المؤلفون: Kyriakidou, Artemis, Kyriazou, Angeliki V., Koufakis, Theocharis, Vasilopoulos, Yiannis, Avramidis, Iakovos, Baltagiannis, Stefanos, Goulis, Dimitrios G., Kotsa, Kalliopi

المصدر: Postgraduate Medicine; Mar2024, Vol. 136 Issue 2, p218-225, 8p

مصطلحات موضوعية: GLUCAGON-like peptide-1 receptor, GLUCAGON-like peptide-1 agonists, TYPE 2 diabetes, GLYCEMIC control, GENE therapy

مستخلص: The factors determining the response to treatment with glucagon-like peptide-1 receptor agonists (GLP-1- RAs) have not been clarified. The present study investigated the association between polymorphisms in TCF7L2, CTRB1/2, and GLP-1 R genes and response to GLP-1 RAs regarding glycemic control and weight loss among Greek patients with type 2 diabetes mellitus (T2DM). Patients (n = 191) treated with GLP-1 RAs for at least 6 months were included. Participants were genotyped for TCF7L2 rs7903146 (C>T), CTRB1/2 rs7202877 (T>G) and GLP-1 R rs367543060 (C>T) polymorphisms. Clinical and laboratory parameters were measured before, 3, and 6 months after treatment initiation. The patients were classified into responders and non-responders according to specific criteria. Carriers of at least one rs7903146 'T' allele and rs7202877 'G' allele presented similar glucose control and weight loss response to GLP-1 RAs with the respective homozygous wild-type genotypes [odds ratio (OR): 1.08, 95% confidence interval (CI): 0.5, 2.31, p = 0.85 and OR: 1.35, 95% CI: 0.66, 2.76, p = 0.42; OR: 1.4, 95% CI: 0.56, 3.47, p = 0.47 and OR: 1.28, 95% CI: 0.55, 2.98, p = 0.57, respectively]. Regarding the GLP-1 R polymorphism, all participants were homozygous for the wild-type allele; thus, no comparisons were feasible. Female sex (p = 0.03) and lower baseline weight (p = 0.024) were associated with an improved glycemic and weight loss response, respectively. There is no evidence suggesting a role for the variants studied in response to GLP-1 RA therapy in people with T2DM. However, specific demographic and clinical factors may be related to a better response to treatment with these agents. [ABSTRACT FROM AUTHOR]

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المؤلفون: Amaro, Anastassia, Sugimoto, Danny, Wharton, Sean

المصدر: Postgraduate Medicine; 2022 Suppl, Vol. 134, p5-17, 13p

مصطلحات موضوعية: REGULATION of body weight, SEMAGLUTIDE, GLUCAGON-like peptide-1 receptor, GLUCAGON-like peptide-1 agonists, WEIGHT loss

الشركة/الكيان: UNITED States. Food & Drug Administration

مستخلص: Obesity is a global health challenge. It is a multifactorial, complex, and progressive disease associated with various health complications and increased mortality. Lifestyle modifications are central to weight management but may be insufficient to maintain clinically meaningful weight loss. Pharmacotherapies are recommended as an adjunct to lifestyle interventions to induce and sustain clinically meaningful weight loss and reduce the risk of comorbidities in appropriate patients. Glucagon-like peptide-1 is an incretin metabolic hormone responsible for a range of physiological effects, including glucose and appetite regulation. Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the treatment of type 2 diabetes since 2005 including exenatide (short- and extended-release), lixisenatide, liraglutide, dulaglutide, albiglutide, and semaglutide. Of these, semaglutide (subcutaneous) and liraglutide are currently US Food and Drug Administration (FDA)-approved for chronic weight management in patients with or without diabetes. The phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program was designed to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with overweight or obesity. Following the submission of the results of the STEP 1–4 trials, the FDA approved once-weekly subcutaneous semaglutide 2.4 mg for chronic weight management in people with overweight or obesity in April 2021. Data from the program demonstrated that semaglutide (2.4 mg once weekly) achieved significant and sustained weight loss, together with improvements in cardiometabolic risk factors compared with placebo, and was generally well tolerated, with a safety profile consistent with other GLP-1RAs. The most common adverse events reported in STEP 1–5 were gastrointestinal events, which were transient, mild-to-moderate in severity, and typically resolved without permanent treatment discontinuation. This article reviews the data from STEP 1–5 and highlights clinically relevant findings for primary care providers. [ABSTRACT FROM AUTHOR]

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المؤلفون: Campos, Carlos, Unger, Jeff

المصدر: Postgraduate Medicine; Nov 2021, Vol. 133 Issue 8, p843-853, 11p

مصطلحات موضوعية: GLUCAGON-like peptide-1 agonists, GLUCAGON-like peptide-1 receptor, TYPE 2 diabetes, CD26 antigen, GLYCEMIC control, PRIMARY care, SUBCUTANEOUS injections

مستخلص: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP4is) exert their effects via the incretin system, which augments glucose-dependent insulin secretion in response to nutrient intake (the 'incretin effect'). Both classes are well-established pharmacologic options for the management of glycemic control in individuals with type 2 diabetes (T2D) after failure of first-line metformin; however, they have inherent differences in their mechanisms of action that are reflected in their clinical safety and efficacy profiles. GLP-1RAs have high glycemic efficacy and are associated with weight loss and, in some cases, cardioprotective effects, with a side-effect profile of predominantly transient gastrointestinal adverse events. Most GLP-1RAs are administered as subcutaneous injection, although an oral formulation of one GLP-1RA, semaglutide, has recently become available. DPP4is provide moderate glycemic control, are weight-neutral, and do not offer any cardiovascular benefits, but are generally well tolerated. DPP4is are all administered orally. This narrative review aims to provide guidance for a primary care audience on the similarities and differences between GLP-1RA and DPP4i therapies, with a focus on their mechanism of action, clinical safety, efficacy, and real-world effectiveness. The role of incretin-based therapies in the T2D treatment paradigm, including key considerations for guiding treatment decisions, will also be discussed. [ABSTRACT FROM AUTHOR]

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المؤلفون: Fitch, Angela, Ingersoll, Amy Beth

المصدر: Postgraduate Medicine; Apr2021, Vol. 133 Issue 3, p310-319, 10p

مصطلحات موضوعية: GLUCAGON-like peptide-1 receptor, GLUCAGON-like peptide-1 agonists, PRIMARY care, OBESITY, PATIENT selection, PNEUMOCYSTIS pneumonia, METABOLIC disorders

مصطلحات جغرافية: UNITED States

مستخلص: Obesity is a chronic, relapsing metabolic disease, linked to a number of health risks and serious complications. Although highly prevalent in adults in the United States, it is underdiagnosed and untreated. Primary care providers (PCPs) are uniquely poised to diagnose and treat patients with obesity, using a selection of treatment strategies including lifestyle modifications and pharmacotherapies. As a physiological regulator of appetite and energy intake, the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide 3.0 mg is approved for chronic weight management in individuals with overweight (pre-obesity) or obesity. In this review, we provide an overview of the clinical data supporting the use of liraglutide 3.0 mg, as well as practical advice for PCPs on the initiation and maintenance of treatment over the long term. This also covers the management of side effects and how to manage patient expectations over time. [ABSTRACT FROM AUTHOR]

: Copyright of Postgraduate Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Brunton, Stephen A., Mosenzon, Ofri, Wright Jr, Eugene E.

المصدر: Postgraduate Medicine; 2020 Supplement, Vol. 132, p48-60, 13p

مصطلحات موضوعية: GLUCAGON-like peptide-1 receptor, TYPE 2 diabetes, GLUCAGON-like peptide-1 agonists, PRIMARY care, TYPE 1 diabetes, MEDULLARY thyroid carcinoma

الشركة/الكيان: UNITED States. Food & Drug Administration

مستخلص: Oral semaglutide is the first US Food and Drug Administration-approved oral glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes (T2D). Prior articles within this supplement reviewed the PIONEER trial program, which demonstrated that oral semaglutide reduced glycated hemoglobin and body weight when given to patients with uncontrolled T2D on various background therapies, and had a safety profile consistent with subcutaneous GLP-1RAs. This article provides guidance on integrating oral semaglutide into clinical practice in primary care. Patient populations with T2D who may gain benefit from oral semaglutide include those with inadequate glycemic control taking one or more oral glucose-lowering medication (e.g. after metformin), patients for whom weight loss would be beneficial, patients at risk of hypoglycemia, those who would historically have been considered for treatment with a subcutaneous GLP-1RA, and those receiving basal insulin who require treatment intensification. Like other GLP-1RAs, oral semaglutide is contraindicated in those with personal/family history of medullary thyroid carcinoma, and in those with multiple endocrine neoplasia syndrome type 2, as noted in a boxed warning in the prescribing information. Oral semaglutide has not been studied in those with a history of pancreatitis, is not recommended in patients with suspected/confirmed pancreatitis, and is not indicated in type 1 diabetes. When initiating oral semaglutide, gradual dose escalation is recommended to minimize the risk of gastrointestinal adverse events. As food and excess liquid reduce oral semaglutide absorption, patients should swallow the tablet with up to 4 fl oz/120 mL of water on an empty stomach upon waking, and should wait at least 30 minutes before eating, drinking, or taking other oral medications. Those managing patients should be aware of the potential impact of these dosing conditions on concomitant medications. When counseling patients, it is important to discuss these administration instructions, realistic therapeutic expectations, and strategies for mitigation of gastrointestinal events. Oral semaglutide provides a new option for add-on to initial T2D therapy (or later in the treatment paradigm), with the potential to enable more patients to benefit from the improvements in glycemic control, reductions in body weight, and low risk of hypoglycemia afforded by GLP-1RAs. [ABSTRACT FROM AUTHOR]

: Copyright of Postgraduate Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Mosenzon, Ofri, Miller, Eden M., Warren, Mark L.

المصدر: Postgraduate Medicine; 2020 Supplement, Vol. 132, p37-47, 11p

مصطلحات موضوعية: OLDER patients, GLUCAGON-like peptide-1 receptor, CARDIOVASCULAR diseases, GLUCAGON-like peptide-1 agonists, CHRONIC kidney failure, TYPE 2 diabetes

مستخلص: Patients with type 2 diabetes (T2D) often have comorbidities, such as cardiovascular disease or chronic kidney disease, and a large and growing proportion of the T2D patient population is over 65 years. There are many therapies for the treatment of T2D but not all are suitable for patients with comorbidities. Oral semaglutide is a tablet formulation of a glucagon-like peptide-1 receptor agonist (GLP-1RA) and was recently approved for the treatment of T2D, representing an oral alternative to injectable GLP- 1RAs. This article reviews data from: PIONEER 6, a phase 3a cardiovascular outcomes trial in patients at high cardiovascular risk; PIONEER 5, a phase 3a trial in patients with moderate renal impairment; a posthoc analysis of PIONEER data by age; and pharmacokinetic trials investigating the effects of renal impairment, gastrointestinal disease, and hepatic impairment on the exposure of oral semaglutide. PIONEER 6 demonstrated the cardiovascular safety of oral semaglutide compared with placebo (hazard ratio: 0.79; 95% confidence interval [CI]: 0.57, 1.11; p < 0.001 for noninferiority), ruling out excess cardiovascular risk. In PIONEER 5, oral semaglutide was superior to placebo in decreasing glycated hemoglobin over 26 weeks (estimated treatment difference [ETD]: -0.8%; 95% CI: -1.0, -0.6; p < 0.0001) and body weight (ETD: -2.5 kg; 95% CI: -3.2, -1.8; p < 0.0001), and renal function was unchanged in both treatment groups. There was no effect of age on glycemic efficacy of oral semaglutide and the presence of upper gastrointestinal disease or hepatic impairment did not affect the pharmacokinetics of semaglutide. Across the trials, the safety profile of oral semaglutide was as expected for a GLP-1RA, with gastrointestinal adverse events most commonly reported. As such, oral semaglutide provides an effective oral GLP-1RA treatment option in older patients and/or those with comorbidities, with no requirements for dose adjustment. [ABSTRACT FROM AUTHOR]

: Copyright of Postgraduate Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Wright Jr, Eugene E., Aroda, Vanita R.

المصدر: Postgraduate Medicine; 2020 Supplement, Vol. 132, p26-36, 11p

مصطلحات موضوعية: TYPE 2 diabetes, DRUG efficacy, GLUCAGON-like peptide-1 agonists, GLUCAGON-like peptide-1 receptor, INSULIN, GLYCOSYLATED hemoglobin

مستخلص: Injectable therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and insulin are high-efficacy options for people with type 2 diabetes (T2D) who require treatment intensification. In addition to high glycemic efficacy, GLP-1RAs offer weight loss benefits, and some agents have been shown to reduce cardiovascular risk. This article summarizes data from two clinical studies with the first oral GLP-1RA, oral semaglutide, in situations where injectable therapy is often considered, and provides guidance on use in primary care. PIONEER 4 compared oral semaglutide 14 mg with an injectable GLP-1RA, liraglutide 1.8 mg, or placebo in patients uncontrolled on oral glucose-lowering therapies. PIONEER 8 compared oral semaglutide with placebo in patients with T2D already on insulin therapy. Treatment with oral semaglutide gave similar reductions in glycated hemoglobin (HbA1c) compared with liraglutide at 26 weeks, and significantly greater reductions at 52 weeks. Changes in body weight with oral semaglutide were significantly greater compared with liraglutide after 26 and 52 weeks. Adding oral semaglutide 7 or 14 mg to insulin resulted in significant reductions in HbA1c and body weight at both 26 and 52 weeks compared with placebo, and facilitated a decrease in total daily insulin dosage. Oral semaglutide was associated with low proportions of patients experiencing severe or blood glucose-confirmed symptomatic hypoglycemia when added to oral glucoselowering therapies, and did not increase the incidence of such events when added to insulin. The tolerability profile of oral semaglutide was consistent with that seen for injectable GLP-1RAs, with gastrointestinal side effects seen most frequently; most were transient and tended to occur during dose escalation. For patients requiring treatment intensification after oral therapy or as add-on to insulin, oral semaglutide provides effective glucose lowering and body weight loss, with low risk of hypoglycemia, thus broadening the range of therapeutic options for treatment of T2D in primary care. [ABSTRACT FROM AUTHOR]

: Copyright of Postgraduate Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Lavernia, Frank, Blonde, Lawrence

المصدر: Postgraduate Medicine; 2020 Supplement, Vol. 132, p15-25, 11p

مصطلحات موضوعية: TYPE 2 diabetes, DRUG efficacy, GLUCAGON-like peptide-1 receptor, GLUCAGON-like peptide-1 agonists, PLACEBOS

مستخلص: Oral semaglutide is a tablet formulation of a glucagon-like peptide-1 receptor agonist (GLP-1RA), recently approved in the USA and other countries. This paper reviews data from clinical trials (PIONEER 1, 2, 3, and 7) comparing oral semaglutide (once-daily doses of 3, 7, or 14 mg) with either once-daily placebo, empagliflozin 25 mg, or sitagliptin 100 mg. After 26 weeks in PIONEER 1, patients randomized to 3, 7, or 14 mg doses of oral semaglutide monotherapy had statistically significant reductions in glycated hemoglobin (HbA1c) of 0.9%, 1.2%, and 1.4%, respectively, versus 0.3% with placebo. In the active-comparator studies, oral semaglutide 14 mg provided better glycemic control than empagliflozin or sitagliptin after 26 weeks, with durable effects. Body weight reductions were significantly greater with oral semaglutide than with placebo and sitagliptin. However, body weight reductions with oral semaglutide 14 mg versus empagliflozin 25 mg were not significantly different. Gastrointestinal adverse events (AEs) with oral semaglutide were mostly mild-to-moderate, occurred early in the course of treatment, and abated over time. Across these trials, 5-13% and 15-20% of patients experienced nausea with oral semaglutide 7 and 14 mg, respectively, and 2.3-3.4% and 5.1- 8.0%, respectively, discontinued treatment due to gastrointestinal AEs. Severe or blood glucose-confirmed symptomatic hypoglycemia occurred infrequently with oral semaglutide and was seen most often in patients taking concomitant sulfonylureas. Findings from these trials indicate that the addition of oral semaglutide reduces HbA1c and body weight and is associated with a low risk of hypoglycemia. Oral semaglutide represents an additional option for treating people with type 2 diabetes in primary care, with the potential to expand the numbers of patients benefiting from GLP-1RAs beyond that currently seen with injectable formulations. [ABSTRACT FROM AUTHOR]

: Copyright of Postgraduate Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Morales, Javier, Shubrook, Jay H., Skolnik, Neil

المصدر: Postgraduate Medicine; Nov2020, Vol. 132 Issue 8, p687-696, 10p

مصطلحات موضوعية: TYPE 2 diabetes, GLUCAGON-like peptide-1 receptor, GLUCAGON-like peptide-1 agonists, PRIMARY care, HYPOGLYCEMIC agents, CLINICAL trials, BLOOD sugar, CARDIOVASCULAR diseases, MEDICAL protocols, HYPOGLYCEMIA, WEIGHT loss, GLUCAGON-like peptides

مستخلص: As the cornerstone of type 2 diabetes (T2D) management within the community, primary care providers are now faced with the challenge of not only managing diabetes itself, but also preventing hypoglycemia and weight gain associated with intensive disease management, and reducing cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well established as efficacious treatments for T2D, and the safety/tolerability profile of this drug class is well defined. However, despite their beneficial effects, GLP-1RAs are under-utilized, highlighting the need for novel approaches to increase their use in primary care. Oral semaglutide is the first oral GLP-1RA approved for the treatment of T2D, offering glucose lowering and body weight loss, a low risk of hypoglycemia, and no increase in cardiovascular risk. Oral semaglutide represents an additional treatment option for patients not achieving their glycemic goal despite treatment with metformin, either alone or with other hypoglycemic agents. Oral semaglutide has the potential to increase usage of GLP-1RAs in the primary care setting by addressing clinician and patient concerns about injections, and may facilitate earlier initiation of GLP-1RA therapy in T2D. Due to the formulation of oral semaglutide, clinicians need to be aware of specific considerations in order to ensure optimal use. Such considerations include dosing conditions and use of concomitant medications. This article provides practical guidance on the use of oral semaglutide in the primary care setting, based on evidence from clinical studies, including the phase 3a PIONEER program, and the authors' clinical experience. [ABSTRACT FROM AUTHOR]

: Copyright of Postgraduate Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Lajara, Rosemarie

المصدر: Postgraduate Medicine; Nov2019, Vol. 131 Issue 8, p555-565, 11p

مصطلحات موضوعية: GLUCAGON-like peptide-1 agonists, TYPE 2 diabetes, GLUCAGON-like peptide-1 receptor, GLYCOSYLATED hemoglobin, GLYCEMIC control, BODY weight

مستخلص: Type 2 diabetes (T2D) has a complex pathophysiology composed of multiple underlying defects that lead to impaired glucose homeostasis and the development of macrovascular and microvascular complications. Of the currently available glucose-lowering therapies, sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) both provide effective glycemic control and have been shown to reduce cardiovascular (CV) events in patients with T2D and a high CV risk or established CV disease. Because these agents have complementary mechanisms of action, they are able to act on multiple defects of T2D when used in combination. This review discusses the rationale for and potential benefits of SGLT-2i plus GLP-1RA combination therapy in patients with T2D. A search of the PubMed database was conducted for studies and reviews describing the combined use of SGLT-2is and GLP-1RAs, with a specific focus on identifying clinical studies of combination therapy in patients with T2D. In clinical studies, glycated hemoglobin (A1c) was significantly reduced over 28-52 weeks with SGLT-2i plus GLP-1RA therapy versus the individual agents or baseline. Several CV risk factors, including body weight, blood pressure, and lipid parameters, were also improved. SGLT-2i plus GLP-1RA therapy was generally well tolerated, with a low risk of hypoglycemia and no unexpected findings. Taken together with results from large CV outcomes trials of SGLT-2is and GLP-1RAs, combination therapy with these agents potentially provides effective durable glycemic control and CV benefits due to their complementary actions on the defects of T2D. [ABSTRACT FROM AUTHOR]

: Copyright of Postgraduate Medicine is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)