Outcomes in GLP-1 RA-Experienced Patients Switching to Once-Weekly Semaglutide in a Real-World Setting: The Retrospective, Observational EXPERT Study.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective for glycaemic control and weight loss in patients with type 2 diabetes (T2D). In this retrospective, observational study, we analysed glycated haemoglobin (HbA1c) and weight following switching to semaglutide from any other GLP-1 RA, using US electronic health records and prescription data. METHODS: Adults (≥ 18 years old) with T2D required at least one prescription for injectable semaglutide at index date (treatment switch), at least one prescription for any other GLP-1 RA in the previous 365 days, a baseline HbA1c and/or weight measurement in the 90 days pre-index and a follow-up measurement at 180 and 365 days post-index. HbA1c and weight cohorts were analysed separately using an ANCOVA model. Sensitivity analyses were conducted in patients with at least two prescriptions for pre-switch GLP-1 RA. A secondary analysis compared subgroups receiving different GLP-1 RAs pre-switch. RESULTS: Patients with HbA1c (n = 710) and weight (n = 921) data had similar baseline characteristics. Significant reductions in HbA1c at 6 months (0.7%; 95% confidence interval [CI] - 0.8, - 0.6) were sustained at 12 months. Weight reductions were significant at 6 months (- 2.1 kg; 95% CI - 2.6, - 1.6) and greater at 12 months (- 2.8 kg; 95% CI - 3.9, - 1.8). These patterns were consistent with the two-prescription sensitivity analysis and independent of the pre-switch GLP-1 RA. CONCLUSION: Switching to injectable semaglutide from any other GLP-1 RA was associated with significant improvements in glycaemic control and weight. Our findings support decision-making in clinical practice in patients with an indication to switch between GLP-1 RAs.

Real-world clinical outcomes following treatment intensification with GLP-1 RA, OADs or insulin in patients with type 2 diabetes on two oral agents (PATHWAY 2-OADs).

INTRODUCTION: Most patients with type 2 diabetes require sequential addition of glucose-lowering agents to maintain long-term glycemic control. In this retrospective, observational study, we compared intensification with a glucagon-like peptide-1 receptor agonist (GLP-1 RA), oral antidiabetic drugs (OADs), and insulin in patients receiving two OADs, using US electronic health records and claims data. RESEARCH DESIGN AND METHODS: For inclusion, patients in the IBM MarketScan Explorys database were required to have claims for two different OADs in the 180-day baseline period and ≥1 claim for a different OAD/GLP-1 RA/insulin at index date (treatment intensification). Changes in glycated hemoglobin (HbA1c) and weight from baseline were assessed at 180 days postindex. Patients were propensity score-matched by baseline characteristics and exact-matched by HbA1c category (HbA1c cohort and weight/composite outcomes cohort) and body mass index (BMI) category (weight/composite outcomes cohort only) to obtain balanced treatment arms. The primary endpoint was the percentage of patients reaching target HbA1c <7% (53 mmol/mol). RESULTS: Significantly more patients intensifying with a GLP-1 RA achieved HbA1c <7% than those receiving OAD(s) (OR: 1.35; 95% CI 1.03 to 1.77; p=0.032) or insulin (OR: 1.77; 95% CI 1.27 to 2.47; p<0.001). GLP-1 RAs were also associated with a significantly greater chance of not gaining weight; significantly greater HbA1c and weight decreases from baseline; and a significantly greater chance of HbA1c <7%, no weight gain and discontinuation of ≥1 baseline OAD (composite outcome), compared with OAD(s) or insulin. CONCLUSIONS: In propensity score-matched cohorts, GLP-1 RAs demonstrated significant benefits for both glycemic control and weight management over additional OAD(s) or insulin, respectively, indicating that they may represent the optimal choice at these points in the treatment pathway.

Cost-effectiveness of switching to insulin degludec from other basal insulins in real-world clinical practice in Italy.

Aims: The costs associated with insulin therapy and diabetes-related complications represent a significant and growing economic burden for healthcare systems. The aim of this study was to evaluate the cost-effectiveness of switching to insulin degludec (degludec) vs continuing previous basal insulin, in Italian patients with type 1 (T1D) or type 2 (T2D) diabetes, using a long-term economic model.Materials and methods: Data were retrieved from a real-world population of patients from clinical practice in Italy. Clinical parameters included in the base-case model were change from baseline in HbA1c, rates of hypoglycemia, and basal and bolus insulin dose, at 6 months following switch to degludec. Costs of treatments were taken from official Italian pharmaceutical list prices and costs of hypoglycemia were based on the literature. The data were used to populate a long-term (lifetime) IQVIA CORE Diabetes Model to evaluate the incremental cost-effectiveness ratio (ICER) - cost per quality-adjusted life-year (QALY). The robustness of these results was tested with extensive sensitivity analyses by varying the time horizons and abolishing each of the treatment differences and previous basal insulins.Results: The total incremental cost for degludec vs previous basal insulin was €-6,310 and €-2,682 for patients with T1D and T2D, respectively; the switch to degludec resulted in a QALY gain of 0.781 and 0.628. The long-term ICER for degludec vs continuing the previous basal insulin regimen showed that degludec was dominant for both T1D and T2D, meaning that patient health was improved in terms of QALYs with lower healthcare costs. Sensitivity analyses showed that degludec remained dominant in most scenarios including after elimination of any benefit in non-severe hypoglycemia and insulin dose, in both T1D and T2D.Conclusions: Under routine care, switching to degludec is dominant, compared with continuing previous basal insulin, in Italian patients with T1D or T2D.

The Burden of Hypoglycemia in Patients With Insulin-Treated Diabetes Mellitus in China: Analysis of Electronic Medical Records From 4 Tertiary Hospitals.

BACKGROUND: Hypoglycemia is a common acute complication in patients with diabetes and markedly impacts on medical resource use. OBJECTIVES: To make an initial assessment of the incidence of hypoglycemia and the associated utilization of medical resources and medical costs in insulin-treated patients with diabetes using medical records from 4 tertiary hospitals in China. METHODS: A retrospective cohort study was conducted using electronic medical records from 4 tertiary hospitals in Beijing, Henan, and Guangzhou from 2012 to 2015. The targeted patients were those diagnosed with either type 1 or type 2 diabetes and treated with insulin. Diabetes was identified with International Classification of Diseases, Tenth Revision diagnosis codes. Hypoglycemia was identified based on glycemic value and the description of diagnosis. The incidence of hypoglycemia, medical resource utilization, and medical costs were analyzed. One-to-one propensity score matching was used to match age, sex, type of diabetes, and complications to patients with and without hypoglycemia and patients with severe and non-severe hypoglycemia, to compare their medical resource utilization and medical costs. RESULTS: A total of 14 044 patients (95.3% had type 2 diabetes and 93.7% with complications) were treated with insulin. There were 1930 patients who had outpatient visits and 310 patients who had inpatient visits owing to hypoglycemia. Incidences of hypoglycemia were 111.3 events per 100 patient-years for outpatient visits and 5.9 events per 100 patient-years for inpatient visits. Patients with hypoglycemia had more outpatient visits (8.09 vs 6.22 times/year, P < .05) and higher annual medical costs ($2147.4 vs $1426.8/person, P < .05) compared with patients without hypoglycemia. Among patients with hypoglycemia, those with severe hypoglycemia had more inpatient visits (2.06 vs 1.13 times/year, P < .05) and higher annual inpatient medical costs ($6204.0 vs $2017.9/person, P < .05) compared with patients with non-severe hypoglycemia. CONCLUSION: The burden of hypoglycemia, especially severe hypoglycemia, is substantial and associated with increased use of medical resources and expenditures among the target population, which serves as a vital first glance at patients with insulin-treated diabetes in China overall.

Short-Term Cost-Effectiveness of Switching to Insulin Degludec in Japanese Patients with Type 2 Diabetes Receiving Basal-Bolus Therapy.

INTRODUCTION: With one of the fastest aging populations in the world, demographic changes in Japan are a major public health concern due to the substantial burden that aging-associated diseases, such as type 2 diabetes (T2D), place on public healthcare systems. The aim of this analysis was to evaluate the short-term cost-effectiveness of switching Japanese patients with T2D receiving basal-bolus insulin therapy from their previous basal insulin to insulin degludec (degludec) under conditions of routine clinical practice. METHODS: A previously published, open-source model developed in Microsoft Excel was used to evaluate the cost-effectiveness of switching basal-bolus insulin therapy from patients' previous basal insulin to degludec versus continuing the previous basal insulin therapeutic regimen in terms of costs (2018 Japanese Yen [JPY]) and quality-adjusted life years (QALYs), from a Japanese public healthcare payer perspective. The model captured hypoglycemia rates and insulin dosing over a 1-year time horizon, and was informed by Japanese real-world evidence from the T2D cohort (N = 135) of the Kumamoto Insulin Degludec Observational study. RESULTS: Treatment with degludec was associated with improved effectiveness (+ 0.0354 QALYs), driven by lower daytime non-severe hypoglycemia rates with degludec, at slightly higher annual treatment costs (JPY 9510) versus continuing the previous basal insulin. Switching basal insulin to degludec was found to be a cost-effective intervention with an incremental cost-effectiveness ratio (JPY 268,811 per QALY gained) substantially below the willingness-to-pay threshold of 5 million JPY per QALY used in the Japanese Health Technology Assessment framework. Sensitivity analyses confirmed the robustness of this finding and indicated that the daytime non-severe hypoglycemia benefit with degludec was a key driver of outcomes in the base case. CONCLUSION: Based on Japanese real-world evidence, our analysis suggests that switching Japanese patients with T2D receiving a basal-bolus regimen from their previous basal insulin to degludec would be highly cost-effective. These data may help decision-makers in Japan allocate healthcare resources efficiently. TRIAL REGISTRATION: The KIDUNA study is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR): UMIN000021569. FUNDING: Novo Nordisk Pharma Ltd. Japan.

A comparative effectiveness study of degludec and insulin glargine 300 U/mL in insulin-naïve patients with type 2 diabetes.

AIMS: To compare the real-world effectiveness of insulin degludec (degludec) and glargine 300 units/mL (glargine U300) in insulin-naïve adult patients with type 2 diabetes in routine US clinical practice. MATERIALS AND METHODS: CONFIRM is a non-interventional comparative effectiveness study following US patients across the continuum of care, through electronic medical records from multiple health systems and integrated delivery networks. Propensity-score matching controlled for confounding. The primary endpoint, change in HbA1c from baseline to 180 days of follow-up, was estimated using a repeated-measure of covariance analysis with subject as random effect. Change in the rate of hypoglycaemic episodes (defined using International Classification of Diseases codes 9/10) and change in proportion of patients with hypoglycaemia were estimated using negative binomial and logistic regression, respectively. Time-to-discontinuation of the initial basal insulin/initiation with another prescribed basal insulin was analysed using a Cox Proportional Hazard model. RESULTS: Data concerning 4056 patients were analysed. After matching, baseline characteristics were comparable (n = 2028 in each group). After 180 days of follow-up, degludec was associated with a larger reduction in HbA1c (estimated treatment difference, -0.27%; P = 0.03), greater reductions in change in rate (rate ratio, 0.70; P < 0.05) and greater reductions in change in the likelihood of hypoglycaemia (odds ratio, 0.64; P < 0.01]) compared with glargine U300. In addition, patients treated with degludec were 27% less likely to discontinue treatment at follow-up compared with those treated with glargine U300 (hazard ratio, 0.73; P < 0.001). CONCLUSIONS: Significantly improved HbA1c, larger reductions in rates and likelihood of hypoglycaemia and lower risk of treatment discontinuation were demonstrated with degludec vs glargine U300.

A European, multicentre, retrospective, non-interventional study (EU-TREAT) of the effectiveness of insulin degludec after switching basal insulin in a population with type 1 or type 2 diabetes.

AIMS: To evaluate the clinical effectiveness of switching to insulin degludec (IDeg) in insulin-treated patients with either type 1 diabetes (T1DM) or type 2 diabetes (T2DM) under conditions of routine clinical care. MATERIALS AND METHODS: This was a multicentre, retrospective, chart review study. In all patients, basal insulin was switched to IDeg at least 6 months before the start of data collection. Baseline was defined as the most recent recording during the 3-month period before first prescription of IDeg. Values are presented as mean [95%CI]. RESULTS: T1DM (n = 1717): HbA1c decreased by -2.2 [-2.6; -2.0] mmol/mol (-0.20 [-0.24; -0.17]%) at 6 months vs baseline (P < .001). Rate ratio of overall (0.79 [0.69; 0.89]), non-severe nocturnal (0.54 [0.42; 0.69]) and severe (0.15 [0.09; 0.24]) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period (P < .001 for all). Total daily insulin dose decreased by -4.88 [-5.52; -4.24] U (-11%) at 6 months vs baseline (P < .001). T2DM (n = 833): HbA1c decreased by -5.6 [-6.3; -4.7] mmol/mol (-0.51 [-0.58; -0.43] %) at 6 months vs baseline (P < .001). Rate ratio of overall (0.39 [0.27; 0.58], P < .001), non-severe nocturnal (0.10 [0.06; 0.16], P < .001) and severe (0.075 [0.01; 0.43], P = .004) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period. Total daily insulin dose decreased by -2.48 [-4.24; -0.71] U (-3%) at 6 months vs baseline (P = .006). Clinical outcomes for T1DM and T2DM at 12 months were consistent with results at 6 months. CONCLUSIONS: This study demonstrates that switching patients to IDeg from other basal insulins improves glycaemic control and significantly reduces the risk of hypoglycaemia in routine clinical practice.

Diabetes management and daily functioning burden of non-severe hypoglycemia in Japanese people treated with insulin.

AIMS/INTRODUCTION: The present study investigated the impact of non-severe hypoglycemic events (NSHE) on patients' diabetes management, daily functioning and well-being. MATERIALS AND METHODS: A survey assessing the impact of NSHEs was completed by insulin-treated Japanese people with diabetes, aged ≥20 years with self-reported diabetes, who had experienced at least one NSHE in the past 3 months. Survey questions captured reasons for and the length of the event, and impacts on diabetes management, daily functioning, sleep and well-being. RESULTS: A total of 3,145 people with type 1 diabetes mellitus and type 2 diabetes mellitus were screened, of which 411 respondents were eligible. Increased glucose monitoring was reported by 57 and 54% of respondents after daytime and night-time NSHE, respectively. The average number of additional glucose monitoring tests was 2.4 and 3.0 for daytime and night-time NSHE. Among all respondents, 19% (daytime) and 16% (night-time) changed their insulin dose after an NSHE. After a daytime NSHE, 25% of respondents reported a negative impact on their daily activities or work. After a night-time NSHE, 34 and 23% of respondents reported a negative impact on sleep and next day emotional state, respectively. CONCLUSIONS: NSHEs have a negative impact on the diabetes management, daily functioning, sleep and well-being of Japanese patients.

Self-reported hypoglycaemia in patients with type 2 diabetes treated with insulin in the Hoorn Diabetes Care System Cohort, the Netherlands: a prospective cohort study.

BACKGROUND: Our aim was to study the prevalence of self-reported hypoglycaemic sensations and its association with mortality in patients with type 2 diabetes (T2D) treated with insulin in usual care. METHODS: Demographics, clinical characteristics and mortality data were obtained from 1667 patients with T2D treated with insulin in the Hoorn Diabetes Care System Cohort (DCS), a prospective cohort study using clinical care data. Self-reported hypoglycaemic sensations were defined as either mild: events not requiring help; or severe: events requiring help from others (either medical assistance or assistance of others). The association between hypoglycaemic sensations and mortality was analysed using logistic regression analysis. RESULTS: At baseline, 981 patients (59%) reported no hypoglycaemic sensations in the past year, 612 (37%) reported only mild sensations and 74 (4%) reported severe hypoglycaemic sensations. During a median follow-up of 1.9 years, 98 patients (5.9%) died. Reporting only mild hypoglycaemic sensations was associated with a lower mortality risk (OR 0.48, 95% CI 0.28 to 0.80), while reporting severe sensations was not significantly associated with mortality (OR 0.76, 95% CI 0.33 to 1.80), compared with reporting no hypoglycaemic sensations, and adjusting for demographic and clinical characteristics. Sensitivity analyses showed an OR of 1.38 (95% CI 0.31 to 6.11) for patients reporting severe hypoglycaemic sensations requiring medical assistance. CONCLUSIONS: Self-reported hypoglycaemic sensations are highly prevalent in our insulin-treated T2D population. Patients reporting hypoglycaemic sensations not requiring medical assistance did not have an increased risk of mortality, suggesting that these sensations are not an indicator of increased short-term mortality risk in patients with T2D.

Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The aim of the study was to evaluate the effect of delay in treatment intensification (IT; clinical inertia) in conjunction with glycaemic burden on the risk of macrovascular events (CVE) in type 2 diabetes (T2DM) patients. METHODS: A retrospective cohort study was carried out using United Kingdom Clinical Practice Research Datalink, including T2DM patients diagnosed from 1990 with follow-up data available until 2012. RESULTS: In the cohort of 105,477 patients mean HbA1c was 8.1% (65 mmol/mol) at diagnosis, 11% had a history of cardiovascular disease, and 7.1% experienced at least one CVE during 5.3 years of median follow-up. In patients with HbA1c consistently above 7/7.5% (53/58 mmol/mol, n = 23,101/11,281) during 2 years post diagnosis, 26/22% never received any IT. Compared to patients with HbA1c <7% (<53 mmol/mol), in patients with HbA1c ≥7% (≥53 mmol/mol), a 1 year delay in receiving IT was associated with significantly increased risk of MI, stroke, HF and composite CVE by 67% (HR CI: 1.39, 2.01), 51% (HR CI: 1.25, 1.83), 64% (HR CI: 1.40, 1.91) and 62% (HR CI: 1.46, 1.80) respectively. One year delay in IT in interaction with HbA1c above 7.5% (58 mmol/mol) was also associated with similar increased risk of CVE. CONCLUSIONS: Among patients with newly diagnosed T2DM, 22% remained under poor glycaemic control over 2 years, and 26% never received IT. Delay in IT by 1 year in conjunction with poor glycaemic control significantly increased the risk of MI, HF, stroke and composite CVE.

Increased Risk of Severe Hypoglycemic Events with Increasing Frequency of Non-severe Hypoglycemic Events in Patients with Type 1 and Type 2 Diabetes.

INTRODUCTION: Severe hypoglycemic events (SHEs) are associated with significant morbidity, mortality and costs. However, the more common non-severe hypoglycemic events (NSHEs) are less well explored. We investigated the association between reported frequency of NSHEs and SHEs among patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the PREDICTIVE study. METHODS: PREDICTIVE was a global, prospective, observational study. Patients with T1DM (n = 7,420) or T2DM (n = 12,981), starting treatment with insulin detemir, reported the number of NSHEs and SHEs experienced during the 4 weeks prior to baseline and follow-up visits (mean 14.4 weeks). Logistic regression was used to determine the odds ratio (OR) of experiencing ≥1 SHE, in patients having 1-4 or ≥5 NSHEs, versus those having 0 NSHEs, while controlling for baseline covariates. RESULTS: Hypoglycemia rates were lower at follow-up than baseline. At baseline 59.2% (T1DM) and 18.8% (T2DM) reported any hypoglycemia and at follow-up 39.5% (T1DM) and 8.6% (T2DM). There was a significant (P < 0.0001) increase in the odds of ≥1 SHEs with increasing frequency of NSHEs in T1DM and T2DM, for both crude and adjusted estimates. At baseline, in T1DM, ORs for ≥1 SHE were 1.92 and 2.13 for 1-4 and ≥5 NSHEs, respectively; the corresponding ORs in T2DM were 10.83 and 15.36, respectively. At follow-up, the ORs for ≥1 SHE were 2.01 and 3.20 (T1DM) and 18.99 and 24.29 (T2DM) for 1-4 and ≥5 NSHEs, respectively. CONCLUSION: A statistically significant association between NSHE and SHE frequency was found in T1DM and T2DM. These data provide a clear rationale for the reduction of hypoglycemic events, regardless of severity, while striving for optimal glycemic control.

Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people.

OBJECTIVE: To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and associated levels of glycemic control. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April 2011. RESULTS: In people with HbA1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA1c cutoff to intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1-43.6% and with insulin 5.1-12.0%. CONCLUSIONS: There are delays in treatment intensification in people with type 2 diabetes despite suboptimal glycemic control. A substantial proportion of people remain in poor glycemic control for several years before intensification with OADs and insulin.