Patterns of new glucagon-like peptide-1 receptor agonist use in patients with type 2 diabetes during 2014-2019 from a US database: prescriber and patient characteristics.
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SUBMITTER: Lingvay I
PROVIDER: S-EPMC9934953 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Patterns of new glucagon-like peptide-1 receptor agonist use in patients with type 2 diabetes during 2014-2019 from a US database: prescriber and patient characteristics.
Lingvay Ildiko I Aroda Vanita R VR Honoré Julie Broe JB Ersbøll Anne S AS Nystrup Husemoen Lise Lotte LL Jensen Anders Boeck AB Sommer Matthiessen Kasper K Kosiborod Mikhail Naum MN
Journal of diabetes 20230201 2
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Project description:Glucagon and glucagon-like peptide-1 (GLP-1) are hormones involved in energy homeostasis. GLP-1 receptor (GLP-1R) agonism reduces food intake and delays gastric emptying, and glucagon receptor (GCGR) agonism increases energy expenditure by thermogenesis. BI 456906 is a subcutaneous, once-weekly injectable dual GLP-1R/GCGR agonist in development for the treatment of obesity or non-alcoholic steatohepatitis. Here we show that BI 456906 is a potent dual agonist with an extended half-life in human plasma. Key GLP-1R-mediated mechanisms of reduced food intake, delayed gastric emptying and improved glucose tolerance were confirmed in GLP-1R knockout mice. GCGR activity was confirmed by reduced plasma amino acids, increased hepatic expression of nicotinamide N-methyltransferase and increased energy expenditure. BI 456906 produced greater bodyweight reductions than maximally efficacious semaglutide doses and modulated gene expression, including genes involved in amino acid metabolism. BI 456906 is a potent dual agonist that produces bodyweight-lowering effects through both GLP-1R and GCGR agonism.
2022-12-09 | GSE211105 | GEO
Project description:IntroductionThe objective of this study was to evaluate real-world treatment patterns of type 2 diabetes (T2D) patients initiating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in Germany (GE), the United Kingdom (UK), France (FR), the Netherlands (NE), Belgium (BE), and Sweden (SE).MethodsAdult T2D patients initiating exenatide twice daily (exBID), liraglutide once daily (LIRA) or exenatide once weekly (exQW) were identified using the IMS LifeLink™ (IMS Health, Danbury, CT, USA): Electronic Medical Records (EMR; GE/UK/FR) and IMS LifeLink™: longitudinal prescriptions (LRx; NE/BE/GE/UK) databases, and national health register data (SE), between 2010 and 2012. Therapy initiation date was termed 'index date'. Eligible patients had ≥180-day pre- and variable follow-up (minimum ≥360-day post-index exBID and LIRA, ≥180-day post-index exQW). Treatment modification and persistence were evaluated over 180 days. Kaplan-Meier (KM) survival curves and Cox proportional hazards models (PHMs; EMR databases only) evaluated stopping of the index therapy (measured as first of discontinuation or switch).Results30,206 exBID, 5,401 exQW, and 52,155 LIRA patients were included in the analysis (46.0-66.9% male; mean age range 55.4-59.3 years). Mean follow-up was 20.3-27.4 months for exBID and LIRA, and 7.6-13.9 months for exQW. Across the databases, the proportion experiencing a treatment modification at 180 days was highest among exBID (37.6-81.7%) compared to LIRA (36.8-56.6%) and exQW (32.3-47.7%). The proportion persistent at 180 days was lowest among exBID patients (46.8-73.5%) compared to LIRA (50.6-80.1%) or exQW (57.5-74.6%). In the KM analyses, LIRA patients had a lower proportion stopping therapy at all time points compared to exBID patients, across the databases. In the Cox PHMs, LIRA was associated with a significantly lower risk of stopping compared to exBID; in GE, exQW was associated with a lower risk compared to exBID and LIRA.ConclusionTreatment patterns varied among GLP-1 RA patients, with persistence highest among either LIRA or exQW across countries, and lowest among exBID. Longer-term data would be useful, particularly given limited exQW follow-up due to more recent launch.
| S-EPMC4269654 | biostudies-literature
Project description:IntroductionThere 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).MethodsThis 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.ResultsThe 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.ConclusionThe 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.
| S-EPMC7843848 | biostudies-literature
Project description:BACKGROUND:Dulaglutide is a new, long-acting glucagon-like peptide analogue in the treatment of type 2 diabetes. It is available in two doses, 0.75 and 1.5 mg, given by injection once weekly. This systematic review reports the effectiveness and safety of dulaglutide in type 2 diabetes in dual and triple therapy. METHODS:MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, and conference abstracts were searched from 2005 to August 2014, and updated in January 2015. Company websites and references of included studies were checked for potentially relevant studies. European Medicines Agency and US Food and Drug Administration websites were searched. RESULTS:Four trials were included. All were manufacturer-funded randomized controlled trials from the Assessment of Weekly Administration of Dulaglutide in Diabetes (AWARD) program. AWARD-1 compared dulaglutide 1.5 mg against exenatide 10 µg twice daily and placebo, AWARD-2 compared dulaglutide 0.75 and 1.5 mg against insulin glargine, AWARD-5 compared dulaglutide 0.75 and 1.5 mg against sitagliptin 100 mg and placebo, and AWARD-6 compared dulaglutide 1.5 mg against liraglutide 1.8 mg. The duration of follow-up in the trials ranged from 26 to 104 weeks. The primary outcome of all the included trials was change in HbA1c. At 26 weeks, greater HbA1c reductions were seen with dulaglutide than with twice daily exenatide (dulaglutide 1.5/0.75 mg: -1.5%/-1.3%; exe: 0.99%) and sitagliptin (1.5/0.75 mg -1.22%/-1.01%; sitagliptin: -0.6%). HbA1c change was greater with dulaglutide 1.5 mg (-1.08%) than with glargine (-0.63%), but not with dulaglutide 0.75 mg (-0.76%). Dulaglutide 1.5 mg was found to be noninferior to liraglutide 1.8 mg. More patients treated with dulaglutide achieved HbA1c targets of <7% and ≤6.5%. Reduction in weight was greater with dulaglutide than with sitagliptin and exenatide. Hypoglycemia was infrequent. The main adverse events were nausea, diarrhea, and vomiting. CONCLUSION:Dulaglutide is effective in the treatment of patients with type 2 diabetes but we need long follow-up data for safety concerns.
| S-EPMC4541559 | biostudies-literature
Project description:BackgroundStimulant medications are commonly prescribed for the treatment of attention-deficit/hyperactivity disorder; however, they also have high potential for diversion and misuse. We estimated national stimulant dispensing trends from 2014 to 2019 and differences in dispensing by age, sex, state, prescriber specialty, payor type, patient copay, and stimulant type.MethodsWe calculated rates of stimulant dispensing using IQVIA National Prescription Audit (NPA) New to Brand, NPA Regional, and NPA Extended Insights data, which provide dispensing estimates from approximately 49,900 pharmacies representing 92 % of prescriptions dispensed in the United States. Average annual percent change (AAPC) from 2014 to 2019 was analyzed using Joinpoint regression.ResultsFrom 2014 to 2019, the national annual rate of stimulant dispensing increased significantly from 5.6 to 6.1 prescriptions per 100 persons. Rates differed by prescription stimulant type, with increases occurring among both amphetamine-type stimulants and long-acting stimulants. Rates among females (AAPC = 3.6 %; P = 0.001) and adults aged 20-39 years (AAPC=6.7 %; P = 0.002), 40-59 years (AAPC=9.7 %; P < 0.001), and ≥60 years (AAPC = 6.9 %; P = 0.001) increased significantly during the study period. Stimulant dispensing rates varied substantially across states, ranging from 1.0 per 100 in Hawaii to 13.6 per 100 in Alabama.ConclusionsNational stimulant dispensing rates increased from 2014 to 2019, driven by notable increases among females and adults aged ≥20 years. These trends should be considered when prescribing stimulants given growing concerns over prescription stimulant diversion, misuse, and related health harms.
| S-EPMC7851748 | biostudies-literature
Project description:Aims/introductionGlucagon-like peptide-1 receptor agonists (GLP-1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP-1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose-lowering effects of GLP-1 receptor agonist liraglutide with and without prior glycemic control.Materials and methodsIn an open-label, parallel trial, participants with poorly controlled type 2 diabetes were recruited and randomized to receive once-daily insulin therapy, degludec (Insulin-GLP-1 RA relay group, mean 16.8 ± 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP-1 RA, liraglutide (GLP-1 RA first group, 0.9 mg), for 24 weeks. The primary efficacy end-points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c).ResultsThe median fasting plasma glucose and HbA1c before the study were 210.0 mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin-GLP-1 RA relay group (P < 0.001) and GLP-1 RA first group (P < 0.001) by week 24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin-GLP-1 RA relay group tended to be larger than that in the GLP-1 RA first group in the lowest CPR (C-peptide immunoreactivity) quartile (P = 0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia.ConclusionsThe GLP-1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin might overcome glucose toxicity-induced GLP-1 resistance.
| S-EPMC9153847 | biostudies-literature
Project description:Aims/introductionGlucagon-like peptide-1 receptor agonists (GLP-1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients do not respond well to the therapy, and caution must be taken for certain patients, including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP-1RA therapy. GLP-1R-targeted imaging has recently emerged to visualize and quantify β-cells. We investigated whether GLP-1R-targeted imaging can predict the efficacy of GLP-1RA treatment.Materials and methodsWe developed 111 Indium-labeled exendin-4 derivative (111 In-Ex4) as a GLP-1R-targeting probe. Diabetic mice were selected from NONcNZO10/LtJ male mice that were fed for different durations with 11% fat chow. After 3-week administration of dulaglutide as GLP-1RA therapy, mice with non-fasting blood glucose levels <300 mg/dL and >300 mg/dL were defined as responders and non-responders, respectively. In addition, ex vivo 111 In-Ex4 pancreatic accumulations (111 In-Ex4 pancreatic values) were examined.ResultsThe non-fasting blood glucose levels after treatment were 172.5 ± 42.4 mg/dL in responders (n = 4) and 330.8 ± 20.7 mg/dL in non-responders (n = 5), respectively. Ex vivo 111 In-Ex4 pancreatic values showed significant correlations with post-treatment glycohemoglobin and glucose area under curve during an oral glucose tolerance test (R2 = 0.76 and 0.80; P < 0.01 and <0.01, respectively). The receiver operating characteristic area under curve for identifying responders by ex vivo 111 In-Ex4 pancreatic values was 1.00 (P < 0.01).ConclusionEx vivo 111 In-Ex4 pancreatic values reflected dulaglutide efficacy, suggesting clinical possibilities for expanding GLP-1R-targeted imaging applications.
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Project description:Periodontitis is one of the diabetic complications due to its high morbidity and severity in patients with diabetes. The prevention of periodontitis is especially important in diabetic patients because the relationship between diabetes and periodontitis is bidirectional. Here, we evaluated the impacts of glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on the amelioration of periodontitis. Five-wk-old Male Sprague-Dawley (SD) rats (n = 30) were divided into 3 groups: normal, periodontitis, and periodontitis with liraglutide treatment groups. Periodontitis was induced by ligature around the maxillary second molar in SD rats. Half of the rats were administered liraglutide for 2 weeks. Periodontitis was evaluated by histological staining, gene expressions of inflammatory cytokines in gingiva, and microcomputed tomography. Periodontitis increased inflammatory cell infiltration, macrophage accumulation, and gene expressions of tumor necrosis factor-α and inducible nitric oxide synthase in the gingiva, all of which were ameliorated by liraglutide. Liraglutide decreased M1 macrophages but did not affect M2 macrophages in periodontitis. Moreover, ligature-induced alveolar bone resorption was ameliorated by liraglutide. Liraglutide treatment also reduced osteoclasts on the alveolar bone surface. These results highlight the beyond glucose-lowering effects of liraglutide on the treatment of periodontitis.
| S-EPMC7695495 | biostudies-literature
Project description:Glucagon-like peptide 1 receptor (GLP1R) agonists are widely used to treat diabetes. However, their function is dependent on adequate GLP1R expression, which is downregulated in diabetes. GLP1R is highly expressed on pancreatic β-cells, and activation by endogenous incretin or GLP1R agonists increases cAMP generation, which stimulates glucose-induced β-cell insulin secretion and helps maintain glucose homeostasis. We now have discovered that the highly β-cell-enriched microRNA, miR-204, directly targets the 3' UTR of GLP1R and thereby downregulates its expression in the β-cell-derived rat INS-1 cell line and primary mouse and human islets. Furthermore, in vivo deletion of miR-204 promoted islet GLP1R expression and enhanced responsiveness to GLP1R agonists, resulting in improved glucose tolerance, cAMP production, and insulin secretion as well as protection against diabetes. Since we recently identified thioredoxin-interacting protein (TXNIP) as an upstream regulator of miR-204, we also assessed whether in vivo deletion of TXNIP could mimic that of miR-204. Indeed, it also enhanced islet GLP1R expression and GLP1R agonist-induced insulin secretion and glucose tolerance. Thus, the present studies show for the first time that GLP1R is under the control of a microRNA, miR-204, and uncover a previously unappreciated link between TXNIP and incretin action.
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Project description:Co-agonists at the glucagon-like peptide-1/glucagon receptors (GLP1R/GCGR) show promise as treatments for metabolic dysfunction-associated steatotic liver disease (MASLD). Unlike GLP1, glucagon directly acts on the liver to reduce fat content. To date most metabolic studies have looked at heavily GLP1R-biased co-agonists and have not distinguished weight-loss versus weight loss-independent effects. We demonstrate that 24 days’ treatment with Dicretin, a GLP1/GCGR co-agonist with high potency at the GCGR, in mice with hepatic steatosis secondary to diet-induced obesity leads to superior reduction of hepatic lipid content when compared to Semaglutide or equivalent weight loss by calorie restriction. Hepatic transcriptomic and metabolomic profiling demonstrated many changes that were unique to Dicretin-treated mice: some known targets of glucagon signalling and others with as yet unclear physiological significance. Our study supports the development of GLP1/GCGR co-agonists for treatment of MASLD and related conditions.
2024-06-11 | GSE243681 | GEO