (ICAUC). Generalized estimating equations (GEE) evaluated multiple determinants of longitudinal changes in IC.ResultsIC declined by 20% over the 9-year follow-up period (pFASTING and ICAUC over time (all pConclusionsOur findings suggest that non-European ethnicity and components of the metabolic syndrome, including central obesity, non-alcoholic fatty liver disease, and subclinical inflammation, may be related to longitudinal declines in IC.

Introduction The objective of this study was to establish the burden of hypoglycemia on family members of people with diabetes (PWDs) and to gain an understanding of how conversations about hypoglycemia can contribute to diabetes care. Methods This was a multinational cross-sectional study of family members of people with type 1 or type 2 diabetes taking insulin and/or secretagogues for ≥ 12 months who voluntarily completed an online questionnaire. Results Overall, 4300 family members of PWDs (type 1 [29%], type 2 [46%], unknown [25%]) were surveyed. Two in three family members (66%) reported thinking about the hypoglycemia of the PWD at least monthly, and 64% felt worried or anxious about the PWD’s risk for hypoglycemia. There was general agreement among family members that more conversations about hypoglycemia would have a positive impact on the PWD’s life (76%). Conclusions Hypoglycemia can present a burden on the lives of family members of PWDs. Conversations about hypoglycemia, facilitated by a healthcare professional, may reduce this burden and hypoglycemia risk. Funding Novo Nordisk A/S. Electronic supplementary material The online version of this article (10.1007/s13300-019-00687-y) contains supplementary material, which is available to authorized users.

In the article cited above, the ClinicalTrials.gov registration number was incorrect in the …

Titration following initiation of BI tends to occur in the first 8-12 weeks. At this time, patients may be at risk of experiencing hypoglycemia, which itself may present a barrier to optimal glycemic control. BRIGHT was the first randomized controlled trial comparing efficacy and safety of two second-generation BI analogs in insulin-naïve patients with T2DM, and showed less hypoglycemia with insulin glargine 300 U/mL (Gla-300) vs. insulin degludec 100 U/mL (IDeg) in the initial 12-week titration period. We investigated patient characteristics and clinical outcomes (including HbA1c change, and hypoglycemia incidence during weeks 13-24) by the occurrence of early confirmed (≤70 mg/dL) hypoglycemia (in the titration period) using descriptive statistics. Participants experiencing hypoglycemia within the first 12 weeks tended to be older, had lower BMI, more impaired renal function, longer duration of diabetes, and were more likely to be using SUs at baseline (Table). Overall, hypoglycemia incidence during weeks 13-24 was lower in the group that did not experience hypoglycemia within the first 12 weeks. HbA1c reductions at week 12 were greater in those with hypoglycemia in the titration period. These findings suggest that patients experiencing early hypoglycemia with second-generation BI analogs have increased hypoglycemia risk in later stages of therapy. Disclosure S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. L. Berard: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Abbott, Ascensia Diabetes Care, AstraZeneca, Bayer AG, Becton, Dickinson and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada, Mylan, Novo Nordisk Inc., Sanofi. Research Support; Self; Montmed Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. F. Lauand: Employee; Self; Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker's Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Funding Sanofi (NCT02738151)

Long-acting insulin analogs have the potential to optimize glycemic control in type 2 diabetes, but the patients’ perspective is key for acceptance and treatment adherence. BRIGHT investigated safety and efficacy of initiating the second-generation basal insulin analogs insulin glargine 300 U/mL (Gla-300) vs. insulin degludec 100 U/mL (IDeg-100) in insulin-naïve people with T2DM. We report data on patient satisfaction from the BRIGHT trial and the EDITION 3 trial (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]). BRIGHT and EDITION 3 were both multicenter, open-label, randomized, parallel-group trials with primary endpoint at 6 months. Randomized participants titrated to a fasting SMPG of 80-100 mg/dL (once-daily evening dosing). The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was completed at baseline and 6 months. Overall, initiating basal insulin analogs was associated with improved treatment satisfaction (Table). There was a numerically greater decrease in perceived hyperglycemia frequency for Gla-300 and IDeg-100 vs. Gla-100 and only a very small increase in the perceived hypoglycemia frequency for all insulins. Similar treatment satisfaction improvement for all insulins was observed. In randomized controlled trials, initiating basal insulin analogs is associated with improved treatment satisfaction, with little increase in perceived hypoglycemia frequency. Disclosure L. Berard: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Abbott, Ascensia Diabetes Care, AstraZeneca, Bayer AG, Becton, Dickinson and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada, Mylan, Novo Nordisk Inc., Sanofi. Research Support; Self; Montmed Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. F.J. Snoek: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Research Support; Self; Sanofi. Speaker's Bureau; Self; Lilly Diabetes. S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Funding Sanofi (NCT02738151)

Impaired awareness of hypoglycemia (IAH) has been linked to an increased rate of severe hypoglycemia (SH) in T1DM. Yet, few investigations have focused on quantifying this relationship in the context of T2DM, particularly from a pragmatic epidemiological lens. This study leverages the value of self-reported SH data to explore the real-world, population-based effect of IAH severity on SH rates in T2DM. A validated questionnaire (InHypo-DMPQ) was administered online to a nationally representative panel comprising Canadians (≥18 years) with T2DM using insulin and/or secretagogues. Data were collected on respondents’ socio-demographic/clinical traits; self-reported incidence of SH (in the past year); and IAH severity, trisected by no, moderate, and severe impairment. Multivariable negative binomial regression (NBR) analysis was used to isolate the effect of IAH on SH. A directed acyclic graph was devised to identify the minimally sufficient adjustment set. Of the 452 complete respondents (mean age: 53.2 (SD: 14.7) years; male: 56%), 6% were classified with severe IAH, 67% with moderate IAH, and 27% with no IAH. Those with severe IAH had the highest crude annual SH rate (5.89 events/person-year, 95% CI: 5.01-6.88), which over doubled and tripled the SH rate in people with moderate IAH (p This real-world, population-based study provides timely insight into the high prevalence of moderate and severe IAH in people with T2DM using insulin and/or secretagogues. The marked impact of IAH on increased SH rates underscores a pressing need for the clinical prioritization of IAH assessment and management in T2DM. Disclosure A. Ratzki-Leewing: None. S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. N.H. Au: None. S. Webster-Bogaert: None. J.B. Brown: None. S.M. Reichert: Advisory Panel; Self; Abbott, AstraZeneca, Novo Nordisk Inc., Sanofi, Servier. Research Support; Self; Canadian Institutes of Health Research. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. B.L. Ryan: None. Funding Sanofi Canada

Patients (pts) with T2D uncontrolled on insulin ± metformin were randomized to oral semaglutide (sema) 3 mg (N=184), 7 mg (N=182) or 14 mg (N=181), or placebo (pbo; N=184) in a 52-week (week) double-blind trial (NCT03021187). Total daily insulin dose was reduced by an optional 20% and capped at baseline (BL) level for week 0-26 and freely adjustable for week 26-52. Endpoints were change from BL to week 26 in HbA1c (primary) and body weight (BW; confirmatory secondary). Two scientific questions were addressed by defining two estimands: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use), and a trial product estimand (on trial product without rescue medication use) in all randomized pts. Oral sema was superior to pbo in reducing HbA1c and BW at week 26 (treatment policy estimand). Significantly greater, dose-dependent HbA1c and BW reductions vs. pbo were achieved at week 26 and 52 (both estimands; Table). Total daily insulin dose was significantly reduced from BL with oral sema vs. pbo at week 26 (except 3 mg) and 52. The rate of hypoglycemia was not significantly different vs. pbo (Table). Most frequent AE with oral sema was nausea (11.4-23.2% of pts vs. 7.1% with pbo) and 7.1-13.3% of pts prematurely discontinued due to AEs (vs. 2.7% with pbo). As add-on to insulin ± metformin, oral sema had superior HbA1c and BW reductions vs. pbo at week 26. It also reduced insulin use by week 52 and was well tolerated without significantly increasing hypoglycemia rate. Disclosure B. Zinman: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. V.R. Aroda: Consultant; Self; ADOCIA, AstraZeneca, Becton, Dickinson and Company, Novo Nordisk Inc., Sanofi, Zafgen, Inc. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; AstraZeneca, Calibra Medical, Eisai Inc., Janssen Research & Development, Novo Nordisk Inc., Sanofi, Theracos, Inc. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc. B. Cariou: Board Member; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals. Consultant; Self; GENFIT, Sanofi-Aventis. Research Support; Self; Amgen Inc., Pfizer Inc. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Merck Sharp & Dohme Corp. S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. S.T. Hoff: Employee; Self; Novo Nordisk A/S. K. Pedersen: Employee; Self; Novo Nordisk A/S. M. Tarp-Johansen: Employee; Self; Novo Nordisk A/S. E. Araki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Novo Nordisk Inc., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Merck & Co., Inc., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi. Funding Novo Nordisk A/S

Aim To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as add‐on to sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor therapy. Materials and methods In this 26‐week, phase IIIb, open‐label, parallel‐group, treat‐to‐target trial, conducted at 74 sites in 11 countries, insulin‐naïve people aged ≥18 years with glycated haemoglobin (HbA1c) 53–97 mmol/mol (7.0–11.0%), body mass index 20–40 kg/m2 and inadequately controlled type 2 diabetes (T2D) on SGLT2 inhibitor ± oral antidiabetic drugs were randomized 1:1 to once‐daily IDegLira or IGlar U100, both as add‐on to existing therapy. The primary endpoint was change in HbA1c from baseline to week 26. Results A total of 210 participants were randomized to each treatment arm. Mean HbA1c reductions were 21 mmol/mol (1.9%‐points) with IDegLira and 18 mmol/mol (1.7%‐points) with IGlar U100; confirming non‐inferiority (P

Diabetes has reached epidemic proportions in Indigenous populations around the globe, and there is an urgent need to improve the health and health equity of Indigenous peoples with diabetes through timely and appropriate diabetes prevention and management strategies. This review describes the evolution of the diabetes epidemic in Indigenous populations and associated risk factors, highlighting gestational diabetes and intergenerational risk, lifestyle risk factors and social determinants as having particular importance and impact on Indigenous peoples. This review further describes the impact of chronic disease and diabetes on Indigenous peoples and communities, specifically diabetes-related comorbidities and complications. This review provides continued evidence that dramatic changes are necessary to reduce diabetes-related inequities in Indigenous populations, with a call to action to support programmatic primary healthcare transformation capable of empowering Indigenous peoples and communities and improving chronic disease prevention and management. Promising strategies for transforming health services and care for Indigenous peoples include quality improvement initiatives, facilitating diabetes and chronic disease registry and surveillance systems to identify care gaps, and prioritizing evaluation to build the evidence-base necessary to guide future health policy and planning locally and on a global scale.

Aim To investigate the safety and efficacy of insulin degludec/liraglutide (IDegLira), a novel combination product, as add‐on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy. Methods In this 26‐week, double‐blind trial, adults with Type 2 diabetes [HbA1c 53–75 mmol/mol (7.0–9.0%)] were randomized to IDegLira (n = 289) or placebo (n = 146) as add‐on to pre‐trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0–6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Results The mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference –11 mmol/mol (95% CI –13; –10) or –1.02% (95% CI –1.18; –0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (, What's new? IDegLira is a combination of insulin degludec and liraglutide. Basal insulins and glucagon‐like peptide‐1 (GLP‐1) receptor agonists have complementary effects in a Type 2 diabetes treatment regimen, with GLP‐1 receptor agonists also being insulin‐sparing.Treatment guidelines often advocate discontinuing sulphonylureas on basal insulin initiation, but widespread concomitant use of these drugs continues in current clinical practice. It is therefore anticipated that many sulphonylurea‐treated people will have IDegLira added to their therapy, yet this combination has not previously been studiedThis randomized controlled trial shows that IDegLira can be used in people uncontrolled with sulphonylureas ± metformin to improve efficacy with a favourable benefit–risk profile.

Objectives To compare the efficacy and safety of canagliflozin, a sodium glucose co‐transporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM), in individuals younger than 75 and those aged 75 and older. Design Randomized Phase 3 studies. Setting International study centers. Participants Adults with T2DM. Measurements Changes from baseline in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), blood pressure (BP), and body weight were measured. Efficacy was evaluated using pooled data from six randomized, double‐blind, placebo‐controlled studies (N = 4,158; n = 3,975 aged