Basal Insulin Initiation Research Articles

816-P: Health Care Resource Utilization and Costs with Timely vs. Delayed Basal Insulin Initiation

816-P: Health Care Resource Utilization and Costs with Timely vs. Delayed Basal Insulin Initiation

817-P: Demographic, Clinical, and Treatment Characteristics of Patients with Timely vs. Delayed Basal Insulin Initiation

817-P: Demographic, Clinical, and Treatment Characteristics of Patients with Timely vs. Delayed Basal Insulin Initiation

Basal Insulin Initiation in Adults With Type 2 Diabetes Mellitus: A Retrospective Cohort Study Using Administrative Health Data in Alberta, Canada

ObjectivesPharmacologic treatment of type 2 diabetes mellitus (T2DM) follows a stepwise approach. Typically, metformin monotherapy is first-line treatment, followed by other noninsulin antihyperglycemic agents (NIAHAs) or progression to insulin if glycated hemoglobin (A1C) targets are not achieved. We aimed to describe real-world patterns of basal insulin initiation in people with T2DM and A1C not at target despite treatment with at least 2 NIAHAs. MethodsA retrospective cohort study was conducted using administrative health data from Alberta, Canada, among adults with T2DM, indexed on the first test with 7.0% < A1C < 9.5% (April 1, 2011, to March 31, 2019), with at least 2 previous NIAHAs but no insulin. Kaplan–Meier (KM) methodology was used to analyze time to basal insulin initiation, with stratification by index A1C. Annual patient status was categorized into 5 groups: basal insulin initiation, death, NIAHA intensification, no change in therapy (subgroups of A1C <7.1% and A1C ≥7.1% [clinical inertia]), or discontinuance. ResultsThe cohort included 14,083 individuals. The KM cumulative probability of initiating basal insulin was 7.7% (95% confidence interval [CI] 7.3% to 8.2%) at 1 year, increasing to 43.1% (95% CI 42.1% to 44.1%) at 8 years of follow-up. Higher A1C levels were associated with greater proportions of basal insulin initiation. By year 8, proportions with NIAHA intensification and clinical inertia were 12.1% and 19.3%, respectively, relative to year 7. ConclusionsDespite current clinical practice guidelines recommending achieving A1C targets within 6 months, less than half of the individuals with T2DM and clear indications for basal insulin initiated treatment within 8 years. Efforts to reduce delays in basal insulin initiation are needed.

Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative

AimsOpportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy.MethodsData on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005–2019).ResultsWe evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target.ConclusionsIn this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

Glucagon-Like Peptide-1 Receptor Agonists and Pancreatic Cancer Risk in Patients With Type 2 Diabetes

Concerns have been raised that glucagon-like peptide-1 receptor agonists (GLP-1RA) may increase the risk of pancreatic cancer. To investigate the association of GLP-1RA treatment with pancreatic cancer incidence over 9 years of follow-up. In this population-based historical cohort study, adult patients (aged 21 to 89 years) with type 2 diabetes insured by Clalit Healthcare Services, the largest state-mandated health organization in Israel, were followed up from 2009, when GLP-1RA became available in Israel, until pancreatic cancer diagnosis, death, reaching age 90 years, or end of follow-up (December 2017). Data were analyzed from June 2022 to November 2023. Treatment with GLP-1RA was compared with basal insulin. Pancreatic cancer incidence was compared according to weighted cumulative exposures to GLP-1RA and to basal insulin in a Cox model implemented in discrete time, with time origin at 2 years after diabetes diagnosis, adjusting for confounding. In sensitivity analyses, propensity score-matched pair new-user design and prevalent new-user design were used for the comparison. Because of risk for reverse-causation bias, results in the fifth to seventh year after medication were emphasized. During a cumulative follow-up of 3 290 439 person-years of 543 595 adults with a mean (SD) age of 59.9 (12.8) years (277 502 women [51%]) with incident diabetes, 1665 patients received pancreatic cancer diagnoses. In total, 33 377 patients (6.1%) used GLP-1RA and 106 849 (19.7%) used basal insulin. The estimated hazard ratio (HR) for pancreatic cancer associated with incremental use of 1 defined daily dose per day of GLP-1RA compared with basal insulin in the fifth to seventh year previously (all other characteristics, including age, sex, ethnic background, sociodemographic status, baseline body mass index, smoking history, history of pancreatitis, other glucose-lowering medications treatment history, and length of diabetes, being equal) was 0.50 (95% CI, 0.15-1.71). The new-user and prevalent new-user designs showed HRs from the fifth year onwards following initiation of GLP-1RA vs basal insulin of 0.52 (95 % CI, 0.19-1.41) and 0.75 (95 % CI, 0.37-1.53), respectively. In this historical cohort study of adults with type 2 diabetes, no support for an increased pancreatic cancer incidence over 7 years following start of GLP-1RA treatment was found. However, monitoring for pancreatic cancer risk beyond 7 years following initiation of therapy is still required. ClinicalTrials.gov Identifier: NCT02072902.

Insulin initiation in patients with type 2 diabetes is often delayed, but access to a diabetes nurse may help—insights from Norwegian general practice

Objective: We opted to study how support staff operational capacity and diabetes competences may impact the timeliness of basal insulin-initiation in general practice patients with type 2 diabetes (T2D). Design/Setting/Outcomes: This was an observational and retrospective study on Norwegian primary care patients with T2D included from the ROSA4-dataset. Exposures were (1) support staff size, (2) staff size relative to number of GPs, (3) clinic access to a diabetes nurse and (4) share of staff with diabetes course (1 and 2 both relate to staff operational capacity, whereas 3 and 4 are both indicatory of staff diabetes competences). Outcomes were ‘timely basal insulin-initiation’ (primary) and ‘attainment of HbA1c<7%’ after insulin start-up (secondary). Associations were analyzed using multiple linear regression, and directed acyclic graphs guided statistical adjustments. Subjects: Insulin naïve patients with ‘timely’ (N = 294), ‘postponed’ (N = 219) or ‘no need of’ (N = 3,781) basal insulin-initiation, respectively. Results: HbA1c [median (IQR)] increased to 8.8% (IQR, 8.0, 10.2) prior to basal insulin-initiation, which reduced HbA1c to 7.3 (6.8–8.1) % by which only 35% of the subjects reached HbA1c <7%. Adjusted risk of ‘timely basal insulin-initiation’ was more than twofold higher if access to a diabetes nurse (OR = 2.40, [95%CI, 1.68, 3.43]), but related only vaguely to staff size (OR = 1.01, [95%CI, 1.00, 1.03]). No other staff factors related significantly to neither the primary nor the secondary outcome. Conclusion: In Norwegian general practice, insulin initiation in people with T2D may be affected by therapeutic inertia but access to a diabetes nurse may help facilitating more timely insulin start-up.

Use of Voice-Based Conversational Artificial Intelligence for Basal Insulin Prescription Management Among Patients With Type 2 Diabetes

Optimizing insulin therapy for patients with type 2 diabetes can be challenging given the need for frequent dose adjustments. Most patients receive suboptimal doses and do not achieve glycemic control. To examine whether a voice-based conversational artificial intelligence (AI) application can help patients with type 2 diabetes titrate basal insulin at home to achieve rapid glycemic control. In this randomized clinical trial conducted at 4 primary care clinics at an academic medical center from March 1, 2021, to December 31, 2022, 32 adults with type 2 diabetes requiring initiation or adjustment of once-daily basal insulin were followed up for 8 weeks. Statistical analysis was performed from January to February 2023. Participants were randomized in a 1:1 ratio to receive basal insulin management with a voice-based conversational AI application or standard of care. Primary outcomes were time to optimal insulin dose (number of days needed to achieve glycemic control), insulin adherence, and change in composite survey scores measuring diabetes-related emotional distress and attitudes toward health technology and medication adherence. Secondary outcomes were glycemic control and glycemic improvement. Analysis was performed on an intent-to-treat basis. The study population included 32 patients (mean [SD] age, 55.1 [12.7] years; 19 women [59.4%]). Participants in the voice-based conversational AI group more quickly achieved optimal insulin dosing compared with the standard of care group (median, 15 days [IQR, 6-27 days] vs >56 days [IQR, >29.5 to >56 days]; a significant difference in time-to-event curves; P = .006) and had better insulin adherence (mean [SD], 82.9% [20.6%] vs 50.2% [43.0%]; difference, 32.7% [95% CI, 8.0%-57.4%]; P = .01). Participants in the voice-based conversational AI group were also more likely than those in the standard of care group to achieve glycemic control (13 of 16 [81.3%; 95% CI, 53.7%-95.0%] vs 4 of 16 [25.0%; 95% CI, 8.3%-52.6%]; difference, 56.3% [95% CI, 21.4%-91.1%]; P = .005) and glycemic improvement, as measured by change in mean (SD) fasting blood glucose level (-45.9 [45.9] mg/dL [95% CI, -70.4 to -21.5 mg/dL] vs 23.0 [54.7] mg/dL [95% CI, -8.6 to 54.6 mg/dL]; difference, -68.9 mg/dL [95% CI, -107.1 to -30.7 mg/dL]; P = .001). There was a significant difference between the voice-based conversational AI group and the standard of care group in change in composite survey scores measuring diabetes-related emotional distress (-1.9 points vs 1.7 points; difference, -3.6 points [95% CI, -6.8 to -0.4 points]; P = .03). In this randomized clinical trial of a voice-based conversational AI application that provided autonomous basal insulin management for adults with type 2 diabetes, participants in the AI group had significantly improved time to optimal insulin dose, insulin adherence, glycemic control, and diabetes-related emotional distress compared with those in the standard of care group. These findings suggest that voice-based digital health solutions can be useful for medication titration. ClinicalTrials.gov Identifier: NCT05081011.

Simultaneous Versus Sequential Initiation of Lixisenatide and Basal Insulin for Type2 Diabetes: Subgroup Analysis of a Japanese Post-Marketing Surveillance Study of Lixisenatide (PRANDIAL).

We aimed to assess the efficacy and safety of lixisenatide and basal insulin (BI) according to timing of treatment initiation, treatment compliance, and number of concomitant daily injections in Japanese individuals with type2 diabetes (T2D). Each substudy analyzed subgroup data from the 3-year post-marketing surveillance PRANDIAL study. Endpoints included glycated hemoglobin (HbA1c), postprandial glucose, treatment response (HbA1c < 7.0% at week24 and 156), and safety. Changes in HbA1c levels were analyzed using paired ttests; between-group comparisons were made using analysis of variance (ANOVA). Of 2679 participants, 46.5% initiated BI before lixisenatide, 12.0% the same day, 2.7% between 1 and 90days, and 2.8% at 91 or more days after lixisenatide; 36.0% did not receive BI. Overall, 85.4% of patients were compliant with lixisenatide treatment. The majority of patients (52.4%) received two injections/day (one was lixisenatide). Compared with other subgroups taking BI and lixisenatide, the subgroup starting them simultaneously had a mean change in HbA1c of - 0.69% [8mmol/mol] (vs + 0.07% [0.8mmol/mol] to - 0.79% [9mmol/mol]) and numerically higher treatment response (21.0% vs 8.3-18.7%), but more hypoglycemia (8.1% vs 2.3-2.8%). Japanese people with T2D achieved better glycemic control by simultaneous as opposed to sequential initiation of lixisenatide and BI.

Expert Opinion on Diabetes Management Challenges and Role of Basal Insulin/GLP-1 RA Fixed-Ratio Combination in People with Type 2 Diabetes from Indonesia.

Indonesia is struggling with a rapidly growing burden of diabetes due to rapid socioeconomic transition. People with type 2 diabetes mellitus (T2DM) need appropriate treatment strategies to maintain glycemic control. New modalities with simplicity, such as fixed-ratio combination of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA), further referred to as FRC, have proven to be an effective and practical therapeutic approach that may address this issue. In January 2021, a scientific expert meeting was held with the participation of endocrinologists from Indonesia to provide expert opinions regarding the optimal practical use of the FRC basal insulin/GLP1-RA. Topics discussed in the meeting included the challenges in diabetes management, clinical inertia with insulin therapy, local and international guideline positioning, initiation, titration, and switching of basal insulin and GLP-1 RA, including FRC, and the management of T2DM.

Practical Guidance on Basal Insulin Initiation and Titration in Asia: A Delphi-Based Consensus.

The global health burden of diabetes is on the rise and has affected more than half a billion people worldwide, particularly in Southeast Asia, North Africa, Africa, and the Western Pacific, Middle East, and South and Central America regions of the International Diabetes Federation (IDF). Despite many new treatments being available for the management of diabetes, glycemic control remains suboptimal in Asia, compared to the rest of the world. Delay in timely insulin initiation and inadequate titration of insulin are regarded to be some of the important reasons for inadequate glycemic control. Additionally, Asian populations have a distinct phenotype, including a younger age of onset and higher glycemic excursions, suggestive of a lower beta-cell function, as compared to non-Asians. Although there are multiple local and international guidelines on insulin initiation and titration, some of these guidelines can be complex. There is an unmet need for guideline recommendations on basal insulin initiation and titration to be simplified and customized for the Asian population with type 2 diabetes mellitus (T2DM). A unified approach would increase adoption of basal insulin initiation by primary care and family medicine physicians, which in turn would help reduce the inertia to insulin initiation. With this background, a consensus-seeking meeting was conducted with 14 experts from seven Asian countries to delineate appropriate practices for insulin initiation and titration in the Asian context. The key objective was to propose a simple insulin titration algorithm, specific for the Asian population, to improve glycemic control and optimize therapeutic outcomes of people with T2DM on basal insulin. Following a detailed review of literature and current guidelines, and potential barriers to insulin initiation and titration, the experts proposed a simplified insulin titration algorithm based on both physician- and patient-led components. The consensus recommendations of the experts related to basal insulin initiation and titration have been summarized in this article, along with the proposed titration algorithm for optimizing glycemic control in the Asian population with T2DM.

809-P: Digital-Tool-Supported Basal Insulin (BI) Titration: Real-World Effectiveness of My Dose Coach (MDC) in People with Type 2 Diabetes (T2D) in Colombia

BI therapy is recommended in people with T2D uncontrolled on oral antidiabetic agents. However, due to delay in BI initiation and titration, many people with T2D fail to achieve recommended glycemic targets. MDC, an FDA-approved digital app, helps people with T2D to adjust their BI doses based on their fasting blood glucose (FBG) readings and hypoglycemic event data. We evaluated real-world outcomes from people with T2D on BI therapy, who registered on MDC app from 08/01/2018 to 09/30/2021 and received insulin glargine 100 U/mL or 300 U/mL. FBG target achievement (≥3 consecutive measurements within the target range) , change in FBG, and hypoglycemia events were assessed. A total of 5MDC users from Colombia with mean (SD) age 56.6 (15.1) years (55.8% female) were included (Table) . Overall, 4 (80.9%) users achieved individualized FBG target, 44 (8.7%) were still titrating and 52 (10.3%) stopped using MDC. The mean (SD) time to reach FBG target was 10.3 (15.8) days. Mean (SD) FBG at baseline was 141.7 (55.0) mg/dL, which decreased to 117.3 (31.7) mg/dL and mean (SD) BI dose increased from 22.2 (11.3) U to 24.2 (12.4) U. Hypoglycemia events were reported in 72 (14%) participants overall. These results show that people with T2D from Colombia using MDC were able to successfully titrate their BI doses and achieve FBG target with low risk of hypoglycemia. Disclosure A.Gomez: Advisory Panel; AstraZeneca, Research Support; Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi. A.Rincon: Advisory Panel; AstraZeneca, Medtronic, Sanofi, Consultant; Abbott, Medtronic, Novo Nordisk, Novo Nordisk, Sanofi, Other Relationship; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi. K.Feriz: Other Relationship; Abbott, Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi, Speaker's Bureau; AstraZeneca, Lilly Diabetes, Medtronic, Merck Sharp &amp; Dohme Corp. C.F.Salamanca: Employee; Sanofi. L.P.Silva: Employee; Merck KGaA, Sanofi. Funding Sanofi

379-P: Patient and Physician Experience of Hypoglycemia during Basal Insulin (BI) Titration in Type 2 Diabetes (T2D) in the U.S.

Introduction: Hypoglycemia after BI initiation can negatively impact patient adherence to titration and glycemic target achievement. We report on 2 surveys to better understand patient and physician perspectives/experiences of hypoglycemia during BI titration. Methods: Adults with T2D and ≥2 claims (≥30 days apart in last 12 months) in the Optum Research Database who initiated BI (February-April 2021) , and physicians who treated ≥30 patients with T2D, ≥1 initiating BI (October 2020-March 2021) , completed a mailed survey. Results: Responders were 416 patients (51% male, 71% white, mean age 70 years, 72% &amp;gt;years T2D duration) and 386 physicians (45% general practice) . Most physicians reported discussing hypoglycemia signs/symptoms (93%) and how to titrate BI in response to blood glucose (BG) levels (81%) with patients. Among patients who experienced hypoglycemia (49%; Table) , 57% felt very/extremely confident titrating BI during hypoglycemia. Only 35% met fasting BG (FBG) targets. Diabetes Treatment Satisfaction Questionnaire hypoglycemia score (1.34/6) suggests patients felt hypoglycemia was infrequent. Conclusion: While physicians educate patients on hypoglycemia awareness and BI titration, nearly half of patients surveyed experienced hypoglycemia during titration, and only a third met FBG targets, suggesting new strategies and tools are needed for effective BI titration. Disclosure S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca. M.Bertolini: Employee; Sanofi. V.Walker: Consultant; Sanofi-Aventis U.S. M.H.Carlyle: None. F.L.Zhou: Employee; Sanofi, Stock/Shareholder; Sanofi. J.Seufert: Advisory Panel; Abbott, Sanofi-Aventis Deutschland GmbH, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. J.E.Anderson: Advisory Panel; Abbott Diabetes, Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gelesis, Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company. Funding Sanofi

Economic burden of diabetes-related hypoglycemia on patients, payors, and employers.

The economic and psychological consequences of diabetes-related hypoglycemic events are multifold and shared across various parties, including patients and their family or caregivers, payors, and employers. Hypoglycemic events contribute to increased morbidity, mortality, and a substantial portion of diabetes economic burden. Both severe and non-severe hypoglycemic episodes contribute to economic and psychological burden, and can have short-term consequences, such as emergency services, hospitalization, clinic visits, and increased use of diabetes supplies. Severe hypoglycemic events also generate additional follow-up costs, and are likely to occur again. Left untreated, hypoglycemia can have long-term consequences including, death, cardiovascular events, and cognitive issues. Costs vary geographically based on the treatment protocols which focus on outpatient treatment versus increased in-patient hospitalization. Certain types of medications are also associated with increased hypoglycemia, which requires closer monitoring of the patient, such as with basal insulin initiation. Some individuals with diabetes may be more vulnerable to hypoglycemia, such as the elderly, postoperative bariatric patients, and adolescent females. Measures to mitigate hypoglycemia are essential to ease the economic burden of these events. Medication management, optimal glucose control, lifestyle modifications and frequent glucose monitoring are some interventions which may help prevent hypoglycemia.

A practical approach to the clinical challenges in initiation of basal insulin therapy in people with type 2 diabetes.

Initiating insulin therapy with a basal insulin analogue has become a standard of care in the treatment of type 2 diabetes mellitus (T2DM). Despite increasing choices in pharmacological approaches, intensified glucose monitoring and improvements in quality of care, many patients do not achieve the desired level of glycaemic control. Although insulin therapy, when optimized, can help patients reach their glycaemic goals, there are barriers to treatment initiation on both the side of the patient and provider. Providers experience barriers based on their perceptions of patients' capabilities and concerns. They may lack the confidence to solve the practical problems of insulin therapy and avoid decisions they perceive as risky for their patients. In this study, we review recommendations for basal insulin initiation, focussing on glycaemic targets, titration, monitoring, and combination therapy with non‐insulin anti‐hyperglycaemic medications. We provide practical advice on how to address some of the key problems encountered in everyday clinical practice and give recommendations where there are gaps in knowledge or guidelines. We also discuss common challenges faced by people with T2DM, such as weight gain and hypoglycaemia, and how providers can address and overcome them.

Real-world evidence of the effectiveness on glycaemic control of early simultaneous versus later sequential initiation of basal insulin and glucagon-like peptide-1 receptor agonists.

AimTo assess the impact of the timing of initiating both basal insulin and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on reaching glycaemic control targets over 6 and 12 months in people with type 2 diabetes (T2D) uncontrolled on oral antihyperglycaemic drugs with an HbA1c of 9% or higher.MethodsThis retrospective cohort study assessed the impact of the timing of initiating both basal insulin and GLP‐1 RA therapies on reaching glycaemic targets (HbA1c < 7% and <8%, and ≥1% and ≥2% HbA1c reduction) over 12 months in people with markedly uncontrolled T2D (HbA1c ≥ 9%) on oral antihyperglycaemic drugs identified on the Optum Humedica database (electronic medical records; 1 January 2011 to 30 June 2017). Study cohorts were defined by the days between initiating each injectable: cohort A, 30 days or less (simultaneous initiation) and cohorts B, 31‐90, C, 91‐180, D, 181‐270 and E, 271‐360 days (sequential initiation).ResultsCohort A had the best glycaemic outcomes at 6 and 12 months for all four endpoints, followed by cohort B. The likelihood of achieving an HbA1c of less than 7% did not significantly differ between cohorts A and B (hazard ratio [95% confidence interval]: 0.87 [0.76‐1.01]); cohorts C, D and E were significantly less likely to achieve an HbA1c of less than 7% than cohort A (0.62 [0.53‐0.72]; 0.62 [0.53‐0.72]; 0.63 [0.54‐0.73]).ConclusionsIn people with uncontrolled T2D requiring treatment with a GLP‐1 RA and basal insulin, greater improvements in glycaemic control were observed when both therapies were initiated within close proximity of one another (≤90 days) compared with initiation 91‐360 days apart.

Effective Initiation and Treatment With Basal Insulin in People With Type 2 Diabetes: Focus on Mitigating Hypoglycemia in Patients at Increased Risk: Executive Summary.

Many people with type 2 diabetes are treated with insulin with the goal of achieving a specific A1C target. The most prominent risk for people on insulin therapy is hypoglycemia. When basal insulin analogs are used appropriately, the risk of hypoglycemia can be reduced while still achieving individualized glycemic goals. In a series of short videos now available on the Clinical Diabetes website, the authors discuss approaches to optimizing basal insulin initiation and treatment in people with type 2 diabetes, including those at high risk such as individuals with renal impairment and older adults, with a focus on reaching A1C goals while mitigating the risk for hypoglycemia. This article is intended to briefly summarize those discussions, and readers are encouraged to view the videos in their entirety at https://clinical.diabetesjournals.org/content/basal-insulin-videos. ### Introduction (Available at https://bcove.video/2Q2Rb9b) Approximately 50% of people with type 2 diabetes have poorly controlled disease and are vulnerable to long-term micro- and macrovascular complications (1). As type 2 diabetes progresses, many patients will require insulin to maintain glycemic control. The appropriate use of insulin requires a balance between the need for tight glucose control and the potential risk for hypoglycemia. Definitions of hypoglycemia have evolved over time, and the American Diabetes Association (ADA) now uses a three-level classification of hypoglycemia severity (2). Mitigating the risk for hypoglycemia is crucial to the successful treatment of people with type 2 diabetes. In the following series of videos, the authors discuss the use of available insulin formulations in the context of hypoglycemia risk. ### Basal Insulin Therapy—Balancing Glycemic Control With Risk for Hypoglycemia (Available at https://bcove.video/3h3Y85h) The achievement of tight glycemic control reduces micro- and macrovascular complications, and adherence to treatment improves quality of life and decreases health care costs (3–9). The authors discuss the association between A1C reduction and microvascular complications, as reported in the UK …

2198-PUB: The Impact of Basal Insulin Initiation to Background Sulfonylurea Treatment on Hypoglycemia Occurrence: Evaluation of the Balkan Cohort of Dune Study

Background: Optimal glycemic control and proper basal insulin initiation timing when non-insulin treatment becomes insufficient is critical in type 2 diabetes mellitus (T2DM). The DUNE study investigated the effectiveness and safety of newly initiated basal insulin in T2DM patients compared to those who already received insulin. The impact of background therapy with sulfonylureas (SU) on insulin dose and hypoglycemia occurrence was also explored. Methods: The DUNE study was a 12-week, prospective, single-arm, observational study of adults with T2DM. The present sub-analysis included the patients from the Balkan region (Slovenia and Serbia). The first group (n=83) included patients with newly initiated basal insulin and the second group (n=94) included patients who were already treated with basal insulin for up to 12 months. Patients also received other non-insulin antihyperglycemic drugs. Results: The proportion of patients receiving SUs was higher in the group with newly initiated basal insulin (72.3% vs. 55.3%; p&amp;lt;0.001). Basal insulin treatment included NPH or 1st generation basal insulin analogues (BIA) (98.8% vs. 1.2% for newly initiated basal insulin and 83% vs. 17% for already initiated basal insulin), due to local reimbursement policy. Daily insulin doses were lower in newly initiated basal insulin group (11.7±5.58U vs. 18.6±9.18U; p&amp;lt;0.001), the difference remained significant also after 12 weeks of observation (17.5±11.8U vs. 22.6±10.69U; p&amp;lt;0.01). A trend towards higher hypoglycemia occurrence in the newly initiated basal insulin group was observed, despite the lower insulin dose, but with higher percentage of treatment with SUs as a background treatment. Conclusions: Continuation of SUs in T2DM patients, both newly initiated and already initiated with basal insulin therapy (NPH or first-generation insulin analog), should be considered with caution due to the potentially enhanced effect on the risk of hypoglycemia. Disclosure A. Janez: None. M. Lunder: None. M. Janic: None. N. Grulovic: None. D. Zdravkovic: None. A.Z. Jotic: None. K. Lalic: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, Sanofi. N. Lalic: None.

965-P: Real-World Evidence of the Effect on Glycemic Control with Relatively Simultaneous vs. Sequential Initiation of Basal Insulin and GLP-1 Receptor Agonists

Injectable therapy initiation in T2D is often delayed. This retrospective cohort study evaluated the impact of the timing of initiating both basal insulin and GLP-1 RA in people with uncontrolled T2D (HbA1c ≥9 %) on OADs within 12 months (Optum Humedica database of electronic medical records and claims; 1/1/2011 to 6/30/2017). Study cohorts were defined by the days between initiating the first and second injectable: cohort A ≤30 (simultaneous); B 31-90; C 91-180; D 181-270; E 271-360 (sequential). Endpoints: proportion achieving HbA1c &amp;lt;7 % or &amp;lt;8 % and achieving ≥1 % or ≥2 % reduction in HbA1c at 6 and 12 months after initiating the second injectable. Baseline characteristics (N=6339): mean ± SD age 54 ± 11 years; HbA1c 10.7 ± 1.5 %; weight 108 ± 25 kg; 47% male. Despite slightly higher baseline HbA1c, cohort A had the best glycemic outcomes at 6 and 12 months for all 4 endpoints, followed by cohort B, then no difference between C, D and E (Table). Cohorts C, D and E were significantly less likely to achieve HbA1c &amp;lt;7 % than cohort A (hazard ratios [95% CI]: 0.62 [0.53-0.72]; 0.62 [0.53-0.72]; 0.63 [0.54-0.73]), but cohort B was not (0.87 [0.76-1.01]). In summary, despite higher baseline HbA1c, addition of a second injectable agent within 90 days of the first led to significantly better glycemic control at 12 months than postponing addition to later in the year in uncontrolled T2D. Disclosure J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. F. Ampudia Blasco: None. R. Lubwama: Employee; Self; Sanofi US. X.V. Peng: Employee; Self; Sanofi. A.H. Boss: Employee; Self; Sanofi. Stock/Shareholder; Self; Novo Nordisk Inc., Sanofi. L. Shi: None. V. Fonseca: Consultant; Self; Abbott, Asahi Kasei Corporation, AstraZeneca, Bayer Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Stock/Shareholder; Self; Amgen, Bravo4health. Funding Sanofi

Basal Insulin Initiation and Maintenance in Adults with Type 2 Diabetes Mellitus in the United States.

ObjectiveA survey of US adults with type 2 diabetes mellitus was conducted to better understand patients’ insulin initiation experiences and treatment persistence behaviors. Research Design and MethodsParticipants were recruited from consumer panels and grouped by basal insulin treatment pattern: continuers (no gap of ≥7 days within 6 months of initiation); interrupters (gap ≥7 days, resumed treatment); discontinuers (stopped for ≥7 days, not resumed). A quota of approximately 50 respondents per persistence category was set.ResultsA total of 154 respondents (52 continuers, 52 interrupters, 50 discontinuers) completed the survey. Mean age was 51.4 years; 51.9% male. Continuers were more likely to report their views being considered during initiation, and less likely to report a sense of failure. Concerns included insulin dependence (64.3% agree/strongly agree), frequent blood glucose monitoring (55.2%), costs/ability to pay (53.9%), fears of or mistakes during self-injection (52.6%), and weight gain (52.6%). Continuers were motivated by benefits of insulin therapy; experienced or potential side effects were notable factors for interruption/discontinuation. Healthcare provider instruction was indicated as a reason for continuing, stopping, and restarting therapy.ConclusionBenefits of basal insulin therapy motivated continuers while side effects impacted interruption/discontinuation. Persistence on basal insulin is often influenced by provider actions. Earlier provider intervention upon signs of treatment discontinuation may promote persistence.

Impact of Simultaneous Versus Sequential Initiation of Basal Insulin and Glucagon-like Peptide-1 Receptor Agonists on HbA1c in Type 2 Diabetes: A Retrospective Observational Study.

IntroductionWhen and how to intensify treatment in patients with type 2 diabetes (T2D) not achieving glycated hemoglobin (HbA1c) targets with oral antidiabetic drugs (OADs) in clinical practice remains a matter of clinical preference. This pilot study was conducted using the retrospective observational data from such patients to evaluate the impact on HbA1c of three treatment sequences: simultaneous initiation of basal insulin (BI) and a glucagon-like peptide-1 receptor agonist (GLP-1 RA; Cohort 1); BI followed by GLP-1 RA initiation within a 90-day timeframe (Cohort 2); or BI followed by GLP-1 RA initiation beyond 90 days (Cohort 3).MethodsData from the regional US electronic medical records database, Research Action for Health Network (REACHnet), were extracted for all patients with T2D aged ≥ 18 years who had encounter dates between January 2011 and August 2017 and ≥ 1 HbA1c laboratory value(s) < 90 days before BI initiation and ≥ 2 HbA1c laboratory values within 1 year after BI initiation and who met the inclusion criteria for GLP-1 RA initiation set for Cohorts 1, 2, or 3. The primary endpoints were the proportion of patients achieving HbA1c < 7.0%, which was estimated via Kaplan–Meier analysis, and change in HbA1c within 12 months.ResultsOverall, 869 patients were analyzed, of whom 109 were in Cohort 1, 301 in Cohort 2, and 459 in Cohort 3. Baseline HbA1c was 10.3 ± 2.1, 10.3 ± 2.0, and 10.2 ± 2.1% for these three cohorts, respectively. Statistically significantly more patients in Cohort 1 than in Cohort 3 achieved HbA1c < 7.0% (33.4 vs. 20.9%, respectively; p = 0.0186). Mean observed reductions in HbA1c at 12 months were − 1.7% (Cohort 1), − 1.5% (Cohort 2), and − 1.3% (Cohort 3).ConclusionsSimultaneous initiation of BI and GLP-1 RA achieves glycemic control more effectively than sequential initiation of BI with GLP-1 RA added beyond 90 days.