Real-world GLP-1 RA therapy in type 2 diabetes: A long-term effectiveness observational study.
01 Jan 2019-Vol. 2, Iss: 1
TL;DR: To evaluate in a real‐world setting the effectiveness and tolerability of available GLP‐1 RA drugs in patients with type 2 diabetes after a prolonged follow‐up.
Abstract: Aims To evaluate in a real-world setting the effectiveness and tolerability of available GLP-1 RA drugs in patients with type 2 diabetes after a prolonged follow-up. Materials and methods Observational, retrospective, single-centre study in patients starting GLP-1 RA therapy. Change in HbA1c, fasting plasma glucose (FPG) and body mass index (BMI) along with gastrointestinal (GI) adverse events and withdrawal from GLP-1 RA therapy were evaluated. Lack of efficacy of GLP-1 RA therapy according to prespecified goals was also measured. Results A total of 735 patients were included, mean age 59.7 years, duration of diabetes 9.01 years, HbA1c 8.18% and BMI 38.56 kg/m2. Average follow-up was 18.97 months (range 4.2-39.09). All HbA1c (0.93%; P < 0.01), FPG (24 mg/dL; P < 0.01) and BMI (1.55 kg/m2; P < 0.05) were significantly reduced from baseline and maintained throughout follow-up, regardless of prescribed GLP-1 RA. GI adverse events were present in 13.81% of patients at first follow-up visit, 37.07% of patients discontinued GLP-1 RA treatment, and 38.63% did not meet efficacy goals. Conclusions In a real-world setting, GLP-1 RA therapy is largely prescribed in severely obese patients with a long-standing and poorly controlled diabetes. All prescribed GLP-1 RAs significantly decreased HbA1c, FPG and BMI. GI adverse events affected a low proportion of patients. Inversely, a high proportion of patients did not meet efficacy goals and/or discontinued GLP-1 RA treatment. Baseline characteristics of patients and lack of adherence may represent important issues underlying differences in effectiveness in real-world studies versus randomized trials.
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TL;DR: The objective of this study was to examine preference between injection devices used for two weekly GLP‐1 receptor agonists.
Abstract: AIM When selecting treatments for type 2 diabetes (T2D), it is important to consider not only efficacy and safety, but also other treatment attributes that have an impact on patient preference. The objective of this study was to examine preference between injection devices used for two weekly GLP-1 receptor agonists. MATERIALS AND METHODS The PREFER study was an open-label, multicentre, randomized, crossover study assessing patient preference for dulaglutide and semaglutide injection devices among injection-naive patients receiving oral medication for type 2 diabetes. After being trained to use each device, participants performed all steps of injection preparation and administered mock injections into an injection pad. Time-to-train (TTT) for each device was assessed in a subset. RESULTS There were 310 evaluable participants (48.4% female; mean age, 60.0 years; 78 participants in the TTT subgroup). More participants preferred the dulaglutide device than the semaglutide device (84.2% vs. 12.3%; P < 0.0001). More participants perceived the dulaglutide device to have greater ease of use (86.8% vs. 6.8%; P < 0.0001). After preparing and using the devices, more participants were willing to use the dulaglutide device (93.5%) than the semaglutide device (45.8%). Training participants to use the dulaglutide device required less time than the semaglutide device (3.38 vs. 8.14 minutes; P < 0.0001). CONCLUSIONS Participants with type 2 diabetes preferred the dulaglutide injection device to the semaglutide injection device. If patients prefer a device, they may be more willing to use the medication, which could result in better health outcomes. Furthermore, a shorter training time for injection devices may be helpful in busy clinical practice settings.
27 citations
TL;DR: Recommendations favor GLP-1 receptor agonists and SGLT2 inhibitors because they have a low risk of hypoglycemia and promote weight loss and should be considered as a second-line treatment option in people with type 2 diabetes when glucose levels are not well controlled on metformin.
Abstract: Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of incretin-based therapies for the management of hyperglycemia and, in some cases, cardiovascular risk in people with type 2 diabetes. These agents act on multiple physiological pathways involved in type 2 diabetes with the effect of increasing insulin secretion and decreasing glucagon to control glucose levels (1,2). They also transiently slow gastric emptying, reduce appetite, and facilitate weight loss and other metabolic improvements (3).
Consensus recommendations from the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) and American Association of Clinical Endocrinologists/American College of Endocrinology advocate that GLP-1 receptor agonists, among other therapies, should be considered as a second-line treatment option in people with type 2 diabetes when glucose levels are not well controlled on metformin (4–6). Additionally, in patients with type 2 diabetes and atherosclerotic cardiovascular disease or chronic kidney disease, a GLP-1 receptor agonist or sodium–glucose cotransporter 2 (SGLT2) inhibitor with proven cardiovascular benefit is recommended as a first-line therapy for the reduction of cardiovascular risk (4–6). GLP-1 receptor agonists may also be used as a first-line treatment in those who cannot use metformin or when reduced renal function precludes metformin use (human-based GLP-1 receptor agonists only) (4–6). In particular, the recommendations favor GLP-1 receptor agonists and SGLT2 inhibitors because they have a low risk of hypoglycemia and promote weight loss (5).
Several GLP-1 receptor agonists are available in the United States and worldwide, some of which are analogs of human GLP-1 (dulaglutide, liraglutide, and semaglutide), whereas others are exendin-based (exenatide and lixisenatide) (7–13). The GLP-1 receptor agonist albiglutide was also approved, but has been withdrawn for commercial reasons. Until recently, all GLP-1 receptor agonists were administered by subcutaneous injection, although a once-daily oral formulation …
21 citations
Cites background from "Real-world GLP-1 RA therapy in type..."
...However, in a contemporary, large, real-world study, 39% of patients receiving GLP-1 receptor agonists did not meet efficacy goals; it was suggested that lack of adherence (aswell as a greater number of comorbidities) compared with trial populationsmay have contributed (47)....
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TL;DR: The study shows real-world benefits of GLP-1 RA therapy for T2DM, including improvements in HbA1c, body weight, and blood lipid profile, and supports the high rates of long-term persistence previously reported with dulaglutide, theGLP- 1 RA most commonly prescribed for T1DM in Japanese clinical practice.
Abstract: There are limited real-world data on the prescribing of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for patients with type 2 diabetes mellitus (T2DM). This was a retrospective analysis of the CoDiC® database of the Japan Diabetes Clinical Data Management Study Group (JDDM). Demographic and clinical characteristics, concomitant treatment patterns, and GLP-1 RA treatment persistence or modification in patients with T2DM initiating GLP-1 RA therapy were evaluated. The analysis included 932 eligible patients with T2DM who had their first GLP-1 RA prescription (index date) between September 2016 and July 2018. Mean age was 63.8 years and 56.0% were male. Most patients had an index GLP-1 RA of dulaglutide (65.7%) or liraglutide (29.1%). Common comorbidities were obesity (58.7%), hypertension (54.7%), dyslipidemia (52.0%), retinopathy (11.3%), and nephropathy (10.2%). Mean hemoglobin A1c (HbA1c) levels decreased from 8.3 to 7.8% over 6 months after GLP-1 RA initiation, and the proportion of patients achieving HbA1c < 7.0% increased from 14.4% at index date to 22.9% at 6 months. Reductions occurred in mean body weight, body mass index, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and adjusted urinary albumin over 6 months. Antidiabetic medication use decreased after GLP-1 RA initiation, whereas non-antidiabetic medication prescribing showed little change. Index GLP-1 RA persistence rates were 80.5%, 66.2%, and 51.6% at 6, 12, and 18 months post-index, respectively, with a median persistence until discontinuation or switch of 600 days. Persistence rates at 6, 12, and 18 months post-index, respectively, were 81.9%, 70.7%, and 65.4% for dulaglutide and 79.7%, 60.0%, and 30.4% for liraglutide. The study shows real-world benefits of GLP-1 RA therapy for T2DM, including improvements in HbA1c, body weight, and blood lipid profile, and supports the high rates of long-term persistence previously reported with dulaglutide, the GLP-1 RA most commonly prescribed for T2DM in Japanese clinical practice. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are drugs that patients with type 2 diabetes mellitus (T2DM) take to help control their blood sugar levels. In Japan, the GLP-1 RAs that doctors can prescribe are dulaglutide, exenatide, liraglutide, and lixisenatide as of May 2020. We conducted a study of how GLP-1 RAs are used to treat patients with T2DM in Japanese real-world clinical practice. We used a large database of anonymous information from hospitals and clinics in Japan. Over 900 adult patients started their first GLP-1 RA treatment for T2DM between September 2016 and July 2018. Before these patients started GLP-1 RA treatment, many were overweight, had high blood pressure, and had abnormal levels of lipids in their blood. Six months after starting GLP-1 RA treatment, on average these patients had lower hemoglobin A1c (a measure of average blood sugar levels), lower body weight, and better blood lipid levels than before they started GLP-1 RA treatment. Dulaglutide was the most common GLP-1 RA prescribed, then liraglutide. After 6 months, most patients (four-fifths) continued to use their GLP-1 RA treatment without stopping or changing to another treatment. After 18 months, half of the patients were still using their GLP-1 RA. Two-thirds of patients on dulaglutide and one-third of patients on liraglutide continued the treatment after 18 months. This study shows that GLP-1 RAs can benefit patients with T2DM in real-world clinical practice. It also shows that patients may be able to take long-term dulaglutide treatment.
9 citations
TL;DR: In real-world T2D patients, dulaglutide versus liraglUTide was associated with better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions.
Abstract: Head-to-head comparison of clinical effectiveness between dulaglutide and liraglutide in Asia is limited. This study was aimed to assess the real-world comparative effectiveness of dulaglutide versus liraglutide. We conducted a retrospective cohort study by utilizing multi-institutional electronic medical records to identify real-world type 2 diabetes patients treated with dulaglutide or liraglutide during 2016–2018 in Taiwan and followed up until 2019. Effectiveness outcomes were assessed at every 3 months in the 1-year follow-up. Propensity score techniques were applied to enhance between-group comparability. Significant differences in changes of effectiveness outcomes between treatment groups during the follow-up were examined and further analyzed using mixed-model repeated-measures approaches. A total of 1512 subjects receiving dulaglutide and 1513 subjects receiving liraglutide were identified. At 12 months, significant HbA1c changes from baseline were found in both treatments (dulaglutide: − 1.06%, p < 0.001; liraglutide: − 0.83%, p < 0.001), with a significant between-group difference (− 0.23%, 95% confidence interval − 0.38 to − 0.08%, p < 0.01). Both treatments yielded significant declines in weight, alanine aminotransferase level, and estimated glomerular filtration rate from baseline (dulaglutide: − 1.14 kg, − 3.08 U/L and − 2.08 mL/min/1.73 m2, p < 0.01; liraglutide: − 1.64 kg, − 3.65 U/L and − 2.33 mL/min/1.73 m2, p < 0.001), whereas only dulaglutide yielded a significant systolic blood pressure reduction (− 2.47 mmHg, p < 0.001). Between-group differences in changes of weight, blood pressure, and liver and renal functions at 12 months were not statistically significant. In real-world T2D patients, dulaglutide versus liraglutide was associated with better glycemic control and comparable effects on changes of weight, blood pressure, and liver and renal functions.
9 citations
TL;DR: In this article, the authors describe utilization patterns, persistence, resource utilization and costs in patients with type-2 diabetes mellitus initiating treatment with glucagon-like peptide-1 receptor agonists in routine clinical practice in Spain.
Abstract: This study aimed to describe utilization patterns, persistence, resource utilization and costs in patients with type 2 diabetes mellitus initiating treatment with glucagon-like peptide 1 receptor agonists in routine clinical practice in Spain. This retrospective study of medical records in the Big-Pac database identified adults starting treatment with once-weekly (QW) dulaglutide, exenatide-QW or once-daily liraglutide between 1 November 2015 and 30 June 2017. Patients were followed for up to 18 months from treatment initiation. Data on clinical characteristics of patients, treatment patterns, average daily dose and costs were obtained for the three cohorts. Persistence over the 18-month period was evaluated using Kaplan–Meier curves. All analyses were descriptive. A total of 1402 patients were included in this study (dulaglutide [n = 492], exenatide-QW [n = 438] or liraglutide [n = 472]); 52.8% were men, and the mean (SD) age was 62 (11) years, glycated haemoglobin (HbA1c) was 8.1% (1.2) and body mass index was 35.5 (3.2) kg/m2 at treatment initiation. Persistence at 18 months was 59.1% (95% confidence interval [CI] 54.8–63.4) for dulaglutide, 45.7% (95% CI 41.0–50.4) for exenatide-QW and 46.6% (95% CI 42.1–51.1) for liraglutide. The average (SD) dose was 1.2 (0.4) mg/week for dulaglutide, 1.9 (0.3) mg/week for exenatide-QW and 1.1 (0.3) mg/day for liraglutide. The average reduction in HbA1c levels at 1 year was − 0.68% for patients who initiated dulaglutide, − 0.54% for patients who initiated exenatide-QW and − 0.50% for patients who initiated liraglutide. The mean (SD) total annual health care costs were €4072 (1946) for dulaglutide, €4418 (2382) for exenatide-QW and €4382 (2389) for liraglutide. Results suggest that patients who started treatment with dulaglutide had higher persistence over 18 months, presented lower HbA1c levels at 12 months and incurred lower annual total healthcare costs than patients who initiated exenatide-QW or liraglutide. Type 2 diabetes has a major impact on patients psychologically and socially, as well as on healthcare costs. The glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are drugs that help maintain blood sugar at healthy levels. They are often used as the first injectable drugs if oral treatments are no longer effective. This study aimed to analyse the use of GLP-1 RAs, and the costs involved, among patients with type 2 diabetes who started treatment with once-weekly dulaglutide, once-weekly exenatide or liraglutide in routine clinical practice in Spain. An electronic database of medical records was used to obtain data from 1402 patients who started treatment with these drugs and were followed for a 1.5-year period. Results of this study suggest that patients who were prescribed dulaglutide stayed on their treatment longer and could reduce their blood sugar levels more efficiently, and at a lower cost, than those who received once-weekly exenatide or liraglutide. These findings could be helpful to physicians prescribing these drugs when considering how to improve the management of type 2 diabetes.
8 citations
References
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University of Texas Southwestern Medical Center1, Harvard University2, Novo Nordisk3, University of Erlangen-Nuremberg4, Ruhr University Bochum5, Cleveland Clinic6, University of London7, Imperial College London8, George Washington University9, University of Toronto10, University of North Carolina at Chapel Hill11
TL;DR: In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, orNonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.
Abstract: BackgroundThe cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. MethodsIn this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. ResultsA total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo ...
4,409 citations
TL;DR: In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, orNonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semag lutide.
Abstract: BackgroundRegulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. MethodsWe randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. ResultsAt baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 10...
3,551 citations
TL;DR: This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
3,103 citations
TL;DR: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events.
Abstract: BackgroundCardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1–receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event. MethodsWe randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable ...
1,745 citations
TL;DR: Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated, suggesting that liragLutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.
1,414 citations