Real-World Treatment Patterns Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

INTRODUCTION: The treatment landscape for type 2 diabetes mellitus (T2DM) is complex and constantly evolving, and real-world evidence of prescribing patterns is limited. The objectives of this study were to characterize lines of therapy (LOTs), calculate the length of time spent on each LOT, and identify the reasons for the LOT end among patients who initiated oral semaglutide for T2DM. METHODS: This retrospective, claims-based study included commercial and Medicare Advantage adults with T2DM. Data from November 1, 2019, and June 30, 2020, were obtained from Optum Research Database. Patients with ≥ 1 claim for oral semaglutide and continuous health plan enrollment for ≥ 12 months prior to (baseline period) and ≥ 6 months following (follow-up period) the date of the first oral semaglutide claim were included. LOT 1 began on the date of the first oral semaglutide claim. The start date of any subsequent LOTs was the date of the first claim for an additional non-insulin anti-diabetic drug class or a reduction in drug class with use of commitment medications. The LOT ended at the first instance of medication class discontinuation, change in regimen or end of follow-up. RESULTS: Of the 1937 patients who initiated oral semaglutide, 950 (49.0%) remained on their initial regimen over the 6-month follow-up period, 844 (43.6%) had at least one subsequent LOT, and 89 (4.6%) had at least two subsequent LOTs. Among patients with more than one LOT, approximately 20%-25% used oral semaglutide as monotherapy or combination therapy during LOTs 2 and 3. Metformin was frequently used during treatment across all LOTs. CONCLUSION: This study provides insight for physicians and payers into the real-world prescribing practices within the first 6 months following oral semaglutide initiation and fills the gap in understanding the frequency of regimen changes in the constantly evolving and complex environment of T2DM care.

Type 2 diabetes mellitus is a disease which, over time, can cause higher than normal levels of sugar in the blood (hyperglycemia) which can be harmful if not treated. Treatment for type 2 diabetes mellitus can be complex, and how doctors prescribe medications is always changing. For some people with type 2 diabetes mellitus who are overweight or obese, it is recommended for patients to use certain medications that can help with weight management such as semaglutide and metformin. This study aims to fill gaps in current treatment knowledge about type 2 diabetes mellitus patients and their treatment of oral semaglutide. Researchers in this study explored how patients treated with oral semaglutide differentiated among line of therapies, how long patients stuck to them and why they stopped. The study found that those patients who started with oral semaglutide, almost half of those patients stuck to their initial treatment plan for the entire 6 months. When it came to the top ten treatment plans, about 20% of patients used oral semaglutide alone and about 25% of patients used oral semaglutide plus an additional treatment option. Metformin was frequently used during treatment across all line of therapies. There is little information on the real-life setting of treatment after the start of therapy for type 2 diabetes mellitus. The results from this study show what happens when patients start using oral semaglutide and helps healthcare providers understand how often treatment plans can change in type 2 diabetes mellitus care.

Randomized Evaluation of a Remote Management Program to Improve Guideline-directed Medical Therapy: The Diabetes Remote Intervention to Improve Use of Evidence-based Medications (DRIVE) Trial.

BACKGROUND: Several sodium-glucose transport protein 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular (CV) events and improve kidney outcomes in patients with type 2 diabetes (T2D); however, utilization remains low despite guideline recommendations. METHODS: A randomized, remote implementation trial in the Mass General Brigham network enrolled patients with T2D at high CV and /or kidney risk. Patients eligible for, but not prescribed, SGLT2i or GLP-1 RA were randomly assigned to simultaneous virtual patient education with concurrent prescription of SGLT2i or GLP-1 RA ("simultaneous") or two months of virtual education followed by medication prescription ("education-first") delivered by a multi-disciplinary team driven by non-licensed navigators and clinical pharmacists who prescribed SGLT2i or GLP-1 RA using a standardized treatment algorithm. The primary outcome was the proportion of patients with prescriptions for either SGLT2i or GLP-1 RA by 6 months. RESULTS: Between March 2021 and December 2022, 200 patients were randomized. Mean age was 66.5 years, 36.5% were female, 22.0% were non-White. Overall, 30.0% had cardiovascular CV disease, 5.0% had cerebrovascular disease, and 1.5% had both. Mean estimated glomerular filtration rate (eGFR) 77.9 mL/min/1.73m2 and mean urine/albumin creatinine ratio (UACR) 88.6mg/g. After two months, 69/200 (34.5%) patients received a new prescription for either SGLT2i or GLP-1 RA: 53.4% of patients in the simultaneous arm vs. 8.3% of patients were in the education-first arm (p<0.001). After six months, 128/200 (64.0%) received a new prescription: 69.8 % of patients in the simultaneous arm vs. 56.0% of patients in education-first (p<0.001). Patient self-report of taking SGLT2i or GLP-1 RA within six months of trial entry was similarly higher in the simultaneous versus education-first arm (69 /116; 59.5% vs 37/84; 44.0%; p<0.001) Median time to first prescription was 24 (IQR 13, 50) vs 85 days (IQR 65, 106), respectively (p<0.001). CONCLUSIONS: In this randomized trial, a remote team-based program that identifies patients with T2D and high CV or kidney risk, provides virtual education, and prescribes SGLT2i or GLP-1 RA improves GDMT. These findings support greater utilization of virtual team-based approaches to optimize chronic disease management.

Real-world glycated haemoglobin changes among type 2 diabetes mellitus patients treated with a maintenance dose of 7 mg or 14 mg of oral semaglutide.

AIM: To describe the change in glycated haemoglobin (HbA1c) among patients with type 2 diabetes following treatment with a 7 or 14 mg maintenance dose of oral semaglutide. MATERIALS AND METHODS: This retrospective, claims-based study included adult patients with type 2 diabetes with a pre-index HbA1c of ≥7%, initiating treatment with oral semaglutide between 1 November 2019 and 30 June 2020; the patients had continuous health plan enrolment for ≥12 months before (pre-index) and ≥6 months following (post-index) the date of the first oral semaglutide claim (index). Patients were required to have a maintenance dose of 7 or 14 mg. Pre-index demographic and clinical characteristics were captured, as were doses at initiation and prescriber specialty. The change in HbA1c between the latest post-index and pre-index HbA1c measurements was calculated among all patients and among those with ≥90 days of continuous treatment (persistent patients). RESULTS: This study included 520 patients, most of whom had a complex medical history, experienced a range of comorbidities and received an average of 11.5 different classes of medications during the pre-index period. The mean HbA1c reduction during the 6-month post-initiation period was 1.2% (p < .001) for all patients and 1.4% (p < .001) for persistent patients. CONCLUSIONS: In this real-world study, patients with a pre-index HbA1c ≥7% who initiated treatment with oral semaglutide with a 7 or 14 mg maintenance dose had significantly lower HbA1c levels following treatment.

Once-weekly glucagon-like peptide-1 receptor agonists vs dipeptidyl peptidase-4 inhibitors: cardiovascular effects in people with diabetes and cardiovascular disease.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have proven cardiovascular benefits, are recommended in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, there is limited real-world evidence comparing the effects of once-weekly (OW) GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). This observational cohort study (1/1/2017-9/30/2021) used data from the Optum Clinformatics® Data Mart to compare time to incident clinical cardiovascular outcomes, health care resource utilization (HCRU), and medical costs in new adult users of OW GLP-1 RAs and DPP-4is with T2D and ASCVD. METHODS: Time to occurrence of ischemic stroke, myocardial infarction (MI), or their composite and ASCVD-related and all-cause HCRU and medical costs were investigated. Baseline characteristics were balanced using inverse probability of treatment weighting. Survival analyses were conducted to compare risks during exposure. RESULTS: OW GLP-1 RA users (weighted N = 25,287) had 26%, 22%, and 24% lower risk of ischemic stroke, MI, and their composite, respectively, compared with DPP-4i users (weighted N = 39,684; all P < 0.01). Compared with DPP-4i users, OW GLP-1 RA users had 25% and 26% lower ASCVD-related and all-cause hospitalization costs, 19% and 23% lower ASCVD-related and all-cause medical costs, 23% and 27% fewer ASCVD-related and all-cause hospitalizations, 13% and 8% fewer ASCVD-related and all-cause outpatient visits, and 8% fewer all-cause ER visits (all P < 0.01). CONCLUSIONS: In adults with T2D and ASCVD, OW GLP-1 RAs are associated with reduced stroke and MI risks and ASCVD-related and all-cause HCRU and costs vs DPP-4is.

Real-World Hemoglobin A1c Changes, Prescribing Provider Types, and Medication Dose Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide.

INTRODUCTION: Given the lack of real-world data on oral semaglutide use outside clinical trials, the purpose of this study was to describe dose, prescriber specialty, and change in hemoglobin A1c (HbA1c) after 6 months of oral semaglutide treatment for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a retrospective study among adult patients with T2DM with ≥ 1 claim for oral semaglutide between November 1, 2019`1-June 30, 2020. Patients had continuous health plan enrollment ≥ 12 months prior to (pre-index) and ≥ 6 months following (post-index) the date of the first oral semaglutide claim (index). Dose at initiation and specialty of the prescribing provider were captured. Change in HbA1c between the last post- and pre-index HbA1c measurement was calculated. Patients were stratified by pre-index HbA1c ≥ 9% (poorly controlled) and HbA1c < 9%. RESULTS: A total of 744 HbA1c < 9% and 268 poorly controlled patients were included in the study. Most patients had an initial oral semaglutide dose of 7 mg (49.3%) or 3 mg (42.9%), prescribed most frequently by a primary care provider (27.8%). Mean HbA1c reduction was 0.8% (p < 0.001). Patients with poorly controlled T2DM had greater HbA1c reductions than patients with HbA1c < 9% (2.0% versus 0.4%, p < 0.001). Patients persistent with oral semaglutide (≥ 90 days continuous treatment) had a mean HbA1c reduction of 0.9% (p < 0.001); persistent patients with poorly controlled T2DM had a mean reduction of 2.5%. CONCLUSIONS: Patients with T2DM in this study experienced significant reductions in HbA1c within 6 months following initiation of oral semaglutide. Patients with a higher starting HbA1c experienced greater HbA1c reductions. The initial dose of oral semaglutide was higher than prescribing instructions indicated for more than half of the study patients.

Increased Healthcare Resource Use and Costs After Discontinuation of Liraglutide in Patients with Type 2 Diabetes from a Commercial- and Medicaid-Insured Claims Database.

INTRODUCTION: Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is effective in patients with type 2 diabetes (T2D), but treatment discontinuation without new T2D therapy initiation may compromise outcomes. METHODS: This retrospective cohort study (July 1, 2012, to December 31, 2019) identified patients ≥ 18 years with T2D in the Optum® Clinformatics® Data Mart who discontinued liraglutide (index date). Patients with continuous enrollment for ≥ 12 months before and after discontinuation (baseline), ≥ 6 months liraglutide coverage pre-index, and no new T2D therapy start during follow-up were included. Changes from baseline in all-cause healthcare resource utilization (HCRU; outpatient visits, emergency room [ER] visits, and hospitalization events), costs, and glycated hemoglobin (HbA1c) over 12 months after discontinuation were evaluated. RESULTS: Overall, 625 of 186,630 patients who discontinued liraglutide during the baseline period (mean [standard deviation (SD)] age, 62.1 [10.1] years) were included in the 12-month analysis. A significant increase in the rate of ER visits (rate ratio [95% confidence interval (CI)]: 1.23 per 100 person-months [1.05, 1.43]; P = 0.0079), hospitalizations (1.36 [1.09, 1.70]; P = 0.0056), and outpatient visits (1.03 [1.01, 1.06]; P = 0.0075) was observed. Total HCRU costs significantly increased after discontinuation ($436.12 per patient per month [$90.07, $782.17]; P = 0.0136), driven by significantly higher outpatient costs ($238.70 [$34.16, $443.25]; P = 0.0223). HbA1c increased significantly by 12 months from mean (SD) 7.37 (1.53) at baseline to 7.63 (1.64; difference: + 0.25 [95% CI 0.14, 0.36]; P < 0.0001). CONCLUSIONS: Patients who discontinued liraglutide showed increases in HCRU; costs, mainly driven by outpatient cost; and HbA1c within 12 months, emphasizing the importance of treatment optimization on clinical and economic outcomes in patients with T2D.

Liraglutide is indicated in patients with type 2 diabetes and elevated cardiovascular risk or established cardiovascular disease. In this study, we observed that adults with type 2 diabetes who discontinued liraglutide showed increases in healthcare resource utilization; costs, which were mainly driven by increases in outpatient visits; and glycated hemoglobin within 12 months. In adults with type 2 diabetes, treatment discontinuation without restarting or initiating a new therapy impacts short-term healthcare resource utilization and economic outcomes, and future work may further investigate the long-term implications of sustained treatment discontinuation.

Insights into the early use of oral semaglutide in routine clinical practice: The IGNITE study.

Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and showed significant benefits in glycaemic control and weight reduction versus active comparators in the PIONEER phase 3a randomized controlled trial programme. In this retrospective study, we present early data on the use of oral semaglutide in clinical practice, from the US IBM Explorys electronic health record database. In 782 patients prescribed oral semaglutide, 54.5% were women, and the mean age (SD) was 57.8 years (11.3); 66.0% of patients received their prescription from a primary care practitioner. Although prescribing information recommends increasing the dose to 7 mg after 30 days, 37.0% of patients received a prescription only for the initial 3 mg dose. Mean body mass index was 36.2 kg/m2 (7.6); mean HbA1c was 8.4% (1.8%). Mean HbA1c change from baseline to approximately 6 months after oral semaglutide initiation was -0.9% (95% CI: -1.1%; -0.6%), with greater reductions in patients with higher baseline HbA1c. These data indicate prevalent early adoption of oral semaglutide in primary care, show real-world improvements in glycaemic control, and identify potential treatment gaps.

Early experiences of nusinersen for the treatment of spinal muscular atrophy: Results from a large survey of patients and caregivers.

BACKGROUND: This study aimed to examine the early experience of nusinersen for spinal muscular atrophy (SMA) from the patient and caregiver perspective. METHODS: A 54-item online survey was administered to adult patients and caregivers of pediatric patients diagnosed with SMA. RESULTS: Overall, respondents (56 patients and 45 caregivers) were satisfied with nusinersen. Satisfaction was highest on changes in energy, stamina, and motor function and lowest on treatment administration and overall time commitment. Differences were noted for treatment effect sustained over time as reported by adult patients vs caregivers reporting on behalf of pediatric patients. Respondents reported insurance approval as a key barrier to access, particularly among adult patients. CONCLUSIONS: Despite therapeutic advances, there remain significant unmet needs for SMA. Challenges with administration and barriers to access potentially limit the number of patients treated or delay treatment. Continued efforts are needed to develop more treatment options and to improve access to treatments.