Use Of Glucagon-like Peptide-1 Agonists Research Articles

Glucagon-like Peptide-1 Agonists: What the Orthopaedic Surgeon Needs to Know.

» Orthopaedic surgeons are increasingly likely to encounter patients with obesity and/or type 2 diabetes taking glucagon-like peptide-1 (GLP-1) agonists for weight loss.» GLP-1 agonists are an effective treatment for weight loss with semaglutide and tirzepatide being the most effective agents. Randomized controlled trials using these agents have reported weight loss up to 21 kg (46 lb).» The use of GLP-1 agonists preoperatively can improve glycemic control, which can potentially reduce the risk of postoperative complications. However, multiple cases of intraoperative aspiration/regurgitation have been reported, potentially related to the effect of GLP-1 agonists on gastric emptying.» While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. Multifactorial approaches to weight loss with focus on lifestyle modification in addition to GLP-1 agonists should be considered in such patients.» Although GLP-1 agonists are efficacious agents for weight loss, they may not be accessible or affordable for all patients. Each patient's unique circumstances should be considered when creating an ideal weight loss plan during optimization efforts.

Practice Patterns and Perspectives of the Off-Label Use of GLP-1 Agonists for Cosmetic Weight Loss.

The off-label use of glucagon-like peptide 1 (GLP-1) agonists for cosmetic weight loss has captured the interest of the public. However, there is a paucity of published data on their utilization, implications, and management, particularly in the plastic surgery community. This study aims to explore the current practice patterns of aesthetic plastic surgeons regarding the off-label implementation of GLP-1 agonists. A 35-question survey was sent to the 2600 members of The Aesthetic Society in July 2023. The survey collected physician demographics, practice settings, patient population demographics, and the use and management of GLP-1 agonists in their practice. No identifying variables were collected; all responses were anonymous. A total of 368 respondents were included. A quarter of respondents (25.3%) prescribed or utilized GLP-1 agonists in their practice. Nearly a third (29.9%) reported personal use of the medication, of which 71 (70.3%) indicated it was for cosmetic weight loss. Many aspects of the current treatment, counseling, and follow-up practices were similar among prescribing plastic surgeons. However, there were discrepancies in screening, nutrition counseling, and perioperative management. The majority believed that GLP-1 agonists were effective for weight loss (68.9%), profitable for business (57.8%), and would recommend its implementation to other plastic surgeons (68.5%). As leaders in the aesthetic field, it behooves plastic surgeons to take charge of shaping public opinion surrounding the growing off-label use of GLP-1 agonists for cosmetic weight loss. Plastic surgeons' leadership is imperative in establishing safe and ethical guidelines and protocols for proper screening, management, and patient care.

Glucagon-Like Peptide-1 Analogue In The Management Of Rebound Intracranial Hypertension: A Case Report

Background: Rebound intracranial hypertension (RIH) is a possible complication of epidural blood patching used in the management of spontaneous intracranial hypotension (SIH). RIH has been reported to occur in up to 27% of patients after SIH treatment and is characterized by elevated intracranial pressure, resulting in severe headache, nausea, and vomiting. Although it typically resolves spontaneously, treatment may be warranted for symptom control. While acetazolamide is the most commonly used agent for RIH, there are side-effects, and its efficacy remains inconclusive. Recently, novel glucagon-like peptide-1 (GLP-1) analogues have been found to modulate CSF secretion and consequently reduce intracranial pressure. However, there are no studies that have evaluated the use of these agents in the treatment of RIH. We report of a case of a 46 year old female patient with persistent RIH after CSF leak repair that was refractory to pharmacologic and interventional treatments. The patient was treated with Semaglutide, an oral GLP-1 analogue and experienced immediate and sustained benefit of her symptoms. Conclusion: RIH is a common complication after successful patching of a CSF leak, a proportion of patients suffer from persistent and debilitating headaches. Our case report showed that GLP-1 agonist Semaglutide appeared to reduce symptoms in this one patient with refractory RIH symptoms. The use of GLP-1 agonists in the treatment of RIH should be evaluated in controlled studies to establish its safety and efficacy in this population.

Use of GLP-1 agonists in high risk patients prior to bariatric surgery: a cohort study.

Body mass index (BMI) > 50kg/m2 is associated with relatively increased morbidity and mortality with bariatric surgery (BS). There is reluctance to consider these patients operative candidates without preoperative weight loss. Glucagon-like peptide-1 (GLP-1) agonists have demonstrated effective weight loss in the post-BS setting. This study aims to determine the safety and efficacy of GLP-1 agonists in the pre-habilitation of patients with BMI > 50kg/m2. This is a retrospective review of bariatric surgery patients with BMI > 50kg/m2 from a single bariatric center. Patients were compared by preoperative GLP-1 therapy status. All patients received medical, surgical, psychiatric, and nutritional evaluation and counseling. Preoperative BMI, change in weight from program intake until surgery, time to surgery, and perioperative complications were evaluated. 31 patients were included in the analysis. 18 (58%) received a GLP-1 agonist preoperatively. GLP-1 agonist use was associated with a 5.5 ± 3.2-point reduction in BMI compared to 2.9 ± 2.4 amongst controls (p = 0.026). There was no difference in the mean length of time in the bariatric program prior to surgery between groups (p = 0.332). There were no reported complications related to GLP-1 use in the preoperative setting and no difference in perioperative complications between groups (p = 0.245). GLP-1 agonist use in patients with a BMI > 50kg/m2 results in significantly more weight loss prior to bariatric surgery, without increased time to surgery or complication rate. Further study is required to evaluate the long-term impact of preoperative GLP-1 agonist use prior to bariatric surgery. This therapy may improve perioperative and long-term outcomes in the very high-risk BMI population.

Public Interest in the Off-Label Use of Glucagon-Like Peptide 1 Agonists (Ozempic) for Cosmetic Weight Loss: A Google Trends Analysis.

Glucagon-like peptide 1 (GLP-1) agonists are a drug class used for the treatment of diabetes that have recently gained FDA approval for medical management of obesity. Particularly, the off-label use of Ozempic, brand name of GLP-1 agonist semaglutide, for cosmetic weight loss has been popularized by social media and celebrity influence. Analyze the recent search popularity of the drug and related GLP-1 agonists using Google Trends. The term "Ozempic" was analyzed using Google Trends. Search popularity was assessed in terms of relative search volume (RSV) over a 5-year period. Changes in RSV were further compared with other GLP-1 agonists, "Wegovy" and "Mounjaro." Between March 2018 to February 2023, overall RSV in "Ozempic" grew exponentially in the United States. Simple linear regression analysis showed significantly increased RSV over time with R2 of 0.915 and regression coefficient of 0.957 (p < 0.001). When comparing "Ozempic," "Wegovy," and "Mounjaro" since June 2021 (FDA approval of Wegovy), Ozempic remained at the greatest RSV. One-way ANOVA found statistically significant differences between the three search terms at all time points between December 2021 and February 2023 (p < 0.001). This study demonstrates a significant and growing public interest in "Ozempic" and related GLP-1 agonists. As the use of GLP-1 agonists for weight loss becomes more prevalent, plastic surgeons, particularly in the aesthetic setting, must be prepared for the downstream implications. Increased awareness, understanding, and further scientific studies led by plastic surgeons will help deliver the safest possible patient outcomes.

NAFLD: A pretransplant and post-transplant conundrum.

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Distribution and function of glucagon-like peptide 1 (GLP-1) in the digestive tract of mammals and the clinical use of its analogues

Recently, interest in glucagon-like peptide-1 (GLP-1) and other peptides derived from preproglucagon has increased significantly. GLP-1 is a 30-amino acid peptide hormone produced in L-type enteroendocrine cells as a response to food intake. GLP-1 is rapidly metabolized and inactivated by the dipeptidyl peptidase IV enzyme before the hormone leaves the intestine, which increases the likelihood that GLP-1 action is transmitted through sensory neurons in the intestine and liver through the GLP-1 receptor. The main actions of GLP-1 are to stimulate insulin secretion (i.e. act as incretin hormone) and inhibit glucagon secretion, thus contributing to the reduction of postprandial glucose spikes. GLP-1 also inhibits motility and gastrointestinal secretion, and therefore acts as part of the „small bowel brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these effects, GLP-1 or GLP-1 receptor agonists are now increasingly used to treat type 2 diabetes. Reduced GLP-1 secretion may contribute to the development of obesity, and excessive secretion may be responsible for postprandial reactive hypoglycemia. The use of GLP-1 agonists opens up new possibilities for the treatment of type 2 diabetes and other metabolic diseases. In the last two decades, many interesting studies covering both the physiological and pathophysiological role of GLP-1 have been published, and our understanding of GLP-1 has broadened significantly. In this review article, we have tried to describe our current understanding of how GLP-1 works as both a peripheral hormone and as a central neurotransmitter in health and disease. We focused on its biological effects on the body and the potential clinical application in relation to current research.

Incretin as a Pathophysiological Component and Target for Treatment in Youth Type 2 Diabetes (T2D)

Incretin hormones have recently been considered an important pathophysiological factor for T2D in adults and youth due to their role in augmenting insulin secretion (Michaliszyn et al., 2014). It is recognized that glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are glucose-dependent hormones released from the gut that stimulate insulin release from pancreatic β-cells (Muscelli et al., 2006). Thus, the insulin response to oral glucose is significantly greater than the intravenous (IV) glucose administration response; this is known as the incretin effect (Michaliszyn et al., 2014). To date, adults with T2D demonstrate a remarkable decrease in the incretin effect (Nauck et al., 1986), whereas there is lack of evidence in pediatric populations. The incretin effect is also associated with β-cell glucose sensitivity (βCGS), attesting incretins as a high-promising target for T2D treatment (Michaliszyn et al., 2014). Utilizing GLP-1 receptor agonists can be advantageous as a therapeutic option for both adults and youth (Tamborlane et al., 2019; Vanderheiden et al., 2016; Yeow et al., 2017). While metformin and insulin were the sole treatment options for Y-T2D prior to FDA approval (in 2019) for the use of GLP-1 agonists, a recent RISE (Restoring Insulin Secretion) clinical trial reported disappointing results that both metformin alone and insulin glargine for three months followed by metformin for nine months were not effective in restoring/preserving β-cell function in youth with prediabetes and T2D (RISE Consortium &amp; RISE Consortium Investigators, 2019). On the contrary, the role of GLP-1 and the efficacy of the GLP-1 receptors in T2D signifies a strong target for potential treatment. Additional clinical trials are warranted to see if monotherapy of GLP-1 agonist vs. combined (metformin + liraglutide) therapy is effective to reserve Y-T2D to prediabetes and/or normal state. More importantly, future research should focus on disease prevention rather than treatment to avoid aggressive complications and metabolic degradations of Y-T2D (RISE Consortium &amp; RISE Consortium Investigators, 2019). Altogether, it would be germane to investigate whether lifestyle changes (diet, physical activity, exercise medicine) can improve the incretin effect in conjunction with glycemic control in youth.

SAT-570 Should Severe Hypertriglyceridemia Also Be Considered as a Contraindication for Use of Glucagon like Peptide 1 (GLP-1) Agonists?

Background: Reported cases of acute pancreatitis have been associated with the use of GLP-1 agonists for treatment of diabetes mellitus. Hypertriglyceridemia is a well-established but underestimated cause of acute and recurrent pancreatitis. At the present time, there is insufficient data to know if there is a casual relationship. Clinical Case: A 46 y.o. male with past medical history of coronary artery disease, hyperlipidemia, type 2 diabetes mellitus, hypertension, and morbid obesity, was admitted to the hospital with severe abdominal pain radiating to the back associated with non-bilious vomiting, for 1 day. Patient endorsed that 4 years ago he was diagnosed with hypertriglyceridemia. Physical exam findings were notable for a distended abdomen with mild epigastric tenderness, heart rate at 120 bpm, and a body mass index of 37 kg/m2. Active medications include: atorvastatin 40 mg PO daily, fenofibrate 45 mg PO daily, metformin 1,000 mg PO twice a day, glipizide 5 mg PO daily, levemir 60 units SQ twice a day, and most recently he had been started on dulaglutide 0.75 mg SQ weekly. Initial tests were consistent with acute pancreatitis and diabetic ketoacidosis: lipase 944 U/L (n 8.0 - 78 U/L), anion gap 18 mEq/L (n 5 - 13 mEq/L), creatinine 1.6 mg/dL (n 0.72 - 1.25 mg/dL), glucose 479 (n 60–100 mg/dL), β-Hydroxybutyrate 5.3 mmol/L (n <0.3mmol/L), urine glucose >1,000 mg/dL (n Negative mg/dL), urine ketones 20 mg/dL (n Negative), Triglycerides (TG) 5,374 mg/dL (n <150 mg/dL) and Hgb A1C 11.9% (n <5.7%). CT abdomen and pelvis without contrast revealed moderate acute pancreatitis. Patient was admitted to the intensive care unit and was started on intravenous insulin, atorvastatin 80 mg PO daily and fenofibrate 145 mg PO daily. Despite optimization of lipid-lowering agents, TG remained above 2,000 mg/dL. Decision was made to start patient on plasmapheresis until TG was <500 mg/dL. Patient’s TG improved to 370 mg/dL after second treatment. Patient’s dulaglutide was discontinued and patient was advised to avoid GLP-1 agonist use, indefinitely. One-month post discharge patient’s TG level was 370 mg/dL. Conclusion: Pancreatitis should be considered in patients on GLP-1 agonists, that present with persistent severe abdominal pain (with or without nausea), and its use should be discontinued in such patients. Use of GLP-1 agonists should be avoided in subjects with severe hypertriglyceridemia. Further research should be made in order to determine if GLP-1 agonists should be contraindicated in patients with severe hypertriglyceridemia, as both increase risk for pancreatitis.

Emotional eating in patients attending a specialist obesity treatment service

ObjectiveThe prevalence of emotional eating (EE) has increased in the general population over past decades. There is limited information on how common EE is among people seeking obesity treatment. We aimed to estimate the proportion of people with EE, and strength of associations between a predefined set of factors and EE in people referred for obesity treatment. MethodsCross-sectional study recruiting 387 adults from a hospital obesity service. “Emotional eating” was defined as Emotional Eating Scale (EES) score ≥25. Strength of associations were estimated by boot-strapped quantile regression analysis. Results are presented as quantile difference (QD) of EES scores at the 25th, 50th or 75th quantile, and 95% confidence intervals (95%CI). ResultsThe study population consisted of 71% women, with a median age of 52 years (interquartile range [IQR]: 42, 61), and a median body mass index of 42 kg/m2 (IQR: 37, 49). 187 participants were managed with lifestyle modification alone, 103 with the addition of obesity pharmacotherapy, 79 with bariatric surgery, and 18 with both bariatric surgery and medications. EE was reported by an estimated 58% (95%CI: 53, 63) of participants. Factors with the largest and most consistent magnitude of association with EES differences include age, sex, use of glucagon-like peptide-1 (GLP-1) agonists, history of sleeve gastrectomy and recent bariatric surgery. ConclusionEmotional eating affected more than half of people referred for obesity treatment. Age, sex, use of GLP-1 agonists, history of sleeve gastrectomy and recent bariatric surgery had the strongest associations with EE. These findings allow hypothesis generation about the underlying physiological mechanisms behind emotional eating for investigation in future research.

Evaluation of Liraglutide Usage for Treatment of Type 2 Diabetes at a Veterans Affairs Medical Center

Approximately 25% of Veterans have diabetes. Both the American Diabetes Association (ADA) and Department of Veterans Affairs/Department of Defense (VA/DoD) guidelines recommend treatment with glucagon-like peptide-1 (GLP-1) agonists, such as liraglutide, as second line options after metformin. In May 2016, the Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives updated criteria for use of GLP-1 agonists, increasing prescribing of this drug class. This coincided with recent data demonstrating cardiovascular benefit of liraglutide and led to increased usage at the Louis Stokes Cleveland Veterans Affairs Medical Center (LSCVAMC). A medication use evaluation was conducted to assess adherence to the criteria for use and to describe the characteristics of liraglutide usage at LSCVAMC. Sixty-two patients with T2DM and a prescription for liraglutide initiated between July 1, 2016 and January 30, 2017 were included. Patients were predominantly male (97%), had a baseline hemoglobin A1c (HgbA1c) of 9.2% and were prescribed metformin (82%). Adherence to the criteria for use was 90%. Follow-up HgbA1c after three to six months was obtained in 87% of patients. Average HgbA1c reduction of 0.76% was achieved in 72% of patients, while 28% were without improvement. Given the less than expected reduction in HgbA1c seen with liraglutide and the pharmacoeconomic impact of this medication, facility changes were implemented to ensure more appropriate prescribing of liraglutide at the LSCVAMC. Disclosure R.L. Rychel: None. M. Low: None. S.A. Watts: None. C. Falck-Ytter: None. K.M. Pascuzzi: None. A. Lyman: None.

Is Exenatide a Treatment for Parkinson's Disease?

There is growing interest in the use of glucagon-like peptide-1 agonists as treatments for Parkinson's disease following the recent publication of the results of the Exenatide-PD trial. In this randomized, double-blind, placebo controlled trial, patients with moderate stage Parkinson's disease treated with once-weekly subcutaneous injections of exenatide 2 mg (Bydureon) for 48 weeks, had a 3.5-point advantage over the placebo group in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (Part 3) in the practically defined OFF medication state, 12 weeks after cessation of the trial drug. In this article, we discuss some of the important issues of relevance to this trial, with regards to trial design, patient selection, choice of outcome measure and also place into context the implications these results have for patients with Parkinson's disease and the wider research community.

GLP-1 Agonists in Type 1 Diabetes Mellitus.

To review the use of GLP-1 agonists in patients with type 1 diabetes mellitus (T1DM). A search using the MEDLINE database, EMBASE, and Cochrane Database was performed through March 2016 using the search terms glucagon-like peptide 1 (GLP-1) agonists, incretin, liraglutide, exenatide, albiglutide, dulaglutide, type 1 diabetes mellitus All English-language trials that examined glycemic end points using GLP-1 agonists in humans with T1DM were included. A total of 9 clinical trials examining the use of GLP-1 agonists in T1DM were identified. On average, hemoglobin A1C (A1C) was lower than baseline, with a maximal lowering of 0.6%. This effect was not significant when tested against a control group, with a relative decrease in A1C of 0.1% to 0.2%. In all trials examined, reported hypoglycemia was low, demonstrating no difference when compared with insulin monotherapy. Weight loss was seen in all trials, with a maximum weight loss of 6.4 kg over 24 weeks. Gastrointestinal adverse effects are potentially limiting, with a significant number of patients in trials reporting nausea. The use of GLP-1 agonists should be considered in T1DM patients who are overweight or obese and not at glycemic goals despite aggressive insulin therapy; however, tolerability of these agents is a potential concern. Liraglutide has the strongest evidence for use and would be the agent of choice for use in overweight or obese adult patients with uncontrolled T1DM.

Clinical use of GLP-1 agonists and DPP4 inhibitors.

Type 2 diabetes is a growing problem, with 387 million people currently affected, and 592 million by 2035. Whilst diet and exercise are the corner stones of treatment, oral hypoglycaemic agents are often needed to achieve glycaemic control, thereby reducing the chance of long term diabetic complications. Biguanides and sulfonylureas have been the standard tablets used for this disorder, until 2005-7 when glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP4) inhibitors became available. Their major advantage over sulfonylureas is that they are weight lowering or weight neutral, and have a very low incidence of hypoglycaemia. GLP-1 agonists are injectables, whereas the DPP4 inhibitors are administered orally. Both agents are best used in combination with other hypoglycaemic medication, especially metformin and sodium glucose co-transporter 2 (SGLT2) inhibtors. Usage is increasing, being roughly equal to that of sulfonylureas, but less than that of metformin. Side effects appear to be minimal.

Efficacy and tolerability of GLP-1 agonists in patients with type 2 diabetes mellitus: an Indian perspective.

Glucagon like peptide-1 (GLP-1) agonists have been able to address the unmet needs of type 2 diabetes patients across the world. Indian patients with type 2 diabetes have also been able to benefit from effects of GLP-1 analogues to a more or less similar extent compared with patients from other parts of the world. As there is no nationwide data on use of GLP-1 agonists in India, we used the clinical data from different studies and compared them with the global data on GLP-1 analogues. The review is limited to only two approved GLP-1 analogues in India: exenatide and liraglutide. The efficacy of GLP-1 analogues, in terms of glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and postprandial glucose (PPG), is found to be similar in Indian patients compared with the global data. The other beneficial effects such as weight loss, incidence of hypoglycaemia were found to be on similar lines in the Indian setting. In a single-centre study, liraglutide reduced the dose of antihypertensive medications due to its effect on blood pressure. The gastrointestinal adverse effects such as nausea and vomiting were major adverse events, but these were transient and varied from one particular agent to another. Liraglutide is found to be superior in terms of compliance compared with exenatide in the Indian setting. Overall, the GLP-1 analogues have presented a treatment option that gives patient a benefit of glycaemic control, weight loss and very low incidence of hypoglycaemia, but the cost of the therapy presents a major barrier.

Ambulatory Treatment of Type 2 Diabetes in the U.S., 1997–2012

OBJECTIVEType 2 diabetes is increasingly common and associated with substantial morbidity and mortality. This study examines trends in the patterns and costs of drug treatment of type 2 diabetes from 1997 to 2012.RESEARCH DESIGN AND METHODSWe conducted descriptive analyses of cross-sectional data using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physician practices in the U.S. We focused on visits for diabetes among patients 35 years of age or older. We used the IMS Health National Prescription Audit of pharmacy dispensing to derive information about drug expenditures.RESULTSAmbulatory diabetes visits increased from 23 million treatment visits in 1997 (95% CI 21–25) to 35 million (32–37) in 2007 and declined to 31 million visits by 2012 (27–31). Between 1997 and 2012 biguanide use increased, from 23% (20–26) to 53% (50–56) of treatment visits. Glitazone use grew from 6% (4–8) in 1997 (41% [39–43] of all visits in 2005), but declined to 16% (14–18) by 2012. Since 2005, dipeptidyl peptidase-4 (DPP-4) inhibitor use increased steadily, representing 21% (18–23) of treatment visits by 2012. Glucagon-like peptide 1 (GLP-1) agonists accounted for 4% of treatment visits in 2012. Visits where two or more drug compounds were used increased nearly 40% from 1997 to 2012. Between 2008 and 2012, drug expenditures increased 61%, driven primarily by use of insulin glargine and DPP-4 inhibitors.CONCLUSIONSDeclining sulfonylurea and glitazone use has been offset by increases in DPP-4 inhibitor use and, to a lesser degree, use of GLP-1 agonists. Treatment of diabetes has grown in complexity while older treatments continue to be replaced or supplemented by newer therapies.

Use of Glucagon-Like Peptide-1 Agonists to Improve Islet Graft Performance

Human islet transplantation is an effective and promising therapy for type I diabetes. However, long-term insulin independence is both difficult to achieve and inconsistent. De novo or early administration of incretin-based drugs is being explored for improving islet engraftment. In addition to its glucose-dependent insulinotropic effects, incretins also lower postprandial glucose excursion by inhibiting glucagon secretion, delaying gastric emptying, and can protect beta-cell function. Incretin therapy has so far proven clinically safe and tolerable with little hypoglycemic risk. The present review aims to highlight the new frontiers in research involving incretins from both in vitro and in vivo animal studies in the field of islet transplant. It also provides an overview of the current clinical status of incretin usage in islet transplantation in the management of type I diabetes.

Journal of Diabetes NEWS

<i>Journal of Diabetes</i> NEWS

Counselling patients for GLP-1 analogue therapy: Comparing GLP-1 analogue with insulin counselling

Counselling patients for GLP-1 analogue therapy: Comparing GLP-1 analogue with insulin counselling