Glycemic Control Following GLP-1 RA or Basal Insulin Initiation in Real-World Practice: A Retrospective, Observational, Longitudinal Cohort Study.

INTRODUCTION: Injectable therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and basal insulin (BI) are well-established agents for people with type 2 diabetes (T2D). This study aimed to investigate real-world effectiveness of GLP-1 RAs or BI in adults with T2D poorly controlled on oral antihyperglycemic drugs (OADs). METHODS: This was a retrospective, observational, longitudinal cohort study of adults with T2D from the US Optum Humedica® database and UK Clinical Practice Research Datalink, who initiated either injectable between January 1, 2010, and June 30, 2016. Baseline characteristics, glycated hemoglobin (HbA1c) change, and cumulative percentage reaching HbA1c < 7% in 24 months after initiation were analyzed in four patient cohorts. RESULTS: In the US and UK databases, respectively, 20,836 and 5508 patients initiated GLP-1 RAs and 60,598 and 5083 initiated BI. Baseline mean HbA1c at initiation ranged between 8.8% and 10.3% across all cohorts. In all cohorts, a decrease of HbA1c occurred 3-6 months after initiation. The cumulative percentage of patients reaching HbA1c < 7% showed the greatest probability in the first 12 months (15-40% of patients across cohorts at 12 months), particularly in the first 6 months after initiation. The probability of reaching glycemic control diminished after the second quarter. The proportion of patients reaching HbA1c < 7% in both GLP-1 RA and BI cohorts at 12 months was < 25% if baseline HbA1c was ≥ 9%. CONCLUSIONS: For adults with T2D inadequately controlled on OADs, this analysis reveals an unmet clinical need. Initiation of first injectable therapy did not occur until HbA1c was considerably above target, when control is harder to achieve. Results suggest that in individuals with baseline HbA1c ≥ 9.0%, only a minority are likely to achieve an HbA1c < 7% with a GLP-1 RA or BI alone.

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.

AIM: To 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. METHODS: This 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). RESULTS: Cohort 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]). CONCLUSIONS: In 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.

A Real-World Observational Study Evaluating the Probability of Glycemic Control with Basal Insulin or Glucagon-Like Peptide-1 Receptor Agonist in Japanese Patients with Type 2 Diabetes.

INTRODUCTION: The effectiveness of basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in providing glycemic control in patients with type 2 diabetes (T2D) in Japanese routine practice is not well known. This real-world observational study evaluated the probability of achieving glycemic control in Japanese patients with T2D uncontrolled by oral antidiabetic drugs (OADs) who initiated BI or GLP-1 RA therapy. METHODS: Patients with T2D aged ≥ 18 years initiating BI or GLP-1 RA therapy following treatment with OADs were selected from real-world data (RWD) retrieved from a large electronic medical record database in Japan, using data from 01 January 2010 to 30 June 2019. Patients were required to have glycated hemoglobin (HbA1c) ≥ 7% within 90 days prior to the first prescription of BI or GLP-1 RA. The probability of reaching first HbA1c < 7% was assessed over a 24-month period in cohorts of patients who initiated BI (n = 3477) or GLP-1 RA (n = 780) and in subcohorts by number of OADs at baseline (1, 2, or ≥ 3), HbA1c at baseline (≥ 7 to < 8%, ≥ 8 to < 9%, or ≥ 9%), and age (< 65 or ≥ 65 years). RESULTS: Mean (standard deviation) baseline HbA1c was 9.4% (1.8%) and 8.8% (1.4%) in patients initiating BI or GLP-1 RA therapy, respectively. The cumulative probability of achieving glycemic control was 50.1% with BI and 60.3% with GLP-1 RA therapy, respectively, at 12 months, and 60.8% and 66.6%, respectively, at 24 months. Quarterly (3-month intervals) conditional probabilities of achieving glycemic control decreased over time and were < 10% after 12 months. Patients with more OADs or higher HbA1c at baseline had a lower probability of achieving glycemic control. CONCLUSION: Among Japanese patients with T2D who initiated BI or GLP-1 RA therapy after treatment with OADs, the probability of reaching first glycemic control diminished over time. Further therapy intensification is warranted in patients who do not achieve glycemic control within 6-12 months with BI or GLP-1 RA, particularly those with high HbA1c or taking multiple OADs.

Patients with type 2 diabetes (T2D) who are taking oral antidiabetic drugs (OADs) but still have high blood glucose often require injectable drugs, such as basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). While BI and GLP-1 RAs have been shown to be effective in controlled clinical trials, it is unclear how well they improve blood glucose in real-world routine practice. Here, we report the results of an observational study that used data retrieved from a large electronic medical records database in Japan to explore how well BI and GLP-1 RAs allow patients to achieve glycemic control [glycated hemoglobin (HbA1c) < 7%].In Japanese patients with T2D receiving treatment with OADs and initiating BI or GLP-1 RA therapy, the probability of achieving glycemic control in the first quarter (3 months) after initiation was 20.3% with BI and 38.6% with GLP-1 RA. Among those patients who had not previously reached glycemic control, the probability of achieving first glycemic control declined over time, as evidenced in each quarterly assessment, and it was < 10% after the first year. Patients who had higher HbA1c levels or were taking multiple OADs were less likely to achieve glycemic control compared with those with lower HbA1c or taking fewer OADs. Our findings suggest that patients who have not achieved their glycemic goals within the first 6­12 months after starting BI or GLP-1 RA therapy have a low likelihood of achieving their target by maintaining the same therapy. For such patients, intensification with additional medication (e.g., combined BI and GLP-1 RA therapy) should be considered early in treatment.

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.

INTRODUCTION: When 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). METHODS: Data 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. RESULTS: Overall, 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). CONCLUSIONS: Simultaneous 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.

Probability of Achieving Glycemic Control with Basal Insulin in Patients with Type 2 Diabetes in Real-World Practice in the USA.

INTRODUCTION: Basal insulin (BI) plays an important role in treating type 2 diabetes (T2D), especially when oral antidiabetic (OAD) medications are insufficient for glycemic control. We conducted a retrospective, observational study using electronic medical records (EMR) data from the IBM® Explorys database to evaluate the probability of achieving glycemic control over 24 months after BI initiation in patients with T2D in the USA. METHODS: A cohort of 6597 patients with T2D who started BI following OAD(s) and had at least one valid glycated hemoglobin (HbA1c) result recorded both within 90 days before and 720 days after BI initiation were selected. We estimated the changes from baseline in HbA1c every 6 months, the quarterly conditional probabilities of reaching HbA1c < 7% if a patient had not achieved glycemic control prior to each quarter (Q), and the cumulative probability of reaching glycemic control over 24 months. RESULTS: Our cohort was representative of patients with T2D who initiated BI from OADs in the USA. The average HbA1c was 9.1% at BI initiation, and decreased robustly (1.5%) in the first 6 months after initiation with no further reductions thereafter. The conditional probability of reaching glycemic control decreased rapidly in the first year (26.6% in Q2; 17.6% in Q3; 8.6% in Q4), and then remained low (≤ 6.1%) for each quarter in the second year. Cumulatively, about 38% of patients reached HbA1c < 7% in the first year; only approximately 8% more did so in the second year. CONCLUSION: Our study of real-world data from a large US EMR database suggested that among patients with T2D who initiated BI after OADs, the likelihood of reaching glycemic control diminished over time, and remained low from 12 months onwards. Additional treatment options should be considered if patients do not reach glycemic control within 12 months of BI initiation. FUNDING: Sanofi Corporation.